[Lactate promotes HMGB1 phosphorylation and release via Akt signaling pathway in gastric cancer cells HGC-27].

Objective: To investigate the molecular mechanism of how lactate induces high mobility group box 1 (HMGB1) release. Methods: Gastric cancer HGC-27 cells were divided into the control group and the lactate group (The cells were treated with lactate for 6 h). The level of HMGB1 in the cell culture medium was detected by enzyme-linked immunosorbent assay (ELISA), the localization of HMGB1 was detected using laser confocal microscopy, and the nuclear translocation of HMGB1 was detected using the nucleoplasmic separation assay. The phosphorylation and acetylation levels of HMGB1 were determined by co-immunoprecipitation, and Western blot was used to measure the phosphorylation of Akt and protein kinase C (PKC). HGC-27 cells were first treated with lactate and LY294002, the inhibitor of Akt, and then the phosphorylation of HMGB1 and Akt was analyzed by co-immunoprecipitation and Western blot, respectively. The localization of HMGB1 in cells was detected by laser confocal microscopy. EdU and Transwell assays were used to detect the proliferation and migration abilities of HGC-27 cells, respectively. HGC-27 cells were then injected into the BALB/C null mice for subcutaneous tumor implantation. Mice in the lactate group were intraperitoneally injected with lactate (0.2 g/kg/2 d), while those in the control group were intraperitoneally injected with an equal amount of PBS for 20 consecutive days. ELISA was used to detect the HMGB1 levels in the blood samples taken from the medial canthus vein of the mice, while co-immunoprecipitation and Western blot were used to detect the phosphorylation of HMGB1 and Akt in tumor tissue proteins, respectively. Results: The release levels of HMGB1 in the lactate group were (2 995.00±660.91) pg/ml and (696.33±22.03) pg/ml, after lactate treatment for 6 h and 12 h, respectively, both higher than those in the control group (485.00±105.83) pg/ml (P<0.001 and P=0.028, respectively). After lactate treatment for 6 h, the relative expression of HMGB1 protein in the cytoplasm of HGC-27 cells was 1.13±0.09, higher than that of the control group (0.83±0.07, P=0.001), while the relative expression of HMGB1 in the nucleus was 0.79±0.06, lower than that of the control group (1.07±0.06, P=0.007). The phosphorylation level of HMGB1 reached 1.41±0.09, which was higher than that of the control group (0.97±0.10, P=0.031). The phosphorylation level of Akt was 11.16±0.06, higher than that of the control group (0.91±0.022, P=0.002). The phosphorylation level and nuclear translocation of HMGB1 induced by lactate decreased obviously after Akt inhibition; the proliferation and migration abilities induced by lactate were also obviously inhibited after Akt inhibition. In vivo, the HMGB1 level in the peripheral blood was (1 280.70±389.66) pg/ml in the lactate group, which was obviously higher than that in the control group (595.11±44.75) pg/ml (P=0.008), and the phosphorylation levels of HMGB1 and Akt in tumor tissues in the lactate group were obviously enhanced compared with the control group. Conclusion: Lactate induces HMGB1 release through enhancing HMGB1 phosphorylation via the Akt signaling pathway.

[Aloin inhibits gastric cancer cell proliferation and migration by suppressing the STAT3/HMGB1 signaling pathway].

OBJECTIVE: To investigate the molecular mechanism underlying the inhibitory effect of aloin on the proliferation and migration of gastric cancer cells. METHODS: Human gastric cancer MGC-803 cells treated with 100, 200 and 300 µg/mL aloin were examined for changes in cell viability, proliferation and migration abilities using CCK-8, EdU and Transwell assays. HMGB1 mRNA level in the cells was detected with RT-qPCR, and the protein expressions of HMGB1, cyclin B1, cyclin E1, E-cadherin, MMP-2, MMP-9 and p-STAT3 were determined using Western blotting. JASPAR database was used to predict the binding of STAT3 to HMGB1 promoter. In a BALB/c-Nu mouse model bearing subcutaneous MGC-803 cell xenograft, the effect of intraperitoneal injection of aloin (50 mg/kg) on tumor growth was observed. The protein expressions of HMGB1, cyclin B1, cyclin E1, E-cadherin, MMP-2, MMP-9 and p-STAT3 in the tumor tissue was examined using Western blotting, and tumor metastasis in the liver and lung tissues was detected using HE staining. RESULTS: Treatment with aloin concentration-dependently inhibited the viability of MGC-803 cells (P < 0.05), significantly reduced the number of EdU-positive cells (P < 0.01), and attenuated the migration ability of the cells (P < 0.01). Aloin treatment dose-dependently down-regulated HMGB1 mRNA expression (P < 0.01), lowered the protein expressions of HMGB1, cyclin B1, cyclin E1, MMP-2, MMP-9 and p-STAT3, and up-regulated E-cadherin expression in MGC-803 cells. Prediction based on JASPAR database suggested that STAT3 could bind to the promoter region of HMGB1. In the tumor-bearing mice, aloin treatment significantly reduced the tumor size and weight (P < 0.01), lowered the protein expressions of cyclin B1, cyclin E1, MMP-2, MMP-9, HMGB1 and p-STAT3 and increased the expression of E-cadherin in the tumor tissue (P < 0.01). CONCLUSION: Aloin attenuates the proliferation and migration of gastric cancer cells by inhibiting the STAT3/HMGB1 signaling pathway.

How Neighborhood Structural and Individual Characteristics Affect Frailty Progression: Evidence from the China Health and Retirement Longitudinal Study.

OBJECTIVES: (1) To characterize the average trajectories of frailty over time in Chinese community-dwelling older adults; (2) To assess the effects of neighborhood structural and individual characteristics on frailty progression. DESIGN: A nationally representative prospective cohort study. SETTING: Communities in 28 provinces, China. PARTICIPANTS: 6238 respondents aged 60 and above in 447 communities from four waves of the China Health and Retirement Longitudinal Study. MEASUREMENTS: Frailty was measured using the 61-item Frailty Index (FI). RESULTS: The trajectory of FI was nonlinear, with an average growth rate of 0.025 that significantly slows down at the rate of 0.002 per year. Older, male, and uninsured respondents showed faster rates of growth in FI over time than younger, female, and insured counterparts. Respondents living in neighborhoods with a higher percentage of the older population and rural villages showed slower rates of growth in FI over time. CONCLUSION: Expanding health insurance coverage and keeping a high clustering of the elderly in neighborhoods may be the potential strategies for population-level frailty prevention and interventions.

[The common morphology and clinical significance of the axillary arch].

Axillary arch is the most common type of axillary muscle fiber variation, with about 10.8% incidence in the Chinese population. Its natural forms are varied and fluid, with different starting points and terminations, and clinicians frequently lack recognition. Under commonly applicated sentinel lymph node biopsy, the axillary arch has been endowed with more clinical significance. The fabric of axillary arch will not only block lymphatic drainage in axilla and unclear anatomical level of axillary dissection, but also compress the axillary neurovascular bundle, causing upper limb venous thrombosis, lymphedema and nerve entrapment. The intumescent axillary arch may also show abnormal axillary bulge. In addition to finding axillary arch during cadaveric study and operation, several of imaging methods availably diagnose axillary arch preoperative, which can create new way for detection of axillary arch and extension of the surgical plan of sentinel lymph node biopsy. Although embryology and comparative anatomy have been used to explain the origin of the axillary arch, most of the ideas are still hypotheses and need further study.

[Atezolizumab therapy in Chinese patients with locally advanced or metastatic solid tumors: An open-label, phase â study].

OBJECTIVE: To evaluate pharmacokinetics (PK), efficacy, and safety of atezolizumab (anti-PD-L1) in high interest cancers in China, including esophageal cancer (EC), gastric cancer (GC), hepatocellular carcinoma (HCC), nasopharyngeal cancer (NPC), and non-small cell lung can-cer (NSCLC). METHODS: This phase I, open-label study was conducted at 6 Chinese sites from August 4, 2016 to April 15, 2019. The patients were ≥18 years old with a histologically documented incurable or metastatic solid tumor that was advanced or recurrent and had progressed since the last anti-tumor the-rapy. The PK phase characterized PK and safety of atezolizumab following multiple-dose administration when atezolizumab was administered as a single agent. The extension phase studied safety and efficacy of atezolizumab, as monotherapy (EC, GC, HCC, NPC) and with chemotherapy (NSCLC). RESULTS: This study enrolled 120 patients (PK phase: n=20; extension phase: n=20/cohort). Fourty-two patients (42.0%) were PD-L1 positive in atezolizumab monotherapy group (100 patients), of the 9 patients (9.0%) with microsatellite instability-high (MSI-H) tumors. Atezolizumab clearance was 0.219 L/d, and steady state was reached after 6 to 9 weeks (2-3 cycles) of repeated dosing. Objective response rates (ORRs) in EC, GC, HCC, NPC, and NSCLC were 10.0%, 15.0%, 10.0%, 5.0%, and 40.0%, respectively. In the patients with PD-L1 positive tumors, ORR was 11.9% with atezolizumab and 46.2% with atezolizumab plus gemcitabine and cisplatin. Two GC patients achieved durable response after pseudo-progression. The most common treatment-related adverse events in the atezolizumab monotherapy group were fatigue, anemia, fever, and decreased white blood cell count. The most common treatment-related adverse events in the combination group were anemia, decreased white blood cell count, and decreased appetite. No new safety signals were identified. CONCLUSION: Atezolizumab's PK, efficacy, and safety were similar in Chinese patients vs. global patients in previous studies.

Physical activity patterns, genetic susceptibility, and risk of hip/knee osteoarthritis: a prospective cohort study based on the UK Biobank.

OBJECTIVES: The effect of physical activity on hip/knee osteoarthritis (OA) and how it varies by genetic susceptibility to OA remains inconclusive. METHODS: In a cohort study of UK Biobank, 436,166 OA-free participants were recruited in 2006-2010 and followed for knee/hip OA until the end of 2020. 28 physical activity-related items were collected at baseline. Cox regression was used to estimate associations between physical activity behaviors, as well as major activity patterns (i.e., significant principal components[PCs] identified by principal component analysis), and risk of OA, adjusting for multiple confounders. We further stratified the analyses by polygenic risk score (PRS) for OA to examine the impact of genetic susceptibility to OA on the studied association. RESULTS: During a mean follow-up of 11.15 years, 13,227 hip and 21,119 knee OA cases were identified. 19, out of 28, studied items showed associations with increased OA risk. Compared with low adherence group(<1st tertile of PC score for each pattern), individuals with high adherence to five identified patterns were associated with increased risk of OA. The moderate adherence to "strenuous sports"(HR = 0.93, 95%CI: 0.89-0.97) and "walking for pleasure"(HR = 0.93, 95%CI: 0.89-0.98) patterns was associated with reduced OA. Similar risk patterns were obtained in the stratified analysis by PRS levels for OA. CONCLUSION: High intensity of most activity patterns were associated with increased OA. However, a protective effect was suggested for moderate adherence to patterns of "strenuous sports" and "walking for pleasure" that consistent across different genetic susceptibilities, underscoring the potential benefits of moderate-intensity physical activity on OA.

[Analysis of caries experience and the dental treatments under general anesthesia in 103 cases of children with autism spectrum disorders].

Objective: To compare the caries experience and the kinds of dental treatment between children with autism spectrum disorders (ASD) and children without systemic disease who were all treated under general anesthesia. Methods: Totally 103 children with ASD who received dental treatments under general anesthesia in 13 professional dental hospitals around China from April to November 2016 were included in the present study. A group of 97 children without systemic disease, according to the age, gender and application propensity score matching method, were chosen as controls, who received dental treatments under general anesthesia between January 2015 to November 2018 in the same hospitals as the children with ASD. Decay missing filling tooth (DMFT/dmft, DMFT for permanent teeth and dmft for primary teeth) indices of two groups of children and the contents of the dental treatments under general anesthesia were analyzed. Results: No significant difference of DMFT/dmft index ï¼»M (Q 25, Q 75)ï¼½ was found between children with ASD group ï¼»0 (0, 3)/11(8, 14)ï¼½ and control group ï¼»0 (0, 3)/9(7, 13)ï¼½ (P>0.05). The average number of dental treatments under general anesthesia and the average number of endodontic treatment in children with ASD were 13 (11, 15) and 3 (2, 6) teeth respectively, while those in the control group were 12 (9, 14) and 2 (1, 4) teeth respectively, the differences were statistically significant (P<0.01, P<0.05). Conclusions: No significant difference was found between children with ASD and the normal controls who receive dental treatments under general anesthesia in DMFT/dmft index, but the treatment needs of children with ASD is relatively higher, and their tooth decay is relatively severer.

Application of Eye Tracker in Lie Detection.

ABSTRACT: Objective To investigate the application value of eye tracking in lie detection. Methods The 40 subjects were randomly divided into two groups. The pupil diameter, fixation duration, points of fixation and blink frequency of the subjects in the experimental group in observing target stimulation and non-target stimulation were recorded with eye tracker after they accomplished the mock crime. The eye movement parameters of subjects in the control group were directly collected. The differences in eye movement parameters of the experimental group and the control group in observing target stimulation and non-target stimulation were analyzed by t-test. Pearson coefficient analysis of correlation between eye movement parameters that had differences was conducted. The effectiveness of eye movement parameters to distinguish between the experimental group and the control group was calculated by the receiver operator characteristic （ROC） curve. Results Participants from the experimental group had shorter average pupil diameter, longer average fixation duration and fewer fixation points （P<0.05）, but the differences in blink frequency had no statistical significance. The differences in the above indicators of the control group in observing target stimulation and non-target stimulation had no statistical significance. The average fixation duration showed a negative correlation with fixation points （r=-0.255, P<0.05）; the average fixation duration showed a negative correlation with average pupil diameter （r=-0.218, P<0.05）; the fixation points showed a positive correlation with average pupil diameter （r=0.09, P<0.05）. The area under the curve of average pupil diameter, average fixation duration and fixation points was 0.603, 0.621 and 0.580, respectively. Conclusion The average pupil diameter, average fixation duration and fixation points obtained by the eye tracker under laboratory conditions can be used to detect lies.

Analysis of risk factors of stage IV gastric cancer from the SEER database.

INTRODUCTION: Gastric cancer is the fourth most common cancer in the world. By the time the patients are diagnosed with stage IV gastric cancer, many patients already have distant metastases. There is no unified systemic treatment plan in existence. The use of gastrectomy is ambiguous in patients with stage IV gastric cancer. The objective of this study was to evaluate the beneficial outcome of gastrectomy in patients with stage IV gastric cancer. METHODS: Clinical information of patients with gastric cancer from 2000 to 2010 in the Surveillance, Epidemiology, and End Results database were extracted and analysed. The risk factors for stage IV gastric cancer were also analysed. RESULTS: We observed that the median survival time for patients after surgery was greater than that for patients not treated surgically. The five-year survival rate for chemotherapy patients was higher than that of non-chemotherapeutic patients. Patients who receive both chemotherapy and surgery could achieve a more significant survival benefit. The risks following gastrectomy (partial, subtotal, hemi-) were lower than those of other surgical procedures, which provided guidance on the choice of surgical method. The numbers of regional lymph node metastasis were found to be related to prognosis. CONCLUSIONS: In patients with stage IV gastric cancer, gastrectomy (partial, subtotal or hemi) should be selected when surgery is necessary. The number of regional lymph node metastasis could be considered as a prognostic factor for patients with stage IV gastric cancer and lymph node dissection could reduce the risk of patients undergoing surgery.

A dialysis-based in vitro drug release assay to study dynamics of the drug-protein transfer of temoporfin liposomes.

Today, a growing number of nanotherapeutics is utilized to deliver poorly soluble compounds using the intravenous route of administration. The drug release and the direct transfer of the active pharmaceutical ingredient to serum proteins plays an important role in bioavailability and accumulation of the drug at the target site. It is closely related to the formation of a protein corona as well as the plasma protein binding of the compound. In the present study, two in vitro drug release methods, the flow-through cell and the dispersion releaser technology, were evaluated with regards to their capability to measure a time-resolved profile of the serum protein binding. In this context, the photosensitizer temoporfin and temoporfin-loaded liposomes were tested. While in the fine capillaries of the flow-through cell a rapid agglomeration of proteins occurred, the dispersion releaser technology in combination with the four-step model enabled the measurement of the transfer of drugs from liposomes to proteins. In presence of 10% of fetal calf serum approximately 20% of the model compound temoporfin were bound to serum proteins within the first 3 h. At higher serum concentration this binding remained stable for approximately 10 h.

MiR-124 changes the sensitivity of lung cancer cells to cisplatin through targeting STAT3.

OBJECTIVE: To investigate the role of micro ribonucleic acid (miR)-124 in drug resistance of non-small cell lung cancer (NSCLC), and to explore its underlying mechanism. MATERIALS AND METHODS: The expression levels of miR-124 and signal transducer and activator of transcription 3 (STAT3) in maternal A549 cells and cisplatin-resistant A549/DDP cells were detected via quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blotting. A549 and A549/DDP cells were transfected with miR-124 mimics and miR-124 negative control (NC), respectively. Changes in the expression of STAT3 were detected via qRT-PCR and Western blotting. Meanwhile, the sensitivity of cells transfected with miR-124 mimics to cisplatin was detected via methyl thiazolyl tetrazolium (MTT) assay. The effects of miR-124 on the apoptosis, invasion and metastasis of cells were detected via flow cytometry, wound healing assay and transwell assay, respectively. Moreover, wild-type and mutant-type STAT3 luciferase reporter plasmids were co-transfected with miR-124 mimics or miR-124 NC. Luciferase activity was analyzed using the dual-luciferase reporter gene assay. RESULTS: QRT-PCR and Western blotting revealed that the expression level of miR-124 in A549/DDP cells was significantly lower than that of A549 cells. However, the expression level of STAT3 in A549/DDP cells was significantly higher than that of A549 cells. Overexpression of miR-124 remarkably reduced the expression level of STAT3 in A549/DDP cells, increased the sensitivity of A549/DDP cells to cisplatin, and inhibited the invasion and metastasis capacities of cells. In addition, luciferase reporter gene assay demonstrated that miR-124 could negatively regulate the protein expression of STAT3 by binding to its 3'-untranslated region (UTR). CONCLUSIONS: MiR-124 regulates the sensitivity of NSCLC to cisplatin. Moreover, it inhibits the invasion and metastasis capacities through targeting STAT3, which can serve as a therapeutic target for cisplatin-based chemotherapy resistance of NSCLC.

Assessing Frailty in Chinese Nursing Home Older Adults: A Comparison between the Frail-NH Scale and Frailty Index.

OBJECTIVE: (1) To establish appropriate FRAIL-NH cutoff points in nursing homes in Mainland China; (2) To compare the FRAIL-NH scale and Frailty Index in assessing frailty prevalence and associated factors in nursing homes. DESIGN: A cross-sectional study. SETTING: Six nursing homes in Changsha, China. PARTICIPANTS: A total of 302 residents aged 60 years or older (mean aged 82.71±8.49, 71.2% female). MEASUREMENTS: Frailty was assessed using the 34-item Frailty Index and the FRAIL-NH scale. RESULTS: The appropriate FRAIL-NH cutoff points to classify frail status and frailest status were 1.5 (87.6% sensitivity, 63.3% specificity) and 7.5 (94.1% sensitivity, 73.4% specificity), respectively. Based on the FRAIL-NH and Frailty Index, 69.5% (48% for frail and 21.5% for frailest), and 66.5% (60.9% for frail and 5.6% for frailest) of residents were at risk of frailty, respectively. There was no statistically significant difference in the total frailty prevalence assessed by FRAIL-NH and Frailty Index (χ2=0.617, P=0.432). The FRAIL-NH Scale is significantly associated with the Frailty Index (correlation coefficient (r) = 0.74, P < 0.001), but there was a Kappa agreement of 0.39 for frailty classification between the FRAIL-NH and Frailty Index, with the Frailty Index classifying a larger number of individuals as frail. When using FRAIL-NH scale, disease and self-reported health status were associated with frail and frailest status while age was just associated with frailest status. regarding the Frailty Index, age, diseases, medications and self-reported health status were associated with frail and frailest status. CONCLUSION: The FRAIL-NH is a simple and effective tool to assess the overall frailty rate in nursing homes, and the Frailty Index may be more suitable capturing the multidimensionality of frailty at an individual level. Careful consideration in the selection of a frailty instrument, based on the intended purpose, is necessary.

[Study on the application of oral magnesium sulfate solution in split doses as bowel preparation for colonoscopy in elderly patients].

Objective: To evaluate the efficacy and safety of oral magnesium sulfate solution in split doses as bowel preparation in elderly patients undergoing colonoscopy. Methods: A total of 368 elderly patients undergoing colonoscopy were enrolled at PLA General Hospital. The patients were randomly divided into magnesium sulfate solution orally in split doses group (group A, n=178) and single dose group (group B, n=190). Parameters including general information, defecation frequency, Boston bowel preparation score (BBPS), detection rate of lesions and adverse reactions. Results: The frequency of defecations in group A was (7.6±1.4), more than that in group B (6.6±1.5) with statistical significance (P<0.05). The duration of bowel preparation in group A was (128.6±25.3) min, shorter than that of group B (165.4±29.7) min (P<0.05). The BBPS in group A was (8.09±0.67), better than that of group B (7.34±0.58) (P<0.05). The detection rates of intestinal polyps and micropolyps (diameter<0.5 cm) in group A were 73/178 (41.0%) and 51/178 (28.7%) respectively, compared with 58/190 (30.5%) and 37/190 (19.5%) in group B (both P<0.05). In group A, 8 patients reported adverse reactions as abdominal distension and discomfort. One patient had ST-T abnormality of electrocardiogram (ECG). No nausea or vomiting occurred, yet 2 cases needed enema for inadequate bowel preparation. Twenty-one cases in group B reported adverse events including 7 with nausea and vomiting. There were 13 patients treated with enema. Abnormal ECG was found in 4 patients in group B. The satisfaction rate of group A was 97.8%, higher than that of group B (91.6%) (P<0.05). Conclusions: The effect of bowel preparation of elderly patients with magnesium sulfate solution in split dose has a better tolerance, good cleaning effect and low incidence of adverse reactions. It is an ideal choice for the elderly to prepare colonoscopy.

Experimental Evidence of Kinetic Effects in Indirect-Drive Inertial Confinement Fusion Hohlraums.

We present the first experimental evidence supported by simulations of kinetic effects launched in the interpenetration layer between the laser-driven hohlraum plasma bubbles and the corona plasma of the compressed pellet at the Shenguang-III prototype laser facility. Solid plastic capsules were coated with carbon-deuterium layers; as the implosion neutron yield is quenched, DD fusion yield from the corona plasma provides a direct measure of the kinetic effects inside the hohlraum. An anomalous large energy spread of the DD neutron signal (∼282 keV) and anomalous scaling of the neutron yield with the thickness of the carbon-deuterium layers cannot be explained by the hydrodynamic mechanisms. Instead, these results can be attributed to kinetic shocks that arise in the hohlraum-wall-ablator interpenetration region, which result in efficient acceleration of the deuterons (∼28.8 J, 0.45% of the total input laser energy). These studies provide novel insight into the interactions and dynamics of a vacuum hohlraum and near-vacuum hohlraum.

Role of methotrexate chronotherapy in collagen-induced rheumatoid arthritis in rats.

AIM: To explore the circadian rhythm of serum interleukin (IL)-6 in collagen-induced arthritis (CIA) rats and compare the safety and effectiveness of methotrexate (MTX) administered traditionally and via chronotherapy. METHODS: CIA rat models were immunized with bovine type II collagen. Serum IL-6 levels in normal and CIA rats were measured at 2, 6, 10, 14, 18, or 22 h after the light was turned on (HALO). MTX was administered to 6 HALO/18 HALO experimental groups of Wistar rats once daily according to the IL-6 rhythm. The control groups (positive, negative, and normal) were given MTX or an equal volume of phosphate buffered saline (PBS) once a week simultaneously. Arthritis score, tumor necrosis factor (TNF)-α, interleukin (IL)-6, and C reactive protein (CRP) levels in the serum were measured by enzyme-linked immunosorbent assay (ELISA). Histological changes in the ankle joint were analyzed. RESULTS: After 6 weeks of treatment, arthritis scores in the experimental group were lower than in the control group. The expression of TNF-α, IL-6, and CRP was lower in the 18 HALO group than in the control or 6 HALO groups. Histopathology scores in the experimental groups were lower than in the control group (p < 0.05). CONCLUSION: The plasma IL-6 levels in CIA rats were higher than in normal rats and showed significant circadian rhythm. Daily administration of MTX is more potent than weekly administration. The therapeutic index of rheumatoid arthritis (RA) may be improved with MTX therapy based on the IL-6 circadian rhythm.

Enhanced toxicity to the cyanobacterium Microcystis aeruginosa by low-dosage repeated exposure to the allelochemical N-phenyl-1-naphthylamine.

It has been puzzling whether and how a plant could exert a strong allelopathic inhibition to the target organisms by releasing low concentrations of allelochemicals. Plant allelochemicals have been proposed to be released continuously, however, direct evidence from specific allelochemicals is urgently required. In the present study, the toxicity of allelochemical N-phenyl-1-naphthylamine (NPN) towards the cyanobacterium Microcystis aeruginosa by two different exposure patterns was compared. One was low-dosage repeated exposure (LRE), in which 50  µg L-1 NPN was repeatedly dosed to simulate the continual release of allelochemicals, and the other one was high-dosage single exposure (HSE) as per the routine toxicity assay. The results showed a significant growth inhibition to M. aeruginosa in the LRE group, where the inhibition rate reached above 90% from day 6 to day 9. The cell-membrane damage ratio increased from 64.05% on day 5 up to 96.60% on day 9. PSII photosynthesis activity expressed as Fv/Fm, ΦPSII, NPQ and ETRmax was also thoroughly inhibited in this group. Whereas the growth and PSII photosynthesis activity of M. aeruginosa in the HSE group were inhibited initially, but recovered gradually from day 4 or 5, which was accompanied by a continuous reduction of NPN content in culture solutions. Although NPN content in the LRE group was relatively lower, it remained at a more stable level throughout the experiment. These results indicate that continual release of low-dosage allelochemicals by aquatic plants plays crucial roles in their potent inhibition against cyanobacteria. Low-dosage continual exposure pattern needs to be investigated further.

Dual antiplatelet therapy after stroke or transient ischaemic attack - how long to treat? The duration of aspirin plus clopidogrel in stroke or transient ischaemic attack: a systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Dual antiplatelet therapy (DAPT) with aspirin and clopidogrel for 90 days was recommended as the secondary prevention of minor ischaemic strokes or transient ischaemic attacks (TIAs) in 2014. However, whether the duration of 90 days is optimal for each patient remains unclear. Therefore, the efficacy and safety of short-term (≤3 months) and prolonged (≥1 year) DAPT after stroke or TIA were assessed via a systematic review and meta-analysis. METHODS: The Cochrane Library, Clinical Trials.gov and PubMed were searched up to December 2014 and nine randomized controlled trials were included involving 21 923 patients. RESULTS: Short-term DAPT significantly reduced the risk of ischaemic stroke recurrence by 41% and major vascular events by 30%, without increasing the risk of intracranial haemorrhage. Prolonged DAPT reduced the risk of ischaemic stroke recurrence by 12% and major vascular events by 10%. However, the risk of major bleeding and intracranial haemorrhage increased. CONCLUSIONS: Short-term DAPT appears to be superior to prolonged DAPT. However, the difference in efficacy outcome needs to be carefully explained and confirmed by further well-designed randomized controlled trials.

Immunoregulatory effect of neuronal-like cells in inducting differentiation of bone marrow mesenchymal stem cells.

OBJECTIVE: To evaluate the immune activity of bone marrow mesenchymal stem cells (BMSCs), and explore the biological characteristics and capabilities of BMSCs and the potential to be differentiated into neuronal cells in vitro. MATERIALS AND METHODS: The BMSCs were isolated and proliferated in vitro to generate the xenogeneic mixed lymphocyte reaction. Moreover, peripheral BMSCs (pBMSCs) were added according to different ratios, which methods were stated as follows: 1: Dulbecco's Modified Eagle Medium (DMEM) + 10% Fetal Bovine Serum (FBS) + 1 µmol/L all-trans-retinoic acid (ATRA) + 20 µg/L basic fibroblast growth factor (bFGF) + 20 µg/L epidermal growth factor (EGF); 2: DMEM + 2% dimethyl sulfoxide (DMSO) + 100 µmol/L butylated hydroxyanisole (BHA). The immunofluorescence and immunohistochemical staining were finally used to evaluate the differentiation capabilities of human BMSCs (hBMSCs) induced in neuronal cells. RESULTS: hBMSCs inhibited the lymphocyte proliferation in the mixed lymphocyte reaction (MLR) system at a proportional inhibition rate with additional numbers of stem cells. At hour 2 after culture with method 1, the plasma of hBMSCs shrank to nuclei and perinuclear bodies and was visualized under the light microscope. At hours 3-5, most of the hBMSCs formed neuron-like cells with total cell number unchanged. Afterward, the hBMSCs turned into bipolar or multipolar shaped cells and interconnected into a large network at Day 3. With immunofluorescence and immunohistochemical staining, 60-70% of the hBMSCs showed neurospecific enolase (NSE) positive and 45-50% glial fibrillary acidic protein (GFAP) positive while the Nestin-positive cells decreased to 3.4%. However, when cultured 2 hours with method 2, the most of the hBMSCs formed bipolar or multipolar shaped cells, then died after 48 hours. 40-50% NSE and 35-40% GFAP were positively expressed. Significantly, the rate of Nestin-positive cells decreased from 63% to 1.6% from hour 2 after culture to hour 48. CONCLUSIONS: hBMSCs may be effective for cell therapy and tissue engineering for the capability of differentiating into neuronal-like cells, as well as the capability of inhibiting lymphocyte proliferation in MLR system.

Patients with brain metastases derived from gastrointestinal cancer: clinical characteristics and prognostic factors.

PURPOSE: This study seeks to evaluate the natural history, outcome, and possible prognostic factors in patients with brain metastases derived from gastrointestinal cancers. METHODS: The clinical features, prognostic factors, and the effects of different treatment modalities on survival were retrospectively investigated in 103 patients with brain metastases derived from gastrointestinal cancers. RESULTS: The median time from diagnosis of primary tumor to brain metastasis was 22.00 months. The interval between diagnosis of primary tumor relapse and brain metastasis was 8.00 months. The median follow-up time was 7.80 months. The median survival time after diagnosis of brain metastases was 4.10 months for all patients and 1.17 months for patients who received only steroids (36.9 %), 3.97 months for patients who only received whole-brain radiation therapy (WBRT 31.1 %), 11.07 months for patients who received gamma-knife surgery alone or/and WBRT (20.4 %), and 13.70 months for patients who underwent surgery and radiotherapy (12 patients, 11.6 %) (P < 0.001). Multivariate analysis revealed that recursive partitioning analysis (RPA) class, extracranial metastasis, and chemotherapy were independent prognostic factors. Brain metastasis derived from gastrointestinal tract cancer is rare, and overall patient survival is poor. CONCLUSION: RPA class, chemotherapy after brain metastases, and treatment regimens were independent prognostic factors for the survival of patients with brain metastases derived from gastrointestinal cancers.