Involvement of GSTP1 in low dose radiation-induced apoptosis in GM12878 cells.

BACKGROUND: Low-dose ionizing radiation-induced protection and damage are of great significance among radiation workers. We aimed to study the role of glutathione S-transferase Pi (GSTP1) in low-dose ionizing radiation damage and clarify the impact of ionizing radiation on the biological activities of cells. RESULTS: In this study, we collected peripheral blood samples from healthy adults and workers engaged in radiation and radiotherapy and detected the expression of GSTP1 by qPCR. We utilized γ-rays emitted from uranium tailings as a radiation source, with a dose rate of 14 µGy/h. GM12878 cells subjected to this radiation for 7, 14, 21, and 28 days received total doses of 2.4, 4.7, 7.1, and 9.4 mGy, respectively. Subsequent analyses, including flow cytometry, MTS, and other assays, were performed to assess the ionizing radiation's effects on cellular biological functions. In peripheral blood samples collected from healthy adults and radiologic technologist working in a hospital, we observed a decreased expression of GSTP1 mRNA in radiation personnel compared to the healthy controls. In cultured GM12878 cells exposed to low-dose ionizing radiation from uranium tailings, we noted significant changes in cell morphology, suppression of proliferation, delay in cell cycle progression, and increased apoptosis. These effects were partially reversed by overexpression of GSTP1. Moreover, low-dose ionizing radiation increased GSTP1 gene methylation and downregulated GSTP1 expression. Furthermore, low-dose ionizing radiation affected the expression of GSTP1-related signaling molecules. CONCLUSIONS: This study shows that low-dose ionizing radiation damages GM12878 cells and affects their proliferation, cell cycle progression, and apoptosis. In addition, GSTP1 plays a modulating role under low-dose ionizing radiation damage conditions. Low-dose ionizing radiation affects the expression of Nrf2, JNK, and other signaling molecules through GSTP1.

Cotransplantation of NSCs and ethyl stearate promotes synaptic plasticity in PD rats by Drd1/ERK/AP-1 signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine views kidney shortage as a significant contributor to the aetiology of Parkinson's disease (PD), a neurodegenerative condition that is closely linked to aging. In clinical, patients with Parkinson's disease are often treated with Testudinis Carapax et Plastrum (Plastrum Testudinis, PT), a traditional Chinese medication that tonifies the kidney. Previous research has demonstrated that ethyl stearate (PubChem CID: 8122), an active component of Plastrum Testudinis Extracted with ethyl acetate (PTE), may encourage neural stem cells (NSCs) development into dopaminergic (DAergic) neurons. However, the effectiveness and mechanism of cotransplantation of ethyl stearate and NSCs in treating PD model rats still require further investigation. AIM OF THE STUDY: PD is a neurodegenerative condition marked by the loss and degradation of dopaminergic neurons in the substantia nigra of the midbrain. Synaptic damage is also a critical pathology in PD. Because of their self-renewal, minimal immunogenicity, and capacity to differentiate into dopaminergic (DAergic) neurons, NSCs are a prospective treatment option for Parkinson's disease cell transplantation therapy. However, encouraging transplanted NSCs to differentiate into dopaminergic neurons and enhancing synaptic plasticity in vivo remains a significant challenge in improving the efficacy of NSCs transplantation for PD. This investigation seeks to examine the efficacy of cotransplantation of NSCs and ethyl stearate in PD model rats and its mechanism related to synaptic plasticity. MATERIALS AND METHODS: On 6-hydroxydopamine-induced PD model rats, we performed NSCs transplantation therapy and cotransplantation therapy involving ethyl stearate and NSCs. Rotating behavior induced by apomorphine (APO) and pole climbing tests were used to evaluate behavioral changes. Using a variety of methods, including Western blotting (WB), immunofluorescence analysis, enzyme-linked immunosorbent assay, and quantitative real-time polymerase chain reaction (qRT-PCR), we examined the function and potential molecular mechanisms of ethyl stearate in combined NSCs transplantation therapy. RESULTS: In the rat PD model, cotransplantation of ethyl stearate with NSCs dramatically reduced motor dysfunction, restored TH protein levels, and boosted dopamine levels in the striatum, according to our findings. Furthermore, the expression levels of SYN1 and PSD95, markers of synaptic plasticity, and BDNF, closely related to synaptic plasticity, were significantly increased. Cotransplantation with ethyl stearate and NSCs also increased the expression levels of Dopamine Receptor D1 (Drd1), an important receptor in the dopamine neural circuit, accompanied by an increase in MMP9 levels, ERK1/2 phosphorylation levels, and c-fos protein levels. CONCLUSIONS: According to the results of our investigation, cotransplantation of ethyl stearate and NSCs significantly improves the condition of PD model rats. We found that cotransplantation of ethyl stearate and NSCs may promote the expression of MMP9 by regulating the Drd1-ERK-AP-1 pathway, thus improving synaptic plasticity after NSCs transplantation. These findings provide new experimental support for the treatment of PD with the kidney tonifying Chinese medicine Plastrum Testudinis and suggest a potential therapeutic strategy for PD based on cotransplantation therapy.

IgA nephropathy treatment with traditional Chinese medicine: A case report.

BACKGROUND: IgA nephropathy (IgAN) is a common primary glomerular disease that leads to end-stage renal disease with poor therapy efficacy. Traditional Chinese medicine (TCM) is effective in the treatment of IgAN and has the potential to become an alternative treatment for IgAN. Professor Yan-Qin Zou is a nephropathy expert, a National Chinese Medicine Master, and an heir to the Menghe School of Medicine. CASE SUMMARY: A 28-year-old man had positive urinary protein and elevated serum creatinine (Scr) results and was diagnosed with IgAN 2-3 years prior to the outpatient department visit at our hospital in 2017. Professor Zou used the following methods to treat the patient: Invigorating the spleen and tonifying the kidney, removing dampness and clearing turbidity, quickening the blood and transforming stasis, and freeing vessels and regulating collaterals. She adjusted the prescription in accordance with the patient's symptoms. After 6 mo of treatment, the symptoms had resolved and serological indexes were also decreased [Scr from 288.5 to 188.6 µmol/L, blood urea nitrogen (BUN) from 10.9 to 9.5 mmol/L, serum uric acid (UA) from 612 to 503 µmol/L]. During follow-up, BUN, Scr, and UA levels remained stable. CONCLUSION: Professor Zou's therapeutic strategy to treat IgAN using TCM was efficacious and a good reference for application.

Chinese Herbal Medicine Suyin Detoxification Granule Inhibits Pyroptosis and Epithelial-Mesenchymal Transition by Downregulating MAVS/NLRP3 to Alleviate Renal Injury.

PURPOSE: Proteinuria is an independent risk factor of chronic kidney disease (CKD). Albumin-induced tubulointerstitial inflammation and epithelial-mesenchymal transition (EMT) via the activation of NLRP3 inflammasome is a potential therapeutic target for CKD. Suyin Detoxification Granule (SDG) improves proteinuria and postpones renal failure. However, the underlying mechanism is still unknown. METHODS: Firstly, the rat model of renal failure was established using intragastric administration of adenine. Renal function, proteinuria, inflammatory indicators in serum, and renal pathology were assessed, and renal immunohistochemical staining of NLRP3 inflammasomes was performed after intervention with low and high concentrations of SDG. Secondly, the model of renal tubular epithelial HK-2 cells was established using albumin in vitro, and the cell viability, EMT phenotype, and the expression of proteins in the NLRP3 inflammasome signaling pathway were measured after the freeze-dried powder of Suyin Detoxification Prescription (SDP) and CY-09, which is a selective and direct NLRP3 inhibitor, were co-incubated with albumin. ATP, SOD, mitochondrial membrane potential, and ROS were further measured in vitro, and changes in the mitochondrial function after SDP intervention were observed. The mitochondrial antiviral signaling protein (MAVS) was knocked down using siRNA, and the interaction between MAVS and NLRP3 was verified using Western blotting, polymerase chain reaction (PCR), and immunofluorescence. RESULTS: SDG improved renal function and proteinuria, alleviated renal fibrosis, and reduced serum inflammation and the expression of the components of the NLRP3 inflammasome in the kidney. In vitro, SDP and CY-09 enhanced cell viability after injury with albumin and inhibited pyroptosis induced by the NLRP3 inflammatory signaling pathway and expression of proteins involved in EMT. It was further found that SDP alleviated the mitochondrial dysfunction caused by albumin. The knockdown of MAVS reduced the expression of NLRP3 pathway proteins and their mRNA levels and also weakened the co-localization of NLRP3, thus, reducing cell pyroptosis. CONCLUSION: SDP protected renal tubular epithelial cells from cell pyroptosis and EMT by regulating the albumin-induced mitochondrial dysfunction/ MAVS/ NLRP3-ASC-caspase-1 inflammasome signaling pathway.

Protective effect of plastrum testudinis extract on dopaminergic neurons in a Parkinson's disease model through DNMT1 nuclear translocation and SNCA's methylation.

The pathological characteristics of Parkinson's disease (PD) include dopaminergic neuron damage, specifically disorders caused by dopamine synthesis, in vivo. Plastrum testudinis extract (PTE) and its bioactive ingredient ethyl stearate (PubChem CID: 8122) were reported to be correlated with tyrosine hydroxylase (TH), which is a biomarker of dopaminergic neurons. This suggests that PTE and its small-molecule active ingredient ethyl stearate have potential for development as a therapeutic drug for PD. In this study, we treated 6-hydroxydopamine (6-OHDA)-induced model rats and PC12 cells with PTE. The mechanism of action of PTE and ethyl stearate was investigated by western blotting, bisulfite sequencing PCR (BSP), real-time PCR, immunofluorescence and siRNA transfection. PTE effectively upregulated the TH expression and downregulated the alpha-synuclein expression in both the substantia nigra and the striatum of the midbrain in a PD model rat. The PC12 cell model showed that both PTE and its active monomer ethyl stearate significantly promoted TH expression and blocked alpha-synuclein, agreeing with the in vivo results. BSP showed that PTE and ethyl stearate increased the methylation level of the Snca intron 1 region. These findings suggest that some of the protective effects of PTE on dopaminergic neurons are mediated by ethyl stearate. The mechanism of ethyl stearate may involve disrupting the abnormal aggregation of DNA (cytosine-5)-methyltransferase 1 (DNMT1) with alpha-synuclein by releasing DNMT1, upregulating Snca intron 1 CpG island methylation, and ultimately, reducing the expression of alpha-synuclein.

iTRAQ-Based Proteomic Profiling of Potential Biomarkers in Rat Serum for Uranium Tailing Suspension Intratracheal Instillation.

Protection against low-dose ionizing radiation is of great significance. Uranium tailings are formed as a byproduct of uranium mining and a potential risk to organisms. In this study, we identified potential biomarkers associated with exposure to low-dose radiation from uranium tailings. We established a Wistar rat model of low dose rate irradiation by intratracheal instillation of a uranium tailing suspension. We observed pathological changes in the liver, lung, and kidney tissues of the rats. Using isobaric tags for relative and absolute quantification, we screened 17 common differentially expressed proteins in three dose groups. We chose alpha-1 antiproteinase (Serpina1), keratin 17 (Krt17), and aldehyde dehydrogenase (Aldh3a1) for further investigation. Our data showed that expression of Serpina1, Krt17, and Aldh3a1 had changed after the intratracheal instillation in rats, which may be potential biomarkers for uranium tailing low-dose irradiation. However, the underlying mechanisms require further investigation.

Ganduqing Granules in Treatment of Common Cold Due to Qi Deficiency and Pathogen Invasion / 中国实验方剂学杂志

Objective:To observe and evaluate the efficacy and safety of Ganduqing Granules in the treatment of common cold due to qi deficiency and pathogen invasion. Method:A multi-center， randomized， double-blind， and placebo-controlled clinical trial was conducted. One hundred and twenty patients were randomly divided into an experimental group （<italic>n</italic>=60） and a control group （<italic>n</italic>=60）. Patients in the experimental group were treated with oral Ganduqing Granules， 6 g per time， 3 times per day， while those in the control group received placebo， 6 g per time， 3 times per day. After treatment for 5 successive days in both groups， the overall remission rate， total score of primary symptoms， total score of secondary symptoms， total score of all symptoms， time required for overall symptom remission， and therapeutic efficacy against traditional Chinese medicine （TCM） syndrome in the two groups were analyzed in both full analysis set （FAS） and per-protocol set （PPS）， followed by the evaluation of safety in the safety set （SS）. Result:No drop-out was found in the experimental group， whereas 3 cases in the control group dropped out. After 5 days of treatment， the overall remission rate of the experimental group was significantly higher than that of the control group （<italic>P</italic><0.01）. The analysis in FAS and PDS revealed identical results. The experimental group was obviously better than the control group in improving the total scores of primary symptoms， secondary symptoms， and all symptoms （<italic>P</italic><0.01）. The analysis results in FAS and PDS were consistent. There was no significant difference in overall remission time between the two groups. The experimental group was remarkably superior to the control group in alleviating such symptoms as aversion to wind and cold， nasal congestion， runny nose， fatigue， shortness of breath， laziness to speak， dry throat， sore throat， cough， and expectoration （<italic>P</italic><0.05，<italic>P</italic><0.01）. The analysis results in FAS were the same as those in PDS. All the patients did not present with significant abnormalities in vital signs， blood routine test， or liver and kidney function tests after medication. There was no significant difference in the incidence of adverse events between the experimental group and the control group. Conclusion:Ganduqing Granules effectively alleviate the symptoms of patients with common cold and shorten the course of disease， without inducing obvious side effects.

Glaucocalyxin A attenuates allergic responses by inhibiting mast cell degranulation through HMGB1/TLR4/NF-κB signaling pathways / 药学学报

The study is to investigate the effect of glaucocalyxin A (GLA) on mast cell-mediated anaphylaxis. The animal welfare and experimental process of this experiment followed the regulations of the Animal Ethics Committee of Yanbian University. BALB/c mice were used in the animal experiment and randomly divided into five groups, control group, model group, and GLA low, medium, and high dose groups (10, 20, and 40 mg·kg-1). Mice were sensitized by intradermal injection of anti-dinitrophenyl-immunoglobulin E (DNP-IgE) into the ears and challenged with a mixture of DNP-human serum albumin (HSA) and 4% evans blue into the tail veins to prepare an animal skin passive cutaneous anaphylaxis (PCA) model, which was collected from both ears for measurement of dye staining and histology. Rat peritoneal mast cells (RPMCs) were used in the cell experiment and divided into control, IgE + antigen (Ag), and IgE + Ag + GLA groups to determine histamine release as well as calcium influx levels. High-affinity IgE receptor (FcεRI)-mediated signaling pathway proteins and HMGB1/TLR4/NF-κB (high mobility group box 1/toll like receptor 4/nuclear transcription factor kappa B) signaling proteins were detected by Western blot. The results of animal experiments suggest that GLA inhibits PCA, reduces evans blue dye exudation, and reduces ear inflammation and ear thickness in mice. The results of cellular experiments suggested that GLA could reduce histamine release and calcium influx, and inhibit tumor necrosis factor-α (TNF-α), interleukin (IL)-4, IL-13, and IL-1β production; Western blot results showed that GLA inhibited FcεRI-mediated phosphorylation levels of spleen tyrosine kinase (Syk), Lck/Yes novel tyrosine kinase (Lyn), tyrosine kinase Fyn (Fyn), growth-factor receptor-bound protein 2 (Gab2), and phospholipase C (PLC) γ1, while GLA inhibited HMGB1/TLR4 signaling pathway to limit NF-κB p65 nuclear metastasis. The results indicate that GLA inhibits mast cell degranulation and attenuates allergic inflammation through the HMGB1/TLR4/NF-κB signaling pathway.

Efficacy and Safety of Chinese Herbal Formula Granules in Treating Chronic Kidney Disease Stage 3: A Multicenter, Randomized, Placebo-Controlled, Double-Blind Clinical Trial.

BACKGROUND: It is generally considered that traditional Chinese medicine (TCM) therapy postpones the progression of some chronic kidney diseases (CKDs). Chinese medicine herbs are widely applied in TCM therapy. We aimed to evaluate clinical efficacy and safety of Chinese herbal formula granules in patients with CKD stage 3 through a prospective randomized controlled study. METHODS: A total of 343 participants with CKD stage 3 were recruited from 9 hospitals in Jiangsu Province between April 2014 and October 2016. Participants were randomly assigned to a treatment or control group. Patients in the treatment group orally took Chinese herbal formula granules twice a day, while controls received placebo granules. The duration of intervention was 24 weeks. Primary outcomes were 24-hour proteinuria, serum creatinine, and eGFR, which were measured every 4 weeks. RESULTS: There was no statistical difference in 24-hour proteinuria between the two groups (0.97 ± 1.14 g/d vs. 0.97 ± 1.25 g/d). Patients in the treatment group had significantly lower serum creatinine level (130.78 ± 32.55 µmol/L versus 149.12 ± 41.27 µmol/L) and significantly higher eGFR level (55.74 ± 50.82 ml/min/1.73·m2 versus 44.46 ± 12.60 ml/min/1.73·m2) than those in the control group (P < 0.05). There was no significant difference between two groups in the incidence of adverse events. CONCLUSION: The treatment adopting Chinese herbal formula granules for 24 weeks improved kidney function of patients with CKD stage 3.

Ethyl Acetate Fraction from Hedyotis diffusa plus Scutellaria barbata Exerts Anti-Breast Cancer Effect via miR-200c-PDE7B/PD-L1-AKT/MAPK Axis.

BACKGROUND: Hedyotis diffusa (HD) Willd. and Scutellaria barbata (SB) D. Don in different ratios have been frequently used to treat various cancers in clinical Traditional Chinese Medicine prescriptions. However, the optimal ratio, active fraction, and molecular mechanisms associated with the anti-breast cancer role of this herbal couplet have not been elaborated. METHODS: To screen out the optimal ratio of this herbal couplet, we compare aqueous extracts of HD, SB, or HD plus SB in different weight ratios (HS11, HS12, HS21) for their anticancer effects on murine breast cancer 4T1 cells in vitro and in vivo. EA11, the ethyl acetate fraction from HS11 (the aqueous extract of the couplet at an equal weight ratio), is further assessed for its antiproliferative effect as well as the antitumorigenic impact with the aid of immunocompetent mice. Colony formation, flow cytometry, western blot, ELISA, and qRT-PCR are used to elucidate mechanisms underlying EA11-led effects. RESULTS: HS11 presents the most potential suppression of 4T1 cell proliferation and tumor growth among these aqueous extracts. The comparison results show that EA11 is more effective than HS11 in vitro and in vivo. EA11 inhibits colony formation and induces apoptosis in a concentration-dependent manner. EA11 reduces the protein expressions of PDE7B, PD-L1, ß-catenin, and cyclin D1 while elevating the concentration of cellular cAMP and miR-200c expression in 4T1 cells. Additionally, EA11 exerts its anticancer effect partially via the inactivation of MAPK and AKT signaling pathways. CONCLUSIONS: This study implicates that EA11 prevents breast tumor development by interfering with the miR-200c-PDE7B/PD-L1-AKT/MAPK axis. EA11 may represent a potential therapeutic candidate for breast cancer.

The Efficacy of Tai Chi and Qigong Exercises on Blood Pressure and Blood Levels of Nitric Oxide and Endothelin-1 in Patients with Essential Hypertension: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: Tai Chi and Qigong are the two similar traditional Chinese wellness exercises. A strong body of published clinical randomized controlled trials (RCTs) has investigated the health benefits of Tai Chi and Qigong exercises (TCQE) in patients with essential hypertension (EH). This is the first meta-analysis to evaluate the efficacy of TCQE on blood pressure (BP) and blood levels of nitric oxide (NO) and endothelin-1 (ET-1) in EH patients and explore the potential antihypertensive mechanism of TCQE. METHODS: We conducted a literature retrieval for Chinese and English studies in seven databases from their respective inceptions until January 14, 2020. All RCTs examining clinical efficacy of TCQE for EH patients were considered. The major therapeutic outcomes of TCQE were changes in the blood levels of NO, ET-1, and BP in EH patients. Methodological quality of the included RCTs was detected via The Cochrane Risk of Bias tool. We evaluated the data reported and performed the meta-analysis by Review Manager 5.3 software. RESULTS: 9 RCTs involving 516 EH patients were included. The intervention duration lasted from 1.5 months to 6 months. The results of comprehensive analysis showed that compared with control interventions, experimental interventions were more effective in reducing the systolic blood pressure and the diastolic blood pressure and contributed higher blood levels of NO and lower blood levels of ET-1. CONCLUSIONS: TCQE could be an effective complementary and alternative therapy for EH. The lower BP in EH patients who practice TCQE may have some connection with exercise-related increased blood NO levels and decreased blood ET-1 levels. However, further research is needed to make clear the efficacy of TCQE in management of EH and the mechanism of lowering BP in TCQE.

An EGFR signature predicts cell line and patient sensitivity to multiple tyrosine kinase inhibitors.

EGFR is an oncogene with a high frequency of activating mutations in nonsmall cell lung cancer (NSCLC). EGFR inhibitors have been FDA-approved for NSCLC and have shown efficacy in patients with certain EGFR mutations. However, only 9% to 26% of these patients achieve objective responses. In our study, we developed an EGFR gene signature based on The Cancer Genome Atlas (TCGA) RNA-seq data of lung adenocarcinoma (LUAD) to direct the preselection of patients for more effective EGFR-targeted therapy. This signature infers baseline EGFR signaling pathway activity (denoted as EGFR score) in tumor samples, which is associated with tumor sensitivity to EGFR inhibitors and other tyrosine kinase inhibitors (TKIs). EGFR score predicted sensitivity of lung cancer cell lines to Erlotinib, Gefitinib and Sorafenib. Importantly, EGFR score calculated from pretreated samples was associated with patient response to Gefitinib and Sorafenib in lung cancer. Additionally, integration of the EGFR signature with TCGA LUAD data showed that it accurately predicted functional effects of different somatic EGFR mutations, and identified other mutations affecting EGFR pathway activity. Finally, using cancer cell line and clinical trial data, the EGFR score was associated with patient response to TKIs in liver cancer and other cancer types. The EGFR signature provides a useful biomarker that can expand the application of EGFR inhibitors or other TKIs and improve their treatment efficacy through patient stratification.

Association between Chinese Medicine Therapy and Survival Outcomes in Postoperative Patients with NSCLC: A Multicenter, Prospective, Cohort Study.

OBJECTIVE: To evaluate the association between Chinese medicine (CM) therapy and disease-free survival (DFS) outcomes in postoperative patients with non-small cell lung cancer (NSCLC). METHODS: This multiple-center prospective cohort study was conducted in 13 medical centers in China. Patients with stage I, II, or IIIA NSCLC who had undergone radical resection and received conventional postoperative treatment according to the National Comprehensive Cancer Network (NCCN) guidelines were recruited. The recruited patients were divided into a CM treatment group and a control group according to their wishes. Patients in the CM treatment group received continuous CM therapy for more than 6 months or until disease progression. Patients in the control group received CM therapy for less than 1 month. Follow-up was conducted over 3 years. The primary outcome was DFS, with recurrence/metastasis rates as a secondary outcome. RESULTS: Between May 2013 and August 2016, 503 patients were enrolled into the cohort; 266 were classified in the CM treatment group and 237 in the control group. Adjusting for covariates, high exposure to CM was associated with better DFS [hazard ratio (HR) = 0.417, 95% confidential interval (CI): 0.307-0.567)]. A longer duration of CM therapy (6-12 months, 12-18 months, >24 months) was associated with lower recurrence and metastasis rates (HR = 0.225, 0.119 and 0.083, respectively). In a subgroup exploratory analysis, CM therapy was also a protective factor of cancer recurrence and metastasis in both stage I-IIIA (HR=0.50, 95% CI: 0.37-0.67) and stage IIIA NSCLC postoperative patients (HR = 0.48, 95% CI: 0.33-0.71), DFS was even longer among CM treatment group patients. CONCLUSIONS: Longer duration of CM therapy could be considered a protective factor of cancer recurrence and metastasis. CM treatment is associated with improving survival outcomes of postoperative NSCLC patients in China. (Registration No. ChiCTR-OOC-14005398).

Association between Chinese Medicine Therapy and Survival Outcomes in Postoperative Patients with NSCLC: A Multicenter, Prospective, Cohort Study / 中国结合医学杂志

OBJECTIVE@#To evaluate the association between Chinese medicine (CM) therapy and disease-free survival (DFS) outcomes in postoperative patients with non-small cell lung cancer (NSCLC).@*METHODS@#This multiple-center prospective cohort study was conducted in 13 medical centers in China. Patients with stage I, II, or IIIA NSCLC who had undergone radical resection and received conventional postoperative treatment according to the National Comprehensive Cancer Network (NCCN) guidelines were recruited. The recruited patients were divided into a CM treatment group and a control group according to their wishes. Patients in the CM treatment group received continuous CM therapy for more than 6 months or until disease progression. Patients in the control group received CM therapy for less than 1 month. Follow-up was conducted over 3 years. The primary outcome was DFS, with recurrence/metastasis rates as a secondary outcome.@*RESULTS@#Between May 2013 and August 2016, 503 patients were enrolled into the cohort; 266 were classified in the CM treatment group and 237 in the control group. Adjusting for covariates, high exposure to CM was associated with better DFS [hazard ratio (HR) = 0.417, 95% confidential interval (CI): 0.307-0.567)]. A longer duration of CM therapy (6-12 months, 12-18 months, >24 months) was associated with lower recurrence and metastasis rates (HR = 0.225, 0.119 and 0.083, respectively). In a subgroup exploratory analysis, CM therapy was also a protective factor of cancer recurrence and metastasis in both stage I-IIIA (HR=0.50, 95% CI: 0.37-0.67) and stage IIIA NSCLC postoperative patients (HR = 0.48, 95% CI: 0.33-0.71), DFS was even longer among CM treatment group patients.@*CONCLUSIONS@#Longer duration of CM therapy could be considered a protective factor of cancer recurrence and metastasis. CM treatment is associated with improving survival outcomes of postoperative NSCLC patients in China. (Registration No. ChiCTR-OOC-14005398).

Differential expression of NPM, GSTA3, and GNMT in mouse liver following long-term in vivo irradiation by means of uranium tailings.

Uranium tailings (UT) are formed as a byproduct of uranium mining and are of potential risk to living organisms. In the present study, we sought to identify potential biomarkers associated with chronic exposure to low dose rate γ radiation originating from UT. We exposed C57BL/6J mice to 30, 100, or 250 µGy/h of gamma radiation originating from UT samples. Nine animals were included in each treatment group. We observed that the liver central vein was significantly enlarged in mice exposed to dose rates of 100 and 250 µGy/h, when compared with nonirradiated controls. Using proteomic techniques, we identified 18 proteins that were differentially expressed (by a factor of at least 2.5-fold) in exposed animals, when compared with controls. We chose glycine N-methyltransferase (GNMT), glutathione S-transferase A3 (GSTA3), and nucleophosmin (NPM) for further investigations. Our data showed that GNMT (at 100 and 250 µGy/h) and NPM (at 250 µGy/h) were up-regulated, and GSTA3 was down-regulated in all of the irradiated groups, indicating that their expression is modulated by chronic gamma radiation exposure. GNMT, GSTA3, and NPM may therefore prove useful as biomarkers of gamma radiation exposure associated with UT. The mechanisms underlying those changes need to be further studied.

Postharvest Ultrasound-Assisted Freeze-Thaw Pretreatment Improves the Drying Efficiency, Physicochemical Properties, and Macamide Biosynthesis of Maca (Lepidium meyenii).

A novel technique of ultrasound-assisted freeze-thaw pretreatment (UFP) was developed to improve the drying efficiency of maca and bioactive amide synthesis in maca. The optimal UFP conditions are ultrasonic processing 90 min at 30 °C with 6 freeze-thaw cycles. Samples with freeze-thaw pretreatment (FP), ultrasound pretreatment (UP), and UFP were prepared for further comparative study. A no pretreatment (NP) sample was included as a control. The results showed that UFP improved the drying efficiency of maca slices, showing the highest effective moisture diffusivity (1.75 × 10-9 m2 /s). This result was further supported by low-field nuclear magnetic resonance (LF-NMR) analysis and scanning electron microscopy (SEM). The rehydration capacity and protein content of maca slices were improved by UFP. More importantly, contents of bioactive macamides and their biosynthetic precursors were increased in 2.5- and 10-fold, respectively. In conclusion, UFP is an efficient technique to improve drying efficiency, physicochemical properties, and bioactive macamides of maca, which can be applied in the industrial manufacture of maca products.

In vivo transdermal penetration enhancing activity of essential oil from Zanthoxyli Pericarpium by using microdialysis technique / 中国中药杂志

The aim of this paper is to investigate the topical pharmacodynamics behavior of different lipophilic model drugs after treatment with essential oil from Zanthoxyli Pericarpium by using the cutaneous microdialysis technique, and then evaluate its in vivo transdermal penetration enhancing properties. Two traditional Chinese medicine active components, namely tetramethylpyrazine and puerarin, were chosen as lipophilic and hydrophilic model drugs, respectively. Firstly, the concentration difference method was employed to measure the in vitro recovery rate and loss of the microdialysis probe, and the in vivo recoveries of two model drugs were determined by using the retrodialysis method. Secondly, the skin pharmacodynamics behaviors of two model drugs were studied after treatment with different concentrations of the essential oil, and the well-established and standard penetration enhancer Azone was selected as a positive control. It was found that the recovery of microdialysis probe was equal to its loss for two model drugs, with no interaction between drugs in dialysis membranes. The retrodialysis studies revealed that the in vivo recovery of tetramethylpyrazine and puerarin were 59.17%, 19.85%, respectively. The skin pharmacodynamics studies showed that the essential oil could facilitate the transdermal absorption of tetramethylpyrazine in a concentration-dependent manner, and the enhancement ratio (ER) for 5% essential oil was 98.64, which was higher than that of the optimum concentration of Azone (3% Azone, ER=89.11). Meanwhile, the Zanthoxyli Pericarpium could effectively promote the transdermal permeation of the puerarin in a concentration-dependent manner. Hence, this study further confirmed that the Zanthoxyli Pericarpium had excellent penetration-enhancing activity as a natural transdermal penetration enhancer, providing data support for its application in traditional Chinese medicine external preparations.

A survey on knowledge of acupuncture disease spectrum and expectation of acupuncture treatment in Chengdu residents / 中国针灸

<p><b>OBJECTIVE</b>To understand the knowledge of acupuncture disease spectrum, expectation of acupuncture treatment in Chengdu residents.</p><p><b>METHODS</b>A questionnaire regarding the knowledge of acupuncture disease spectrum and expectation of acupuncture treatment in Chengdu residents was established. By field sampling and internet survey, related data were collected and analyzed.</p><p><b>RESULTS</b>Totally 1 548 valid questionnaires were collected, including 1 041 from field survey and 507 from internet survey. The results indicated the knowledge of acupuncture and its disease spectrum were moderate in Chengdu residents; among the disease spectrum of acupuncture, the disease with the highest cognition was insomnia, accounting for 45.0% in field survey and 75.4% in internet survey; while the disease with the lowest cognition was infertility, accounting for 8.3% in field survey and 34.3% in internet survey.</p><p><b>CONCLUSIONS</b>The knowledge of acupuncture in Chengdu residents could be further improved, and the promotion of popular science of acupuncture should be strengthened in future.</p>

Review on skin temperature of acupoints / 中国针灸

We retrieve and analyze the articles on body surface temperature of acupoints in the recent 50 years. Surface temperatures have been compared between acupoints and nonacupoints, and among acupoints in different states. The impacts of interventions for acupoint temperature are explored, including acupuncture,moxibustion and cupping, etc. We summarize the features and the rules of acupoint skin temperature. It is considered that there exists distribution rule for healthy people's acupoint skin temperature. That means acupoints have higher surface temperature than nonacupoints. In the same meridian the nearer acupoints close to the head and trunk, the higher the temperature is. The difference in symmetrical acupoints temperatures between the left and right side is about 0.5℃. In the different meridians the skin temperatures of adjacent acpoints are similar. The changes of acupoint's skin temperature in illness can be used as the auxiliary diagnosis. Acupuncture, moxibustion and cupping can produce acupoints stimulating, metabolism improving,balance, acupoint temperature regulating. Thus,diseases are relieved. The specificity and regularity that acupoint's skin temperature presents may be one of the manifestations of the acupoint specificity, also it is an important starting point of the research on acupoint sensitization. The further studies should consider different diseases and modern biological engineering techniques, so that more rules of acupoints temperature can be found by more sensitive and objective temperature measurements as well as experimental and the mathematical models.

Comparison of essential oil from Mentha haplocalyx and menthol used as penetration enhancers / 中国中药杂志

The aim of this paper was to investigate and compare the penetration-enhancing characteristics of menthol and essential oil from Mentha haplocalyx(M.haplocalyx oil) on the transdermal absorption of the complex traditional Chinese medicine(TCM) components. A series of TCM components were selected as model drugs based on their lipophilicity (logP value), namely osthole(OT, logP=3.85), tetramethylpyrazine(TMP, logP=2.34), ferulic acid(FA, logP=1.26), puerarin(PR, logP=-0.35) and geniposide(GP, logP=-1.01), in order to simply and characterize the TCM complex components system. Transdermal experiment in vitro was employed to investigate and compare the penetration-enhancing characteristics of menthol and M.haplocalyx oil on the transdermal absorption of these model drugs. Meanwhile, Fourier transform infrared spectroscopy(FTIR) was used to further compare the effect of menthol and M. haplocalyx oil on the molecular structure of stratum corneum(SC). The results showed that both of menthol and M.haplocalyx oil at proper concentration could promote the transdermal absorption of the selected model drugs. After application of menthol, the drug logP values gradually tended to have negative linear relationship with the logarithm of penetration enhancement ratio(ER); while after application of M.haplocalyx oil, the logP values tended to have parabolic relationship with the logarithm of ER. However, both menthol and M.haplocalyx oil exhibited higher efficiency for the drugs with relative low lgP value(ie hydrophilic drugs), with similar penetration-enhancing characteristics between these two. Infrared spectroscopy results showed that menthol and M.haplocalyx oil could affect the skin barrier functions mainly via stratum corneum lipids, with similar effect intensity, and this was consistent with the results of transdermal experiment in vitro. Thus, Menthol had similar penetration-enhancing characteristics with M.haplocalyx oil, and had same effect on the SC molecular structure. Therefore, as transdermal penetration enhancer, the menthol with single composition could be considered to replace M.haplocalyx oil with complex compositions.