GHS-R1a deficiency protects against lipopolysaccharide-induced spatial memory impairment in mice.

Neuroinflammation has been implicated in cognitive deficits of neurological and neurodegenerative diseases. There is abundant evidence that the application of ghrelin, an orexigenic hormone regulating appetite and energy balance, abrogates neuroinflammation and rescues associated memory impairment. However, the underlying mechanism is uncertain. In this study, we find that both intraperitoneal (i.p.) and intracerebroventricular (i.c.v.) administration of lipopolysaccharide (LPS) impairs spatial memory in mice. LPS treatment causes neuroinflammation and microglial activation in the hippocampus. Ghsr1a deletion suppresses LPS-induced microglial activation and neuroinflammation, and rescued LPS-induced memory impairment. Our findings thus suggest that GHS-R1a signaling may promote microglial immunoactivation and contribute to LPS-induced neuroinflammation. GHS-R1a may be a new therapeutic target for cognitive dysfunction associated with inflammatory conditions.

Engineered Basic Fibroblast Growth Factor Specifically Bonded with Injectable Extracellular Matrix Hydrogel for the Functional Restoration of Cerebral Ischemia in Rats.

Cerebral ischemia was one of the leading causes of mortality and disability worldwide. Extracellular matrix (ECM) hydrogel held great potential to replace volumetric brain tissue loss following ischemic injury but with limited regenerative effect for functional restoration when implanted alone. In the present study, an engineered basic fibroblast growth factor (EBP-bFGF) was constructed, which fused a specific ECM-binding peptide (EBP peptide) with bFGF. The recombinant EBP-bFGF showed typical binding capacity with ECM without affecting the bioactivity of bFGF both in vitro and in vivo. Furthermore, the EBP-bFGF was used for bioactive modification of ECM hydrogel to repair cerebral ischemia. The combination of EBP-bFGF and ECM hydrogels could realize the sustained release of bFGF in the ischemic brain and improve the regenerative effect of ECM, which protected the survival of neurons, enhanced angiogenesis, and decreased the permeability of blood-brain barrier, ultimately promoted the recovery of motor function. In addition, transcriptome analysis revealed neuregulin-1/AKT pathway involved in this process. Therefore, EBP-bFGF/ECM hydrogel would be a promising therapeutic strategy for cerebral ischemia.

Endovascular Therapy for Basilar Artery Occlusion in Sudden Onset to Maximal Deficit Ischemic Events.

BACKGROUND: The presence of sudden onset to maximal deficit (SOTMD) in patients with acute basilar artery occlusion often results in more severe outcomes. However, the effect of endovascular therapy on SOTMD and whether the outcome is affected by onset-to-puncture time remain unclear. METHODS AND RESULTS: This retrospective analysis was conducted using data from the prospective BASILAR (Endovascular Treatment for Acute Basilar Artery Occlusion Study Registry). Consecutive patients with basilar artery occlusion receiving endovascular therapy were dichotomized into SOTMD and non-SOTMD cohorts. The primary outcomes included a favorable outcome (modified Rankin scale 0-3), recanalization, and mortality at 90 days. The outcomes of patients with SOTMD were analyzed using multivariable logistic regression. In the multivariate analysis, a favorable outcome was similar between the two cohorts (odds ratio [OR], 0.88 [95% CI, 0.58-1.34]; P=0.5), although the mortality of patients with SOTMD was higher than that of patients with non-SOTMD (OR, 1.67 [95% CI, 1.14-2.44]; P=0.008). The probability of mortality increased from 40.0% at 1 hour to 70.0% at 6 hours in the SOTMD cohort, and favorable outcomes of patients with non-SOTMD declined from 38.0% at 1 hour to 18.0% at 8 hours. CONCLUSIONS: No significant difference was observed in favorable outcomes between the SOTMD and non-SOTMD groups, although mortality was higher in the SOTMD cohort. The patients with SOTMD had a stronger time dependence for endovascular therapy in terms of mortality, while the time dependency regarding favorable outcome in the NSOTMD group was even higher. REGISTRATION: URL: https://www.chictr.org.cn; Unique identifier: ChiCTR1800014759.

Efficacy and Safety of Butylphthalide in Patients With Acute Ischemic Stroke: A Randomized Clinical Trial.

Importance: DL-3-n-butylphthalide (NBP) is a drug for treating acute ischemic stroke and may play a neuroprotective role by acting on multiple active targets. The efficacy of NBP in patients with acute ischemic stroke receiving reperfusion therapy remains unknown. Objective: To assess the efficacy and safety of NBP in patients with acute ischemic stroke receiving reperfusion therapy of intravenous thrombolysis and/or endovascular treatment. Design, Setting, and Participants: This multicenter, double-blind, placebo-controlled, parallel randomized clinical trial was conducted in 59 centers in China with 90-day follow-up. Of 1236 patients with acute ischemic stroke, 1216 patients 18 years and older diagnosed with acute ischemic stroke with a National Institutes of Health Stroke Scale score ranging from 4 to 25 who could start the trial drug within 6 hours from symptom onset and received either intravenous recombinant tissue plasminogen activator (rt-PA) or endovascular treatment or intravenous rt-PA bridging to endovascular treatment were enrolled, after excluding 20 patients who declined to participate or did not meet eligibility criteria. Data were collected from July 1, 2018, to May 22, 2022. Interventions: Within 6 hours after symptom onset, patients were randomized to receive NBP or placebo in a 1:1 ratio. Main Outcomes and Measures: The primary efficacy outcome was the proportion of patients with a favorable outcome based on 90-day modified Rankin Scale score (a global stroke disability scale ranging from 0 [no symptoms or completely recovered] to 6 [death]) thresholds of 0 to 2 points, depending on baseline stroke severity. Results: Of 1216 enrolled patients, 827 (68.0%) were men, and the median (IQR) age was 66 (56-72) years. A total of 607 were randomly assigned to the butylphthalide group and 609 to the placebo group. A favorable functional outcome at 90 days occurred in 344 patients (56.7%) in the butylphthalide group and 268 patients (44.0%) in the placebo group (odds ratio, 1.70; 95% CI, 1.35-2.14; P < .001). Serious adverse events within 90 days occurred in 61 patients (10.1%) in the butylphthalide group and 73 patients (12.0%) in the placebo group. Conclusions and Relevance: Among patients with acute ischemic stroke receiving intravenous thrombolysis and/or endovascular treatment, NBP was associated with a higher proportion of patients achieving a favorable functional outcome at 90 days compared with placebo. Trial Registration: ClinicalTrials.gov Identifier: NCT03539445.

Comparing a novel Catfish flow restoration device and the Solitaire stent retriever for thrombectomy revascularisation in emergent largevessel occlusion stroke: a prospective randomised controlled study.

BACKGROUND: The Catfish stent retriever is a newly developed mechanical thrombectomy device for rapid recanalisation in emergent large vessel occlusion (ELVO) stroke. The current trial aimed to assess whether the Catfish stent retriever is non-inferior to the Solitaire stent retriever in terms of outcomes in ELVO stroke. METHODS: This was a randomised, prospective, parallel-group, multicentre, open-label, non-inferiority study conducted at 18 sites in China. The primary outcome was the proportion of cases with successful recanalisation (modified thrombolysis in cerebral infarction score of 2b or 3) following the procedure. Secondary efficacy outcomes included the National Institutes of Health Stroke Scale scores at 24 hours and 7 days or discharge if earlier, time from artery puncture to successful recanalisation and good clinical outcome (modified Rankin scale score ≤2) at 90 days. Safety outcomes included symptomatic intracranial haemorrhage, all cause-death and severe adverse events at 90 days. RESULTS: Between 3 March 2019 and 5 June 2021, 118 and 120 patients were randomly allocated to the Catfish and Solitaire groups, respectively. The primary endpoint after all endovascular procedures was non-inferior in the Catfish group (88.5%, 100/113) than in the Solitaire group (87.7%, 100/114), with a rate difference (RD) of 0.78% (95% CI -7.64 to -9.20; p=0.001). Sensitivity analysis only considering the per-protocol set also yielded similar results, with an RD of 0.83% (95% CI -7.03 to -8.70; p<0.001). Additionally, the proportions of cases with good clinical outcomes (47.8% vs 50.0%, p=0.739) and all-cause death rates (17.7% vs 18.8%, p=0.700) were similar in both groups at 90 days. CONCLUSIONS: The Catfish stent retriever is an effective and safe device for endovascular recanalisation in ELVO stroke. TRIAL REGISTRATION NUMBER: NCT03820882.

Effectiveness and safety of the Trevo® Retriever for mechanical thrombectomy in Chinese patients with acute ischemic stroke: Trevo Retriever China Registry.

BACKGROUND: To quantify the effectiveness and safety of the Trevo® Retriever for endovascular treatment of acute ischemic stroke (AIS) patients in China. METHODS: Trevo Retriever Registry (China) was a prospective, multicenter, non-comparative, open-label study of patients with AIS treated with the Trevo Retriever. The primary outcome was the proportion of patients achieving an expanded Thrombolysis in Cerebral Infarction (eTICI) score ≥2b at the end of endovascular treatment. Secondary outcomes included first-pass eTICI score ≥2b and 90-day modified Rankin Scale (mRS) score ≤2. RESULTS: The Trevo Retriever Registry (China) enrolled and followed 201 patients (62.1 ± 12.5 years-old; 70.6% male) at 11 centers. The pre-procedure NIHSS score and ASPECTS were 16 (interquartile range (IQR), 13-21) and 7 (IQR, 6-9), respectively, and 188 (93.5%) patients had an mRS score of 0 prior to the stroke. The main stroke etiology was large artery atherosclerosis, accounting for 71.6% (144/201) of patients. Post-procedure eTICI ≥2b was 98.4% (187/190). First-pass eTICI ≥2b was 74.7% (136/182). The 90-day good outcome (mRS ≤2) rate was 73.6% (148/201). The 90-day all-cause mortality was 5.5% (11/201). Neurological deterioration at 24 h post-procedure was observed in 7.7% (15/195) patients. Embolism in a new territory was seen in one patient (0.5%). Two (1.0%) procedure-related adverse events (AEs) occurred, which were intra-procedure cerebral artery embolism. No Trevo related AEs occurred. CONCLUSIONS: This real-world study of the Trevo Retriever in China demonstrated a high rate of revascularization and first-pass success that resulted in an overall high good function outcome rate and low mortality.

New Insights into Microglial Mechanisms of Memory Impairment in Alzheimer's Disease.

Alzheimer's disease (AD) is the most common progressive and irreversible neurodegeneration characterized by the impairment of memory and cognition. Despite years of studies, no effective treatment and prevention strategies are available yet. Identifying new AD therapeutic targets is crucial for better elucidating the pathogenesis and establishing a valid treatment of AD. Growing evidence suggests that microglia play a critical role in AD. Microglia are resident macrophages in the central nervous system (CNS), and their core properties supporting main biological functions include surveillance, phagocytosis, and the release of soluble factors. Activated microglia not only directly mediate the central immune response, but also participate in the pathological changes of AD, including amyloid-beta (Aß) aggregation, tau protein phosphorylation, synaptic dissection, neuron loss, memory function decline, etc. Based on these recent findings, we provide a new framework to summarize the role of microglia in AD memory impairment. This evidence suggests that microglia have the potential to become new targets for AD therapy.

Early argatroban and antiplatelet combination therapy in acute non-lacunar single subcortical infarct associated with mild intracranial atherosclerosis.

BACKGROUND: Patients with acute non-lacunar single subcortical infarct (SSI) associated with mild intracranial atherosclerosis (ICAS) have a relatively high incidence of early neurological deterioration (END), resulting in unfavorable functional outcomes. Whether the early administration of argatroban and aspirin or clopidogrel within 6-12 h after symptom onset is effective and safe in these patients is unknown. METHODS: A review of the stroke database of Weihai Municipal Hospital, Cheeloo College of Medicine, Shandong University and Qingdao Center Hospital, Qingdao University Medical College in China was undertaken from May 2017 to January 2020 to identify all patients with non-lacunar SSI caused by ICAS within 6-12 h of symptom onset based on MRI screening. Patients were divided into two groups, one comprising those who received argatroban and mono antiplatelet therapy with aspirin or clopidogrel on admission (argatroban group), and the other those who received dual antiplatelet therapy (DAPT) with aspirin and clopidogrel during hospitalization (DAPT group). The primary outcome was recovery by 90 days after stroke based on a modified Rankin scale (mRS) score (0 to 1). The secondary outcome was END incidence within 120 h of admission. Safety outcomes were intracranial hemorrhage (ICH) and major extracranial bleeding. The probability of clinical benefit (mRS score 0-1 at 90 days) was estimated using multivariable logistic regression analysis. RESULTS: A total of 304 acute non-lacunar SSI associated with mild ICAS patients were analyzed. At 90 days, 101 (74.2%) patients in the argatroban group and 80 (47.6%) in the DAPT group had an mRS score that improved from 0 to 1 (P < 0.001). The relative risk (95% credible interval) for an mRS score improving from 0 to 1 in the argatroban group was 1.50 (1.05-2.70). END occurred in 10 (7.3%) patients in the argatroban group compared with 37 (22.0%) in the DAPT group (P < 0.001). No patients experienced symptomatic hemorrhagic transformation. CONCLUSIONS: Early combined administration of argatroban and an antiplatelet agent (aspirin or clopidogrel) may be beneficial for patients with non-lacunar SSI associated with mild ICAS identified by MRI screening and may attenuate progressive neurological deficits. TRIAL REGISTRATION: Our study is a retrospectively registered trial.

Minimally invasive strategy for type I choledochal cyst in adult: combination of laparoscopy and choledochoscopy.

BACKGROUND: Choledochal cyst (CC)is a rare disease entity, more commonly occurring in Asian populations. In case of no contraindication, CC is resected to avoid future malignancies and future complications. OBJECTIVE: To determine the optimal technique for treatment of patients with type I choledochal cyst by comparisons of indicators, including the duration of surgery, loss of blood, rates of complication, duration of hospitalization, and outcomes of long-term follow-up. METHODS: From January 2009 to September 2017, a combination of laparoscopy and choledochoscopy surgery was implemented for type I choledochal cyst in adult. Patients' demographics data and treatment outcomes were collected prospectively during the follow-up. RESULTS: Fifty-eight patients with type I choledochal cyst were managed using this strategy. The combination of laparoscopic and intraoperative choledochoscopy was successfully performed in all patients without conversion or morbidity. When compared with a historical cohort of 71 patients who underwent a surgery for CC, this group of patients had significantly shorter duration of hospitalization (9.0 ± 6.5 days vs. 13.0 ± 8.0 days, P < 0.05). We also observed a lower blood loss (128.8 ± 60.2 mL vs. 178.1 ± 58.2 mL, P < 0.05), although the duration of the surgery (320.0 ± 50.0 min vs. 190.0 ± 24.5 min, P < 0.05) was longer. However, no significant difference was found in the rate of postoperative bleeding complication (3.45% vs. 4.23%, P = 0.82) and bile leakage complication (6.90% vs. 4.23%, P = 0.51). The two groups had similar rates of anastomotic stenosis (0.96% vs. 0.61%%, P = 0.47), jaundice (0.58% vs. 0.61%, P = 0.95), cholangitis (0.38% vs. 0.30%, P = 0.81), and reoperation (0.38% vs. 0.15%, P = 0.43). CONCLUSION: The type I choledochal cyst in adult can be effectively managed by laparoscopic surgery combined with inoperative choledochoscopy, which is feasible and minimally invasive. With the development of laparoscopic techniques and instruments, laparoscopic surgery may become the first-choice treatment for type I choledochal cyst treatment.

Mechanism Investigation of Hyaluronidase-Combined Multistage Nanoparticles for Solid Tumor Penetration and Antitumor Effect.

BACKGROUND: Hyaluronic acid (HA) is a major component of extracellular matrix (ECM) and its over expression in tumor tissues contributes to the increase of interstitial fluid pressure (IFP) and hinders the penetration of nanoparticles into solid tumors. MATERIALS AND METHODS: We here reported a tumoral microenvironment responsive multistage drug delivery system (NPs-EPI/HAase) which was formed layer by layer via electrostatic interaction with epirubicin (EPI)-loaded PEG-b-poly(2-(diisopropylamino)ethyl methacrylate)-b-poly(2-guanidinoethylmethacrylate) (mPEG-PDPA-PG, PEDG) micelles (NPs-EPI) and hyaluronidase (HAase). In this paper, we focused on the hyaluronidase-combined nanoparticles (NPs-EPI/HAase) for tumor penetration in tumor spheroid and solid tumor models in vitro and in vivo. RESULTS: Our results showed that NPs-EPI/HAase effectively degrade the HA in ECM and facilitate deep penetration of NPs-EPI into solid tumor. Moreover, NPs-EPI mainly employed clathrin-mediated and macropinocytosis-mediated endocytic pathways for cellular uptake and were subsequently directed to the lysosomes for further drug release triggered by proton sponge effect. Compared with NPs-EPI, the HAase coating group showed an enhanced tumoral drug delivery efficacy and inhibition of tumor growth. CONCLUSION: Overall, our studies demonstrated that coating nanoparticles with HAase can provide a simple but efficient strategy for nano-drug carriers to enhance solid tumor penetration and chemotherapeutic efficacy.

Endovascular Thrombectomy with or without Intravenous Alteplase in Acute Stroke.

BACKGROUND: In acute ischemic stroke, there is uncertainty regarding the benefit and risk of administering intravenous alteplase before endovascular thrombectomy. METHODS: We conducted a trial at 41 academic tertiary care centers in China to evaluate endovascular thrombectomy with or without intravenous alteplase in patients with acute ischemic stroke. Patients with acute ischemic stroke from large-vessel occlusion in the anterior circulation were randomly assigned in a 1:1 ratio to undergo endovascular thrombectomy alone (thrombectomy-alone group) or endovascular thrombectomy preceded by intravenous alteplase, at a dose of 0.9 mg per kilogram of body weight, administered within 4.5 hours after symptom onset (combination-therapy group). The primary analysis for noninferiority assessed the between-group difference in the distribution of the modified Rankin scale scores (range, 0 [no symptoms] to 6 [death]) at 90 days on the basis of a lower boundary of the 95% confidence interval of the adjusted common odds ratio equal to or larger than 0.8. We assessed various secondary outcomes, including death and reperfusion of the ischemic area. RESULTS: Of 1586 patients screened, 656 were enrolled, with 327 patients assigned to the thrombectomy-alone group and 329 assigned to the combination-therapy group. Endovascular thrombectomy alone was noninferior to combined intravenous alteplase and endovascular thrombectomy with regard to the primary outcome (adjusted common odds ratio, 1.07; 95% confidence interval, 0.81 to 1.40; P = 0.04 for noninferiority) but was associated with lower percentages of patients with successful reperfusion before thrombectomy (2.4% vs. 7.0%) and overall successful reperfusion (79.4% vs. 84.5%). Mortality at 90 days was 17.7% in the thrombectomy-alone group and 18.8% in the combination-therapy group. CONCLUSIONS: In Chinese patients with acute ischemic stroke from large-vessel occlusion, endovascular thrombectomy alone was noninferior with regard to functional outcome, within a 20% margin of confidence, to endovascular thrombectomy preceded by intravenous alteplase administered within 4.5 hours after symptom onset. (Funded by the Stroke Prevention Project of the National Health Commission of the People's Republic of China and the Wu Jieping Medical Foundation; DIRECT-MT ClinicalTrials.gov number, NCT03469206.).

Acupuncture Combined with Early Enteral Nutrition on Patients with Postoperative Laparoscopic Common Bile Duct Exploration: A Prospective Randomized Trial.

OBJECTIVE: To assess the efficiency of acupuncture combined with early enteral nutrition (EEN) in patients with postoperative laparoscopic common bile duct exploration. METHODS: A total of 200 patients with postoperative laparoscopic bile duct exploration was randomized using sealed envelopes and assigned to the convenitional, EEN, acupuncture plus convenitional and acupuncture plus EEN groups, 50 cases in each group. Twelve hours after operation, the patients in EEN groups began to receive oral enteral nutrition, and the acupuncture approach was performed by acupuncturist in acupuncture plus conventional and acupuncture plus EEN groups. Acupuncture was given at Zusanli (ST 36), Shangjuxu (ST 37) and Xiajuxu (ST 39) with a depth of 15-20 mm, using the lifting-thrusting and twisting method to obtain Deqi sensation. The needles were maintained for 30 min. Treatment was given once daily, 3 times per section. After the intervention, the patients' characteristics, operation time, bleeding volume, postoperative time to first anal exhaust, postoperative complications including abdominal distension, diarrhea, gastric dilatation, intestinal obstruction, pharyngodynia, incision, abdominal and pulmonary infection and postoperative hospitalization days were assessed and compared in patients among 4 groups. RESULTS: Postoperative time to first anal exhaust in the convenitional group was longer compared with the other 3 groups (P<0.05), and was shorter in the acupuncture plus EEN group than those of the convenitional, acupuncture plus convenitional and EEN groups (P<0.01). The acupuncture plus EEN group showed significant decrease in the incidence of complications and less postoperative hospitalization days compared with the other groups (P<0.05 or P<0.01). There was no readmission. CONCLUSION: After laparoscopic bile duct exploration, acupuncture combined with EEN treatment significantly improves the patients' gastrointestinal function, reduces complications, and shortens postoperative hospitalization days.

miR-183 inhibits microglia activation and expression of inflammatory factors in rats with cerebral ischemia reperfusion via NF-κB signaling pathway.

Ischemic stroke represents 87% of all strokes, and is the third leading cause of disability and mortality worldwide. The cause of ischemic stroke is the obstruction of blood flow through the artery that supplies oxygen-rich blood to the brain, with ischemia-reperfusion injury as its major cause. microRNAs (miRNA) are small non-coding RNAs, which serve important roles in the regulation of gene expression at the post-transcription level. The aim of the present study was to investigate the effect of miRNA-183 (miR-183) on microglia activation in rats with cerebral ischemia-reperfusion injury. To this end, a rat cerebral ischemia-reperfusion injury model was established. The results indicated that miR-183 expression was decreased by cerebral ischemia-reperfusion. In addition, treatment using miR-183 agomir significantly reduced the neurological function scores, percentage of cerebral infarction volume, and ionized calcium-binding adapter molecule-1 (IBA-1)-positive cells in the CA1 area of the hippocampus in rats subjected to cerebral ischemia-reperfusion injury, implicating a neuroprotective role for miR-183. MiR-183 agomir treatment also decreased the expression of pro-inflammatory-associated proteins interleukin (IL)-1ß, IL-6 and tumor necrosis factor (TNF)-α. Finally, the expression of the nuclear factor (NF)-κB p65 and IκBα was decreased and increased by miR-183 agomir treatment, respectively, indicating inhibition of the NF-κB signaling pathway. These observations suggest that miR-183 regulates the activation of microglia in rats with cerebral ischemia-reperfusion injury by inhibiting the NF-κB signaling pathway.

Effect of early enteral nutrition on laparoscopic common bile duct exploration with enhanced recovery after surgery protocols.

BACKGROUND/OBJECTIVES: Protocols for enhanced recovery after surgery (ERAS) provide comprehensive and evidence-based guidelines to improve perioperative care. It remains elusive whether early enteral nutrition (EEN) will play an active role in the ERAS protocols. Laparoscopic common bile duct exploration (LCBDE) is a safe and efficient method to treat patients with bile duct stones. This study aims to assess the safety, tolerability, and outcomes of EEN after LCBDE. SUBJECTS /METHODS: From January 2014 to April 2017, a total of 100 patients with postoperative LCBDE were chosen and randomly divided into control group and EEN group. Patients in the control group were treated with traditional management with regular diet when tolerated, while patients in the EEN group were fed with EEN 3 h after LCBDE. The patients' characteristics, time to first flatus, complications, hospitalization stay, and hospitalization expenses were assessed and compared between patients in these two groups. RESULTS: EEN accelerated the recovery of gastrointestinal function, being indicated by reduced time to first flatus when compared with control group (P = 0.00). In accordance, the quick recovery of gastrointestinal function resulted in shorter hospitalization stay for the EEN group (P = 0.00); however, no significant difference was shown when comparing the hospitalization expenses. On another hand, early oral feeding increased the occurrence of abdominal distension and diarrhea complications (P = 0.00 and P = 0.03). CONCLUSIONS: EEN effectively improves gastrointestinal function, but raises complications such as abdominal distension and diarrhea after LCBDE. It is recommended to implement the EEN as early as possible if the patients are reasonably expected to have high compliance.

Effects of varying radiation dosages on MMP1 expression, and MMP1 knockdown on the viability and migration of SW620 cells.

Colorectal cancer (CRC), also known as bowel cancer, is one of the leading causes of cancer­associated mortality worldwide at present. The aim of the present study was to detect the effects of matrix metalloproteinase 1 (MMP1) on the viability and migration of a CRC cell line in the presence or absence of variation X­ray radiation doses. The CRC cell line, SW620, was cultured and treated with different X­ray doses (0, 0.1, 0.5, 1, 3 and 6 Gy). MMP1 expression was downregulated via the application of a specific small interfering (si)­RNA. The viability and migration of SW620 cells prior to and following transfection were detected with MTT and Transwell chamber assays, respectively. The application of siRNA transfection to silence MMP1 in SW620 cells resulted in reduced cell viability and migration (P<0.05). Compared with the control, the cell viability and migration of cells were significantly reduced when exposed to 0.5, 1, 3, and 6 Gy X­ray radiation (P<0.05). In SW620 cells treated with different X­ray doses, the mRNA expression levels of MMP1 were significantly reduced (P<0.05). Cells treated with 0.5 Gy X­ray exposure exhibited the lowest mRNA expression levels of MMP1 when compared with other doses of X­ray radiation. The expression of MMP1 was associated with the promotion of the viability and migration of SW620 cells. X­ray radiation with 6 Gy dosages significantly reduced cell viability when compared with the control. Thus, MMP1­targeted therapy combined with radiotherapy could be used for treating CRC.

Euxanthone Attenuates Aß1-42-Induced Oxidative Stress and Apoptosis by Triggering Autophagy.

Alzheimer's disease (AD) is the most common neurodegenerative disorder and is characterized by the deposition of ß-Amyloid (Aß) plaques which contribute to its pathology. The present study was aimed at exploring the protective effects of euxanthone against Aß-induced neurotoxicity both in vivo and in vitro. We found that euxanthone significantly attenuated Aß1-42-induced memory and spatial learning dysfunction and also significantly reversed Aß1-42-induced neuronal apoptosis and autophagy in the hippocampal region. Euxanthone also protected the neuroblastic PC12 cells against Aß1-42-induced oxidative stress and apoptosis by inducing autophagy. In conclusion, euxanthone exerts its neuroprotective effect against Aß1-42 by inducing autophagy, indicating its potential therapeutic role in AD.

A Minimally Invasive Strategy for Mirizzi Syndrome Type II: Combined Endoscopic With Laparoscopic Approach.

BACKGROUND: Mirizzi syndrome (MS) is a rare complication of the gallstone disease. Despite the fact that successful laparoscopic treatments have been reported for MS type I, open surgery remains the gold standard approach for MS type II because of the technical difficulties involved. OBJECTIVE: The aim of this study is to determine the best technique for patients with MS type II by comparing the duration of surgery, loss of blood, rates of complication, duration of hospitalization, and outcomes of long-term follow-up. MATERIALS AND METHODS: From January 2009 to September 2014, combined endoscopic retrograde cholangiopancreatography with laparoscopic surgery for MS type II was implemented. Patients' demographics and treatment outcomes were collected prospectively and during the follow-up. RESULTS: Forty-nine patients with MS type II were managed with this strategy. Laparoscopic subtotal cholecystectomy was successfully performed in all the patients without conversion or morbidity. When compared with a historical cohort of 57 patients who underwent a surgery for MS, this group of patients had significantly shorter duration of hospitalization (7.21±1.61 vs. 15.31±3.82 d, P<0.01). It also showed less blood loss (162.81±40.83 vs. 207.55±37.01 mL, P=0.425) and less postoperative complications (10.20% vs. 14.04%, P=0.594), although the duration of surgery (165.73±54.33 vs. 156.04±48.61 min, P=0.334) was longer, but these were not statistically significant. However, no significant difference in the rate of recurrence (4.55% vs. 9.52%, P=0.522) of choledocholithiasis was found. CONCLUSIONS: The MS type II can be effectively managed with a laparoscopic surgery combined with preoperative endoscopic retrograde cholangiopancreatography, which is feasible and minimally invasive.

Timing of Cholecystectomy for Biliary Pancreatitis in Chinese Patients.

BACKGROUND: The aim of this study was to determine the most feasible and cost-effective time of cholecystectomy following gallstone pancreatitis in Chinese patients. MATERIALS AND METHODS: A total of 233 patients who underwent cholecystectomy for biliary pancreatitis (January 2004 to July 2012) were categorized into one of 2 groups: group A patients underwent cholecystectomy during admission (n=123), and group B patients delayed cholecystectomy after discharge from admission (n=110). RESULTS: The groups were comparable in demographics, comorbidities, and disease severity. In total, 100% of patients in group A had a cholecystectomy within 3 weeks after admission, and 60.9% of patients in group B experienced precholecystectomy gallstone-related events (including 15 cases of recurrent pancreatitis) after discharge. The median total length of hospital stay was greater for group B than for group A [12 d (range, 4 to 24 d) vs. 17 d (range, 9 to 39 d), respectively, P=0.000]. The average cost of management was greater in group B than group A [23,036.11 Yuan (range, 9073.53 to 85,132.33 Yuan) vs. 36,643.27 Yuan (range, 14,096.36 to 69,642.02 Yuan), respectively, P=0.000]. CONCLUSION: In Chinese patients, cholecystectomy should be performed within 3 weeks after admission without delay, and is feasible and cost-effective.

Single-step versus 2-step management of huge pancreatic pseudocysts: a prospective randomized trial with long-term follow-up.

OBJECTIVES: Single-step endoscopic ultrasonography-guided puncture through the stomach to insert a double-pigtail stent to drain a pseudocyst usually resulted in a high infection rate. The 2-step method, which combines the single-step method with a nasocystic drain, was created to help alleviate infections. Our study compared the 2 management strategies. METHODS: Between January 2007 and December 2011, patients with huge pancreatic pseudocysts were randomized into either a single-step or a 2-step treatment. Complications from infections and long-term results assessed during follow-up for the 2 groups were compared. RESULTS: Forty-seven patients were enrolled-23 in the single-step group and 24 in the 2-step group. There were significant differences in the infection rates (56.52 vs 20.83, P < 0.05), the average days of hospitalization (22.96 ± 2.82 days vs 10.38 ± 1.35 days, P < 0.05), postoperative hospital stay (15.31 ± 3.82 days vs 7.21 ± 1.61 days, P < 0.05), and the disappearance time of the pseudocyst (14.10 ± 2.33 weeks vs 11.70 ± 2.21 weeks, P < 0.05) between the 2 groups; however, there was no significant difference in the pseudocyst recurrence rate. CONCLUSIONS: The preferred treatment of a huge pancreatic pseudocyst is a combined endoscopic ultrasonography method using 2 double-pigtail stents and a nasocystic drain.

Systematic analysis of gene expression and molecular interactions in cardiac and non-cardiac gastric carcinomas.

BACKGROUND/AIMS: : This study aims to comparing the gene expression profiles and molecular interactions among gastric cardiac adenocarcinomas (GCA), gastric noncardiac adenocarcinomas (GNCA) and their adjacent normal tissues. METHODOLOGY: Gene expression profile of GSE29272 was downloaded from Gene expression omnibus. Differentially expressed genes (DEGs) were identified at the cut-off of p-value ≤ 0.01. Gene ontology (GO) enrichment analysis was further performed for the DEGs, and then the binding sites of the transcriptional factors and the specific protein-protein interactions were analyzed. RESULTS: Total 1024 DEGs were screened, including 741 up-regulated genes and 283 down-regulated genes. VSNL1 (visinin-like protein-1) is expressed relatively higher in the GNCA and could be its molecular biomarker, as KRT14 (cytokeratin 14) in the GCA. GO analysis showed that the analogous cancer-relevant factors network appears in these two cancer subgroups. The DEGs in the GCA tend to be bound by SPIB and ZNF354C. FN1 lies in the center of the protein-protein interaction networks of the two cancer subgroups. CONCLUSIONS: We found out the RNA expression level of the two gastric cancers varied greatly from the normal tissues while gene expression profile of them were very similar, however, the different biomarker and transcriptional factors indicate the differences of two mechanisms.