Treatment of Post-Stroke Dysphagia with Repetitive Transcranial Magnetic Stimulation Based on the Bimodal Balance Recovery Model: A Pilot Study.

BACKGROUND: Brain plasticity and functional reorganization are the main mechanisms of stroke rehabilitation and the theoretical basis for transcranial magnetic therapy. Bimodal balance recovery model suggests that the structural integrity of neural pathways affects the functional reorganization mode of brain recovery after stroke. The principal neural pathway that innervates swallowing is the corticobulbar tract (CBT). The goal is to investigate the impact of corticobulbar tract integrity on swallowing function recovery in post-stroke dysphagia (PSD) patients treated with repetitive transcranial magnetic stimulation (rTMS). METHODS: Thirty-five patients with high CBT integrity (relative fractional anisotropy (rFA) >0.5) and 32 patients with low CBT integrity (rFA ≤0.5) were respectively assigned to three subgroups through a random number table: 5 Hz frequency rTMS group, 1 Hz frequency rTMS group, and Sham rTMS group. The Standardized Swallowing Assessment (SSA), Penetration Aspiration Scale (PAS), and Dysphagia Outcome Severity Scale (DOSS) were analyzed before and after therapy. RESULTS: Significant improvements in SSA (p < 0.05), PAS (p < 0.05), and DOSS scores (p < 0.05) were seen in the high frequency (HF) and low frequency (LF) groups compared with the Sham group for patients with high CBT integrity. Increased SSA (p < 0.05), PAS (p < 0.05), and DOSS scores (p < 0.05) demonstrated that the HF group achieved greater remediation than the LF and Sham groups for patients with low CBT integrity. CONCLUSIONS: Both 5 Hz and 1 Hz rTMS over the contralateral hemisphere are effective for the treatment of swallowing disorders for patients with high CBT integrity after stroke; 5 Hz rTMS over the contralateral hemisphere is more effective than 1 Hz and sham stimulation for patients with low CBT integrity.

Single-Cell Sequencing Reveals that DBI is the Key Gene and Potential Therapeutic Target in Quiescent Bladder Cancer Stem Cells.

Background: Drug resistance and recurrence often develop during the treatment of muscle-invasive bladder cancer (MIBC). The existence of cancer stem cells (CSCs) in MIBC makes the formulation of effective treatment strategies extremely challenging. We aimed to use single-cell RNA sequencing approaches to identify CSCs and evaluate their molecular characteristics and to discover possible therapeutic measures. Methods: GEO data sets GSE130001 and GSE146137 were used to construct an expression matrix. After cells were identified by type, malignant epithelial cells inferred by InferCNV were extracted for stemness evaluation. The subset of cells with the highest stemness was subjected to weighted gene coexpression network analysis (WGCNA) and pseudotime analysis to identify key genes. In addition, we predicted drug sensitivity relationships for key genes in CTD and predicted the correlation between drugs and survival through siGDC. Results: We found that there were some CSCs in MIBC samples. The CSC population was heterogeneous during tumor development and was divided into quiescent and proliferating CSCs. We identified DBI as the key gene in quiescent CSCs. Analysis of a TCGA data set showed that higher DBI expression indicated higher histological grade. In addition, we predicted that acetaminophen can reduce DBI expression, thereby reducing the stemness of CSCs. Thus, we identified a potential new use of acetaminophen. Conclusion: We systematically explored CSCs in tumors and determined that DBI may be a key gene and potential therapeutic target in quiescent CSCs. In addition, we confirmed that acetaminophen may be a candidate drug targeting CSCs, improving our understanding of CSC-targeting therapeutic strategies.

Coptisine Blocks Secretion of Exosomal circCCT3 from Cancer-Associated Fibroblasts to Reprogram Glucose Metabolism in Hepatocellular Carcinoma.

Coptisine, extracted from rhizoma coptidis, has been shown to inhibit a variety of cancers. However, the underlying mechanism by which coptisine regulates hepatocellular carcinoma (HCC) progression remains unknown. MTT assay, transwell invasion assay, and TUNEL assay were employed to examine cell viability, invasion, and apoptosis. In vivo tumor growth was determined by xenograft experiment. Reverse transcription-quantitative PCR was used to detect circCCT3 and HK2 gene expression. We utilized glucose consumption and lactate production assay to examine glucose metabolism state. Conditioned medium of coptisine-treated cancer-associated fibroblast (CAF) suppressed cell viability and invasion of HepG2 and Huh-7, whereas increased cell apoptosis. Coptisine significantly inhibited tumor growth of HepG2 cells in immunodeficient mice. Mechanistically, coptisine blocked secretion of exosomal circCCT3 from CAF. More notably, circCCT3 was upregulated in clinical HCC tumors. Moreover, circCCT3 was confirmed to affect glucose metabolism of HCC cells. We identified HK2 as a key downstream effector for circCCT3-modulated HCC tumorigenesis. In summary, our research revealed novel molecular mechanism of coptisine-blocked HCC progression, thereby providing solid rationale for using coptisine to treat HCC.

An Unusual Etiology of Urinary Retention - Small Cell Prostate Carcinoma.

We report the case of a 63-year-old male who presented with painless gross hematuria and urinary retention. Pathology obtained from transurethral resection of the prostate revealed pure small cell carcinoma of the prostate. Metastatic evaluation confirmed stage IV disease with lymphatic and hepatic metastasis. Despite aggressive systemic chemotherapy, the patient succumbed to his disease eleven months after initial diagnosis. Small cell carcinoma is an aggressive variant of prostate cancer that often presents late in the clinical course. We review the literature and discuss the clinical features associated with this rare subset of prostate cancer.

Studies on the active constituents in radix salviae miltiorrhizae and their protective effects on cerebral ischemia reperfusion injury and its mechanism.

BACKGROUND: To extract, purify and identify the active constituents in ethanol extract of Radix Salviae Miltiorrhizae, and to analyze the protective effects of tanshinone IIA on cerebral ischemia-reperfusion injury in rats. MATERIALS AND METHODS: Radix Salviae Miltiorrhizae was extracted by ultrasonic extraction, effective parts were extracted by extraction method, compounds were isolated by preparative TLC and preparative HPLC, and structures of compounds were identified by (1)H NMR and (13)C NMR; the effects of tanshinone IIA on cerebral ischemia-reperfusion injury in rats were determined by establishing rat model of middle cerebral artery occlusion (MCAO). RESULTS: The experimental data show four compounds were isolated, namely tanshinone IIB, hydroxymethylene tanshinone, salvianolic acid B and 9"'-methyl lithospermate B. Tanshinone IIA could alleviate the symptoms of neurological deficit in rats, the neurological deficit alleviating effect became more obvious with the increase of dose; tanshinone IIA experimental groups could reduce the cerebral infarction size and brain water content in rats, different concentrations of tanshinone IIA could decrease the SOD content and increase the MDA content in the frontal and parietal cortices of ischemic hemisphere in the ischemia reperfusion group, the differences were statistically significant compared with the ischemia reperfusion group. CONCLUSION: Radix Salviae Miltiorrhizae has the protective effects on cerebral ischemia reperfusion injury in rats.

Massage therapy for fibromyalgia: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Although some studies evaluated the effectiveness of massage therapy for fibromyalgia (FM), the role of massage therapy in the management of FM remained controversial. OBJECTIVE: The purpose of this systematic review is to evaluate the evidence of massage therapy for patients with FM. METHODS: Electronic databases (up to June 2013) were searched to identify relevant studies. The main outcome measures were pain, anxiety, depression, and sleep disturbance. Two reviewers independently abstracted data and appraised risk of bias. The risk of bias of eligible studies was assessed based on Cochrane tools. Standardised mean difference (SMD) and 95% confidence intervals (CI) were calculated by more conservative random-effects model. And heterogeneity was assessed based on the I(2) statistic. RESULTS: Nine randomized controlled trials involving 404 patients met the inclusion criteria. The meta-analyses showed that massage therapy with duration ≥ 5 weeks significantly improved pain (SMD, 0.62; 95% CI 0.05 to 1.20; p = 0.03), anxiety (SMD, 0.44; 95% CI 0.09 to 0.78; p = 0.01), and depression (SMD, 0.49; 95% CI 0.15 to 0.84; p = 0.005) in patients with FM, but not on sleep disturbance (SMD, 0.19; 95% CI -0.38 to 0.75; p = 0.52). CONCLUSION: Massage therapy with duration ≥ 5 weeks had beneficial immediate effects on improving pain, anxiety, and depression in patients with FM. Massage therapy should be one of the viable complementary and alternative treatments for FM. However, given fewer eligible studies in subgroup meta-analyses and no evidence on follow-up effects, large-scale randomized controlled trials with long follow-up are warrant to confirm the current findings.