Engineered DBCO+PD-1 Nanovesicles Carrying 1-MT for Cancer-Targeted Immunotherapy.

Liver cancer cells evade immune surveillance and anticancer response through various pathways, including the programmed death-ligand 1 (PD-L1)/programmed death-1 (PD-1) immune checkpoint axis that exhausts CD8+ T cells. Inhibitors or antibodies of the PD-L1/PD-1 signaling axis are considered promising drugs for cancer immunotherapy and exhibit favorable clinical responses. However, adverse effects, immune tolerance, and delivery barriers of most patients limit the clinical application of PD-L1/PD-1 antibodies. Thus, it is critical to develop a novel delivery strategy to enhance anticancer immunotherapy. In this study, we bioengineered cell membrane-derived nanovesicles (NVs) presenting PD-1 proteins and dibenzocyclooctyne (DBCO) to encapsulate 1-methyltryptophan (1-MT) (DBCO+PD-1@1-MT NVs). DBCO can specifically interact with N-azidoacetylmannosamine-tetraacetylate (Ac4ManN3) labeled onto metabolic cells for targeted killing of cancers. We next explored the effects of DBCO+PD-1@1-MT NVs on anticancer Hepa1-6 cells in vitro and in vivo. Results showed that PD-1@1-MT NVs dramatically inhibited Hepa1-6 proliferation, promoted peripheral blood mononuclear cell (PBMC) expansion, and strengthened anticancer therapy via blockading the PD-1/PD-L1 immune checkpoint axis, owing to the 1-methyltryptophan (1-MT) enhancement of anticancer immunotherapy efficacy through suppressing the activity of indoleamine 2,3-dioxygenase (IDO). Thus, 1-MT was encapsulated into PD-1 NVs to synergistically enhance cancer immunotherapy. Results have shown that PD-1@1-MT NVs obviously attenuated tumor growth, promoting IFN-γ production, increasing the T cells infiltration in tumors and spleens, and improving the survival period of tumor-bearing mice compared to monotherapy. Therefore, we propose a promising delivery strategy of the combination of DBCO+PD-1 NVs and 1-MT for specific and effective cancer-targeted immunotherapy.

Gastrointestinal cytomegalovirus disease secondary to measles in an immunocompetent infant: A case report.

BACKGROUND: Gastrointestinal cytomegalovirus (CMV) disease occurs commonly in immunocompromised/immunodeficient patients with advanced human immunodeficiency virus infection, neoplasm, solid organ transplantation, hematopoietic stem cell transplantation, or treatment with immunosuppressants, but is rarely reported in association with measles infection. CASE SUMMARY: We describe a case of extensive gastrointestinal CMV disease secondary to measles infection in a 9-mo-old boy who presented with persistent fever and bloody diarrhea. His condition was improved after ganciclovir treatment. Serological analysis of CMV showed negative immunoglobulin (Ig) M and positive IgG. Blood CMV-DNA was 9.26 × 103 copies/mL. The diagnosis of gastrointestinal CMV disease was confirmed by histopathological findings of intranuclear and intracytoplasmic inclusions and Owl's eye inclusion. This case highlights the differential diagnosis and histopathological characteristics of gastrointestinal CMV infection and laboratory tests. CONCLUSION: Extensive gastrointestinal CMV lesions can be induced by the immune suppression secondary to measles infection. Rational, fast, and effective laboratory examinations are essential for suspected patients.

Prevention program for the COVID-19 in a children's digestive endoscopy center.

The pneumonia caused by the coronavirus disease-2019 (COVID-19) outbreak in Wuhan, China constitutes a public health emergency of international concern. The gastrointestinal symptoms of vomiting, diarrhea and abdominal pain and the detection of COVID-19 nucleic acid from fecal specimens in a small number of patients suggest the possibility of transmission via the gastrointestinal tract. People of all ages are vulnerable to this virus, including children. Digestive endoscopy is an invasive procedure during which children cannot wear masks; therefore, they have higher risks of exposure to COVID-19, and the digestive endoscopy center is a relatively high-risk area for COVID-19 infection. Based on these factors and in combination with related policies and regulations, a prevention and control program for the COVID-19 pneumonia in a children's digestive endoscopy center was established to prevent the COVID-19 nosocomial infection.

Accuracy of multi-echo Dixon sequence in quantification of hepatic steatosis in Chinese children and adolescents.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is currently the outstanding cause of chronic liver disease in children and adolescents, especially in overweight and obese groups. Liver biopsy is the reference standard to diagnose NAFLD but invasive, thus it is not the best choice in clinical diagnosis and follow-up. Magnetic resonance (MR) is widely used in clinical trials to noninvasively quantify liver fat content in adults and children in foreign countries. While currently, it is rarely used in Chinese children and adolescents. We postulated that quantifying hepatic steatosis by MR could be extended to children and adolescents in China. AIM: To investigate the accuracy of MR imaging (MRI) in quantifying liver fat with MR spectroscopy (MRS) as a reference. A secondary goal was to assess the prevalence of NAFLD in overweight and obese Chinese children and adolescents. METHODS: There were 86 children and adolescents enrolled in this study, including 65 overweight and obese children and 21 healthy children. The participants underwent MRI and MRS. MRI and MRS were performed using multi-echo Dixon and HISTO sequences, respectively, to calculate hepatic proton density fat fraction (PDFF). Hepatic steatosis was diagnosed using MRS-PDFF > 5% as the threshold. Spearman's analysis was used to evaluate the correlation between MRI and MRS. The agreement between these two methods was assessed by Bland-Altman analysis. RESULTS: The MRI-PDFF in the MRS region of interest and the entire liver was 9.9% ± 10.3% with a range of 0.3%-39.9%, and 10.6% ± 9.4% with a range of 1.9%-38.9%, respectively. The MRS-PDFF was 9.1% ± 10.0%, with a range of 0.5%-37.8%. The incidence of hepatic steatosis detected by MRS-PDFF was 46.5% (40/86) of all participants, all of whom belonged to the overweight and obese group. Spearman's analysis indicated an excellent correlation between multi-echo Dixon and MRS (r > 0.9, P < 0.01). Bland-Altman analysis also demonstrated a good agreement between these two methods. CONCLUSION: Multi-echo Dixon shows an excellent correlation and agreement with MRS in quantifying liver fat content and could be a potential tool to detect hepatic steatosis in Chinese children and adolescents.

[Analysis of 3 cases with Mycoplasma pneumoniae-associated hemophagocytic syndrome and review of literature].

OBJECTIVE: To analyze the clinical characteristics of Mycoplasma pneumoniae-associated hemophagocytic syndrome (MP-HLH). METHOD: A retrospective investigation of the clinical manifestation, laboratory test, imagelogy, clinical course and outcome of 3 cases with MP-HLH seen between June 2013 and July 2013 in Shenzhen Children's Hospital, and review of relevant literature were conducted. RESULT: Of the 3 cases of MP-HLH, 2 were males, one was female, the ages were 1 year, 3 years and 6 years, respectively. They had no underlying disease previously. All the 3 cases had onset of fever, cough as main symptoms. Diagnosis of refractory Mycoplasma pneumoniae pneumonia was made, which was accompanied by decreased neutrophils [(0.08-0.68)×10(9)/L], hemoglobin [(79-103) g/L], platelet [(64-157)×10(9)/L], plasma fibrinogen [(1.3-1.5) g/L], lactate dehydrogenase [(1,170-1,285) U/L] and increased serum ferritin [(936.7-39 789.0) µg/L] in the third week of course. In two cases the T lymphocytes decreased, and the NK cell activity decreased significantly in one. Bone marrow cytology showed prompted bone marrow hyperplasia, and the phenomenon of phagocytosed blood cells. CT scan was performed for all the cases and consolidation with pleural effusion were shown. Two cases were admitted to PICU, and required endotracheal intubation and mechanical ventilation. Flexible bronchoscopy and bronchial lavage were performed and bronchial cast was found in two cases. All of them were treated with macrolide combined with other antibiotics, glucocorticoids and gamma globulin combination therapy, including one case given dexamethasone [10 mg/(m2·d)], cyclosporine[6 mg/(kg·d)], etoposide [150 mg/(m2·d)] chemotherapy. Two cases were cured, and 1 case died. The authors summarized the 18 cases reported in domestic and foreign literature. Foreign children were diagnosed and treated with steroids in 1-2 weeks, and 10 cases were cured, and 2 cases died. They died of massive hemorrhage and meningoencephalitis, and domestic children were diagnosed and treated within two to 4 weeks after onset, 5 cases were cured, one case died of severe pneumonia. CONCLUSION: MP-HLH is a rare disease in children, and had acute onset, rapid progression and high mortality. Early treatment with steroids was associated with a good prognosis, the key to successful treatment is early diagnosis and treatment, avoiding the immune cascade. Too late a diagnosis or development of serious complications may lead to death.

[Roles of bile and gastrin in the pathogenesis of childhood gastroesophageal reflux disease].

OBJECTIVE: To explore the incidence of acid and bile reflux in children with gastroesophageal reflux disease (GERD) and to study the roles of bile and gastrin in the pathogenesis of childhood GERD. METHODS: Forty-two cases of GERD were divided into two groups according to endoscopic findings: reflux esophagitis (RE) and non-erosive reflux disease (NERD). The patients underwent 24-hr ambulatory esophageal pH and bilirubin monitoring. The serum concentration of gastrin was detected by radioimmunoassay. Thirteen children without gastroesophageal reflux symptoms, digestive tract disease and severe systemic organic disease served as the Control group. RESULTS: Of the 42 cases of GERD, 24 cases were confirmed with RE, with esophageal mucosal lesions, and 18 were NERD without esophageal mucosal lesions by endoscopy. Both acid and bile reflux parameters, including the percentage of total time with pH < 4 and bilirubin absorbance >/= 0.14, the total number of reflux episodes and the number of bile reflux episodes lasting longer than 5 minutes, were significantly higher in the GERD patients than those in the Control group (P < 0.05). The time of esophageal acid exposure (pH < 4) and the percentage of total time with bilirubin absorbance >/= 0.14 increased significantly in the RE group compared with in the NERD group (P < 0.05). Sixteen RE patients had a mixed reflux of bile and acid (66.7%) but only 6 NERD patients (33.3%) had (P < 0.01). The serum concentration of gastrin in the RE group (125.12 +/- 45.06 pg/mL) and the NERD group (98.22 +/- 27.92 pg/mL) was significantly higher than that of the Control group (74.22 +/- 20.34 pg/mL) (P < 0.01, P < 0.05 respectively). A significant difference was noted in the serum concentration of gastrin between the RE and the NERD groups (P < 0.05). CONCLUSIONS: Mixed reflux of bile and acid are common in children with GERD. Bile reflux may play a role in the development of GERD. Gastrin parasecretion may participate in the development of GERD. Gastrin and bile reflux may have synergistic effects on the development of childhood GERD.