TOPK Inhibition Enhances the Sensitivity of Colorectal Cancer Cells to Radiotherapy by Reducing the DNA Damage Response.

OBJECTIVE: Abnormal expression of T-lymphokine-activated killer cell-originated protein kinase (TOPK) was reported to be closely related to the resistance of prostate cancer to radiotherapy and to targeted drug resistance in lung cancer. However, the role of TOPK inhibition in enhancing radiosensitivity of colorectal cancer (CRC) cells is unclear. This study aimed to evaluate the radiosensitization of TOPK knockdown in CRC cells. METHODS: The expression of TOPK was detected in CRC tissues by immunohistochemistry, and the effect of TOPK knockdown was detected in CRC cells by Western blotting. CCK-8 and clonogenic assays were used to detect the growth and clonogenic ability of CRC cells after TOPK knockdown combined with radiotherapy in CRC cells. Furthermore, proteomic analysis showed that the phosphorylation of TOPK downstream proteins changed after radiotherapy. DNA damage was detected by the comet assay. Changes in the DNA damage response signaling pathway were analyzed by Western blotting, and apoptosis was detected by flow cytometry. RESULTS: The expression of TOPK was significantly greater in CRC tissues at grades 2-4 than in those at grade 1. After irradiation, CRC cells with genetically silenced TOPK had shorter comet tails and reduced expression levels of DNA damage response-associated proteins, including phospho-cyclin-dependent kinase 1 (p-CDK1), phospho-ataxia telangiectasia-mutated (p-ATM), poly ADP-ribose polymerase (PARP), and meiotic recombination 11 homolog 1 (MRE11). CONCLUSIONS: TOPK was overexpressed in patients with moderately to poorly differentiated CRC. Moreover, TOPK knockdown significantly enhanced the radiosensitivity of CRC cells by reducing the DNA damage response.

[Clinical random trial of thumbtack needling therapy for analgesia after cesarean section].

OBJECTIVE: To observe the analgesic effect of thumbtack needling therapy and the quality of life in puerpera underwent cesarean section. METHODS: One hundred and thirty-five puerpera underwent cesarean section were randomly divided into a medication group, a sham-thumbtack needling group and a thumbtack needling group, 45 cases in each group. In the medication group, the patient control analgesia (PCA) was given. In the thumbtack needling group, on the base of the regimen as the medication group, acupuncture with thumbtack needles was applied to lower abdominal point (Extra), Zusanli (ST36), Sanyinjiao (SP6), Geshu (BL17), Shenshu (BL23) and Dachangshu (BL25). The needles were retained for 48 hours. During the needle retaining, the sites with the needle embedded were pressed and kneaded for 3 times, 1 min each time, at the interval of 4 to 12 h. In the sham-thumbtack needling group, the sham-thumbtack needles were used; the acupoint selection, operation and treatment course were all the same as the thumbtack needling group. The visual analogue scale (VAS) scores of incision pain and ute-rine contraction pain, the incidence of postoperative adverse reactions, the amount of vaginal bleeding and milk amount in lactation were observed at each time point after the operation separately in each group. RESULTS: Compared with the medication group, the VAS score of incision pain was decreased 8, 12 and 24 h after operation (P<0.05), the VAS score of uterine contraction pain was decreased 8, 12, 24 and 48 h after operation (P<0.05), the lactation score was increased in 24 to 48 h after operation (P<0.05) in both the sham-thumbtack needling group and thumbtack needling group. Compared with the sham-thumbtack needling group, the VAS score of incision pain was decreased 8, 12 and 24 h after operation (P<0.05), the VAS score of uterine contraction pain was decreased 24 and 48 h after operation (P<0.05) in the thumbtack needling group. Compared with those from 2 to 24 h after operation, the vaginal bleeding amount was decreased and the lactation score increased from 24 to 48 h after operation (P<0.05) in all of the three groups. CONCLUSION: The conventional PCA combined with thumbtack needling therapy obtained better analgesic effects on incision dynamic pain and uterine contraction pain in patients after cesarean section as compared with either the simple PCA or the combined treatment with sham-thumbtack needling and medication, and both the thumbtack needling and the sham-thumbtack needling therapy can increase the milk amount of lactation from 24 to 48 h after operation.

[Advances in the clinical research on acupuncture in treatment of respiratory diseases].

This article reviews the clinical studies on acupuncture in the treatment of asthma, chronic bronchitis, and acute exacerbation and stable phase of chronic obstructive pulmonary disease in China over the past 10 years, and the results suggest that acupuncture has a good clinical effect. At present, there are still several problems in related clinical studies, including lacking of standard operation procedure for acupuncture, unreasonable design of control group, and low quality of clinical research. Therefore, in the future, top-level design should be standardized and large-sample multicenter clinical studies should be conducted to provide stronger evidence of evidence-based medicine for acupuncture in the treatment of respiratory diseases.

[Pollution Characteristics of Perfluorinated Alkyl Substances (PFASs) in Seawater, Sediments, and Biological Samples from Jiaozhou Bay, China].

In order to explore the pollution levels and characteristics of perfluorinated alkyl substances (PFASs), seawater, sediment, and Ruditapes philippinarum samples were collected near the Jiaozhou Bay coast in April 2018. All samples were analyzed by using the high performance liquid chromatography-mass spectrometry method to determine the content of 35 types of PFASs. The results showed that 12 different PFASs were tested in the seawater with ∑PFASs concentrations of 21.1-38.0 ng·L-1; 10 types of PFASs were detected in sediments, with ∑PFASs content (dry weight) ranging from 0.459 to 1.20 µg·kg-1; 19 types of PFASs were measured in Ruditapes philippinarum, with ∑PFASs content (dry weight) of 15.5-27.5 µg·kg-1. Compared with other areas reported in the literature, the total pollution of Jiaozhou Bay was at medium or high levels. In addition, perfluorooctanoic acid (PFOA) was the dominant PFAS in the seawater, sediments, and Ruditapes philippinarum with a detection rate of 100%. 6:2 fluorotelomer phosphate diester (6:2 diPAP) was observed for the first time in seawater and sediments from Jiaozhou Bay and had the highest detection frequency and concentration of the precursor. Perfluorooctanesulfonamide (PFOSA) was the main precursor in Ruditapes philippinarum, of which the detection rate was 93.8%. Moreover, the organic carbon normalized sediment-water distribution coefficient (lg KOC) values were 5.24-6.37 and increased with an increase in carbon chain length. The bioaccumulation factors (lg BAF) and field-based biota-sediment accumulation factors (lg BSAF) were 2.53-4.32 and 1.30-2.50, respectively. The lg BAF values positively correlated with the carbon chain length, whereas the lg BSAF values decreased with an increase in the carbon chain length (C8-C13).

Investigation of diarrhetic shellfish toxins in Lingshan Bay, Yellow Sea, China, using solid-phase adsorption toxin tracking (SPATT).

Early detection of toxin contamination in shellfish (i.e., prior to harvest) would be of considerable advantage to fish farmers, researchers and food safety administrators. In 2004, a solid-phase adsorption toxin tracking (SPATT) technique was developed to study algal toxins in New Zealand shellfish harvesting areas. In subsequent years, the basic idea have been further developed. Using a SPATT method, an investigation into diarrhetic shellfish toxins (DSTs) was conducted over a 10.5-month period in 2012 in shellfish farming areas in Lingshan Bay (Yellow Sea, China). This paper discusses the relationship among DSTs in toxic algae, seawater and contaminated shellfish. OA, DTX1 and PTX2 toxins were found in this shellfish farming area from summer to autumn. In shellfish the maximum concentrations of OA and DTX1 were 81 and 41 ng g(-1) respectively. PTX2 was very low. The maximum levels of OA and DTX1 in seawater were 165 and 56 ng g(-1) respectively, and were detected on June, separated by a 14-day period. Shellfish had accumulated the highest levels of OA and DTX1 recorded in this study. Comparison of the variations in DST levels in seawater showed there to be about 2 weeks for administrators to warn of the potential for toxin contamination in shellfish. Further research to explore the relationship between the variables of seawater temperature, sunlight and salinity, and DSTs in shellfish may help to establish a more suitable model for forecasting DST contamination in shellfish.

Hippocampal cAMP/PKA/CREB is required for neuroprotective effect of acupuncture.

Acupuncture has beneficial effects in vascular dementia (VaD) patients. The underlying mechanism, however, remains unknown. The present study was designed to investigate whether the cAMP/PKA/CREB cascade is involved in the mechanism of acupuncture in cerebral multi-infarction rats. In this study, cerebral multi-infarction was modeled in adult Wistar rats by homologous blood clot emboli. After a two-week acupuncture treatment at Zusanli (ST36), hippocampal-dependent memory was tested by employing a radial arm maze test. The hippocampus was isolated for analyses of cAMP concentration, phosphodiesterase (PDE) activity and CREB/pCREB and ERK/pERK expressions. The Morris water maze (MWM) task and CREB phosphorylation were evaluated in the presence of PKA-selective peptide inhibitor (H89). The radial arm maze test results demonstrated that acupuncture treatment at ST36 reversed hippocampal-dependent memory in impaired animals. Compared to those of the impaired group, cAMP concentration, PKA activity and pCREB and pERK expressions were increased following acupuncture therapy. Finally, the blockade of PKA reversed the increase in CREB phosphorylation and the improvement in recognitive function induced by acupuncture treatment. These results suggest that acupuncture could improve hippocampus function by modulating the cAMP/PKA/CREB signaling pathway, which represents a molecular mechanism of acupuncture for recognitive function in cerebral multi-infarction rats.

[Development of studies on influence of patients' expectations on therapeutic effects of acupuncture and moxibustion interventions].

The patient's expectations (placebo effects) refer to the anticipation or the belief about what is to be encountered in a consultation in the healthcare system. Currently, it is a hot-spot for researching its influence on clinical outcomes of acupuncture and moxibustion interventions. How to evaluate the magnitude of patients'expectations is a problem needing to be solved urgently at the moment. The authors of the present paper make a summary about researches on the mechanism of expectations. For example, placebo analgesia was related to decreased brain activity in pain-sensitive brain regions (thalamus, insula, and anterior cingulate cortex), and to the increased activity of the prefrontal cortex showed by fMRI, and to the release of endogenous opioids. In addition, the authors also introduce some methods (psychological scales) for assessing expectations and related influencing factors (physicians or acupuncturists, and medical environment) for future research in this area. In the coming clinical trials on acupuncture or moxibustion treatment of clinical disorders, we should further better our experimental design, and try our best to exclude placebo effect-associated or expectation-induced bias of clinical outcomes for confirming the therapeutic effects in the treatment of different clinical problems.

Pharmacokinetics of sulfamonomethoxine in tongue sole (Cynoglossus semilaevis) after intravenous and oral administration.

The pharmacokinetic profiles of sulfamonomethoxine (SMM) were investigated in flatfish tongue soles in the present study. After a single injection of SMM (40 mg/kg BW) to caudal vein of tongue sole at 20 °C, plasma drug concentration versus time data were best fitted to a three-compartment model, characterized with 0.2, 5.7, and 80.4 h for the half-life (t 1/2) of fast distribution, slow distribution, and elimination, respectively. The apparent volume of distribution was 0.1 L/kg, and the body clearance was 0.03 L/h/kg. After oral administration of SMM (200 mg/kg BW) to tongue soles at 20 °C, plasma drug concentrations were best fitted to a two-compartment model, of which the mean half-life of absorption (t 1/2ka) and elimination (t 1/2ß ) were 1.7 and 95.7 h, respectively. The maximal absorption concentration (C max) was estimated as 58 mg/L at 2.5 h, and the mean systemic bioavailability (F) was 39.5 % in tongue soles after oral administration.

Efficacy and safety of acupuncture for chronic dizziness: study protocol for a randomized controlled trial.

BACKGROUND: Dizziness is one of the most challenging symptoms in medicine. No medication for dizziness in current use has well-established curative or prophylactic value or is suitable for long-term palliative use. Unconventional remedies, such as acupuncture, should be considered and scientifically evaluated. However, there has been relatively little evidence in randomized controlled clinical trials on acupuncture to treat chronic dizziness. The aim of our study is to evaluate the efficacy and safety of acupuncture in patients with dizziness. METHODS/DESIGN: This trial is a randomized, single-blind, controlled study. A total of 80 participants will be randomly assigned to two treatment groups receiving acupuncture and sham acupuncture treatment, respectively, for 4 weeks. The primary outcome measures are the Dizziness Handicap Inventory (DHI) and the Vertigo Symptom Scale (VSS). Treatment will be conducted over a period of 4 weeks, at a frequency of two sessions per week. The assessment is at baseline (before treatment initiation), 4 weeks after the first acupuncture session, and 8 weeks after the first acupuncture session. DISCUSSION: The results from this study will provide clinical evidence on the efficacy and safety of acupuncture in patients with chronic dizziness. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number Register: ISRCTN52695239.