Preclinical Evidence and Possible Mechanisms of Rhodiola rosea L. and Its Components for Ischemic Stroke: A Systematic Review and Meta-Analysis.

Background: Rhodiola rosea L. has long been used as traditional medicines in Europe and Asia to treat a variety of common conditions and diseases including Alzheimer's disease, cardiovascular disease, cognitive dysfunctions, cancer, and stroke. Previous studies reported that Rhodiola rosea L. and its components (RRC) improve ischemia stroke in animal models. Here, we conducted a systematic review and meta-analysis for preclinical studies to evaluate the effects of RRC and the probable neuroprotective mechanisms in ischemic stroke. Methods: Studies of RRC on ischemic stroke animal models were searched in seven databases from inception to Oct 2021. The primary measured outcomes included the neural functional deficit score (NFS), infarct volume (IV), brain water content, cell viability, apoptotic cells, terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL)-positive cells, B-cell lymphoma-2 (Bcl-2) level and tumor necrosis factor-α (TNF-α) level. The secondary outcome measures were possible mechanisms of RRC for ischemic stroke. All the data were analyzed via RevMan version 5.3. Results: 15 studies involving 345 animals were identified. Methodological quality for each included studies was accessed according to the CAMARADES 10-item checklist. The quality score of studies range from 1 to 7, and the median was 5.53. Pooled preclinical data showed that compared with the controls, RRC could improve NFS (Zea Longa (p < 0.01), modified neurological severity score (mNSS) (p < 0.01), rotarod tests (p < 0.01), IV (p < 0.01), as well as brain edema (p < 0.01). It also can increase cell viability (p < 0.01), Bcl-2 level (p < 0.01) and reduce TNF-α level (p < 0.01), TUNEL-positive cells (p < 0.01), apoptotic cells (p < 0.01). Conclusion: The findings suggested that RRC can improve ischemia stroke. The possible mechanisms of RRC are largely through antioxidant, anti-apoptosis activities, anti-inflammatory, repressing lipid peroxidation, antigliosis, and alleviating the pathological blood brain barrier damage.

Calcification sign for prediction of benignity in pulmonary nodules: A meta-analysis.

BACKGROUND: The calcification sign assessed by computed tomography appears to be a potential marker for benignities among patients diagnosed with pulmonary nodules (PNs). The following meta-analysis has been purposefully designed to figure-out the diagnostic value of the calcification signature as a way of identifying benignities from PNs. METHODS: Cochrane Library, Embase and PubMed were considered as a reference to obtain the required data from January 2000 until October 2020. Stata v12.0 was used as a standard tool for statistical assessment. RESULTS: Eleven retrospective studies were assessed via this meta-analysis, which included 6136 PNs (1827 benign and 4309 malignant). The pooled diagnostic odd ratios, positive likelihood ratio (PLR), negative likelihood ratio (NLR), sensitivity and specificity were 6.79, 6.06, 0.89, 13% and 98%, respectively. The value obtained for the area under the curve was 0.65, showing moderate overall diagnostic accuracy. A significant heterogeneity was found while calculating the pooled sensitivity (I2  = 85.5%), specificity (I2  = 75.0%), PLR (I2  = 59.0%), NLR (I2  = 79.5%) and DOR (I2  = 100.0%) in the current analysis. Sub-group analyses presented better PLR and specificity values for the study with a sample size ≥ 400. Deeks' funnel plot asymmetry test detected no potential evidence of significant publication bias (p = 0.091). CONCLUSIONS: Calcification signs have been identified as moderate regulators corresponding to overall diagnostic performance (via marking a distinct differentiation between malignant and benign) for PNs. However, the manifestation of the calcification sign had a good directive property for benign PNs.

Activation of CD3+ T cells by Helicobacter pylori DNA vaccines in potential immunotherapy of gastric carcinoma.

Most of gastric carcinoma (GC) is attributed to infection by Helicobacter pylori (H. pylori) but there is increasing evidence that the positive H. pylori status correlates with better prognosis in GC. The H. pylori-induced cellular immune response may suppress cancer and in this work, recombinant pcDNA3 plasmids encoding various fragments of H. pylori virulence genes of cagA, vacA and babA are constructed and combined into groups to immunize BALB/c mice. The activated splenic CD3+ T cells are purified and the anticancer effects are investigated in vitro and in vivo. The H. pylori DNA vaccines induce a shift in the response from Th1 to Th2 that mimicks the immune status in patients of GC with chronic H. pylori infection. The stimulated CD3+ T cells inhibit the growth of human GC cells in vitro and adoptive transfusions of the CD3+ T cells suppress the growth of GC xenograft in vivo. The effects may be caused by the larger ratios of infiltrated CD8+/CD4+ T cells, reduced infiltration of regulatory FOXP3+ T cells, and enhanced apoptosis induced by upregulation of Caspase-9/Caspase-3 and downregulation of Survivin. Our results reveal the potential immunotherapeutic value of H. pylori vaccine-activated CD3+ T cells in those with advanced GC.

Sensitivity and Specificity of Double-Track Sign in the Detection of Transverse Sinus Stenosis: A Multicenter Retrospective Study.

BACKGROUND: Transverse sinus stenosis (TSS) is common among patients with cerebral venous sinus thrombosis. No previous studies have reported on double-track sign detected on axial Gd-enhanced T1WI in TSS. This study aimed to determine the sensitivity and specificity of the double-track sign in the detection of TSS. METHODS: We retrospectively reviewed medical records of 383 patients with transverse sinus thrombosis (TST) and 30 patients with normal transverse sinus from 5 participating hospitals in china from January 2008 to June 2014. 167 feasible transverse sinuses included in this study were categorized into TSS (n = 76), transverse sinus occlusion (TSO) (n = 52) and transverse sinus normal (TSN) groups (n = 39) according to imaging diagnosis on digital subtraction angiography (DSA) or magnetic resonance venography (MRV). Double-track sign on axial Gd-enhanced T1WI was compared among the three groups. Sensitivity and specificity of double-track sign in detection of TSS were calculated, with final imaging diagnosis of TSS on DSA or MRV as the reference standard. RESULTS: Of 383 patients with TST recruited over a 6.5-year period, 128 patients were enrolled in the study, 255 patients were excluded because of insufficient clinical data, imaging finding and delay time, and 30 matched patients with normal transverse sinus were enrolled in the control group. Therefore, double-track sign assessment was conducted in 167 available transverse sinuses of 158 patients. Of the 76 sinuses in TSS group, 51 had double-track sign. Of the other 91 sinuses in TSO and TSN groups, 3 had a false-positive double-track sign. Thus, double-track sign on axial Gd-enhanced T1WI was 67.1% (95% CI 55.3-77.2) sensitive and 96.7% (95% CI 89.9-99.1) specific for detection of TSS. CONCLUSIONS: The double-track sign on axial Gd-enhanced T1WI is highly specific and moderate sensitive for detection of TSS. Nevertheless, it could be a direct sign and might provide an early clue for TSS.

FOXM1 expression correlates with tumor invasion and a poor prognosis of colorectal cancer.

FOXM1, a member of the Forkhead Box (Fox) family of transcription factors, plays a critical role in tumor development and metastasis. The aim of this study was to elucidate its role in colorectal cancer (CRC), particularly prognosis and metastasis. Semi-quantitative RT-PCR and Western blot assays were used to measure the expression levels of FOXM1 mRNA and protein in 15 CRC and adjacent normal mucosa tissues. Immunohistochemical assay was performed to detect FOXM1 protein expression in 112 CRC tissues and further determine its clinicopathological and prognostic significance. RNA interference (RNAi) was used to knockdown endogenous FOXM1 expression in CRC cell lines and to analyze the effects of FOXM1 knockdown on migration and invasion of CRC cells. The relative expression levels of FOXM1 mRNA and protein were significantly higher in CRC tissues than in adjacent normal mucosa tissues (P<0.01). In addition, the immunostaining of FOXM1 protein was stronger in CRC tissues than in adjacent normal mucosa tissues. By statistical analysis, we showed that high FOXM1 expression was closely correlated with the presence of lymph node metastasis, incidence of liver metastasis, and advanced TNM stage. Moreover, the cumulative 5-year survival rate of CRC patients with high FOXM1 expression was lower than that of those with low FOXM1 expression (P=0.0047). Multivariate analysis showed that the status of FOXM1 expression was an independent prognostic factor for CRC patients (P=0.025). Furthermore, RNAi-mediated FOXM1 knockdown could significantly inhibit growth, migration and invasion of CRC cells. Our results showed that FOXM1 over-expression is a molecular marker predicting increased invasive/metastatic potential of CRC and a poorer prognosis.

Overexpression of survivin is correlated with increased invasion and metastasis of colorectal cancer.

BACKGROUND: The aim of this study was to investigate the association of survivin expression with metastasis of colorectal cancer (CRC). METHODS: RT-PCR and Western blot assays were performed to detect survivin expression in CRC cells and normal intestinal epithelial cell. The expression of survivin gene was also detected in 15 CRC tissues, surrounding and adjacent colon tissues. Moreover, survivin expression in 48 CRC tissues with or without lymph node metastasis was analyzed. Multivariate analysis for lymph node metastasis was performed using logistic regression model. RNA interference was used to inhibit survivin expression in CRC cells and analyze its effect on invasion and metastasis of CRC cells. RESULTS: The expression levels of survivin mRNA and protein were higher in CRC cells than in normal intestinal epithelial cell line. The average levels of survivin mRNA and protein were higher in CRC tissues than surrounding or adjacent colon tissues (P < 0.05). High survivin expression was an independent factor for predicting lymph node metastasis of CRC (P = 0.043). RNAi-mediated survivin knockdown could significantly inhibit in vitro invasion and in vivo metastasis of CRC cells, which might be inactivation of matrix metalloproteinases. CONCLUSION: Targeting survivin will be a potential strategy to suppress metastasis of CRC.

Rapid Remission in Peripheral T-Cell Lymphoma of the Nasal Type by the Bortezomib plus CHOP Therapy.

Peripheral T-cell lymphoma (PTCL) is rare and difficult to treat for its high relapse rate. The authors report a case of PTCL of the skin, regarding which clinical and pathological features, treatment, and prognosis were discussed. A 66-year-old woman was admitted with complaints of enlarging erythematous noduloplaques on the right anterior tibial skin for one year and similar lesions on the left for 6 months. Surgical resection of right leg lesion and biopsy of enlarged inguinal lymph nodes histologically indicated a PTCL of the nasal type. The patient was treated by CHOP plus bortezomib, reached complete remission just after two courses of chemotherapy and then received another two as consolidation. The patient remained in remission for 11 months until local relapse. As for cutaneous lesions, detailed lymph node examination and prompt tissue biopsy are judicious choices prior to any medical management. The chemotherapy consisting of bortezomib and CHOP is safe and efficient in PTCL of the skin.