Efficacy and safety of Huachansu combined with adjuvant chemotherapy in resected colorectal cancer patients: a prospective, open-label, randomized phase II study.

Although some studies in China have suggested Huachansu (HCS) combined with chemotherapy is effective in the treatment of various cancers, there are few studies on colorectal cancer (CRC), especially in postoperative adjuvant chemotherapy. The aim of this study was to test the hypothesis that HCS combined with adjuvant chemotherapy would improve survival probability in resected CRC patients. This was a prospective, open-label, randomized phase II study. Patients with stage III or high-risk stage II resected CRC were randomly assigned to the chemotherapy and HCS + chemotherapy groups. The Chemotherapy group was treated with the FOLFOX regimen for ≥ 6 cycles or the CAPEOX regimen for ≥ 4 cycles. The HCS + chemotherapy group was treated with HCS on the basis of the chemotherapy group. The primary endpoint was 3-year disease-free survival (DFS), and the secondary endpoints were 3-year overall survival (OS) and toxicity. A total of 250 patients were included in this study (126 chemotherapy, 124 HCS + chemotherapy). There were significant differences in 3-year DFS between the two groups (median 28.7 vs. 31.6 months, respectively; P = 0.027), but no significant differences in 3-year OS between the two groups (median 32.7 vs. 34 months, respectively; P = 0.146). No patients experienced grade four adverse events, and the rates of leukopenia, neutropenia, and diarrhea in the HCS + chemotherapy group were lower than that those in the chemotherapy group. HCS combined with adjuvant chemotherapy after radical resection for patients with stage III or high-risk stage II CRC was demonstrated to be an effective and feasible treatment.

Twisted Bilayer Graphene Induced by Intercalation.

Twisted bilayer graphene (tBLG) has gained significant attention due to its unique physical and electronic properties. However, efficient fabrication of high-quality tBLG with diverse twist angles is crucial to expedite research on angle-dependent physics and potential applications. In this study, an intercalation strategy utilizing organic molecules, such as 1,2-dichloroethane, is developed to weaken the interlayer interaction and induce slide or rotation of the topmost graphene layer for tBLG fabrication. The proportion of tBLGs in the resulting 1,2-dichloroethane-treated BLG (dtBLG) reaches up to 84.4% for twist angles ranging from 0° to 30°, surpassing previously reported methods using chemical vapor deposition (CVD). Moreover, the twist angle distribution is not uniform and tends to concentrate in the ranges of 0-10° and 20-30°. This facile and rapid intercalation-based methodology provides a practical solution for studying angle-dependent physics and advancing the utilization of twisted two-dimensional materials.

Diabetic Bone Marrow Cell Injection Accelerated Acute Pancreatitis Progression.

Acute pancreatitis (AP) is one of the leading causes of hospital admission, 20% of which could progress to the severe type with extensive acinar cell necrosis. Clinical studies have reported that diabetes is an independent risk factor of the incidence of AP and is associated with higher severity than nondiabetic subjects. However, how diabetes participates in AP progression is not well defined. To investigate this question, wild-type (wt) and diabetic db/db mice at the age of 16 weeks were used in the study. AP was induced in wt recipients by 10 injections of 50 µg/kg caerulein with a 1 h interval. One hour after the last caerulein injection, bone marrow cells (BMC) isolated from wt and db/db mice were injected intraperitoneally into the recipients (1 × 107cells/recipient). The recipients with no BMC injection served as controls. Thirteen hours after BMC injection, serum lipase activity was 1.8- and 1.3-folds higher in mice that received db/db BMC, compared with those with no injection and wt BMC injection, respectively (p ≤ 0.02 for both). By H&E staining, the overall severity score was 14.7 for no cell injection and 16.6 for wt BMC injection and increased to 22.6 for db/db BMC injection (p ≤ 0.002 for both). In particular, mice with db/db BMC injection developed more acinar cell necrosis and vacuolization than the other groups (p ≤ 0.03 for both). When sections were stained with an antibody against myeloperoxidase (MPO), the density of MPO+ cells in pancreatitis was 1.9- and 1.6-folds higher than wt BMC and no BMC injection groups, separately (p ≤ 0.02 for both). Quantified by ELISA, db/db BMC produced more IL-6, GM-CSF, and IL-10 compared with wt BMC (p ≤ 0.04 for all). In conclusion, BMC of db/db mice produced more inflammatory cytokines. In response to acinar cell injury, diabetic BMC aggravated the inflammation cascade and acinar cell injury, leading to the progression of acute pancreatitis.

Identification of Key lncRNA-mRNA Pairs and Functional lncRNAs in Breast Cancer by Integrative Analysis of TCGA Data.

Long non-coding RNAs (lncRNAs) play an important role in many diseases and are involved in the post-transcriptional regulatory network of tumors. The purpose of this study is to mine new lncRNA-mRNA regulatory pairs and analyze the new mechanism of lncRNA involvement in breast cancer progression. Using breast cancer miRNA and mRNA expression profiling from The Cancer Genome Atlas (TCGA), we identified 59 differentially expressed lncRNAs, 88 differentially expressed miRNAs, and 1,465 differentially expressed mRNAs between breast cancer tissue and adjacent normal breast cancer. Whereafter, four candidate lncRNAs (FGF14-AS2, LINC01235, AC055854.1, and AC124798.1) were identified by the Kaplan-Meier (K-M) plotter. Furthermore, we screened the hub lncRNA (LINC01235) through univariate Cox analysis, multivariate Cox analysis, and qPCR validation, which was significantly correlated with breast cancer stage, ER status, and pathological N. Subsequently, 107 LINC01235-related mRNAs were obtained by combining differentially expressed miRNAs, differentially expressed mRNAs, and LINC01235 targeting miRNAs and mRNAs. The protein-protein interaction (PPI) network was established by Cytoscape software, and 53 key genes were screened. Function and pathway enrichment showed that LINC01235-related key genes might be involved in the process of cell differentiation, cell proliferation, and p53 signal pathway. In addition, LINC01235 has been confirmed to regulate the proliferation, migration, and invasion of MCF-7 cells in in vitro experiments. Furthermore, we screened three mRNAs (ESR1, ADRA2A, and DTL) associated with breast cancer drug resistance from key genes. Through RNA interference experiments in vitro and correlation analysis, we found that there was a negative feedback mechanism between LINC01235 and ESR1/ADRA2A. In conclusion, our results suggest that LINC01235-ESR1 and LINC01235-ADRA2A could serve as important co-expression pairs in the progression of breast cancer, and LINC01235 plays a key role as an independent prognostic factor in patients with breast cancer. The findings of this work greatly increase our understanding of the molecular regulatory mechanisms of lncRNA in breast cancer.

Anomalous thickness dependence of Curie temperature in air-stable two-dimensional ferromagnetic 1T-CrTe2 grown by chemical vapor deposition.

The discovery of ferromagnetic two-dimensional van der Waals materials has opened up opportunities to explore intriguing physics and to develop innovative spintronic devices. However, controllable synthesis of these 2D ferromagnets and enhancing their stability under ambient conditions remain challenging. Here, we report chemical vapor deposition growth of air-stable 2D metallic 1T-CrTe2 ultrathin crystals with controlled thickness. Their long-range ferromagnetic ordering is confirmed by a robust anomalous Hall effect, which has seldom been observed in other layered 2D materials grown by chemical vapor deposition. With reducing the thickness of 1T-CrTe2 from tens of nanometers to several nanometers, the easy axis changes from in-plane to out-of-plane. Monotonic increase of Curie temperature with the thickness decreasing from ~130.0 to ~7.6 nm is observed. Theoretical calculations indicate that the weakening of the Coulomb screening in the two-dimensional limit plays a crucial role in the change of magnetic properties.

Histopathological features of multiorgan percutaneous tissue core biopsy in patients with COVID-19.

AIMS: The global outbreak of COVID-19 has resulted in an increased mortality. However, whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can affect multiple organs is still unclear. In this study, postmortem percutaneous biopsies of multiple organs from deceased patients were performed to understand the histopathological changes caused by COVID-19. METHODS: Biopsy specimens of pulmonary, cardiac, hepatic and lymphoid tissues were obtained from three patients, who died due to COVID-19 pneumonia. H&E stain, Masson trichrome stain, immunohistochemistry stain and in-situ hybridisation were used. RESULTS: Pulmonary damages caused by SARS-CoV-2 infection was diffuse alveolar damage (DAD). In the early phase, the histological findings were mainly those of exudative features of DAD. The later phase was characterised by organisation of DAD combined with bacterial pneumonia. No serious damage was found in the bronchiolar epithelium and submucosal glands. The hepatic tissue revealed features of ischaemic necrosis, but findings suggestive of mild lobular hepatitis were also observed. The lymphoid tissue revealed features of non-specific acute lymphadenitis. The cardiac tissue revealed changes of underlying disease. SARS-CoV-2 RNAs were not detected in hepatocytes, cholangiocytes and lymphocytes of lymph nodes. CONCLUSIONS: COVID-19 predominantly involves the pulmonary tissue, causes DAD and aggravates the cardiovascular disease. However, other extrapulmonary tissues did not reveal any virus-specific findings, but were affected by multiple factors. The findings in this report caution the pathologists that they should not mistakenly attribute all the histological features to CoV infection. Moreover, the clinicians should pay attention to the potentially injurious and correctable causes.

MEX3A promotes triple negative breast cancer proliferation and migration via the PI3K/AKT signaling pathway.

Triple-negative breast cancer (TNBC) has the characteristics of fast growth, easy invasion, metastasis, poor prognosis, low tumor-free survival rate and overall survival rate. In this study, the RNA-binding protein MEX3A was selected by using the methods of TCGA database analysis, mRNA microarrays, and tissue chip immunohistochemistry experiments. The high expression of MEX3A is associated with malignancy and poor prognosis of TNBC. In addition, MEX3A knockdown can inhibit the growth and migration of TNBC cells while MEX3A overexpression shows the opposite effect. In vivo experiments, we also demonstrated that downregulating MEX3A can inhibit the tumorigenicity of TNBC cells. The mRNA microarrays and Ingenuity pathway analysis (IPA) were used to explore the downstream of MEX3A, and verified the relationship between PI3K/AKT signaling pathway and MEX3A. Additionally, we have simultaneously up-regulated MEX3A and treated with pathway inhibitors in vitro experiments and found that it can slow down the growth of TNBC cells. In short, we identified MEX3A as a tumor promoter, potential prognostic indicator and therapeutic target for TNBC, may function through the regulation of the PI3K/AKT signaling pathway.

Evolution of severe acute respiratory syndrome coronavirus 2 RNA test results in a patient with fatal coronavirus disease 2019: a case report.

A 65-year-old man was hospitalized owing to fever (38.6 °C) and dry cough since 4 days. He visited Wuhan 8 days ago. At admission, nasopharyngeal swab samples were taken, and polymerase chain reaction analysis confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA positivity. On day 9, after admission, the chest computed tomography scan showed diffuse ground-glass shadows in the patient's bilateral lungs. On day 11, his respiratory symptoms worsened. Subsequently, type I respiratory failure was diagnosed, coinciding with kidney injury, and subsequently, type II respiratory failure occurred, coupled with multiorgan failure including the heart and liver. However, the patient's constitution worsened although SARS-CoV-2 tests were negative since day 13. He died on day 21. Lung biopsy showed areas of diffuse alveolar damage, characterized by extensive acute alveolitis with numerous intra-alveolar neutrophil, lymphocyte, and macrophage infiltrations. Microthrombi were seen in the dilated pulmonary capillaries. Immunohistochemistry staining for SARS-CoV-2 N protein was negative. Taken together, the patient died of multiorgan failure although the SARS-CoV-2 infection was cleared already, implicating that for disease worsening, no active SARS-CoV-2 infection is required.

[Effect of GR24 on accumulation of diterpenoids in Tripterygium wilfordii suspension cells].

Terpenoids are main bioactive components in Tripterygium wilfordii,but the contents of some terpenoids are relatively low. In order to provide scientific evidence for the regulation of terpenoids in T. wilfordii,this research explored the effect of GR24 on accumulations of four diterpenoids( triptolide,tripterifordin,triptophenolide,and triptinin B) in T. wilfordii suspension cells by biological technology and UPLC-QQQ-MS/MS. The results indicated that 100 µmol·L-1 GR24 inhibited the accumulations of triptolide,tripterifordin,triptophenolide,and triptinin B to different degrees. Compared with the control group,the contents of 4 diterpenoids( in the induced group) were down to 96.59%,63.80%,61.02% and 33.59% in 240 h,respectively. Among them,the accumulation of triptinin B iswas significantly inhibited. In addition,the key time point of inhibitory effect was 120 h after induction with GR24 in some diterpenoids. This is the first systematic study focusing on the effect of GR24 on the accumulations of diterpenoids in T. wilfordii suspension cells. The dynamic accumulation ruleregularity of four diterpenoids after induced by GR24 was summarized,which laid a foundation for further study on the chemical response mechanism of terpenoids to GR24.