Humans ; Lung Transplantation/adverse effects* ; Risk Factors

Molecular knowledge of human gastric corpus epithelium remains incomplete. Here, by integrated analyses using single-cell RNA sequencing (scRNA-seq), spatial transcriptomics, and single-cell assay for transposase accessible chromatin sequencing (scATAC-seq) techniques, we uncovered the spatially resolved expression landscape and gene-regulatory network of human gastric corpus epithelium. Specifically, we identified a stem/progenitor cell population in the isthmus of human gastric corpus, where EGF and WNT signaling pathways were activated. Meanwhile, LGR4, but not LGR5, was responsible for the activation of WNT signaling pathway. Importantly, FABP5 and NME1 were identified and validated as crucial for both normal gastric stem/progenitor cells and gastric cancer cells. Finally, we explored the epigenetic regulation of critical genes for gastric corpus epithelium at chromatin state level, and identified several important cell-type-specific transcription factors. In summary, our work provides novel insights to systematically understand the cellular diversity and homeostasis of human gastric corpus epithelium in vivo.
Humans ; Epigenesis, Genetic ; Gastric Mucosa/metabolism* ; Chromatin/metabolism* ; Stem Cells ; Epithelium/metabolism* ; Fatty Acid-Binding Proteins/metabolism*

Venous thromboembolism (VTE) is a complication in children with acute lymphoblastic leukemia (ALL). The Chinese Children's Cancer Group-ALL-2015 protocol was carried out in China, and epidemiology, clinical characteristics, and risk factors associated with VTE were analyzed. We collected data on VTE in a multi-institutional clinical study of 7640 patients with ALL diagnosed in 20 hospitals from January 2015 to December 2019. First, VTE occurred in 159 (2.08%) patients, including 90 (56.6%) during induction therapy and 108 (67.92%) in the upper extremities. T-ALL had a 1.74-fold increased risk of VTE (95% CI 1.08-2.8, P = 0.022). Septicemia, as an adverse event of ALL treatment, can significantly promote the occurrence of VTE (P < 0.001). Catheter-related thrombosis (CRT) accounted for 75.47% (n = 120); and, symptomatic VTE, 58.49% (n = 93), which was more common in patients aged 12-18 years (P = 0.023), non-CRT patients (P < 0.001), or patients with cerebral thrombosis (P < 0.001). Of the patients with VTE treated with anticoagulation therapy (n = 147), 4.08% (n = 6) had bleeding. The VTE recurrence rate was 5.03% (n = 8). Patients with VTE treated by non-ultrasound-guided venous cannulation (P = 0.02), with residual thrombus (P = 0.006), or with short anticoagulation period (P = 0.026) had high recurrence rates. Thus, preventing repeated venous puncture and appropriately prolonged anticoagulation time can reduce the risk of VTE recurrence.
Humans ; Child ; Venous Thromboembolism/etiology* ; East Asian People ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/epidemiology* ; Risk Factors ; Thrombosis/chemically induced* ; China/epidemiology* ; Anticoagulants/adverse effects* ; Recurrence

Positive-sense RNA viruses modify intracellular calcium stores, endoplasmic reticulum and Golgi apparatus (Golgi) to generate membranous replication organelles known as viral factories. Viral factories provide a conducive and substantial enclave for essential virus replication via concentrating necessary cellular factors and viral proteins in proximity. Here, we identified the vital role of a broad-spectrum antiviral, peruvoside in limiting the formation of viral factories. Mechanistically, we revealed the pleiotropic cellular effect of Src and PLC kinase signaling via cyclin-dependent kinase 1 signaling leads to Golgi-specific brefeldin A-resistance guanine nucleotide exchange factor 1 (GBF1) phosphorylation and Golgi vesiculation by peruvoside treatment. The ramification of GBF1 phosphorylation fosters GBF1 deprivation consequentially activating downstream antiviral signaling by dampening viral factories formation. Further investigation showed signaling of ERK1/2 pathway via cyclin-dependent kinase 1 activation leading to GBF1 phosphorylation at Threonine 1337 (T1337). We also showed 100% of protection in peruvoside-treated mouse model with a significant reduction in viral titre and without measurable cytotoxicity in serum. These findings highlight the importance of dissecting the broad-spectrum antiviral therapeutics mechanism and pave the way for consideration of peruvoside, host-directed antivirals for positive-sense RNA virus-mediated disease, in the interim where no vaccine is available.

The Chinese Neonatal Network(CHNN) was established in 2018 with the mission of establishing a national collaboration platform, conducting high-quality and collaborative research, and ultimately improving the quality of neonatal-perinatal care and health in China.At present, 112 hospitals across the country have joined CHNN.CHNN has established a national standardized cohort of very premature infants/very low birth weight infants with >10 000 enrollments each year, has been leading data-driven collaborative quality improvement initiatives, conducting multicenter clinical studies, and performing multi-level training programs.Guided by the principles of collaboration and sharing, data-driven, continuous improvement, and international integration, CHNN has become an important platform for clinical and research collaboration in neonatal medicine in China.

Objective:To analyze the accuracy of lung ultrasound and chest X-ray in the diagnosis of neonatal pulmonary disease.Methods:We prospectively collected newborns that needed chest X-ray examination to diagnose pulmonary disease from twelve neonatal intensive care units across the country between June 2019 and April 2020.Each newborn was examined by lung ultrasound within two hours after chest X-ray examination.All chest X-ray and lung ultrasound images were independently read by a radiologist and a sonographer.When there was a disagreement, a panel of two experienced physicians made a final diagnosis based on the clinical history, chest X-ray and lung ultrasound images.Results:A total of 1 100 newborns were enrolled in our study.The diagnostic agreement between chest X-ray and lung ultrasound(Cohen′s kappa coefficient=0.347) was fair.Lung ultrasound(area under the curve=0.778; 95% CI 0.753-0.803) performed significantly better than chest X-ray(area under the curve=0.513; 95% CI 0.483-0.543) in the diagnosis of transient tachypnea of the newborn( P<0.001). The accuracy of lung ultrasound in diagnosing neonatal respiratory distress syndrome, meconium aspiration syndrome, pneumonia and neonatal pulmonary atelectasis was similar to that of chest X-ray. Conclusion:Lung ultrasound, as a low-cost, simple and radiation-free auxiliary examination method, has a diagnostic accuracy close to or even better than that of chest X-ray, which may replace chest X-ray in the diagnosis of some neonatal lung diseases.It should be noted that both chest X-ray and lung ultrasound can only be used as auxiliary means for the diagnosis of lung diseases, and it is necessary to combine imaging with the clinical history and presentation.

Humans ; Adenocarcinoma/pathology* ; Lung/pathology* ; Lung Neoplasms/pathology* ; Neoplasm Invasiveness ; Retrospective Studies

Humans ; Frozen Sections ; Adenoma/diagnosis* ; Bronchial Neoplasms/surgery*

Humans ; Adenocarcinoma of Lung/pathology* ; Adenocarcinoma/pathology* ; Lung Neoplasms/pathology* ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Adenocarcinoma, Papillary/pathology*

Objective: To examine a predictive model that incorporating high risk pathological factors for the prognosis of stage Ⅰ to Ⅲ colon cancer. Methods: This study retrospectively collected clinicopathological information and survival outcomes of stage Ⅰ~Ⅲ colon cancer patients who underwent curative surgery in 7 tertiary hospitals in China from January 1, 2016 to December 31, 2017. A total of 1 650 patients were enrolled, aged (M(IQR)) 62 (18) years (range: 14 to 100). There were 963 males and 687 females. The median follow-up period was 51 months. The Cox proportional hazardous regression model was utilized to select high-risk pathological factors, establish the nomogram and scoring system. The Bootstrap resampling method was utilized for internal validation of the model, the concordance index (C-index) was used to assess discrimination and calibration curves were presented to assess model calibration. The Kaplan-Meier method was used to plot survival curves after risk grouping, and Cox regression was used to compare disease-free survival between subgroups. Results: Age (HR=1.020, 95%CI: 1.008 to 1.033, P=0.001), T stage (T3:HR=1.995,95%CI:1.062 to 3.750,P=0.032;T4:HR=4.196, 95%CI: 2.188 to 8.045, P<0.01), N stage (N1: HR=1.834, 95%CI: 1.307 to 2.574, P<0.01; N2: HR=3.970, 95%CI: 2.724 to 5.787, P<0.01) and number of lymph nodes examined (≥36: HR=0.438, 95%CI: 0.242 to 0.790, P=0.006) were independently associated with disease-free survival. The C-index of the scoring model (model 1) based on age, T stage, N stage, and dichotomous variables of the lymph nodes examined (<12 and ≥12) was 0.723, and the C-index of the scoring model (model 2) based on age, T stage, N stage, and multi-categorical variables of the lymph nodes examined (<12, 12 to <24, 24 to <36, and ≥36) was 0.726. A scoring system was established based on age, T stage, N stage, and multi-categorical variables of lymph nodes examined, the 3-year DFS of the low-risk (≤1), middle-risk (2 to 4) and high-risk (≥5) group were 96.3% (n=711), 89.0% (n=626) and 71.4% (n=313), respectively. Statistically significant difference was observed among groups (P<0.01). Conclusions: The number of lymph nodes examined was an independent prognostic factor for disease-free survival after curative surgery in patients with stage Ⅰ to Ⅲ colon cancer. Incorporating the number of lymph nodes examined as a multi-categorical variable into the T and N staging system could improve prognostic predictive validity.
Male ; Female ; Humans ; Prognosis ; Neoplasm Staging ; Retrospective Studies ; Nomograms ; Lymph Nodes/pathology* ; Risk Factors ; Colonic Neoplasms/surgery*