Optimization of perioperative approaches for advanced and late stages of gastric cancer: clinical proposal based on literature evidence, personal experience, and ongoing trials and research.

BACKGROUND: The high incidence of gastric cancer (GC) and paradoxical high prevalence of advanced stage GC, amounting to around 2/3 at time of diagnosis, have urged doctors and researchers around the world not only to ameliorate the detection rate of GC at early stages but also to optimize the clinical management of GC at advanced stages. CONTENT: We hereby recommend a more goal-oriented multimodality approach with objectives to increase survival rate and improve survival status. Based on precision and accurate clinical staging at diagnosis, we suggest that advanced stage GC (AGC) patients should be channeled into different treatment plans according to their disease status where they can be subjected to comprehensive measures involving chemo, radio, immunological, or target therapies depending on the pathophysiological behavior of their tumor. Patients assessed as potentially resectable cT4N + M0 can undergo neoadjuvant chemotherapy with intent of tumor downsizing and downgrading followed by surgery with intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) to decrease the incidence of peritoneal dissemination due to surgical trauma and adjuvant chemotherapy and radiation in cases of bulky nodal metastasis. In cases with distal metastasis, conversion therapy is recommended with the possibility of surgery of curative intent in case of favorable response. The options of alternate treatment options such as trans-catheter arterial chemoembolization (TACE) for limited liver lesions or neoadjuvant intraperitoneal plus systemic chemotherapy (NIPS) for peritoneal carcinomatosis have to be negotiated. With surgery as the cornerstone for cancer treatment, there is acknowledgment of the significance of perioperative comprehensive approaches but there has not been some consensus guiding clinical application. Henceforth, in this review, based on past literature, current guidelines and ongoing clinical trials, we have shared a proposal of the current treatment modalities in practice for the advanced stages of gastric cancer. CONCLUSION: Even though surgery is the golden standard of radical cancer treatment, clinical reality shows that without proper perioperative management, patients undergoing radical resections manifest high rates of recurrence and metastasis. Hence, in this review, we have outlined a clinical agenda to optimize the management of advanced stage GC with objective to improve survival outcome and quality of life of patients.

In vivo detection and automatic analysis of GABA in the mouse brain with MEGA-PRESS at 9.4 T.

The goals of this study were to develop an acquisition protocol and the analysis tools for Meshcher-Garwood point-resolved spectroscopy (MEGA-PRESS) in mouse brain at 9.4 T, to allow the in vivo detection of γ-aminobutyric acid (GABA) and to examine whether isoflurane alters GABA levels in the thalamus during anesthesia. We implemented the MEGA-PRESS sequence on a Bruker 94/20 system with ParaVision 6.0.1, and magnetic resonance spectra were acquired from nine male wild-type C57BL/6 J mice at the thalamus. Four individual scans were obtained for each mouse in a 2-h time course whilst the mouse was anesthetized with isoflurane. We developed an automated analysis program with improved correction for frequency and phase drift compared with the standard creatine (Cr) fitting-based method and provided automatic quantification. During MEGA-PRESS acquisition, a single voxel with a size of 5 × 3 × 3 mm3 was placed at the thalamus to evaluate GABA to Cr (GABA/Cr) ratios during anesthesia. Detection and quantitative analysis of thalamic GABA levels were successfully achieved. We noticed a significant decrease in GABA/Cr during the 2-h anesthesia (by linear regression analysis: slope < 0, p < 0.0001). In summary, our findings demonstrate that MEGA-PRESS is a feasible technique to measure in vivo GABA levels in the mouse brain at 9.4 T.

[Dog Fecal Contamination by Echinococcus in Cuomei County of Tibet in 2015].

Objective: To understand dog fecal contamination by Echinococcus in Lhoka Prefecture of Tibet and provide basis for development of prevention and control strategies. Methods: Survey spots were sampled around the Zhegu Village of Zhegu Town in Cuomei County of Tibet using the mechanical sampling method in May, 2015. The positions of spots, amount of dog feces, types of camps, pastures, terrains, vegetations and land cover, as well as information concerning the existence of household garbage, were recorded. The linear distance from survey spot to the center of the village was calculated. Dog feces were sampled in survey spot and examined the copro-antigen for Echinococcus contamination by ELISA. The distribution characteristics of fecal contamination were analyzed by chi-square test, Fisher's exact test, Kruskal-Wallis test and Nemenyi test. Results: Seventy-nine survey spots were selected for sampling. A total of 226 feces samples were obtained in 37 of the spots. ELISA results showed that the copro-antigen positive rate was 23.9%（54/226）, the averaged density of feces and the averaged density of positive feces were 0.317 9/100 m2 and 0.075 9/100 m2, with a maximum of 2.555 6/100 m2 and 0.555 6/100 m2 respectively. The density of feces and the density of positive feces were both higher in summer camps（0.601 9/100 m2 and 0.157 4/100 m2 respectively） than in non-camps（0.170 2/100 m2 and 0.033 1/100 m2）（χ2=18.248 4，P<0.01；χ2=15.274 3，P<0.01）. In addition, the density of feces and the density of positive feces were both higher in survey spots with household garbage（0.679 0/100 m2, 0.177 0/100 m2） than in those without household garbage （0.130 3/100 m2 and 0.023 5/100 m2）（χ2=34.634 7，P<0.01；χ2=26.109 1，P<0.01）; as well as higher in survey spots ≥10 km from the center of the village（0.403 7/100 m2, 0.107 4/100 m2） than in those <10 km（0.265 3/100 m2, 0.056 7/100 m2）（χ2=4.432 7，P<0.05；χ2=4.045 5，P<0.05）. Conclusion: The Cuomei County of Tibet is facing a serious situation of dog fecal contamination by Echinococcus. Summer camps, areas with household garbage, and districts with a ≥10 km linear distance from the village center may provide reference for determining the regions for hydatidosis prevention and control.

Magnesium sulfate for acute traumatic brain injury.

BACKGROUND: The purpose of this systematic review was to evaluate the effect of magnesium sulfate in the treatment of acute traumatic brain injury. MATERIALS AND METHODS: A systematic search of ClinicalTrials.gov, the Cochrane Library database, EMBASE, MEDLINE, Web of Science, and the World Health Organization trial registry, plus manual searches of gray literature, was undertaken in April 2013. Two reviewers independently extracted the data with a predefined data extraction form. RevMan 5 software was used to synthesize data and calculate the risk ratio for mortality with the 95% confidence interval. For the Glasgow Outcome Scale and posttreatment Glasgow Coma Scale data, the weighted mean difference was calculated with the 95% confidence interval. RESULTS: A total of 8 randomized controlled trials with a total of 786 patients were included. Meta-analysis showed that there was no significant difference between the groups for mortality. The Glasgow Outcome Scale of the treatment group was higher than that of the control group, although the significance was borderline. The Glasgow Coma Scale score change posttreatment was significantly higher than that of the control. CONCLUSIONS: The present meta-analysis of existing randomized controlled trials does not identify a significant beneficial effect in the mortality of traumatic brain injury patients; however, it suggests that magnesium sulfate shows a tendency to improve the Glasgow Outcome Scale and Glasgow Coma Scale scores, which is a promising result for traumatic brain injury therapy. Further effort is necessary to explore which subgroup of traumatic brain injury patients could benefit from magnesium sulfate.

A rare remote epidural hematoma secondary to decompressive craniectomy.

Remote epidural hematoma (REDH) is an uncommon complication of decompressive craniectomy. Remote epidural hematomas of the parietal occiput region have been reported only rarely. We report a unique case of delayed-onset bilateral extensive straddle postsagittal sinus and bilateral lateral sinus parietal occiput REDH after decompressive craniectomy, of which volume was approximately 130 mL, with left deviating midline structures. The patient was immediately taken back to the operating room for evacuation of the REDH via bilateral parietal and occiput craniectomy. Postoperatively, serial computed tomographic scans performed 3 days later showed that the REDH had been completely evacuated. Two months later, the patient regained full consciousness and obtained a near-complete recovery except for right facial paralysis.

Early pressure dressing for the prevention of subdural effusion secondary to decompressive craniectomy in patients with severe traumatic brain injury.

This study was performed to investigate the effect of early pressure dressing on the prevention of postoperative subdural effusion secondary to decompressive craniectomy (DC) in patients with severe traumatic brain injury (STBI). Patients with STBI who had undergone DC for refractory increased intracranial pressure between January 2008 and December 2011 (n = 169) were randomly divided into early pressure dressing (n = 82) and control (n = 87) groups. Early pressure dressing with an elastic bandage or general wrapping (control treatment) was applied 7 to 10 days after DC. Patients' age, sex, preoperative Glasgow Coma Scale score, incidence rate of subdural effusion, hospitalization time, and postoperative Glasgow Outcome Scale score were compared between groups. Intracranial pressure was measured immediately before and on the day after pressure dressing. No significant difference in age, sex, preoperative Glasgow Coma Scale score, or postoperative Glasgow Outcome Scale score was observed between groups (P > 0.05). Subdural effusion incidence rates were significantly lower in the early pressure dressing group than those in the control group (χ² = 5.449, P = 0.021), and a larger proportion of patients in the early pressure dressing group was hospitalized for 30 days or less (χ² = 5.245, P = 0.027). Early pressure dressing 7 to 10 days after DC, which is a noninvasive, simple procedure, reduced the incidence rate of subdural effusion and shortened hospitalization time after DC for STBI.

[Clinical analysis of childhood Henoch-Schonlein purpura on the Tibetan Plateau, China].

OBJECTIVE: To study the clinical characteristics of childhood Henoch-Schonlein purpura (HSP) on the Tibetan Plateau, China. METHODS: One hundred and twenty-five HSP children admitted to Shannan People's Hospital, Tibet, were assigned to the observation group, and 96 HSP children admitted to Wuhan Children's Hospital were assigned to the control group. The disease characteristics, clinical manifestations, treatment, and prognosis in both groups were retrospectively analyzed and compared. RESULTS: The mean age of HSP onset and the female-to-male ratio in the observation group were both significantly higher than in the control group (P<0.05). There was a significant difference in seasonal onset between two groups. Significant differences in the etiological factors were observed between the two groups (P<0.05). The gastrointestinal manifestation was more prominent in the observation group compared with that in the control group (P<0.05). Laboratory findings showed that the mean erythrocyte sedimentation rate, counts of white blood cells and platelets, and percentage of neutrophil leucocytes were significantly lower, while the hemoglobin level was significantly higher in the observation group than in the control group (P<0.05). A total of 124 HSP patients (99.2%) in the observation group had a full recovery or improvement, and the overall cure rate and improvement rate showed no significant differences between two groups (P>0.05). Only 2.4% of the patients (3 cases) in the observation group had recurrent attack during follow-up, which was significantly lower than that in the control group (16.7%; P<0.05). CONCLUSIONS: Childhood HSP on the Tibetan Plateau shows partial differences in disease characteristics, clinical manifestations, and laboratory measurements compared with that in the plain area. The overall prognosis is better and the recurrent rate is lower among HSP children on the Tibetan Plateau.

Construction of a Nomogram Prediction Model for Prognosis in Patients with Large Artery Occlusion-Acute Ischemic Stroke.

BACKGROUND: Patients with large artery occlusion-acute ischemic stroke (LAO-AIS) can experience adverse outcomes, such as brain herniation due to complications. This study aimed to construct a nomogram prediction model for prognosis in patients with LAO-AIS in order to maximize the benefits for clinical patients. METHODS: Retrospective analysis of 243 patients with LAO-AIS from January 2019 to January 2022 with medical history data and blood examination at admission. Univariate and multivariate analyses were conducted through binary logistic regression equation analysis, and a nomogram prediction model was constructed. RESULTS: Results of this study showed that hyperlipidemia (odds ratio [OR] = 2.849, 95% confidence interval [CI] = 1.100-7.375, P = 0.031), right cerebral infarction (OR = 2.144, 95% CI = 1.106-4.156, P = 0.024), D-Dimer>500 ng/mL (OR = 2.891, 95% CI = 1.398-5.980, P = 0.004), and neutrophil-lymphocyte ratio >7.8 (OR = 2.149, 95% CI = 1.093-4.225, P = 0.027) were independent risk factors for poor early prognosis in patients with LAO-AIS. In addition, hypertension (OR = 1.947, 95% CI = 1.114-3.405, P = 0.019), hyperlipidemia (OR = 2.594, 95% CI = 1.281-5.252, P = 0.008), smoking (OR = 2.414, 95% CI = 1.368-4.261, P = 0.002), D-dimer>500 ng/mL (OR = 3.170, 95% CI = 1.533-6.553, P = 0.002), and neutrophil-lymphocyte ratio >7.8 (OR = 2.144, 95% CI = 1.231-3.735, P = 0.007) were independent risk factors for poor long-term prognosis. The early prognosis nomogram receiver operating characteristic curve area under the curve value was 0.688 for the training set and 0.805 for the validation set, which was highly differentiated. The mean error was 0.025 for the training set calibration curve and 0.016 for the validation set calibration curve. Both the training and validation set decision curve analyses indicated that the clinical benefit of the nomogram was significant. The long-term prognosis nomogram receiver operating characteristic curve area under the curve values was 0.697 for the training set and 0.735 for the validation set, showing high differentiation. The mean error was 0.041 for the training set calibration curve and 0.021 for the validation set calibration curve. Both of the training and validation set decision curve analyses demonstrated a substantial clinical benefit of the nomogram. CONCLUSIONS: The nomogram prediction model based on admission history data and blood examination are easy-to-use tools that provide an accurate individualized prediction for patients with LAO-AIS and can assist in early clinical decisions and in obtaining an early prognosis.

[A prospective randomized control clinical trial about clopidogrel combined with warfarin versus clopidogrel alone in the prevention of restenosis after femoral-popliteal artery angioplasty].

OBJECTIVE: Using two antithrombotic treatment (clopidogrel vs. clopidogrel combined warfarin) strategies after femoral-popliteal artery angioplasty prospectively, to evaluate which strategy is more effective for the restenosis prevention. METHODS: Totally 50 patients referred for endovascular treatment (including the percutaneous transluminal angioplasty (PTA) and stent implantation) of the superficial femoral artery and popliteal artery from January 2008 to May 2009 were randomly divided into clopidogrel group (group A, 25 cases, 30 limbs) and clopidogrel plus warfarin group (group B, 25 cases, 33 limbs) before operation. Clinical outcomes and restenosis rate of the target lesions were evaluated at 3, 6 and 12 months after operation. RESULTS: Totally 88 patients were screened for participation in the study, 56 patients were included after the follow-up of 12 months. At 3 months, the rates of restenosis were 16.7% in group A and 18.2% in group B (χ² = 0.025, P = 0.874). At 6 months, the accumulated restenosis rates were 36.7% in group A and 36.4% in group B (χ² = 0.001, P = 0.98). At 12 months, the accumulated restenosis rates were 53.3% in group A and 42.4% in group B (χ² = 0.75, P = 0.387). Analysis for the critical limb ischemia sub-group showed that follow-up of 12 months, the accumulated restenosis rate was 8/10 in group A and 6/12 in group B (χ² = 1.023, P = 0.312). CONCLUSION: The clopidogrel alone treatment for PTA or PTA plus stent implantation of femoral popliteal artery has no statistically significant difference in comparison with the clopidogrel combined warfarin treatment in terms of the cumulative vascular restenosis rate at 3, 6, 12 months postoperatively.

Why the postoperative mortality rate of gastric cancer is lower in our center?

BACKGROUND/AIMS: There was obvious disparity in postoperative mortality rate of gastric cancer surgery among different centers. We analyzed the postoperative complications of gastric cancer surgery at a pioneer surgical center in China and discussed the possible reason behind lower postoperative mortality rate at this center. METHODOLOGY: A total of 697 patients of gastric cancer surgery were analyzed. The median age of the patients was 58 years. POSSUM (Physiological and operative severity score for the enumeration of morbidity and mortality) was applied to calculate risk adjusted morbidity rate. RESULTS: About 82 percent patients were discharged uneventfully in less than 15 days after surgery. Overall 159 patients had postoperative complications, majority of complication were mild or moderate, only about 4 percent of patients had severe complications. Postoperative anastomotic leak and mortality rate was 1.3 and 0.3 percent respectively. CONCLUSION: The postoperative complications especially the mortality rate was significantly lower in our center. The clinical and surgical experience may have influenced the surgical outcome; however, a well controlled prospective study is necessary to postulate this assumption. Regardless of the reason behind the disparity in postoperative mortality rate among different centers, it is mandatory to minimize the postoperative mortality rate of oncological disease like gastric cancer.

Valproate reverses stress-induced somatic hyperalgesia and visceral hypersensitivity by up-regulating spinal 5-HT2C receptor expression in female rats.

Sodium valproate (VPA) has analgesic effects in clinical and experimental studies, but the mechanisms are still unclear. The present study examined the effects of VPA on stress-induced somatic hyperalgesia and visceral hypersensitivity and the role of 5-HT2C receptors in the spinal cord. Repeated 3 day forced swim (FS) significantly reduced the thermal withdrawal latency and mechanical withdrawal threshold, and increased the magnitude of the visceromotor response to colorectal distention compared to the baseline values in rats. The somatic hyperalgesia and visceral hypersensitivity were accompanied by significant down-regulation of 5-HT2C receptor expression in the L4-L5 and L6-S1 dorsal spinal cord. Intraperitoneal administration of VPA (300 mg/kg) before each FS and 1 day post FS prevented the development of somatic hyperalgesia and visceral hypersensitivity induced by FS stress, as well as down-regulation of 5-HT2C receptors in the spinal cord. The reversal of somatic hyperalgesia and visceral hypersensitivity by VPA in FS rats was blocked by intrathecal administration of the selective 5-HT2C receptor antagonist RS-102221 (30 µg/10 µL) 30 min after each VPA injection. The results suggest that VPA attenuates FS-induced somatic hyperalgesia and visceral hypersensitivity by restoring down-regulated function of 5-HT2C receptors in the spinal cord.

Report of the third Asian Prostate Cancer study meeting.

The Asian Prostate Cancer (A-CaP) study is an Asia-wide initiative that was launched in December 2015 in Tokyo, Japan, with the objective of surveying information about patients who have received a histopathological diagnosis of prostate cancer (PCa) and are undergoing treatment and clarifying distribution of staging, the actual status of treatment choices, and treatment outcomes. The study aims to clarify the clinical situation for PCa in Asia and use the outcomes for the purposes of international comparison. Following the first meeting in Tokyo in December 2015, the second A-CaP meeting was held in Seoul, Korea, in September 2016. This, the third A-CaP meeting, was held on October 14, 2017, in Chiang Mai, Thailand, with the participation of members and collaborators from 12 countries and regions. In the meeting, participating countries and regions presented the current status of data collection, and the A-CaP office presented a preliminary analysis of the registered cases received from each country and region. Participants discussed ongoing challenges relating to data input and collection, institutional, and legislative issues that may present barriers to data sharing, and the outlook for further patient registrations through to the end of the registration period in December 2018. In addition to A-CaP-specific discussions, a series of special lectures were also delivered on the situation for health insurance in the United States, the correlation between insurance coverage and PCa outcomes, and the outlook for robotic surgery in the Asia-Pacific region. Members also confirmed the principles of authorship in collaborative studies, with a view to publishing original articles based on A-CaP data in the future.

Importance of surgical audit: postop complication of gastric cancer surgery among different units.

BACKGROUND/AIMS: Comparative surgical audit is a very important issue in surgical practice. The POSSUM (Physiological and Operative Severity Score for the enumeration of Morbidity and mortality) system has been proposed as the most efficient risk adjusting tool which can be used to compare surgical outcome among different units. POSSUM was applied for risk-adjusted auditing of different units in a single hospital. METHODOLOGY: In total, 357 gastric cancer patients who underwent radical resection or palliative procedures were analyzed retrospectively to evaluate predictive value of POSSUM scoring system and postop morbidity was compared among 5 different units in a single hospital. RESULTS: POSSUM predicted well by correct analysis; the observed to expected morbidity ratio (O:E ratio) was 1.01 for patients overall. But there were significant differences in complication rates among different units, the O: E ratio ranging from 0.7-1.63. CONCLUSIONS: POSSUM is a credible tool for predicting postop morbidity in gastric surgery. It provides risk-adjusted morbidity which can be compared directly. There was surprising difference in surgical outcome among different units of a single hospital, this demands more prospective researches to evaluate surgical outcome of different units. We conclude gastric cancer surgery should be performed in specialized centers.

Low-Level Laser Therapy for Temporomandibular Disorders: A Systematic Review with Meta-Analysis.

Objectives: We systematically reviewed randomized controlled trials (RCTs) of the effect of low-level laser therapy (LLLT) versus placebo in patients with temporomandibular disorder (TMD). Methods: A systematic search of multiple online sources electronic databases was undertaken. The methodological quality of each included study was assessed using the modified Jadad scale, and the quality of evidence was evaluated using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system. Results: A total of 31 RCTs were included. Total modified Jadad scale scores showed that the methodological quality was high in 30 studies and low in 1 study. Combining data from all clinically heterogeneous studies revealed positive effects of LLLT on pain relief, regardless of the visual analogue scale (VAS) score or the change of VAS score between the baseline and the final follow-up time point, while dosage analyses showed discrepant results about the effects of high or low doses for patients with TMD. Follow-up analyses showed that LLLT significantly reduced pain at the short-term follow-up. Temporomandibular joint function outcomes indicated that the overall effect favored LLLT over placebo. Conclusion: This systematic review suggests that LLLT effectively relieves pain and improves functional outcomes in patients with TMD.

[Effects of Herbal-cake-separated Moxibustion on Blood Lipid Protein Levels and Expression of Toll-like Receptor and Nuclear Factor Genes in Atherosclerotic Plaques in Hyperglycemia Rabbits].

OBJECTIVE: To observe the effect of herbal cake-separated moxibustion on blood lipid-apoprotein levels and the expression of Toll-like receptor 2 (TLR 2), TLR 4 and nuclear factor kappa B(NF-κB) mRNAs in atherosclerotic (AS) vulnerable plaques of hyperglycemia rabbits, so as to explore its mechanism underlying improvement of atherosclerosis. METHODS: Sixty New Zealand rabbits were randomly divided into 5 groups: control, model, direct moxibustion, herbal-cake-separated moxibustion and medication groups(n＝12 rabbits in each group). The AS vulnerable plaque model was established by high-fat forage feeding plus balloon-induced abdominal aorta injury and gene transfection of Ad 5-p 53 recombinant vector. Direct moxibustion or herbal-cake-separated moxibustion was applied to "Juque" (CV 14) and bilateral "Tianshu" (ST 25), "Fenglong" (ST 40), or bilateral "Xinshu" (BL 15), "Pishu" (BL 20) and "Ganshu" (BL 18) for 15－20 min every time. The medication group was treated by feeding Atorvastatin. All the treatments were conducted once daily for 8 weeks. Plasma total cholesterol(TC) and triglyceri-de(TG) contents were detected by enzyme method, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) contents detected by colorimetric determination, and plasma apolipoprotein A(Apo-A) and apolipoprotein B(Apo-B) levels determined by electrophoretic method. The pathological changes of vulnerable plaque and the aortic intima and media thickness were observed under light microscope after H．E. staining. The expression levels of TLR 2, TLR 4 and NF-κB mRNAs in AS plaques were determined by quantitative real-time PCR. RESULTS: After modeling, the levels of plasma TC, TG, LDL and Apo-B in the model group were remarkably increased (P<0.01), and Apo-A and HDL/LDL were significantly decreased in comparison with the control group (P<0.01). Additionally, the aortic intima and media thickness and the expression levels of TLR 2, TLR 4 and NF-κB mRNAs in AS plaques were significantly increased (P<0.01). After the treatment, the elevated levels of plasma TC, TG, LDL and Apo-B, the aortic intima thickness and media thickness, and the expression levels of TLR 2, TLR 4 and NF-κB mRNAs in the 3 treatment groups were significantly down-regulated in comparison with the model group (P<0.05, P<0.01), while the decreased levels of Apo-A and HDL/LDL were considerably increased (P<0.01). Comparison among the 3 treatment groups showed that the therapeutic effects of the herbal-cake-separated moxibustion and medication were significantly superior to those of the direct moxibustion in down-regulating the levels of TC, TG, LDL, Apo-B, TLR 2 mRNA, TLR 4 mRNA and NF-κB mRNA, and reducing the thickness of the aortic intima and media, as well as in up-regulating the levels of Apo-A and HDL/LDL (P<0.05, P<0.01). No significant differences were found between the herbal-cake-separated moxibustion and medication groups in the above-mentioned indexes (P>0.05). CONCLUSION: Herbal-cake-separated moxibustion has a positive role in stabilizing AS vulnerable plaque in hyperglycemia rabbits, which may be associated with its effects in regulating blood lipid-apolipoprotein levels and inhibiting the expression of TLR 2, TLR 4 and NF-κB mRNAs in vulnerable plaques.

Complementary and alternative interventions for fatigue management after traumatic brain injury: a systematic review.

BACKGROUND: We systematically reviewed randomized controlled trials (RCTs) of complementary and alternative interventions for fatigue after traumatic brain injury (TBI). METHODS: We searched multiple online sources including ClinicalTrials.gov, the Cochrane Library database, MEDLINE, CINAHL, Embase, the Web of Science, AMED, PsychINFO, Toxline, ProQuest Digital Dissertations, PEDro, PsycBite, and the World Health Organization (WHO) trial registry, in addition to hand searching of grey literature. The methodological quality of each included study was assessed using the Jadad scale, and the quality of evidence was evaluated using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system. A descriptive review was performed. RESULTS: Ten RCTs of interventions for post-TBI fatigue (PTBIF) that included 10 types of complementary and alternative interventions were assessed in our study. There were four types of physical interventions including aquatic physical activity, fitness-center-based exercise, Tai Chi, and aerobic training. The three types of cognitive and behavioral interventions (CBIs) were cognitive behavioral therapy (CBT), mindfulness-based stress reduction (MBSR), and computerized working-memory training. The Flexyx Neurotherapy System (FNS) and cranial electrotherapy were the two types of biofeedback therapy, and finally, one type of light therapy was included. Although the four types of intervention included aquatic physical activity, MBSR, computerized working-memory training and blue-light therapy showed unequivocally effective results, the quality of evidence was low/very low according to the GRADE system. CONCLUSIONS: The present systematic review of existing RCTs suggests that aquatic physical activity, MBSR, computerized working-memory training, and blue-light therapy may be beneficial treatments for PTBIF. Due to the many flaws and limitations in these studies, further controlled trials using these interventions for PTBIF are necessary.

Inflammatory Regulation by Driving Microglial M2 Polarization: Neuroprotective Effects of Cannabinoid Receptor-2 Activation in Intracerebral Hemorrhage.

The cannabinoid receptor-2 (CB2R) was initially thought to be the "peripheral cannabinoid receptor." Recent studies, however, have documented CB2R expression in the brain in both glial and neuronal cells, and increasing evidence suggests an important role for CB2R in the central nervous system inflammatory response. Intracerebral hemorrhage (ICH), which occurs when a diseased cerebral vessel ruptures, accounts for 10-15% of all strokes. Although surgical techniques have significantly advanced in the past two decades, ICH continues to have a high mortality rate. The aim of this study was to investigate the therapeutic effects of CB2R stimulation in acute phase after experimental ICH in rats and its related mechanisms. Data showed that stimulation of CB2R using a selective agonist, JWH133, ameliorated brain edema, brain damage, and neuron death and improved neurobehavioral outcomes in acute phase after ICH. The neuroprotective effects were prevented by SR144528, a selective CB2R inhibitor. Additionally, JWH133 suppressed neuroinflammation and upregulated the expression of microglial M2-associated marker in both gene and protein level. Furthermore, the expression of phosphorylated cAMP-dependent protein kinase (pPKA) and its downstream effector, cAMP-response element binding protein (CREB), were facilitated. Knockdown of CREB significantly inversed the increase of M2 polarization in microglia, indicating that the JWH133-mediated anti-inflammatory effects are closely associated with PKA/CREB signaling pathway. These findings demonstrated that CB2R stimulation significantly protected the brain damage and suppressed neuroinflammation by promoting the acquisition of microglial M2 phenotype in acute stage after ICH. Taken together, this study provided mechanism insight into neuroprotective effects by CB2R stimulation after ICH.

Erlotinib for advanced hepatocellular carcinoma. A systematic review of phase II/III clinical trials.

OBJECTIVES: To evaluate the efficacy and safety of erlotinib for the treatment of advanced hepatocellular carcinoma (HCC). METHODS: A systematic literature search was undertaken in June 2015. Phase II/III trials of erlotinib for the treatment of advanced HCC were included. A descriptive analysis was applied. The study was conducted in College of Medicine, Honghui Hospital, Xi'an Jiaotong University, Xi'an, China, between June 2015 and January 2016. RESULTS: Ten trials, comprising 9 phase II and one phase III trial, were included in the systematic review. The tumor response rate was 0% in 4 of the phase II trials, less than 10% in 3 of the phase II trials and the phase III trial, and greater than 20% in 2 of the phase II trials. The disease control rate was 42.5-79.6% in most studies. Three studies reported a median progression-free survival (PFS) of 6.5-9.0 months, although PFS was less than 3.5 months in most studies. Most trials reported a median overall survival of 6.25-15.65 months. The most frequent grade 3/4 toxicities were fatigue (11.9%), diarrhea (10%), increased alanine and aspartate transaminases (7.3%), and rash/desquamation (6.9%). Conclusion: Erlotinib provides efficacious and well-tolerated treatment for advanced HCC. However, more detailed investigations of HCC pathogenesis and evaluation of sensitive patient subsets are needed to improve outcomes of patients with advanced HCC. Additional well-designed, randomized, controlled trials are needed to evaluate the efficacy and safety of erlotinib as monotherapy or combination with other drugs for advanced HCC.

Fibulin-5 is a prognostic marker that contributes to proliferation and invasion of human glioma cells.

Fibulin-5 has recently been considered as a potential tumor suppressor in human cancers. Several studies have shown that it is down-regulated in a variety of tumor types and inhibits tumor growth and metastasis. This study was aimed to investigate the clinical significance of fibulin-5 in glioma and its role in cell proliferation and invasion. We found that the expression of fibulin-5 in glioma tissues was significantly lower than those in normal brain (NB) tissues. Negative expression was significantly correlated with advanced clinical stage (grade III+IV). Furthermore, Fibulin-5 negative expression was correlated with a shorter overall survival of glioma patients. Multivariate Cox repression analysis indicated that fibulin-5 was an independent factor for predicting overall survival of glioma patients. Overexpression obviously inhibited cell proliferation in U251 and U87 cells. Furthermore, it significantly reduced the number of migrating and invading glioma cells. In conclusion, impaired expression of fibulin-5 is correlated with the advanced tumor stage in glioma. Otherwise, Fibulin-5 is an independent prognostic marker for predicting overall survival of glioma patients. Mechanistically, it may function as a tumor suppressor via inhibiting cell proliferation and invasion in gliomas.