AIM: To investigate the effect of inhibiting Ca2+/calmodulin-dependent protein kinase Ⅱ(CAMKⅡ)expression in adult retinal pigment epithelial cell line-19(ARPE-19)cells on the migration, invasion, and tube formation of human umbilical vein endothelial cells(HUVECs)in a non-contact co-culture system.METHODS: RNA sequencing was performed on ARPE-19 cells overexpressing CAMKⅡ-δ, and bioinformatics was used to analyze the biological functions of the differentially expressed genes. Transwell inserts was used to construct a non-contact co-culture system of ARPE-19 and HUVECs. The experimental groups included: blank group: only HUVECs were inoculated without ARPE-19 cells; control group: ARPE-19 and HUVECs cells were co-cultured with complete medium; AIP group(CAMKⅡ inhibition group): ARPE-19 cells in AIP(160 nmol/L)were co-cultured with HUVECs in complete medium. The migration, invasion and tube formation abilities of HUVECs were detected. The protein expression levels of CAMKⅡ/AMPK/mTOR/VEGFA were detected by Western blotting.RESULTS:Bioinformatics analysis found that the differentially expressed genes could affect biological processes such as cell growth and death and cell movement. The scratch test and transwell migration test showed that the relative mobility of HUVECs in the AIP group was significantly lower than that in the control group(all P<0.05). However, the invasion and tube formation assay showed that the relative invasion rate and tube formation rate of the AIP group were not significantly different from those of the control group(both P>0.05). Western blotting results showed that the expression levels of CAMKⅡ, P-mTOR, and VEGFA proteins in the AIP group were significantly lower than those in the control group, while the expression level of the P-AMPK protein was significantly higher than that in the control group(all P<0.05).CONCLUSION:In the non-contact co-culture system, inhibition of CAMKⅡ expression in ARPE-19 cells significantly reduced the migration ability of HUVECs, but it cannot change the invasion and tube formation ability, which may be achieved by AMPK/mTOR/VEGFA.

Dysphagia is a common non-motor symptom of Parkinson's disease (PD). The pathogenesis of the disease includes central changes and peripheral changes. The mechanism of acupuncture intervention is mainly to protect DA neurons and central acetylcholinergic neurons, and the research on the peripheral mechanism of action is currently lacking. Acupuncture, electro-acupuncture, warm acupuncture, and combined acupuncture therapy have showed satisfactory clinical curative effects. Among them, Lianquan (CV 23),Fengchi (GB 20), Yamen (GV 15) and Yifeng (TE 17) are commonly used in routine acupuncture. The acupoints with high frequency of bloodletting are Jinjin (EX-HN 12) and Yuye (EX-HN 13). However, the existing studies have the problems such as small sample size, inconsistent operation plans, and effect evaluation standards difference, which need to be further improved.

Purpose: Reduced quality of life after cystectomy has made bladder preservation a popular research topic for muscle-invasive bladder cancer (MIBC). Previous research has indicated significant tumor downstaging after neoadjuvant chemotherapy (NAC). However, maximal transurethral resection of bladder tumor (TURBT) was performed before NAC to define the pathology, impacting the real evaluation of NAC. This research aimed to assess real NAC efficacy without interference from TURBT and apply combined modality therapies guided by NAC efficacy. Materials and Methods: Patients with cT2-4aN0M0 MIBC were confirmed by cystoscopic biopsy and imaging. NAC efficacy was assessed by imaging, urine cytology, and cystoscopy with multidisciplinary team discussion. Definite responders (≤ T1) underwent TURBT plus concurrent chemoradiotherapy. Incomplete responders underwent radical cystectomy or partial cystectomy if feasible. The primary endpoint was the bladder preservation rate. Results: Fifty-nine patients were enrolled, and the median age was 63 years. Patients with cT3-4 accounted for 75%. The median number of NAC cycles was three. Definite responders were 52.5%. The complete response (CR) was 10.2%, and 59.3% of patients received bladder-sparing treatments. With a median follow-up of 44.6 months, the 3-year overall survival (OS) was 72.8%. Three-year OS and relapse-free survival were 88.4% and 60.0% in the bladder-sparing group but only 74.3% and 37.5% in the cystectomy group. The evaluations of preserved bladder function were satisfactory. Conclusion After stratifying MIBC patients by NAC efficacy, definite responders achieved a satisfactory bladder-sparing rate, prognosis, and bladder function. The CR rate reflected the real NAC efficacy for MIBC. This therapy is worth verifying through multicenter research.

Objective:To investigate the mechanism of crush syndrome (CS) induced by crush injury on myocardial cells in rats.Methods:Thirty two male Sprague Dawley (SD) rats were randomly divided into control group, CS-0 group, CS-12 group and CS-24 group with 8 rats in each group. CS model was made by self-made extruder and perfused with 4% paraformaldehyde for 0, 12 and 24 h. The morphological changes of myocardial tissue were observed by hematoxylin staining. The apoptosis of cardiomyocytes was detected by terminal dexynucleotide transferase-mediated nick end labeling (TUNEL). The levels and activities of malondialdehyde (MDA), superoxide dismutase (SOD), lactose dehydrogenase (LDH), interleukin-6 (IL-6), interleukin-1 β (IL-1 β), tumor necrosis factor-α (TNF- α) in myocardial homogenate were detected by enzyme-linked immunosorbent assay (ELISA). The expressions of Caspase-3, Bax, Bcl-2 and necrosis factor-κB (NF-κ B) were detected by Western blot.Results:Compared with the control group, the myocardial tissue of CS model group had different degrees of morphological damage; compared with the control group, the apoptosis rate, Caspase-3 and Bax protein expression levels of CS-0 group, CS-12 group and CS-24 group were significantly increased ( P<0.05), and the expression level of Bcl-2 protein was significantly decreased ( P<0.05); compared with the control group, the levels of MDA, LDH, IL-6, IL-1β, TNF-α and p65 protein phosphorylation in the myocardial homogenate of CS-0 group, CS-12 group and CS-24 group were significantly increased ( P<0.05), and SOD activity was significantly decreased ( P<0.05). Conclusions:CS may inhibit oxidative stress and induce inflammatory reaction by activating NF-κ B pathway, thus damaging myocardial cells in rats.

Acute pancreatitis (AP) is a common and severe disease causing multiple organ dysfunction. With the deepening of research on AP pathogenesis, it has been found that macrophages play an important role in the initiation and progress of AP. The systemic innate macrophage populations, such as the pancreatic macrophages, Kupffer cells, peritoneal macrophages and pulmonary macrophages, can be activated by inflammatory mediators in different stages of pancreatitis, triggering inflammatory cascade reaction and systemic inflammatory response syndrome. This review focused on the recent progress in the role of macrophages in AP.

Objective:To provide basis for the rational use of valproic acid(VPA) in the patients with epilepsy through the analy-sis on the therapeutic monitoring data. Methods:The VPA plasma concentration and the other related information of 233 cases were analyzed retrospectively. Results:The total daily dose of VPA increased with age (P<0.05) in children group. Compared with that in adults group (19-50 years old),the target rate of VPA concentration was significantly higher in children group(4-14 years old) (P<0.001). VPA had similar antiepileptic effect in children and adults. Oral solution was the main dosage form for children and con-ventional tablets for adults. Children had higher target rate of VPA concentration than adults (P<0.05). Compared with the group with VPA alone,VPA combined with enzyme inducers such as carbamazepine,phenobarbital and phentoin significantly decreased the target rate of VPA concentration(P<0.001). Moreover,VPA combined with phenobarbital significantly decreased the total daily dose of VPA (P<0.05). Conclusion:With great inter-individual variance,VPA plasma concentration is associated with efficacy and side effects. Monitoring of VPA plasma concentration is useful to the individualized treatment of VPA.

China ; Depressive Disorder, Major ; genetics ; Humans ; Polymorphism, Single Nucleotide ; Sirtuin 1 ; genetics

OBJECTIVETo assess the quantitative risk of the polycyclic aromatic hydrocarbons (PAHs) dietary exposure from edible fats and oils in China.

METHODSOne hundred samples of edible fats and oils were collected from the supermarkets and the farmers markets in 11 provinces of China from December in 2013 to May in 2014. Then they were tested for EU15+1 PAHs (16 PAHs were controlled in priority by European Food Safety Authority) by two test methods which were QuECHERS-GC-MS-MS and GPC-HPLC-FLD. Data of PAHs concentration and edible fats and oils consumption which were from Chinese National Nutrition and Health Survey in 2002 were combined to evaluate carcinogenic risk of PAHs in edible fats and oils by the method of margin of exposure (MOE). In this process, we divided the population into 6 groups, namely male adults (older than 18 years old), female adults (older than 18), male youths (13-17), female youths (13-17), school-agers (6-12) and preschoolers (2-5), and thought carcinogenicity as the critical toxicity end point of PAHs. Two quantitative risk assessment methods, i.e. point assessment and probability assessment, were used to evaluate the dietary exposure and MOEs.

RESULTSEU15+1 PAHs in one of 100 samples were not detected, other samples were polluted in different degrees; the detection rates were 3%-98% and the average contents were 0.26-3.26 μg/kg. The results of PAHs dietary exposure from both of point assessment and probability assessment were the same. The average exposures of PAH8 were as the following: male adults were 10.03 and (9.34 ± 12.61) ng·kg(-1)·d(-1)(The former was from point assessment and the latter from probability assessment, the same below), female adults were 9.95 and (9.60 ± 15.04) ng · kg(-1)·d (-1), male youths were 11.09 and (10.84 ± 16.54) ng·kg(-1)·d(-1), female youths were 10.06 and (9.58 ± 12.87) ng·kg(-1)·d(-1),school-agers were 15.29 and (15.62 ± 25.54) ng·kg(-1)·d(-1), preschoolers were 19.27 and (19.22 ± 28.91) ng·kg(-1)·d(-1). MOEs of mean and 50% exposure levels in different group of people were more than 10,000, while MOEs of 95% exposure levels in school-agers and preschoolers were less than 10,000.

CONCLUSIONFor general consumers, the health risk of PAHs exposure is very low. However, for high-end consumers (95% exposure level) from the sensitive groups (school-ager and preschooler) has a potential health risk.

Adolescent ; Adult ; Child ; Child, Preschool ; China ; Chromatography, High Pressure Liquid ; Diet ; Environmental Exposure ; Fats ; chemistry ; Female ; Food Safety ; Humans ; Male ; Plant Oils ; chemistry ; Polycyclic Aromatic Hydrocarbons ; analysis ; Risk Assessment ; Tandem Mass Spectrometry ; Young Adult

Objective:To observe effects of wrist-ankle acupuncture (WAA) onβ-endorphin (EP), nitric oxide (NO) in uterus tissue and prostaglandin F2α (PGF2α), substance P (SP) in serum of rats with primary dysmenorrhea. Methods:A total of 45 non-pregnant Wistar rats were randomly divided into a control group, a model group and a WAA group, 15 rats in each group. Rats in the model group and the WAA group received continuous abdominal subcutaneous injection of Diethylstilbestrol to establish dysmenorrhea rat models. On the first day after modeling, rats in the WAA group began to receive acupuncture on Point Lower 1 and Point Lower 2, once a day for 10 d. The control group and the model group didn’t receive any treatment. Writhing latencies and frequencies were recorded.β-EP and NO in uterus tissue homogenates and PGF2α, SP in serum were detected. Results:In the model group,β-EP and NO levels were the lowest among the groups, the serum PGF2α level was the highest, and serum SP level was the lowest. These measurements showed significantly difference between the model group and the control group (P<0.05). PGF2α in the WAA group was lower than that in the model group;β-EP, NO and SP levels were higher than those in the model group, with inter-group statistically significant differences (P<0.05). Conclusion: WAA may achieve analgesic effect through decreasing PGF2α, increasingβ-EP, NO and SP to relieve uterine cramps, increase blood flow and promote functional improvement.

Objective To assess the effect of ultrasound-guided percutaneous 125I seed implantation for the treatment of osteolytic metastases. Methods From February 2011 to December 2013, a total of 18 patients with advanced cancer complicated by osteolytic metastases received ultrasound-guided percutaneous implantation of 125I seeds. According to visual analog score (VAS) the pain was estimated before and 3 days as well as one month after the treatment. One month after the treatment follow-up CT scan was performed in all patients to check the tumor size and the distribution of 125I seeds, and the therapy was repeated if necessary. The efficacy was evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST). Results A total of 33 times of procedure were carried out in the 18 patients. Three days after the treatment, local pain was obviously relieved in all cases. Compared with preoperative VAS, the postoperative VAS was significantly improved (P=0.000). The pain was well controlled even one month after the treatment (P=0.000). One month after the last treatment the complete remission (CR) rate was 0% (n=0), partial remission (PR) rate 61.1% (n=11), stable disease (SD) 33.3% (n=6) and progress disease (PD) 5.6% (n=1), and local control rate (CR+PR) was 61.1%. No severe brachytheray-related complications occurred. Conclusion Ultrasound-guided percutaneous 125I seed implantation brachytherapy is technically simple and repeatable, it can safely and effectively guide the performance of percutaneous 125I seed implantation for the treatment of osteolytic metastases. Even in the circumstance of not using TPS, this technique can also obtain satisfactory local control rate and significant pain relief.