A Novel Chinese Medicine Formula Inhibits Non-small Cell Lung Cancer by Triggering Oxidative Stress Dependent on Pentose Phosphate Pathway / 中国肺癌杂志

BACKGROUND@#Non-small cell lung cancer (NSCLC) is one of the most lethal malignancies worldwide. A novel Chinese medicine formula-01 (NCHF-01) has shown significant clinical efficacy in the treatment of NSCLC, but the mechanism of this formula in the treatment of NSCLC is not fully understood. The aim of this study is to investigate the molecular mechanism of NCHF-01 in inhibiting NSCLC.@*METHODS@#Lewis lung cells (LLC) tumor bearing mice were established to detect the tumor inhibitory effect of NCHF-01. The morphological changes of tissues and organs in LLC tumor-bearing mice were detected by hematoxylin-eosin (HE) staining. NSCLC cells were treated by NCHF-01. The effects of cell viability and proliferation were detected by MTT and crystal violet staining experiment. Flow cytometry was used to detect cell cycle, apoptosis and reactive oxygen species (ROS). Network pharmacology was used to predict the mechanism of its inhibitory effect of NSCLC. Western blot and immunohistochemistry (IHC) were used to detect the expression of related proteins.@*RESULTS@#NCHF-01 can inhibit tumor growth in LLC tumor-bearing mice, and has no obvious side effects on other tissues and organs. NCHF-01 could inhibit cell viability and proliferation, induce G2/M phase arrest and apoptosis, and promote the increase of ROS level. Network pharmacological analysis showed that NCHF-01 exerts anti-NSCLC effects through various biological processes such as oxidative stress and central carbon metabolism. NCHF-01 can reduce the protein expression and enzyme activity of the key enzymes 6-phosphate glucose dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase (6PGD) in the pentose phosphate pathway (PPP).@*CONCLUSIONS@#NCHF-01 can inhibit NSCLC through oxidative stress dependent on the PPP.

Mechanism of astragaloside Ⅳ alleviating PC12 cell injury by activating PI3K/AKT signaling pathway: based on network pharmacology and in vitro experiments / 中国中药杂志

In this study, the molecular mechanism of astragaloside Ⅳ(AS-Ⅳ) in the treatment of Parkinson's disease(PD) was explored based on network pharmacology, and the potential value of AS-Ⅳ in alleviating neuronal injury in PD by activating the PI3 K/AKT signaling pathway was verified through molecular docking and in vitro experiments. Such databases as SwissTargetPrediction, BTMAN-TAM, and GeneCards were used to predict the targets of AS-Ⅳ for the treatment of PD. The Search Tool for the Retrieval of Interacting Genes/Proteins(STRING) was employed to analyze protein-protein interaction(PPI) and construct a PPI network, and the Database for Annotation, Visualization and Integrated Discovery(DAVID) was used for Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis. Based on the results of GO enrichment analysis and KEGG pathway analysis, the PI3 K/AKT signaling pathway was selected for further molecular docking and in vitro experiments in this study. The in vitro cell model of PD was established by MPP~+. The cell viability was measured by MTT assay and effect of AS-Ⅳ on the expression of the PI3 K/AKT signaling pathway-related genes and proteins by real-time polymerase chain reaction(RT-PCR) and Western blot. Network pharmacology revealed totally 122 targets of AS-Ⅳ for the treatment of PD, and GO enrichment analysis yielded 504 GO terms, most of which were biological processes and molecular functions. Totally 20 related signaling pathways were screened out by KEGG pathway analysis, including neuroactive ligand-receptor interaction, PI3 K/AKT signaling pathway, GABAergic synapse, and calcium signaling pathway. Molecular docking demonstrated high affinity of AS-Ⅳ to serine/threonine-protein kinases(AKT1, AKT2), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma(PIK3 CG), and phosphoinositide-3-kinase, catalytic, alpha polypeptide(PIK3 CA) on the PI3 K/AKT signaling pathway. In vitro experiments showed that AS-Ⅳ could effectively inhibit the decrease of the viability of PC12 induced by MPP~+ and up-regulate the mRNA expression levels of AKT1 and PI3 K as well as the phosphorylation levels of AKT and PI3 K. As an active component of Astragali Radix, AS-Ⅳ acts on PD through multiple targets and pathways. Furthermore, it inhibits neuronal apoptosis and protects neurons by activating the PI3 K/AKT signaling pathway, thereby providing reliable theoretical and experimental supports for the treatment of PD with AS-Ⅳ.

Combined Assessment of Serum Alpha-Synuclein and Rab35 is a Better Biomarker for Parkinson's Disease

BACKGROUND AND PURPOSE: It is essential to develop a reliable predictive serum biomarker for Parkinson's disease (PD). The accumulation of alpha-synuclein (αSyn) and up-regulated expression of Rab35 participate in the etiology of PD. The purpose of this investigation was to determine whether the combined assessment of serum αSyn and Rab35 is a useful predictive biomarker for PD. METHODS: Serum levels of αSyn or Rab35 were determined in serum samples from 59 sporadic PD patients, 19 progressive supranuclear palsy (PSP) patients, 20 multiple system atrophy (MSA) patients, and 60 normal controls (NC). Receiver operating characteristics (ROC) curves were calculated to determine the diagnostic accuracy of αSyn or/and Rab35 in discriminating PD patients from NC or atypical parkinsonian patients. RESULTS: The levels of αSyn and Rab35 were increased in PD patients. The serum level of Rab35 was positively correlated with that of αSyn in PD patients. Compared to analyzing αSyn or Rab35 alone, the combined analysis of αSyn and Rab35 produced a larger area under the ROC curve and performed better in discriminating PD patients from NC, MSA patients, or PSP patients. When age was dichotomized at 55, 60, 65, or 70 years, the combined assessment of αSyn and Rab35 for classifying PD was better in the group below the cutoff age than in the group above the cutoff age. CONCLUSIONS: Combined assessment of serum αSyn and Rab35 is a better biomarker for discriminating PD patients from NC or atypical parkinsonian patients, and is a useful predictive biomarker for younger sporadic PD patients.

Interpretation of 2016 Chinese Expert Consensus on Diagnosis and Treatment of Papillary Thyroid Microcarcinoma / 中国实用内科杂志

Led by the Thyroid Cancer Professional Committee of the China Anti-cancer Association(CATO), experts from 21 thyroid centers jointly formulated the 2016 Chinese expert consensus on the diagnosis and treatment of papillary thyroid microcarcinoma.Its content covers surgical, pathological, imaging, endocrine and nuclear medicine and other professional fields, and summarizes the latest clinical research results in the field of papillary thyroid microcarcinoma in recent years and the actual situation in China.The expert consensus includes 23 recommendations, including the epidemiology, diagnosis, treatment, follow-up and outlook of papillary thyroid microcarcinoma, which provides a more reasonable and standard diagnosis and treatment plan.The purpose of this paper is to interpret the application of the consensus two years after its release and the reactions in the industry.

Preparation of palmatine-loaded flexible nano-liposomes films based on Bletilla striata polysaccharides / 中草药

Objective To prepare palmatine-loaded flexible nano-liposomes (PFL) films with Bletilla striata polysaccharide (BSP) as membrane material, and evaluate its pharmacy related performance in order to lay the foundation for further application. Methods The PFL was prepared by injection method and the films of PFL based on Bletilla striata polysaccharide (PFL-BPF) was prepared by homogenate coating method. The PFL-BPF was characterized and evaluated by electron microscopy, differential scanning calorimeter (DSC), and in vitro transmucosal membrane experiment. Results The PFL and BSP had good compatibility and easy to film with BSP as membrane material. The appearance of PFL-BPF obtained was smooth, non-bubble, flexible, and suitable stiffness; PFL-BPF had good biological adhesion. The time of scouring the film agent from mucous membrane with normal saline was (130 ± 7) min. At 0.5 h, the dose of PFL-BPF promoting palmatine (PA) infiltration to mucosa was 32.41 μg/g. It was 3.17 times higher than those of PA solution based on BSP (PL-BPF) and 1.9 times for PA common liposomes based on BSP (BLP + PA-BPF) (t-test, P < 0.05); At 2.5 h, it was 2.67 times and 1.89 times higher than those of PL-BPF and BLP + PA-BPF, respectively. It showed that PFL-BPF could significantly promote the water-soluble drug PA through mucosa membrane and release it slowly. The results of DSC showed that the possible mechanism for promoting the absorption of PA through mucosa membrane was that the flexible liposomes disturbed the mucosal epithelial cells and carried the drug into the mucosal tissue. Conclusion The PFL-BPF had the advantages of good film-forming property, lasting adhesive attraction, strong scour resistance, simple and feasible preparation process, and could promote drug permeation into mucosa obviously. Therefore, the flexible nano-liposomes film is a good drug carrier for the transmucosal drug delivery applications and has a wide application prospect.

Proteomics analysis on brain cortex of ischemic cerebral stroke in rats / 复旦学报（医学版）

Objective To explore brain cortex proteomics changes during ischemic cerebral stroke (ICS),and to seek the biomarkers associated with ICS.Methods A total of 42 male SD rats were randomly divided into sham group (n =12) and ICS group (n =30).ICS model was induced by distal middle cerebral artery occlusion.Brain cortex tissues were collected at 1,6,24 and 48 h after ICS,respectively,after cerebral ischemia.Samples from different groups were subjected to tandem mass tag (TMT)-based quantitative proteomics analysis for identification of differentially expressed proteins.Gene Ontology enrichment analysis was utilized to classify the differentially expressed proteins.Western blot was used to verify the quantitative proteomics results.Results Compared with sham group,25 proteins were considered to be differentially expressed in ICS group.Gene Ontology enrichment analysis revealed that the differentially expressed proteins were related to acute-phase response,inflammatory response,lipoprotein metabolic process,complement activation,classical pathway and innate immune response.The expression change of heat shock protein 27 (HSP27) was basically consistent with the quantitative proteomics results.Conclusions These 25 differentially expressed proteins may serve as potential biomarkers for ICS.

A prospective randomized and controlled study on no drainage after surgery for benign thyroid disorders / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To evaluate the necessity of drainage after thyroidectomy for benign thyroid disorders.</p><p><b>METHODS</b>A total of 272 patients who underwent thyroidectomy for benign thyroid disorders were randomly divided into drainage group or non-drainage group. Operating time, postoperative stay time in hospital, comfort of neck assessed by visual analogue scale (VAS) on postoperative day (POD) 0 and POD1 were and the incidence of complications, including post-thyroidectomy bleeding, hematoma, seroma, wound infection, hoarseness, and hypoparathyroidism, were assessed and compared between two groups.</p><p><b>RESULTS</b>Both groups were similar in the mean age, the sex ratio and the underwent procedure types. There was no significant difference in the mean operating time between two groups (87.5 ± 32.0) min and (93.8 ± 30.1) min (t = 0.12, P = 0.45). The mean postoperative hospital stay time of non-drainage group (1.9 ± 0.3) d was significantly shorter than that of drainage group (2.6 ± 0.6) d (t = 1.45, P = 0.02). The mean VAS scores of neck comfort on POD0 and POD1 in non-drainage group were significantly high than those in non-drainage group(t = 2.67, P = 0.03 and t = 0.33, P = 0.006). There were no significant difference in postoperative complications, including permanent hoarseness and hypoparathyroidism, between two groups.</p><p><b>CONCLUSIONS</b>No drainage after thyroidectomy for benign thyroid disorders does not increase postoperative complications, with the increase in postoperative neck comfort, the decrease in hospital stay time and potential wound infections. The routine drainage is not necessary after thyroid surgery for benign disorders.</p>

Thyroid lymphography:a new clinical approach for protecting parathyroid in surgery / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To research the role of lymph tracers to protect parathyroid in surgery for papillary thyroid carcinoma.</p><p><b>METHODS</b>Patients with papillary thyroid carcinoma who met selected criteria were enrolled in this study. Patients were divided into carbon nanoparticle group, methylene blue group, and conventional surgery group.</p><p><b>RESULTS</b>No significant complication occurred in the patients of carbon nanoparticle and methylene blue groups. In carbon nanoparticle group, methylene blue group and conventional surgery group, the mean numbers of parathyroid glands detected during surgery were 3.1 ± 0.3, 2.9 ± 0.4 and 2.3 ± 0.3 (F = 3.78, P < 0.01) , the rates that parathyroid was cut mistakenly were 1.37% (2/146) , 2.62% (2/97) and 7.14% (6/84) respectively (χ(2) = 17.372, P < 0.05) ; and the incidence of postoperative hypocalcemia were 10.4% (5/48) , 9.1% (3/33) and 17.5% (7/40,χ(2) = 0.671, P = 0.037) .</p><p><b>CONCLUSION</b>Thyroid lymphography technique is helpful to protect from the injury to the parathyroid glands in surgery.</p>

Efficacy and safety of tramadol/ acetaminophen in the treatment of breakthrough pain in cancer patients

We evaluated the analgesic efficacy and safety of tramadol 37.5 mg/ acetaminophen 325 mg combination tablet, for the treatment of breakthrough pain in cancer patients. This study was conducted at Changhua Christian Hospital, Changhua, Taiwan from January 2006 to February 2007. The single-center and open-label study enrolled 59 opioid-treated cancer patients with at least moderate breakthrough pain [visual analog scale [VAS] score >/= 40 mm on a 100-mm scale]. The efficacy measures included VAS scores and adverse effect assessment 10, 30, and 60 minutes after the administration of tramadol/ acetaminophen. Visual analog scale score at time of pain relief was reported. The mean VAS score when the breakthrough pain episode began [0 minute] was 77.8. Analysis showed significant better mean pain VAS scores at 10, 30, 60 minutes after the administration of tramadol/ acetaminophen [p

Clinical observation of XELOX (Capecitabine puls Oxaliplatin): an adjuvant chemotherapy regimen used in stage III colorectal cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of an adjuvant chemotherapy regimen: XELOX (Capecitabine puls Oxaliplatin) used after curative resection for stage III colorectal cancer.</p><p><b>METHODS</b>From Jan. 1998 to Jan. 2004, 256 cases with stage III colorectal cancer randomized received de Gramont, modified FOLFOX4 (mFOLFOX4) and XELOX regimens. The 3-year disease-free survival (DFS) and overall survival (OS) were compared within the three groups and relative prognosis factors within mFOLFOX4 and XELOX groups. Therapeutic adverse events were recorded and analyzed with Kaplan-Meier test.</p><p><b>RESULTS</b>98, 87 and 71 cases were respectively enrolled in the de Gramont, mFOLFOX4 and XELOX groups, mFOLFOX4 and XELOX had superior efficacy compared with de Gramont regimen. The two former could significantly improve 3-year DFS (79.7% vs. 66.2%, P = 0.015; 81.5% vs. 66.2%, P = 0.004) and medium survival time (40.2 mon vs. 37.8 mon, P = 0.024; 41.4 mon vs. 37.8 mon, P = 0.014). Meanwhile they could respectively decrease the ratio of recurrence risk by 18.0% (P = 0.024) and 21.0% (P = 0.003). The relative benefit of mFOLFOX4 versus XELOX didn't differ for 3-year DFS [hazard ratio (HR): 0.84, 95% confidence interval (CI): 0.79-1.12, P = 0.13] and OS (HR: 0.87, 95% CI: 0.84-1.06, P = 0.54). In the analysis of DFS in relative prognosis factors, XELOX had a better trend of survival advantage. mFOLFOX4 had higher adverse events within these regimens, especially in grade 3 or 4 neutropenia and peripheral neurologic adverse events.</p><p><b>CONCLUSION</b>XELOX maintains its efficacy and safety ratio in advanced colorectal cancer. Patients have good tolerance and compliance. The regiment is deserves to be applied in clinical treatment. Oxaliplatin;</p>

Morphological and histological studies on the telencephalon of the salamander Onychodactylus fischeri / 神经科学通报·英文版

<p><b>OBJECTIVE</b>To probe into the morphological and histological characteristics of the telencephalon of Onychodactylus fischeri, and to enrich the comparable neurobiology.</p><p><b>METHOD</b>HE-staining method was used to describe the characters of the telencephalon of Onychodactylus fischeri.</p><p><b>RESULTS</b>The olfactory bulb of Onychodactylus fischeri locates in the rastral and lateral to the cerebral hemisphere, and six distinct layers can be identified from the lateral to the medial, quite similar to Batrachuperus tibetanus and Hynobius leechii. In the cerebrum, the primordial hippocampus developed better than the primordial piriform. The former belongs to archipallium and the latter is paleopallium. Ventral to the primordial hippocampus there is a septal area which cannot be divided into medial and lateral parts. In the ventrical wall, there is neither medial limiting sulcus nor lateral limiting sulcus to separate the primordial hippocampus and the septal area, or the primordial piriform and the corpus striatum. The corpus striatum of Onychodactylus fischeri is paleostriatum. There is choroids plexus anterior in the lateral ventricle. The cell group that located at two sides of the third ventricle is the amygdale. Besides, the shape and size of neurons within the telencephalon are poorly differentiated.</p><p><b>CONCLUSION</b>Onychodactylus fischeri is a relatively primitive type in the amphibian. The present data will help us to further understand the nerve system of tailed amphibian.</p>

Triplex-forming oligonucleotide inhibits the expression of tissue factor gene in endothelial cells induced by the blood flow shear stress in rats / 药学学报

<p><b>AIM</b>To study the effect of antiparallel phosphorothioate triplex-forming oligonucleotide (apsTFO) matching with the shear stress response element (SSRE) of tissue factor (TF) gene promoter region on the expression of TF in endothelial cells (ECs) of rat common carotid artery stenosis.</p><p><b>METHODS</b>The model of common carotid artery middle segment stenosis was established by silica gel pipe loop ligation in SD rats. The mRNA expression and protein synthesis of TF, early growth response-1 (Egr-1) and specificity protein 1 (Sp1) were measured by in situ hybridization (ISH) and immunohistochemistry (IHC) technique. GT21-apsTFO, GT20-apsTFO, GT20-psTFO and FITC-labeled apsTFO, matching with the SSRE of TF gene promoter region, were designed, and intravenously injected into rats at 0.5 h before operation. TFO was detected 4 h after the operation, and the mRNA expression and protein synthesis of TF, Egr-1 and Sp1 were detected 6 h after the operation.</p><p><b>RESULTS</b>There were much fluorescence in vascular tissue, especially in the nuclear of ECs 4.5 h after the injection of apsTFO. The mRNA expression and protein synthesis of TF reduced by 22% - 23% with injection of GT20-apsTFO 6.5 h after stenosis (P < 0.01) and by 10% - 11% with GT21-apsTFO at the same time (P < 0.05). The inhibition by GT20-apsTFO was stronger than that of the GT21-apsTFO (P < 0.05). The expression of TF was not inhibited by the GT20-psTFO (P > 0.05). The mRNA expression and protein synthesis of Egr-1 and Sp1 did not change in the rat treated with GT20-apsTFO, GT20-psTFO and GT21-apsTFO (P > 0.05).</p><p><b>CONCLUSION</b>apsTFO could mero-inhibit the expression of TF gene but could not change the expression of Egr-1 and Sp1 protein.</p>

Fine mapping of susceptibility genes by Lewontin's linkage disequilibrium measure with application to Alzheimer's disease / 中华医学杂志(英文版)

<p><b>OBJECTIVES</b>To formulate an equation for fine mapping of disease loci under complex conditions and determine the marker-disease distance in a specific case using this equation.</p><p><b>METHODS</b>Lewontin's linkage disequilibrium (LD) measure D' was used to formulate an equation for mapping disease genes in the presence of phenocopies, locus heterogeneity, gene-gene and gene-environment interactions, incomplete penetrance, uncertain liability and threshold, incomplete initial LD, natural selection, recurrent mutation, high disease allele frequency and unknown mode of inheritance. This equation was then used to determine the distance between a marker ( epsilon 4 within the apolipoprotein E gene, APOE) and Alzheimer's disease (AD) loci using published data.</p><p><b>RESULTS</b>An equation was formulated for mapping disease genes under the above conditions.If these conditions are present but ignored, then recombination fraction theta between marker and disease loci will be either overestimated or estimated with little bias. Therefore, an upper limit of theta can be obtained. AD has been found to be associated with the marker allele epsilon 4 in Africans, Asians, and Caucasians. This suggests that the AD- epsilon 4 allelic LD predates the divergence of peoples occurring 100 000 years ago. With the age of AD- epsilon 4 allelic LD so estimated, the maximal distance was calculated to be 23.2 kb (mean 5.8 kb).</p><p><b>CONCLUSIONS</b>(1) A method is developed for LD mapping of susceptibility genes. (2) A mutation within the APOE gene itself, among others, is responsible for the susceptibility to AD, which is supported by recent evidence from studies using transgenic mice.</p>