Patients with intestinal type gastric cancer (GC), well-differentiated GC and poorly-differentiated GC without lymph node metastasis, may all represent suitable candidates for targeted therapy using Herceptin.

Long noncoding RNA (lncRNA) MEG3 is an important tumor suppressor in several types of human cancers. However, the biological function and underlying mechanism of MEG3 in vascular endothelial cells (VECs) remain unknown. In the present study, we demonstrated the functional importance of lncRNA MEG3 in proliferation and angiogenesis of VECs. MEG3 overexpression significantly suppressed the proliferation and in vitro angiogenesis in VECs, whereas knockdown of MEG3 had the opposite effect. Furthermore, we found that MEG3 exerts its function through negatively regulating miR-9 by acting as a microRNA sponge. Taken together, MEG3-miR-9 plays an important role in proliferation and angiogenesis in VECs.

The characteristics of COVID-19 patients with persistent SARS-CoV-2 infection are not yet well described. Here, we compare the clinical and molecular features of patients with long duration of viral shedding (LDs) with those from patients with short duration patients (SDs), and healthy donors (HDs). We find that several cytokines and chemokines, such as interleukin (IL)-2, tumor necrosis factor (TNF) and lymphotoxin α (LT-α) are present at lower levels in LDs than SDs. Single-cell RNA sequencing shows that natural killer (NK) cells and CD14+ monocytes are reduced, while regulatory T cells are increased in LDs; moreover, T and NK cells in LDs are less activated than in SDs. Importantly, most cells in LDs show reduced expression of ribosomal protein (RP) genes and related pathways, with this inversed correlation between RP levels and infection duration further validated in 103 independent patients. Our results thus indicate that immunosuppression and low RP expression may be related to the persistence of the viral infection in COVID-19 patients.

, a cluster of viral pneumonia cases identified as coronavirus disease 2019 (COVID-19) was reported in Wuhan, China. We aimed to explore the frequencies of nasal symptoms in patients with COVID-19, including loss of smell and taste, as well as their presentation as the first symptom of the disease and their association with the severity of COVID-19. In this retrospective study, 1206 laboratory-confirmed COVID-19 patients were included and followed up by telephone one month after discharged from Tongji Hospital, Wuhan. Demographic data, laboratory values, comorbidities, symptoms, and numerical rating scale scores (0-10) of nasal symptoms were extracted from the hospital medical records, and confirmed or reevaluated by the telephone follow-up. From patients (n=1172) completing follow-up, 199 (17%) subjects had severe COVID-19 and 342 (29.2%) reported nasal symptoms. 20.6% COVID-19 patients had loss of taste (median score=6), while 11.4% had loss of smell (median score=5). Loss of taste scores, but not loss of smell scores, were significantly increased in severe vs. nonsevere COVID-19 patients. Interleukin (IL)-6 and lactose dehydrogenase (LDH) serum levels were positively correlated with loss of taste scores. About 80% of COVID-19 patients recovered from smell and taste dysfunction in 2 weeks. In this cohort, only 1 out of 10 hospital admitted patients had loss of smell while 1 out of 5 reported loss of taste which was associated to severity of COVID-19. Most patients recovered smell and taste dysfunctions in 2 weeks.

The pseudo-tumoral expansion of fibroblast-like synoviocytes is a hallmark of rheumatoid arthritis (RA), and targeting rheumatoid arthritis fibroblast-like synoviocytes (RAFLSs) may have therapeutic potentials in this disease. Andrographolide, a diterpenoid compound isolated from the herb Andrographis paniculata, has been reported to have potent anti-inflammatory activity. In the present study, we aimed to investigate the effects of andrographolide on human RAFLSs and the underlying molecular mechanism(s). RAFLSs were isolated from patients with RA and treated with or without various concentrations (i.e., 10, 20, and 30 μM) of andrographolide for 48 h. 3-[4,5-Dimethyl-2-yl]-2,5-diphenyl tetrazolium bromide assay revealed that andrographolide treatment decreased the proliferation of RAFLSs in a dose-dependent manner. Cell cycle analysis using propidium iodide (PI) staining showed a G0/G1 cell cycle arrest in andrographolide-treated RAFLSs. Immunoblotting analysis of key cell cycle regulators demonstrated that andrographolide treatment caused a dose-dependent increase in the expression of cell-cycle inhibitors p21 and p27 and a concomitant reduction of cyclin-dependent kinase 4. Exposure to andrographolide-induced apoptosis of RAFLSs measured by annexin V/PI double staining, which was coupled with promotion of cytochrome C release from mitochondria and activation of caspase-3. Moreover, andrographolide-treated RAFLSs displayed a significant decrease in the Bcl-2/Bax ratio compared to untreated cells. In conclusion, our data demonstrate that andrographolide exerts anti-growth and pro-apoptotic effects on RAFLSs, thus may have therapeutic potential for the treatment of RA.

To the Editor, Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), affects more than 17 million of people and results in more than 666 000 deaths all over the world. Although allergic diseases are highly prevalent globally, their risks for the development of COVID-19 remain poorly understood. Severe acute respiratory syndrome coronavirus 2 entry host cells via angiotensin-converting enzyme II (ACE2). 1 Upregulated ACE2 expression has been associated with increased risk of COVID-19 in patients with chronic obstructive pulmonary disease, diabetes, and hypertension. 2 ACE2 gene expression is enriched in nasal epithelial cells, highlighting the importance of nose as a portal for initial SARS-CoV-2 infection and transmission. Allergic rhinitis (AR) is the most common disorder of nose and affects 10%-40% of the population. 3 Previous studies reported low incidences of AR in COVID-19 patients, ranging from 0% to 1.8% in China. 4,5 However, those results were generated solely based on the medical records, and AR comorbidity might not be well considered under actual emergency situation. 4,5 Moreover, the association between AR comorbidity and the disease severity of COVID-19 and the role of ACE2 in this association are largely unknown. Here, we retrospectively analyzed 1172 etiologically confirmed COVID-19 patients discharged from Tongji Hospital, Wuhan, China from January 27, 2020 to March 10, 2020. Hospital electronic medical records were extracted and comorbidities were reevaluated by the telephone follow-up. Both multivariate logistic regression and propensity score matching (PSM) analysis were performed to exclude the influ

In this study, we investigated the roles of RIP1/RIP3 mediated cardiomyocyte necroptosis in CVB3-induced acute myocarditis. Serum concentrations of creatinine kinase (CK), CK-MB, and cardiac troponin I were detected using a Hitachi Automatic Biochemical Analyzer in a mouse model of acute VMC. Histological changes in cardiac tissue were observed by light microscope and expression levels of RIP1/RIP3 in the cardiac tissue were detected via Western blot and immunohistochemistry. The data showed that RIP1/RIP3 was highly expressed in cardiomyocytes in the acute VMC mouse model and that the necroptosis pathway specific blocker, Nec-1, dramatically reduced the myocardial damage by downregulating the expression of RIP1/RIP3. These findings provide evidence that necroptosis plays a significant role in cardiomyocyte death and it is a major pathway for cell death in acute VMC. Blocking the necroptosis pathway may serve as a new therapeutic option for the treatment of acute viral myocarditis.

As being radiation-free, portable, and capable of repetitive use, ultrasonography is playing an important role in diagnosing and evaluating the COVID-19 Pneumonia (PN) in this epidemic. By virtue of lung ultrasound scores (LUSS), lung ultrasound (LUS) was used to estimate the excessive lung fluid that is an important clinical manifestation of COVID-19 PN, with high sensitivity and specificity. However, as a qualitative method, LUSS suffered from large interobserver variations and requirement for experienced clinicians. Considering this limitation, we developed a quantitative and automatic lung ultrasound scoring system for evaluating the COVID-19 PN. A total of 1527 ultrasound images prospectively collected from 31 COVID-19 PN patients with different clinical conditions were evaluated and scored with LUSS by experienced clinicians. All images were processed via a series of computeraided analysis, including curve-to-linear conversion, pleural line detection, region-of-interest (ROI) selection, and feature extraction. A collection of 28 features extracted from the ROI was specifically defined for mimicking the LUSS. Multilayer fully connected neural networks, support vector machines, and decision trees were developed for scoring LUS images using the fivefold cross validation. The model with 128 × 256 two fully connected layers gave the best accuracy of 87%. It is concluded that the proposed method could Manuscript