Gastric cancer ranks fifth in global cancer mortality,which is highly aggressive and heterogeneous.How-ever,the research and treatment of gastric cancer is hindered by short of research models that may characterize the developmental properties of gastric cancer.Gastric cancer organoid is a multicellular three-dimensional structure de-veloped in vitro,which can mimic the structure and function of native gastric cancer.Gastric cancer organoids have great application potential and development prospects in establishing gastric cancer research models,mimicking the tumor microenvironment,high-throughput screening of drugs,discovering new therapeutic targets,predicting clinical therapeutic responses,and guiding individualized treatment.In this paper,the progress of gastric cancer or-ganoids in basic research and clinical application is reviewed aiming for promoting the progress of preclinical re-search and supporting the clinical treatment of gastric cancer.

Humans ; Multiple Myeloma/drug therapy* ; Thalidomide/therapeutic use* ; Dexamethasone/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols ; Neoplasm Recurrence, Local/drug therapy*

Humans ; Asthma/drug therapy* ; Biological Therapy

Thyroid-associated ophthalmopathy(TAO)is an autoimmune disease associated with thyroid dysfunction that can significantly impact quality of life, result in visual impairment and facial disfigurement. Traditional treatments are often unsatisfactory. Studies have shown that teprotumumab, a human monoclonal antibody that can inhibit insulin-like growth factor 1 receptor(IGF-1R), has become an emerging targeted drug for TAO. Although the drug has proven to be effective and relatively safe in the treatment of TAO, adverse reactions are worthy of attention of ophthalmologists with the continuous promotion of clinical application, including hearing impairment, hyperglycemia, diarrhea, muscle spasms, infusion reactions, cognitive decline, thyroid suppression, alopecia, nausea and fatigue. Teprotumumab was generally well tolerated, with most adverse events being mild or moderate in severity. This paper aims to review the adverse reactions and precautions of teprotumumab in the treatment of TAO.

Objective To rapidly explore the chemical components of Xiaotan Tongfu formula, and to provide scientific basis for the basic research and clinical treatment of the formula. Methods Analysis was performed on an Agilent 1290 ultra-performance liquid chromatography system coupled with an Agilent 6530 accurate quality Q-TOF/MS system, by using a Waters ACQUITY UPLC BEH C₁₈ column (2.1 mm × 100 mm, 1.7 μm), with a gradient elution applying 0.1% aqueous formic acid solution and acetonitrile as a mobile phase. The flow rate was 0.3 ml/min. The column temperature was 30°C. The injection volume was 1 μl, and the detection wavelength was 254 nm. Mass spectrometry (MS) data were collected in both positive and negative ESI ion modes. Components in the formula were identified by using the in-house compound database, and comparing the retention time (tR), MS1 and MS2 data with the standard compounds, and the online compound MS database. Results A total of 55 compounds were identified from Coptis coptidis, Pseudomonas solani, Rhubarb, Araceae artemisiae and Pinellia chinensis. Conclusion The established UHPLC-Q-TOF/MS method could systematically and accurately identify the chemical components from Xiaotan Tongfu formula, and provided a reference for the quality marker selection and the research on the active ingredient.

Tumor-associated macrophages (TAMs), one of the dominating constituents of tumor microenvironment, are important contributors to cancer progression and treatment resistance. Therefore, regulation of TAMs polarization from M2 phenotype towards M1 phenotype has emerged as a new strategy for tumor immunotherapy. Herein, we successfully initiated antitumor immunotherapy by inhibiting TAMs M2 polarization via autophagy intervention with polyethylene glycol-conjugated gold nanoparticles (PEG-AuNPs). PEG-AuNPs suppressed TAMs M2 polarization in both in vitro and in vivo models, elicited antitumor immunotherapy and inhibited subcutaneous tumor growth in mice. As demonstrated by the mRFP-GFP-LC3 assay and analyzing the autophagy-related proteins (LC3, beclin1 and P62), PEG-AuNPs induced autophagic flux inhibition in TAMs, which is attributed to the PEG-AuNPs induced lysosome alkalization and membrane permeabilization. Besides, TAMs were prone to polarize towards M2 phenotype following autophagy activation, whereas inhibition of autophagic flux could reduce the M2 polarization of TAMs. Our results revealed a mechanism underlying PEG-AuNPs induced antitumor immunotherapy, where PEG-AuNPs reduce TAMs M2 polarization via induction of lysosome dysfunction and autophagic flux inhibition. This study elucidated the biological effects of nanomaterials on TAMs polarization and provided insight into harnessing the intrinsic immunomodulation capacity of nanomaterials for effective cancer treatment.

Objective:To analyze the molecular characteristics of Echovirus 11 (Echo11) strains isolated in Xiangyang, Hubei Province from 2016 to 2017 based on the sequences of VP1 gene.Methods:Rectal and throat swab specimens were collected from children with hand, foot and mouth disease (HFMD) in Xiangyang from 2016 to 2017. Echo11 strains were detected by real-time reverse transcriptase PCR (RT-PCR) and isolated after cultured in human rhabdosarcoma (RD) cells. The VP1 regions of Echo11 strains isolated from RD cells and the whole genomes of three representative Echo11 strains were amplified by conventional RT-PCR and the sequences were analyzed. DNAStar7.0 (MegAlign) and MEGA6.0 (Data) were used to analyze the homology and mutation sites in nucleotide and amino acid sequences. Neighbor-joining method was used to construct phylogenetic trees. Recombination analysis was performed with SimPlot software (BootScanning).Results:A total of 11 Echo11 strains were isolated from 3 494 HFMD cases, accounting for 0.31%. They were highly homologous in the VP1 gene. These strains shared 98.4%-100.0% homology in nucleotide sequences and 98.3%-100.0% homology in amino acid sequences. The homology between the 11 Echo11 strains and the prototype strain (Echo11/Gregory, X80059) was 73.9%-74.8% in nucleotide sequences and 87.7%-88.7% in amino acid sequences. All of the Echo11 strains circulating in Xiangyang were classified into lineage D, having a similarity to the strains circulating in some regions of mainland China since 2013. In multiple regions of the genome, the Echo11 strains isolated in Xiangyang were highly similar to the Henan Echo1 strains in 2010 and the Hubei Echo6 strains in 2015, suggesting there was recombination within the genome of Echo11 strains in Xiangyang.Conclusions:The Echo11 strains circulating in Xiangyang from 2016 to 2017 belonged to lineage D and were recombinant strains.

Objective    To investigate the safety and efficacy of 3D single-portal inflatable mediastinoscopic and laparoscopic esophagectomy for esophageal cancer. Methods    Clinical data of 28 patients, including 25 males and 3 females, aged 51-76 years, with esophageal squamous cell carcinoma undergoing single-portal inflatable mediastinoscopic and laparoscopic esophagectomy from June 2018 to June 2019 were retrospectively analyzed. Patients were divided into two groups according to different surgical methods including a 3D mediastinoscopic group (3D group, 10 patients) and a 2D mediastinoscopic group (2D group, 18 patients). The perioperative outcome of the two groups were compared. Results    Compared with the 2D group, the 3D group had shorter operation time (P=0.017), more lymph nodes resected (P=0.005) and less estimated blood loss (P=0.015). There was no significant difference between the two groups in the main surgeon's vertigo and visual ghosting (P>0.05). The other aspects including the indwelling time, postoperative hospital stay, pulmonary infection, arrhythmia, anastomotic fistula, recurrent laryngeal nerve injury were not statistically significant between the two groups (P>0.05). Conclusion    The 3D inflatable mediastinoscopic and laparoscopic esophagectomy for esophageal cancer, which optimizes the surgical procedures of 2D, is safe and feasible, and is worthy of clinical promotion in the future.

Objective    To investigate the short-term follow-up results of inflatable mediastinoscopy combined with laparoscopy in the treatment of esophageal cancer. Methods    Clinical data of 102 patients with esophageal cancer who underwent minimally invasive esophagectomy were enrolled in our hospital from January 2017 to January 2019. Patients were divided into two groups according to different surgical methods, including a single-port inflatable mediastinoscopy combined with laparoscopy group (group A, n=59, 53 males and 6 females, aged 63.3±7.6 years, ranging from 45 to 75 years) and a video-assisted thoracoscopy combined with laparoscopy group (group B, n=43, 35 males and 8 females, aged 66.7±6.7 years, ranging from 50-82 years). The short-term follow-up results of the two groups were compared. Results    Compared with the group A, the rate of postoperative pulmonary complication of the group B was significantly lower (18.64% vs. 4.65%, P<0.05). There was no significant difference between the two groups in other postoperative complications (P>0.05). The 6-month, 1-year, and 2-year survival rates were 96.61%, 89.83%, and 73.33%, respectively in the group A, and were 95.35%, 93.02%, and 79.17%, respectively in the group B. There was no significant difference in short-term survival rate after operation (P>0.05). Conclusion    In the treatment of esophageal cancer, the incidence of pulmonary complications of inflatable mediastinoscopy combined with laparoscopy is lower than that of traditional video-assisted thoracoscopy combined with laparoscopy, and there is no significant difference in other postoperative complications or short-term survival rate between the two methods. Inflatable mediastinoscopy combined with laparoscopy for radical esophageal cancer is a relatively safe surgical method with good short-term curative effects, and long-term curative effects need to be further tested.

BACKGROUND: The study aims to investigate the performance of a metagenomic next-generation sequencing (NGS)-based diagnostic technique for the identification of potential bacterial and viral infections and effects of concomitant viral infection on the survival rate of intensive care unit (ICU) sepsis patients. METHODS: A total of 74 ICU patients with sepsis who were admitted to our institution from February 1, 2018 to June 30, 2019 were enrolled. Separate blood samples were collected from patients for blood cultures and metagenomic NGS when the patients’ body temperature was higher than 38 °C. Patients’ demographic data, including gender, age, ICU duration, ICU scores, and laboratory results, were recorded. The correlations between pathogen types and sepsis severity and survival rate were evaluated. RESULTS: NGS produced higher positive results (105 of 118; 88.98%) than blood cultures (18 of 118; 15.25%) over the whole study period. Concomitant viral infection correlated closely with sepsis severity and had the negative effect on the survival of patients with sepsis. However, correlation analysis indicated that the bacterial variety did not correlate with the severity of sepsis. CONCLUSIONS: Concurrent viral load correlates closely with the severity of sepsis and the survival rate of the ICU sepsis patients. This suggests that prophylactic administration of antiviral drugs combined with antibiotics may be beneficial to ICU sepsis patients.