Cropping with Vicia villosa and native grass improves soil's bacterial structure and ecological network in a jujube orchard.

In a jujube orchard, cropping withgrass may influence bacterial diversity and ecological networks due to changes of physicochemical properties in soil, which has a serious effect on the stability of soil ecosystems. The aim of this study was to analyze the effects of different cultivation methods (CK: cleaning tillage; NG: cropping with native grass; VV: cropping with Vicia villosa) on the soil's bacterial structure and its co-occurrence network in a jujube orchard. The results showed that the highest moisture content, total nitrogen, and organic matter in the rhizosphere soil of a jujube orchard was found in the VV group. The soil's moisture content, total nitrogen, and organic matter in the VV group were 2.66%, 0.87 g kg-1, and 5.55 mg kg-1 higher than that found in the CK group. Compared to the CK group, the number of unique species in the rhizosphere soil in the NG and the VV groups increased by 7.33% and 21.44%. The PICRUSt and FAPROTAX analysis showed that sown grass had a greater influence on the ecological function of the soil's bacteria. Cropping with Vicia villosa and native grass significantly increased aerobic chemoheterotrophy, nitrogen respiration, nitrate reduction related to biochemical cycles, and the relative abundance of genes related to carbohydrate metabolism and the biodegradation of xenobiotics. The bacterial network complexity in the NG group was higher than that in the CK and VV groups and was greatest in the hub nodes (OTU42, Bacteroidota; OTU541, Nitrospiraceae). In this study, the ecological benefit seen in the soil's microbial function provides support to the theory that cropping with grass (Vicia villosa) increases the sustainable development of a jujube orchard.

A combined nomogram based on radiomics and hematology to predict the pathological complete response of neoadjuvant immunochemotherapy in esophageal squamous cell carcinoma.

BACKGROUND: To predict pathological complete response (pCR) in patients receiving neoadjuvant immunochemotherapy (nICT) for esophageal squamous cell carcinoma (ESCC), we explored the factors that influence pCR after nICT and established a combined nomogram model. METHODS: We retrospectively included 164 ESCC patients treated with nICT. The radiomics signature and hematology model were constructed utilizing least absolute shrinkage and selection operator (LASSO) regression, and the radiomics score (radScore) and hematology score (hemScore) were determined for each patient. Using the radScore, hemScore, and independent influencing factors obtained through univariate and multivariate analyses, a combined nomogram was established. The consistency and prediction ability of the nomogram were assessed utilizing calibration curve and the area under the receiver operating factor curve (AUC), and the clinical benefits were assessed utilizing decision curve analysis (DCA). RESULTS: We constructed three predictive models.The AUC values of the radiomics signature and hematology model reached 0.874 (95% CI: 0.819-0.928) and 0.772 (95% CI: 0.699-0.845), respectively. Tumor length, cN stage, the radScore, and the hemScore were found to be independent factors influencing pCR according to univariate and multivariate analyses (P < 0.05). A combined nomogram was constructed from these factors, and AUC reached 0.934 (95% CI: 0.896-0.972). DCA demonstrated that the clinical benefits brought by the nomogram for patients across an extensive range were greater than those of other individual models. CONCLUSIONS: By combining CT radiomics, hematological factors, and clinicopathological characteristics before treatment, we developed a nomogram model that effectively predicted whether ESCC patients would achieve pCR after nICT, thus identifying patients who are sensitive to nICT and assisting in clinical treatment decision-making.

Accurate location describe and management of lymph node recurrence after esophagectomy for thoracic esophageal squamous cell carcinoma: a retrospective cohort study.

BACKGROUND: Describe the accurate locations of lymph node recurrence (LNR) of Chinese patients with postoperative thoracic esophageal squamous cell carcinoma (ESCC) is essential for determining the need for further surveillance protocols and treatments. The authors aimed to evaluate the patterns of postoperative ESCC and its current risk stratification with LNR. METHODS: This population-based cohort study included a retrospective review of the medical records and image material of patients with ESCC who underwent LNR after radical surgery between January 2013 and September 2022, with a median follow-up time of 5.71 years. Clinical features were extracted from these records, and survival analysis was performed. The primary endpoint was the accurate location and range of LNR according to the nomenclature of the Japanese Society for Esophageal Diseases. The second endpoints was to explore the related factors of recurrence range and overall survival. RESULTS: A total of 3268 lymph node regions were recurrence from 1129 patients, with a mean of 2.89 regions per patient. No.104, 106, and 107 was the most common recurrence of thoracic ESCC with an LNR rate higher than 15%. In upper thoracic ESCC, No.105 was a common recurrence site and abdominal LNR was rare. In lower thoracic ESCC, retroperitoneal lymph node was a unique regions (15.4%). Anastomotic recurrence is an important recurrence pattern in patients with postoperative esophageal cancer, with an incidence of 24.5%. Rates of LNR in range of lymph node dissection was low (13.9%). The median time of LRT was 20.0 (1.5-184.0) months. High range of recurrence was associated with significantly poorer OS in patients. Multiple linear regression analysis identified demonstrated N stage, tumor differentiation, adjuvant radiotherapy, and total lymph nodes removed were association with recurrence range for patients. CONCLUSIONS: Supraclavicular and upper mediastinums lymph nodes were common recurrence site for ESCC patients, and careful initial staging and surveillance are needed. Thorough lymph node dissection may reduce the range of regional recurrence.

A Phase 1b Clinical Trial of Neoadjuvant Radio-immunotherapy for Esophageal Squamous Cell Cancer.

PURPOSE: Neoadjuvant chemoradiotherapy is the recommended treatment for patients with resectable esophageal cancer but is associated with a higher incidence of adverse effects. Given the efficacy of immunotherapy, we propose a chemotherapy-free regimen of neoadjuvant radio-immunotherapy (NRIT) to balance therapeutic efficacy and potential side effects or overtreatment. METHODS AND MATERIALS: In this phase 1b clinical trial, we assessed the safety and efficacy of NRIT in esophageal squamous cell cancer. The enrolled patients received 41.4 Gy of radiation and 4 cycles of 240 mg of toripalimab injection before surgery. The primary endpoint was treatment-related adverse events and the secondary endpoints were pathologic complete response and major pathologic response. Immunohistochemistry and multiplex immunofluorescence staining were used to evaluate the tumor microenvironment before and after neoadjuvant treatment. RESULTS: Of the 22 patients enrolled, 19 underwent R0 surgery. One patient discontinued neoadjuvant immune therapy due to experiencing a grade 3 treatment-related adverse event. Three patients did not undergo surgery due to tumor progression or side effects. Among the patients who underwent surgery, 3 patients experienced serious complications shortly after surgery. Upon pathologic evaluation, the pathologic complete response and major pathologic response rates were 47.4% and 68.4%, respectively. CONCLUSIONS: The NRIT regimen is safe and feasible for patients with esophageal squamous cell cancer.

YY1 modulates the radiosensitivity of esophageal squamous cell carcinoma through KIF3B-mediated Hippo signaling pathway.

Radiotherapy is an important strategy in the comprehensive treatment of esophageal squamous cell carcinoma (ESCC). However, effectiveness of radiotherapy is still restricted by radioresistance. Herein, we aimed to understand the mechanisms underlying ESCC radioresistance, for which we looked into the potential role of YY1. YY1 was upregulated in radioresistant tissues and correlated with poor prognosis of patients with ESCC. YY1 depletion enhanced the radiosensitivity of ESCC in vitro and in vivo. Multi-group sequencing showed that downregulation of YY1 inhibited the transcriptional activity of Kinesin Family Member 3B (KIF3B), which further activated the Hippo signaling pathway by interacting with Integrin-beta1 (ITGB1). Once the Hippo pathway was activated, its main effector, Yes-associated protein 1 (YAP1), was phosphorylated in the cytoplasm and its expression reduced in the nucleus, thus enhancing the radiosensitivity by regulating its targeted genes. Our study provides new insights into the mechanisms underlying ESCC radioresistance and highlights the potential role of YY1 as a therapeutic target for ESCC.

Generation of Simulated "Natural" Nanoplastics from Polypropylene Food Packaging as the Experimental Standard.

Current toxicology research on nanoplastics (NPs) generally uses commercial spherical NPs. However, the physicochemical characteristics of commercial NPs are significantly different from those of NPs formed under natural conditions, possibly affecting the validity of the results. In analytical chemistry, a reference sample is selected such that its physicochemical properties are as similar as possible to the target. Therefore, a simulated "natural" NP synthesized in the laboratory that closely resembles naturally derived NPs would be used as an authentic standard. Here, we established the assay of scanning electron microscope (SEM)-particle size distribution analyzer (PSDA)-surface-enhanced Raman scattering (SERS) to detect NPs and prepared simulated "natural" NPs from polypropylene food packaging material using a method that mimics natural conditions. Nanofiltration was used to isolate three sets of simulated NPs with particle sizes ranging from 50-100 nm, 100-200 nm, and 200-400 nm. These simulated "natural" NPs were more similar to naturally occurring counterparts when compared with commercial NPs. These new standard NPs, which should be scalable for large-scale use, will improve the accuracy, reliability, and translatability of toxicological studies of NPs.

Lentinan protects Caenorhabditis elegans against fluopyram-induced toxicity through DAF-16 and SKN-1 pathways.

Fluopyram, a SDH inhibitor fungicide, is widely used in agriculture to control fungi and nematodes. However, fluopyram has been proved toxic that caused damage to organs through oxidative stress. The development of natural extracts that can reduce oxidative damage is a promising method. Lentinan is isolated from Lentinus edodes and has been verified its antioxidant activity. In this study, Caenorhabditis elegans was used to evaluate the protective effects of lentinan against fluopyram-induced toxicity and the possible mechanisms. Results showed that lentinan pretreatment notably increased the survival rate of N2 nematodes by 15.0 % and extended the lifespan by 91.5 %, compared with the fluopyram treatment. Lentinan pretreatment reverted the inhibition of the locomotion and reproduction of C. elegans under the fluopyram stress. In addition, lentinan pretreatment significantly decreased the contents of ROS and MDA in N2 nematodes. Moreover, pretreated with lentinan significantly recovered the decreased activities of CAT, SOD, GST and SDH induced by fluopyram. Lentinan pretreatment enhanced the mRNA levels of daf-16 and skn-1 and their downstream genes in the nematodes compared with the fluopyram group. In daf-16 and skn-1 mutants, the lifespan, ROS and related genes expression were not significantly changed in lentinan pretreatment. Pretreated with lentinan significantly enhanced the fluorescence intensity of SOD-3::GFP and GST-4::GFP, and promoted the nuclear translocation of DAF-16 and SKN-1 under the fluopyram stress. In summary, these findings indicated that lentinan protected C. elegans from fluopyram-induced toxicity via DAF-16 and SKN-1.

Simulation and Characterization of Nanoplastic Dissolution under Different Food Consumption Scenarios.

Understanding of the potential leaching of plastic particles, particularly nanoplastics (NPs), from food packaging is crucial in assessing the safety of the packaging materials. Therefore, the objective of this study was to investigate potential exposure risks by simulating the release of NPs from various plastic packaging materials, including polypropylene (PP), general casting polypropylene (GCPP) or metalized casting polypropylene (MCPP), polyethylene (PE), polyethylene terephthalate (PET), and polyphenylene sulfone (PPSU), under corresponding food consumption scenarios. Surface-enhanced Raman scattering (SERS) and scanning electron microscopy (SEM) were utilized to identify and characterize the NPs leached from plastic packaging. The presence of separated NPs was observed in PP groups subjected to 100 °C hot water, GCPP plastic sterilized at a high temperature (121 °C), and PE plastic soaked in 100 °C hot water, exhibited a distorted morphology and susceptibility to aggregation. The findings suggest that the frequent consumption of takeaway food, hot beverages served in disposable paper cups, and foods packaged with GCPP materials may elevate the risk of ingestion of NPs. This reminds us that food packaging can serve as an important avenue for human exposure to NPs, and the results can offer valuable insights for food safety management and the development of food packaging materials.

Sintilimab as maintenance treatment for local/regional recurrent esophageal squamous carcinoma after concurrent chemoradiotherapy: a single-arm Ib/II phase study.

Background: Esophageal cancer (EC) is an aggressive neoplasm of the gastrointestinal tract that is usually treated with a combination of chemotherapy, radiotherapy (RT), and/or surgery, according to disease status. Despite the availability of multimodal therapeutic strategies, local recurrence is frequently observed. However, there is no standard treatment or promising therapeutic approach for local recurrence or metastatic esophageal carcinoma after the RT. This study tended to investigate the efficacy and safety of sintilimab maintenance after concurrent chemoradiotherapy (CCRT) for local/regional recurrent esophageal squamous carcinoma. Methods: This study was a single-arm, phase Ib/II trial conducted in a single site in China. Patients previously radically treated (surgery or CCRT), histologically confirmed, local or regional recurrence esophageal squamous carcinoma, qualified for the study design, were treated with 25-28 times radiotherapy plus raltitrexed once every 3 weeks for up to two cycles. Patients who have not progressed after CCRT received sintilimab as maintenance once every 3 weeks up to 1 year. Primary endpoints were overall survival (OS) and safety. Secondary endpoints were progression-free survival (PFS), objective response rate (ORR), and duration of response (DOR). Results: Between September 2019 and March 2022, in a total of 36 enrolled patients, 34 pts completed CCRT. Three patients excluded due to violation of the exclusion criteria (1 pt) and consent withdrawal (2 pts). Finally, 33 pts were included in the final analysis, in which 3 pts had disease progression, and the remaining 30 entered maintenance therapy with sintilimab. The median follow-up time was 12.3 months. Median OS was 20.6 months (95%CI 10.5-NA) and the 1-year OS rate was 64%. Median PFS was 11.5 months (95%CI 5.29-21.3) and the 1-year PFS rate was 43.6%. The ORR was 63.6% (95%CI 44.6-77.8), including 2 cases of CR and 19 cases of PR. The DCR was 19.9%, the median DOR was 19.5 months, and the median TTR was 2.4 months. The rate of any grade TRAEs was 96.7%; ≥Grade 3 TRAE was 23.4%. The incidence of immune-related AE was 60%, most of which were grade 1-2, and only one case of thyroid-stimulating hormone increased was irAE with grade 3 or above. Conclusion: Sintilimab has shown promising clinical efficacy and a manageable safety profile as maintenance therapy after CCRT for local/regional recurrent esophageal squamous carcinoma. In addition, further confirmation from a large-scale real-world study is still needed.

Brassinosteroids alleviate nanoplastic toxicity in edible plants by activating antioxidant defense systems and suppressing nanoplastic uptake.

As emerging pollutants of global concern, absorbed nanoplastics might have negative impacts on plant development and nutrient uptake, thereby decreasing yields. If nanoplastics are transferred to the edible parts of plants, they may pose a threat to human health when large quantities are ingested. While nanoplastic-induced phytotoxicity is attracting increasing attention, little is known about how to inhibit nanoplastic accumulation in plants and reduce the subsequent adverse effects. Here we investigated the absorption and accumulation of polystyrene nanoplastics (PS-NPs) in different plant species and the role of brassinosteroids in alleviating PS-NP toxicity. Brassinosteroids inhibited accumulation of PS-NPs in tomato fruit and reversed PS-NP-induced phytotoxicity to promote plant growth and increase fresh weight and plant height. Brassinosteroids also reversed the induction of aquaporin-related genes by PS-NPs including TIP2-1, TIP2-2, PIP2-6, PIP2-8, PIP2-9, SIP2-1, and NIP1-2, providing a potential stress mechanism by which PS-NPs accumulate in the edible parts and targets for inhibition. In transcriptomic analyses, brassinosteroids enhanced fatty acid and amino acid metabolism and synthesis. In conclusion, exogenous application of 50 nM brassinosteroids alleviated the adverse effects of PS-NPs on plants, and exogenous application of brassinosteroids might be an effective means to minimize PS-NP-induced phytotoxicity.

Advances in transport and toxicity of nanoparticles in plants.

In recent years, the rapid development of nanotechnology has made significant impacts on the industry. With the wide application of nanotechnology, nanoparticles (NPs) are inevitably released into the environment, and their fate, behavior and toxicity are indeterminate. Studies have indicated that NPs can be absorbed, transported and accumulated by terrestrial plants. The presence of NPs in certain edible plants may decrease harvests and threaten human health. Understanding the transport and toxicity of NPs in plants is the basis for risk assessment. In this review, we summarize the transportation of four types of NPs in terrestrial plants, and the phytotoxicity induced by NPs, including their impacts on plant growth and cell structure, and the underlying mechanisms such as inducing oxidative stress response, and causing genotoxic damage. We expect to provide reference for future research on the effects of NPs on plants.

Photothermal-based nanomaterials and photothermal-sensing: An overview.

Based on the excellent properties, photothermal nanomaterials have been widely used in many fields, such as trace substance detection, optical imaging, medical diagnosis and treatment. Different from colorimetric, fluorescent and electrochemical methods which often suffer from the problems of high background interference, operation procedure dependence and high cost, photothermal sensing can effectively break the limitations of the above methods and become an alternative strategy due to its high resolution and spatial controllability. Especially in recent years, the continuous development of new materials and the introduction of portable, low-cost and precision photothermal measuring equipment can significantly improve the application potential of photothermal detection. Here, we conducted comprehensive analyses on those studies. This review summarized the progress of photothermal detection over recent years, including the main types of photothermal nanomaterials and the generation principle of the photothermal effect, the relevant matching thermometry tools, and the applications in the designing of sensing strategies. It aims to provide a reference for researchers to synthesize nanomaterials with stable and high photothermal conversion efficiency and develop more effective and sensitive detection methods.

Efficacy and safety of sintilimab plus docetaxel in patients with previously treated advanced non-small cell lung cancer: a prospective, single-arm, phase II study in China.

PURPOSE: Although immune checkpoint inhibitor monotherapy has been used as a second-line treatment in advanced non-small cell lung cancer (NSCLC), the improvement in progression-free survival (PFS) remains unsatisfactory. We investigated the feasibility of sintilimab plus chemotherapy as a second-line treatment in advanced NSCLC. METHODS: This was a phase II, single-arm, prospective study in advanced NSCLC patients who had failed standard platinum-based chemotherapy (ChiCTR1900027634, Registered 22 November 2019). Eligible patients received docetaxel 75 mg/m2 (day 1) plus sintilimab 200 mg (day 3) Q3W. Those did not progress after 4-6 cycles received sintilimab 200 mg Q3W as maintenance treatment. The primary endpoint was PFS. RESULTS: Forty patients were enrolled between October 2019 and October 2020. With a median follow-up of 12.2 months, the median PFS was 5.8 months, and the PFS rates at 6 and 12 months were 48% and 30%, respectively. The median overall survival (OS) was 12.6 months, with a 12-month OS rate of 62.0%. The overall response rate was 32.4%, and the disease control rate was 89.2%. The incidence of all and ≥ grade 3 treatment-related adverse events (TRAEs) were 65% (26/40) and 17.5% (7/40), respectively. No TRAEs-related permanent treatment discontinuation or death occurred. bTMB reduction at 6 weeks was associated with a longer PFS (NR vs 3.0 months, P < 0.0001). CONCLUSION: This prospective phase II study in China suggested that sintilimab plus docetaxel might improve PFS and tumor response with good tolerability for Chinese patients with previously treated advanced NSCLC. bTMB reduction at 6 weeks could serve as a potential predictive biomarker for this regimen.

Low-acidity ALUMINUM-DEPENDENT MALATE TRANSPORTER4 genotype determines malate content in cultivated jujube.

Jujube (Ziziphus jujuba Mill.), the most economically important fruit tree in Rhamnaceae, was domesticated from sour jujube (Z. jujuba Mill. var. spinosa (Bunge) Hu ex H.F.Chow.). During domestication, fruit sweetness increased and acidity decreased. Reduction in organic acid content is crucial for the increase in sweetness of jujube fruit. In this study, the determination of malate content among 46 sour jujube and 35 cultivated jujube accessions revealed that malate content varied widely in sour jujube (0.90-13.31 mg g-1) but to a lesser extent in cultivated jujube (0.33-2.81 mg g-1). Transcriptome sequencing analysis showed that the expression level of Aluminum-Dependent Malate Transporter 4 (ZjALMT4) was substantially higher in sour jujube than in jujube. Correlation analysis of mRNA abundance and fruit malate content and transient gene overexpression showed that ZjALMT4 participates in malate accumulation. Further sequencing analyses revealed that three genotypes of the W-box in the promoter of ZjALMT4 in sour jujube associated with malate content were detected, and the genotype associated with low malate content was fixed in jujube. Yeast one-hybrid screening showed that ZjWRKY7 binds to the W-box region of the high-acidity genotype in sour jujube, whereas the binding ability was weakened in jujube. Transient dual-luciferase and overexpression analyses showed that ZjWRKY7 directly binds to the promoter of ZjALMT4, activating its transcription, and thereby promoting malate accumulation. These findings provide insights into the mechanism by which ZjALMT4 modulates malate accumulation in sour jujube and jujube. The results are of theoretical and practical importance for the exploitation and domestication of germplasm resources.

Distributions of fallout 137Cs, 239+240Pu and 241Am in a soil core from South Central China.

The source and vertical distribution of 137Cs,239+240Pu and 241Am activity concentrations in a soil core from Hunan Province, China were investigated. The maximum 137Cs and 239+240Pu activity concentrations were 15.45 ± 0.76 mBq/g and 0.819 ± 0.066 mBq/g, respectively. While the maximum 241Am activity concentration in samples obtained from the core was 0.341 ± 0.019 mBq/g. The 240Pu/239Pu atom ratio and the 137Cs/239+240Pu activity ratio were 0.183 ± 0.011 and 19.5 ± 1.8, respectively, and both were consistent with the characteristic value of global fallout. The integrated 241Am/239+240Pu activity ratio for global fallout was also re-estimated. The measured 241Am/239+240Pu activity ratio (average 0.43 ± 0.07) in the samples was very close to the estimated value (0.45), which suggested their 241Am also came from the global fallout. Regarding the vertical distribution of 137Cs, 239+240Pu and 241Am in these red soil samples, all these radionuclides had higher concentrations in upper layers of several centimeters of soil while they had slightly lower concentrations in lower soil layers down to 30 cm. Vertical distributions of 137Cs/239+240Pu and 241Am/239+240Pu activity ratios indicated the migration velocity was Am ≈ Pu > Cs. The intrinsic chemical properties of the radionuclides as well as soil type and properties (acidic, nutrient-deficient and low in organic matter and cation exchange capacity) might be reasons for the differences in their migration behaviors.

Risk factors of esophageal fistula induced by re-radiotherapy for recurrent esophageal cancer with local primary site.

PURPOSE: The purpose of the present study was to investigate risk factors for esophageal fistula (EF) in patients with recurrent esophageal cancer receiving re-radiotherapy with or without chemotherapy. METHODS: We reviewed retrospectively the clinical characters and dosimetric parameters of 96 patients with recurrent esophageal cancer treated with re-radiotherapy in Cancer Hospital Affiliated to Shandong First Medical University between August 2014 and January 2021.Univariate and multivariate logistic regression analyses were provided to determine the risk factors of EF induced by re-radiotherapy. RESULTS: The median time interval between two radiotherapy was 23.35 months (range, 4.30 to 238.10 months). EF occurred in 19 patients (19.79%). In univariate analysis, age, T stage, the biologically equivalent dose in the re-radiotherapy, total biologically equivalent dose, hyperfractionated radiotherapy, ulcerative esophageal cancer, the length of tumor and the maximum thickness of tumor had a correlation with the prevalence of EF. In addition, age (HR = 0.170, 95%CI 0.030-0.951, p = 0.044), T stage (HR = 8.369, 95%CI 1.729-40.522, p = 0.008), ulcerative esophageal cancer (HR = 5.810, 95%CI 1.316-25.650, p = 0.020) and the maximum thickness of tumor (HR = 1.314, 95%CI 1.098-1.572, p = 0.003) were risk factors of EF in multivariate logistic regression analysis. CONCLUSIONS: The incidence of EF was significantly increased in patients with recurrent esophageal cancer who underwent re-radiotherapy. This study revealed that age, T stage, ulcerative esophageal cancer and the maximum thickness of the tumor were risk factors associated with EF. In clinical work, patients with risk factors for EF ought to be highly concerned and individualized treatment plans should be taken to reduce the occurrence of EF.

Efficacy and safety comparison of PD-1 inhibitors vs. PD-L1 inhibitors in extensive-stage small-cell lung cancer: a retrospective comparative cohort study.

Background: Evidence from clinical research and meta-analyses have suggested that programmed cell death 1 (PD-1) inhibitors and programmed cell death ligand 1 (PD-L1) inhibitors plus chemotherapy could achieve a significant survival benefit for extensive-stage small-cell lung cancer (ES-SCLC) patients. However clinical researches concerned about the comparation between the PD-1 and PD-L1 inhibitors were relatively lacking. Methods: We collected the data of ES-SCLC patients treated with PD-1 inhibitors or PD-L1 inhibitors. The primary endpoints were overall survival (OS) and progression-free survival (PFS). Secondary endpoint included adverse events (AEs). Results: The data of 221 ES-SCLC patients treated with PD-1 (n=146) or PD-L1 inhibitors (n=75) between February 2017 and June 2020 were retrospectively collected. The median OS (mOS) and median PFS (mPFS) were 19.07 and 8.27 months, respectively, in patients treated with PD-1 inhibitors. In the PD-L1 group, mOS has not been reached, and mPFS was 7.95 months. No significant differences were observed between the 2 groups in OS [hazard ratio (HR), 1.472; 95% confidence interval (CI), 0.847-2.220; P=0.198] and PFS (HR, 0.816; 95% CI, 0.577-1.155; P=0.251). The rates of patients showed AEs of any grade treated with PD-1 or PD-L1 were 67.12% and 64.00%, with no significant difference (P=0.642, χ2=0.216), ≥3 grade AEs occurred in 42 (28.76%) and 16 (21.33%) patients treated with PD-1 and PD-L1 inhibitors separately, also no significant difference (P=0.234, χ2=1.415) was observed. According to subgroup analysis, camrelizumab revealed a longer mPFS (15.17 months) compared with other immune-checkpoint inhibitors (ICIs). PD-1 and PD-L1 inhibitors revealed comparable efficacy in ES-SCLC patients with brain metastases, with no significant differences in OS (HR, 1.505; 95% CI, 0.684-3.311; P=0.309) and PFS (HR, 0.649; 95% CI, 0.356-1.182; P=0.157). Conclusions: PD-1 and PD-L1 inhibitors might achieved comparable survival benefit and safety in ES-SCLC patients. A longer PFS was observed in patients treated with PD-1 inhibitors in the first-line treatment, and the PD-1 inhibitor camrelizumab might have achieved a better PFS compared with other ICIs.

The landscape of m6A regulators in esophageal cancer: molecular characteristics, immuno-oncology features, and clinical relevance.

Background: Squamous cell carcinoma (SCC) and adenocarcinoma (AC) are the two main pathological types of esophageal cancer (EC), which differ in molecular features, genetic variation, and treatment sensitivity. However, as a key process in tumorigenesis and development, the role of N6-methyladenosine (m6A) regulators in esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) is not fully understood. Methods: This study systematically compared the role of m6A regulators of ESCC and EAC in terms of molecular characteristics, immuno-oncology characteristics, and clinical relevance, and validated our findings in a long-term follow-up patient cohort. Results: There were many differences in m6A regulators between ESCC and EAC in terms of expression patterns, genetic variation, association with tumor pathways, immune signatures, and immunotherapy sensitivity. Furthermore, VIRMA was identified as a factor with opposite functional and prognostic effects in ESCC and EAC. ESCC patients with high VIRMA expression and EAC patients with low VIRMA expression had a better prognosis. Single-center data showed that low expression of FTO may be associated with superior immunotherapy efficacy in ESCC patients. Conclusions: The results herein provide novel ideas for understanding the tumor characteristics, occurrence, and development of ESCC and EAC, and suggest new targets for the treatment and intervention of EC.

Short-term dynamics of circulating tumor DNA predicting efficacy of sintilimab plus docetaxel in second-line treatment of advanced NSCLC: biomarker analysis from a single-arm, phase 2 trial.

OBJECTIVE: Robust biomarker predicting efficacy of immunotherapy is limited. Circulating tumor DNA (ctDNA) sought to effectively monitor therapeutic response as well as disease progression. This study aims to investigate predictive role of ctDNA short-term dynamic change (6 weeks postimmunotherapy) in a single-arm, phase 2 trial of sintilimab plus docetaxel for previously treated advanced non-small cell lung cancer (NSCLC) patients. METHODS: A total of 33 patients with advanced NSCLC with disease progression during or after any first-line treatment were prospectively enrolled between 2019 and 2020. Patients received sintilimab (200 mg, day 1, every 3 weeks) plus docetaxel (75 mg/m2, day 3, every 3 weeks) for 4-6 cycles, followed by maintenance therapy with sintilimab (200 mg, day 1, every 3 weeks) until disease progression or unacceptable toxic effects. Blood samples were prospectively collected at baseline, and after 2 cycles of treatment (6 weeks post-treatment). All samples were subjected to targeted next-generation sequencing with a panel of 448 cancer-related genes. The landscape of high-frequency genomic profile of baseline and 6th week was described. Major molecular characteristics in preselected genes of interest associated with response to second-line chemoimmunotherapy were analyzed. The curative effects and prognosis of patients were evaluated. RESULTS: Patients with ctDNA clearance at 6th week had decreased tumor volume, while most patients with positive ctDNA at 6th-week experienced an increase in tumor volume. Positive 6th-week ctDNA was associated with significantly shorter progression-free survival (PFS) (91 vs NR days; p<0.0001) and overall survival (47 vs 467 days; p =0.0039). Clearance of clonal mutations and none new clonal formation at 6th week were associated with longer PFS (mPFS 89 vs 266 days, p =0.003). ctDNA clearance at 6th week was an independent risk factor for progression or death (HR=100 (95% CI 4.10 to 2503.00), p=0.005). CONCLUSION: ctDNA status and ctDNA mutation clearance putatively serve as predictive biomarkers for sintilimab combined with docetaxel chemotherapy in pretreated advanced NSCLC patients.

Hypofractionated Simultaneous Integrated Boost Radiotherapy Versus Conventional Fractionation Radiotherapy of Early Breast Cancer After Breast-Conserving Surgery: Clinical Observation and Analysis.

Purpose: The objective of this retrospective study is to evaluate the efficacy and safety of hypofractionated simultaneous integrated boost radiotherapy for early breast cancer patients undergoing breast-conserving surgery. Methods: A total of 185 women with early breast cancer undergoing breast-conserving surgery were retrospectively divided into hypofractionated simultaneous integrated boost group and conventional fractionation group. Hypofractionated simultaneous integrated boost included 104 patients and the dose of whole-breast radiation reached 42.56 Gy in 16 fractions and simultaneously tumor bed boost to 48 Gy in 16 fractions, which course of radiotherapy was 22 days. The 81 patients of the conventional fractionation group received whole breast radiation to 50 Gy in 25 fractions and followed by tumor bed boost to 10 Gy in 5 fractions, which course of radiotherapy was 40 days. Clinical information including patients' characteristics, skin toxicity, myelosuppression, radiation pneumonia, and cosmetic effects was recorded to analyze the influence of age, chemotherapy, position, and breast volume on the results of radiotherapy. Results: Hypofractionated simultaneous integrated boost group had no case of recurrence after a median follow-up of 25.6 months (9-47 months)) as compared with 2 after a median follow-up of 33.4 months (25-45 months) in the conventional fractionation group. The 2 groups had similar results in skin toxicity, cosmetic outcomes, and radiation pneumonia. In terms of myelosuppression, grade 1, grade 2, and grade 3 of myelosuppression in the hypofractionated simultaneous integrated boost group accounted for 16.7%, 12.3%, and 3.5% as compared with 30.0%, 21.1%, and 12.3% of the conventional fractionation group, respectively (P = .000). Conclusions: HF-SIB RT is a considerable option in patients after breast-conserving surgery with a lower degree of myelosuppression and shorter treatment time.