Typical Zollinger-Ellison syndrome-atypical location of gastrinoma and absence of hypergastrinemia:A case report and review of literature

BACKGROUND Zollinger–Ellison syndrome(ZES)results from hypersecretion of gastrin from pancreatic or duodenal neuroendocrine tumors,commonly referred to as gastrinomas.The high levels of gastrin lead to a typical presentation involving watery diarrhea and multiple ulcers in the duodenum.Here,we have presented the rare case of a patient with ZES and absence of hypergastrinemia as well as an atypical location of gastrinoma.CASE SUMMARY A 72-year-old woman presented with the typical clinical manifestations of ZES,including upper abdominal pain,significant watery diarrhea,and acidic liquid vomitus.Surprisingly,however,she did not have an increased level of serum gastrin.In addition,there was no evidence of gastrinoma or any other ulcerogenic tumor.Esophagogastroduodenoscopy was conducted to examine the upper digestive tract.Revised diagnoses were considered,and an individualized treatment plan was developed.The patient responded to antacid medication while experiencing intermittent,recurring bouts of ZES.18F-AlF-NOTAoctreotide positron emission tomography(18F-OC PET)/computed tomography(CT)helped locate the tumor.Postoperative pathology and immunohistochemistry results suggested that the tumor was a gastrinoma located at an unconventional site.CONCLUSION This present case study demonstrates the possibility of ZES-like manifestation in patients with absence of hypergastrinemia.18F-OC PET/CT is a relatively new imaging technique that can be applied for diagnosing even tiny gastrinomas that are atypical in terms of location.

CD97 promotes gastric cancer cell proliferation and invasion through exosome-mediated MAPK signaling pathway

AIM: To investigate the mechanism underlying the promoting role of CD97 in gastric cancer cell proliferation and invasion. METHODS: Two types of exosomes released by gastric cancer cells with high(SGC/wt) or low(SGC/kd) CD97 expression were isolated by ultracentrifugation and identified by electron microscopy and western blot analysis. The influences of the two exosomes on gastric cancer cell proliferation and invasion were investigated by proliferation and Matrigel invasion assays. Exosomal mi RNAs were subsequently isolated from the two samples and their mi RNA profiles were compared via microarray assay analysis. Reverse transcriptionquantitative real-time polymerase chain reaction was used to validate the microarray assay. Target genes of the differently expressed micro RNAs were predicted based on five independent algorithms and were then subjected to gene oncology enrichment and Kyoto encyclopedia of genes and genomes(KEGG) pathway analysis. After identifying the pathway that was the most likely altered, tumor cells were treated with the two exosomes at different concentrations, and the pathway activation was identified through western blot analysis.RESULTS: Exosomes isolated from SGC/wt cells significantly promoted tumor cell proliferation in a dose-dependent manner in vitro. SGC/wt exosomesalso significantly elevated the invasiveness of both SGC/wt(129.67 ± 8.327 vs 76.00 ± 5.292, P < 0.001) and SGC/kd(114.52 ± 9.814 vs 45.73 ± 4.835, P < 0.001) cells as compared to the exosomes released by SGC/kd cells. Microarray assay of the two exosomes revealed that 62 mi RNAs were differently regulated with a signal intensity of > 500 and a false discovery rate < 0.05. The following KEGG analysis defined the MAPK signaling pathway as the most likely candidate pathway that regulated tumor cell proliferation and invasion. Through western blot analysis, significant up-regulations of phosphorylated MAPKs, including extracellular signal-regulated kinase, Jun NH2-terminal kinase, and p38 mitogen-activated protein kinase, were detected in a dose-dependent manner in the SGC/wt exosomes treated groups, confirming activation of the MAPK signaling pathway stimulated by SGC/wt exosomes.CONCLUSION: CD97 promotes gastric cancer cell proliferation and invasion in vitro through exosomemediated MAPK signaling pathway, and exosomal mi RNAs are probably involved in activation of the CD97-associated pathway.

Influence of up-regulation of Notch ligand DLL4 on biological behaviors of human gastric cancer cells

AIM: To investigate the potential roles of Delta-like ligand 4 (DLL4) on the biological behavior of gastric cancer cells and its molecular mechanisms. METHODS: A recombinant eukaryotic expression vector containing human DLL4 gene was constructed and transfected into the human gastric cancer cell line SGC7901. Clones with up-regulated DLL4 were selected and amplified. The effect of DLL4 up-regulation on gastric cancer cell growth was assessed using cell growth assay. The migration and invasion were assessed using a transwell migration assay and matrigel invasion assay. Matrix metalloproteinases were detected using the zymogram technique. Cells were implanted subcutaneously into male BALB/c nu/nu mice. Tumor volumes were then calculated and compared. DLL4 staining in the implanted tumor was performed using immunohistochemistry technique. RESULTS: Growth curves over a six-day time course showed significantly promoted cell proliferation of SGC7901 cells with up-regulated DLL4. DLL4 up-regulation in SGC7901 cells promoted the migration (205.4 ± 15.2 vs 22.3 ± 12.1, P < 0.05) and invasion (68.8 ± 5.3 vs 18.2 ± 6.0, P < 0.05) in vitro and tumorigenicity in vivo (2640.5 ± 923.6 mm 3 vs 1115.1 ± 223.8 mm 3 , P < 0.05). Furthermore, significantly increased mRNA level and increased secretion of matrix metalloproteinase-2 (MMP-2) proenzyme were observed in SGC7901 cells with up-regulated DLL4. However, increased MMP-9 mRNA level but decreased extracellular MMP-9 proenzyme level was observed. CONCLUSION: Our observations indicated a mechanism by which activation of DLL4-mediated Notch signaling promotes the expression and secretion of MMP-2 proenzyme and influences the progress of gastric cancer.

Expression of MAPK1 in cervical cancer and effect of MAPK1 gene silencing on epithelial-mesenchymal transition,invasion and metastasis

Objective:To discuss the expression of mitogen-activated protein kinase 1(MAPK1) in the cervical cancer and effect of MAPK1 gene silencing on epithelial-mesenchymal transition and invasion and metastasis.Methods:Immunohistoehemistry,western blot and RT-PCR method were employed to detect the expression of MAPKl protein and mRNA in cervical cancer tissue and adjacent normal tissue.The constructed siRNA-MAPKI was transferred into human cervical cancer HeLa cells using Lipofectamine^(?)2000.MTT method was used to detect the cell vitality,transwell method to detect the cell invasion,and western blot to detect the expression of matrix metalloproteinases(MMP)-2,MMP-9,tissue inhibitor of metalloproteinase(TIMP)-1,TIMP-2,zinc finger transcription factor(Snail),epithelialmesenchymal transition related protein(EMT) E-cadherin and vimentin in cells.Results:The expression of MAPKl protein and mRNA in the cervical cancer tissue was significantly higher than the one in the adjacent normal tissue(P<0.01):after transfecting the siRNA-MAPKI into the human cervical cancer HeLa cells through liposome,compared with the control group,its cell vitality was significantly decreased(P<0.01),cell invasion was significantly decreased(P<0.01);expressed of MMP2.MMP-9,Snail and vimentin was significantly decreased(P<0.01),and expression of TIMP-1,TIMP-2 and E-cadherin was significantly increased(/J<0.01).Conclusions:Because of the high expression of MAPKl in the cervical cancer tissue,the interference in the expression of MAPK1 can significantly inhibit the invasion and metastasis of cervical cancer HeLa cells,which is related to the interference in the expression of MMPs/TIMP and Snail-mediated generation of EMT.

Mechanism underlying carbon tetrachloride-inhibited protein synthesis in liver

AIM: To study the mechanism underlying carbon tetrachloride (CCl4)-induced alterations of protein synthesis in liver. METHODS: Male Sprague-Dawley rats were given CCl4 (1 mL/100 g body weight) and 3H-leucine incorporation. Malondialdehyde (MDA) level in the liver, in vitro response of hepatocyte nuclei nucleotide triphosphatase (NTPase) to free radicals, and nuclear export of total mRNA with 3'-poly A+ were measured respectively. Survival response of HepG2 cells to CCl4 treatment was assessed by methyl thiazolyl tetrazolium. Km and Vmax values of nuclear envelope NTPase activity in liver of rats treated with CCl4 were assayed by a double-reciprocal plot. RESULTS: The protein synthesis was inhibited while the MDA level was signif icantly increased in liver of rats treated with CCl4. In addition, CCl4 decreased the NTPase binding capacity of nuclear envelope (Km value) in cultured HepG2 cells. Moreover, in vitro ferrous radicals from Fenton's system suppressed the NTPase activity of liver nuclear envelope in a dose-dependent manner. Down-regulation of the nuclear envelope NTPase activity indicated a lower energy provision for nucleocytoplasmic transport of mRNA molecules, an evidence in CCl4-treated HepG2 cells correspondingly supported by the nuclear sequestration of poly (A)+ mRNA molecules in morphological hybridization research. CONCLUSION: Inhibition of mRNA transport, suggestive of decreased NTPase activity of the nuclear envelope, may be involved in carbon tetrachloride-inhibited protein synthesis in liver.

Silver dressing in the management of an infant's urachal anomaly infected with methicillin-resistant Staphylococcus aureus:A case report

BACKGROUND Symptomatic urachal anomalies are rare disorders.The management of urachal remnants has historically been surgical excision because of the connection between urachal remnants and risk of malignancy development later in life.However,recent literature suggests that urachal anomalies that do not extend to the bladder can be treated with conservative management.In this case,we report a newborn with an infected urachal remnant who was treated with a combination of antibiotics and a silver-based dressing and finally recovered well.CASE SUMMARY Female baby A,weighing 2.88 kg at 38^(+5) wk of gestational age,was referred to the hospital because of a red,swollen umbilicus approximately 2 cm×2 cm in size with yellow purulent exudate.Through physical and ultrasound examination,the baby was finally diagnosed with a urachal anomaly.We first used oxacillin to prevent infection for 3 d.On the 4^(th) day,microbiology testing of the umbilical exudate revealed the presence of methicillin-resistant Staphylococcus aureus(MRSA).We changed the treatment with oxacillin to vancomycin for systemic infection and treated the umbilical inflammation with a silver sulfate dressing.After 5 d,the symptoms of the umbilicus disappeared,and we discontinued silver dressing application.On the 12^(th) day,umbilical exudate testing was negative for MRSA.On the 14^(th) day,the baby's blood testing showed a white blood cell count of 14.7×10^(9)/L,neutrophil percentage of 27.8%,and C-reactive protein level of 1.0 mg/L,suggesting that the infection had been controlled.We stopped treatment,and the baby was discharged with no complications.In this case,the infected urachal anomaly was cured with silver dressing and antibiotic application instead of surgical methods,which was a different course from that of some other urachal remnant cases.CONCLUSION Anomalies that do not connect with the bladder can be treated with nonoperative management,including application of conservative antibiotics and local intervention with silver-based dressings.Silver sulfate dressings are absolutely safe for neonates with judicious use,and they play an established role in preventing infection without resistance,which is a common problem with other antibiotics and antiseptics.

重症肺炎经支气管镜灌洗联合常规治疗的临床疗效的Meta分析

目的分析常规治疗联合肺泡灌洗对重症肺炎的临床疗效。方法计算机检索知网、万方、百度学术等国内数据库,以及检索Pub Med外文数据库,收集有关重症肺炎常规治疗联合肺泡灌洗的随机对照试验(RCT),检索时限为2019年1月-2021年12月,对照组为重症肺炎常规治疗,实验组为常规治疗联合肺泡灌洗(以下简称联合治疗)。根据Cochrane协作网风险评估手册中对纳入文献的评估方法,2名研究员将纳入的RCT进行质量评价和资料提取。采用Rev Man 5.4软件进行Meta分析。结果共纳入21篇文献,包括1735例患者,实验组868例,对照组867例。Meta分析结果显示:实验组总有效率高于对照组(OR=0.16,95%CI:0.13~0.19,P=0.000);两组患者发热恢复时间(MD=-3.41,95%CI:-3.67~-3.15,P=0.000)、肺部啰音消失时间(MD=-2.36,95%CI:-2.70~-2.01,P=0.000)、咳嗽消失时间(MD=-2.56,95%CI:-2.97~-2.15,P=0.000)、住院时间(MD=-4.38,95%CI:-5.53~-3.23,P=0.000)、氧分压(PO_(2))(MD=6.74,95%CI:5.79~7.68,P=0.000)、二氧化碳分压(PCO_(2))(MD=-8.84,95%CI:-11.02~-6.66,P=0.000)、血氧饱和度(SO_(2))(MD=5.85,95%CI:4.89~6.81,P=0.000)、降钙素原(PCT)浓度(MD=-1.95,95%CI:-2.96~-0.95,P=0.000)、C反应蛋白(CRP)浓度(MD=-11.33,95%CI:-19.68~-2.97,P=0.008)、白细胞(WBC)浓度(MD=-2.69,95%CI:-3.27~-2.11,P=0.000)和白细胞介素-6(IL-6)浓度(MD=-9.21,95%CI:-11.03~-7.39,P=0.000)比较,差异均有统计学意义。结论联合治疗和常规方法治疗重症肺炎,前者整体有效率高于后者,临床症状、住院时间、血气分析和感染指标都有明显改善。但有一些组间Meta分析结果具有高度异质性,结果可靠性仍有待进一步探讨。

胆囊并发胆总管结石患者的微创外科治疗研究

目的探究胆囊并发胆总管结石患者的微创外科治疗。方法选取2013年1月-2018年1月该院收治的92例胆囊并发胆总管结石患者为研究对象,采用随机数字表法将患者分为对照组(n=46)和观察组(n=46)。两组患者中存在胰腺炎的患者先行控制腹膜炎,对照组患者行腹腔镜胆囊切除术(LC)联合胆总管探查取石术(LCBDE),观察组患者行十二指肠乳头括约肌切开取石术(EST),术后3 d行LC治疗。比较两组患者围术期情况、费用情况和并发症情况。结果两组患者均未出现中转开腹手术情况,观察组患者的手术时间、止痛药使用率、住院时间均低于对照组患者,耗材费用和住院总费用多于对照组患者,差异具有统计学意义(P<0.05);两组患者的术中出血量、术后排气时间和手术费用比较差异无统计学意义(P>0.05)。观察组患者各项并发症总发生率为6.51%低于对照组患者的19.53%,差异具有统计学意义(P<0.05)。结论胆囊并发胆总管结石患者控制腹膜炎后行EST+LC治疗较LC+LCBDE治疗能够缩短手术时间,减轻术后疼痛,降低并发症发生率,缩短住院时间,但所需费用较高。

Expression Patterns of Inducible Cre Recombinase Driven by Differential Astrocyte-Specific Promoters in Transgenic Mouse Lines

Astrocytes are the most abundant cell type in the central nervous system(CNS).They provide trophic support for neurons,modulate synaptic transmission and plasticity,and contribute to neuronal dysfunction.Many transgenic mouse lines have been generated to obtain astrocyte-specific expression of inducible Cre recombinase for functional studies;however,the expression patterns of inducible Cre recombinase in these lines have not been systematically characterized.We generated a new astrocyte-specific Aldh1 l1-CreER^(T2)knock-in mouse line and compared the expression pattern of Cre recombinase between this and five widely-used transgenic lines(hGfap-CreER^(T2)from The Jackson Laboratory and The Mutant Mouse Resource and Research Center,Glast-CreER^(T2),Cx30-CreER^(T2),and Fgfr3-iCreER^(T2))by crossing with Ai14 mice,which express tdTomato fluorescence following Cre-mediated recombination.In adult Aldh1 l1-CreER^(T2):Ai 14 transgenic mice,tdTomato was detected throughout the CNS,and five novel morphologicallydefined types of astrocyte were described.Among the six evaluated lines,the specificity of Cre-mediated recombination was highest when driven by Aldh1 l1 and lowest when driven by hGfap;in the latter mice,co-staining between tdTomato and NeuN was observed in the hippocampus and cortex.Notably,evident leakage was noted in Fgfr3-iCreER^(T2)mice,and the expression level of tdTomato was low in the thalamus when Cre recombinase expression was driven by Glast and in the capsular part of the central amygdaloid nucleus when driven by Cx30.Furthermore,tdTomato was clearly expressed in peripheral organs in four of the lines.Our results emphasize that the astrocyte-specific CreER^(T2)transgenic lines used in functional studies should be carefully selected.

Predictive scores for mortality in full-term infants with necrotizing enterocolitis: experience of a tertiary hospital in Southwest China

Background: Although many risk factors for mortalityof necrotizing enterocolitis (NEC) were investigated,most of them were obtained from preterm infants, andfew works focused on the prognostic risk factors in fullterminfants. This study aimed to identify risk factors anddevelop a prediction score model for mortality in fulltermneonates with NEC.Methods: The risk factors were analyzed retrospectivelyby bivariate and multivariate logistic regression analysis in153 full-term neonates with NEC, who were hospitalizedin Children's Hospital of Chongqing Medical Universityfrom 2000 to 2013. A prediction score model was developedaccording to the regression coeffi cients of risk factors.Results: The mortality of the infants was 19.6%(30/153). The non-survivors had a younger age of diagnosisand advanced stage of NEC (P<0.05). They had a higherprevalence of respiratory failure, intestinal perforation,peritonitis and other complications, compared with thesurvivors (P<0.05). On the day of diagnosis, the nonsurvivorswere more likely to have abnormal laboratoryindicators than survivors (P<0.05). Age at diagnosis [oddsratio (OR)=0.91, 95% confidence interval (CI)=0.836-0.99], respiratory failure (OR=2.76, 95% CI=1.10-6.92),and peritonitis (OR=26.36, 95% CI=7.52-173.92) hadsignificant independent contributions to death. A scoremodel predicting death was developed, and the area underthe receiver operating characteristic curve was 0.869 (95%CI=0.803-0.935). All infants with scores ≥8 died.Conclusions: Younger age at diagnosis, peritonitis,and respiratory failure might be risk factors for themortality of full-term infants with NEC. Infants with apredictive score of 8 were at high risk for death.

Electron-Ion Coupling Mechanism to Construct Stable Output Performance Nanogenerator

Recently,triboelectric nanogenerators(TENGs)have been promoted as an effective technique for ambient energy harvesting,given their large power density and high energy conversion efficiency.However,traditional TENGs based on the combination of triboelectrification effect and electrostatic induction have proven susceptible to environmental influence,which intensively restricts their application range.Herein,a new coupling mechanism based on electrostatic induction and ion conduction is proposed to construct flexible stable output performance TENGs(SOP-TENGs).The calcium chloride doped-cellulose nanofibril(CaCl_(2)-CNF)film made of natural carrots was successfully introduced to realize this coupling,resulting from its intrinsic properties as natural nanofibril hydrogel serving as both triboelectric layer and electrode.The coupling of two conductive mechanisms of SOP-TENG was comprehensively investigated through electrical measurements,including the effects of moisture content,relative humidity,and electrode size.In contrast to the conventional hydrogel ionotronic TENGs that require moisture as the carrier for ion transfer and use a hydrogel layer as the electrode,the use of a CaCl_(2)-CNF film(i.e.,ion-doped natural hydrogel layer)as a friction layer in the proposed SOP-TENG effectively realizes a superstable electrical output under varying moisture contents and relative humidity due to the compound transfer mechanism of ions and electrons.This new working principle based on the coupling of electrostatic induction and ion conduction opens a wider range of applications for the hydrogel ionotronic TENGs,as the superstable electrical output enables them to be more widely applied in various complex environments to supply energy for low-power electronic devices.

Electron-Ion Coupling Mechanism to Construct Stable Output Performance Nanogenerator

Recently,triboelectric nanogenerators(TENGs)have been promoted as an effective technique for ambient energy harvesting,given their large power density and high energy conversion efficiency.However,traditional TENGs based on the combination of triboelectrification effect and electrostatic induction have proven susceptible to environmental influence,which intensively restricts their application range.Herein,a new coupling mechanism based on electrostatic induction and ion conduction is proposed to construct flexible stable output performance TENGs(SOP-TENGs).The calcium chloride doped-cellulose nanofibril(CaCl_(2)-CNF)film made of natural carrots was successfully introduced to realize this coupling,resulting from its intrinsic properties as natural nanofibril hydrogel serving as both triboelectric layer and electrode.The coupling of two conductive mechanisms of SOP-TENG was comprehensively investigated through electrical measurements,including the effects of moisture content,relative humidity,and electrode size.In contrast to the conventional hydrogel ionotronic TENGs that require moisture as the carrier for ion transfer and use a hydrogel layer as the electrode,the use of a CaCl_(2)-CNF film(i.e.,ion-doped natural hydrogel layer)as a friction layer in the proposed SOP-TENG effectively realizes a superstable electrical output under varying moisture contents and relative humidity due to the compound transfer mechanism of ions and electrons.This new working principle based on the coupling of electrostatic induction and ion conduction opens a wider range of applications for the hydrogel ionotronic TENGs,as the superstable electrical output enables them to be more widely applied in various complex environments to supply energy for low-power electronic devices.

Systematic review of laparoscopy-assisted versus open gastrectomy for advanced gastric cancer

Objective:The study compared laparoscopy-assisted gastrectomy(LAG) with open gastrectomy(OG) in the management of advanced gastric cancer(AGC).Methods:Literature search was performed in the Medline,Embase,and Cochrane Library databases to identify control studies that compared LAG and OG for AGC.A meta-analysis was conducted to examine the surgical safety and oncologic adequacy,using the random-effect model.Results:Seven eligible studies including 815 patients were analyzed.LAG was associated with less blood loss,less use of analgesics,shorter time of flatus and periods of hospital stay,but longer time of operation.The incidence of most complications was similar between the two groups.However,LAG was associated with a lower rate of pulmonary infection(odds ratio(OR) 0.19;95% confidence interval(CI) 0.05 to 0.68;P<0.05).No significant differences were noted in terms of the number of harvested lymph nodes(weighted mean difference(WMD) 1.165;95% CI-2.000 to 4.311;P>0.05),overall mortality(OR 0.65;95% CI 0.39 to 1.10;P>0.05),cancer-related mortality(OR 0.64;95% CI 0.32 to 1.25;P>0.05),or recurrence(OR 0.62;95% CI 0.33 to 1.16;P>0.05).Conclusions:LAG could be performed safely for AGC with adequate lymphadenectomy and has several short-term advantages compared with conventional OG.No differences were found in long-term outcomes.However,these results should be validated in large randomized controlled studies(RCTs) with sufficient follow-up.

Astrocytic GABA_B Receptors in Mouse Hippocampus Control Responses to Behavioral Challenges through Astrocytic BDNF

Major depressive disorder(MDD) is a common mood disorder that affects almost 20% of the global population.In addition,much evidence has implicated altered function of the gamma-aminobutyric acid(GABAergic) system in the pathophysiology of depression.Recent research has indicated that GABA_B receptors(GABA_BRs) are an emerging therapeutic target in the treatment of stress-related disorders such as MDD.However,which cell types with GABA_BRs are involved in this process is unknown.As hippocampal dysfunction is implicated in MDD,we knocked down GABA_BRs in the hippocampus and found that knocking down these receptors in astrocytes,but not in GABAergic or pyramidal neurons,caused a decrease in immobility in the forced swimming test(FST) without affecting other anxiety-and depression-related behaviors.We also generated astrocytespecific GABABR-knockout mice and found decreased immobility in the FST in these mice.Furthermore,the conditional knockout of GABA_BRs in astrocytes selectively increased the levels of brain-derived neurotrophic factor protein in hippocampal astrocytes,which controlled the decrease in immobility in the FST.Taken together,our findings contribute to the current understanding of which cell types expressing GABA_BRs modulate antidepressant activity in the FST,and they may provide new insights into the pathological mechanisms and potential targets for the treatment of depression.

Astrocyte-Derived Lactate Modulates the Passive Coping Response to Behavioral Challenge in Male Mice

Every organism inevitably experiences stress. In the face of acute, intense stress, for example, periods of passivity occur when an organism's actions fail to overcome the challenge. The occurrence of inactive behavior may indicate that struggling would most likely be fruitless.Repeated serious stress has been associated with mood disorders such as depression. The modulation of passive coping response patterns has been explored with a focus on the circuit level. However, the cellular and molecular mechanisms are largely uncharacterized. Here, we report that lactate is a key factor in the astrocytic modulation of the passive coping response to behavioral challenge in adult mice. We found increased extracellular lactate in the medial prefrontal cortex(mPFC) when mice experienced the forced swimming test(FST). Furthermore, we discovered that disturbing astrocytic glycogenolysis, which is a key step for lactate production in the mPFC, decreased the duration of immobility in the FST. Knocking down monocarboxylate transporter 4(MCT4), which is expressed exclusively in astrocytes and transports lactate from astrocytes to the extracellular space, caused similar results in the FST. The behavioral effect of both the pharmacological disturbance of astrocytic glycogenolysis and viral disruption of MCT4 expression was rescued via the administration of L-lactate. Moreover, we found that both pharmacological and viral modulation of astrocytederived lactate in mPFC slices increased the excitability of layer V pyramidal neurons, and this enhancement was reversed by exogenous L-lactate administration. These results highlight astrocyte-derived lactate as a biological mechanism underlying the passive coping response to behavioral challenge and may provide new strategies to prevent mood disorders.

Prognostic significance of the hemoglobin A1c level in non-diabetic patients undergoing percutaneous coronary intervention: a meta-analysis

Background:The predictive value of hemoglobin A1c(HbA1c)levels in non-diabetic patients with myocardial infarction undergoing percutaneous coronary intervention(PCI)is still controversial.This study aimed to evaluate whether HbA1c levels were independently associated with adverse clinical outcomes in non-diabetic patients with coronary artery disease(CAD)who had undergone PCI by performing a meta-analysis of cohort studies.Methods:This meta-analysis included non-diabetic patients with CAD who had undergone PCI.A systematic search for publications listed in the PubMed,Embase,and Cochrane Library databases from commencement to December 2018 was conducted.Studies evaluating the adverse clinical outcomes according to abnormal HbA1c levels in non-diabetic patients diagnosed with CAD who had undergone PCI were eligible.The primary outcomes were long-term all-cause deaths and long-term major adverse cardiac events,and the secondary outcome was short-term all-cause deaths.The meta-analysis was conducted with RevMan 5.3 and Stata software 14.0.Odds ratios(ORs)were pooled using a random or fixed-effects model,depending on the heterogeneity of the included studies.Sub-group analysis or sensitivity analysis was conducted to explore potential sources of heterogeneity,when necessary.Results:Six prospective cohort studies involving 10,721 patients met the inclusion criteria.From the pooled analysis,abnormal HbA1c levels were associated with increased risk for long-term all-cause death(OR 1.39,95%confidence interval[CI]1.16-1.68,P=0.001,I2=45%).Sub-group analysis suggested that abnormal HbA1c levels between 6.0%and 6.5%predicted higher long-term major adverse cardiac event(including all-cause deaths,non-fatal myocardial infarction,target lesion revascularization,target vessel revascularization,recurrent acute myocardial infarction,heart failure requiring hospitalization,and stent thrombosis)risk(OR 2.05,95%CI 1.46-2.87,P<0.001,I2=0).Contrarily,elevated HbA1c levels were not associated with increased risk of short-term all-cause death(OR 1.16,95%CI 0.88-1.54,P=0.300,I2=0).Conclusions:An abnormal HbA1c level is an independent risk factor for long-term adverse clinical events in non-diabetic patients with CAD after PCI.Strict control of HbA1c levels may improve patient survival.Further studies in different countries and prospective cohort studies with a large sample size are required to verify the association.

HER-2高表达与结直肠癌生存期关系的meta分析(英文)

研究目的:探讨人类表皮生长因子受体2(HER-2)的高表达与结直肠癌患者术后生存期的关系。创新要点:采用meta分析的方法,精确地探讨HER-2高表达与结直肠癌患者生存期的关系,解决不同研究产生不同结论的矛盾。研究方法:系统收集近20年来所有与HER-2表达和结直肠癌生存期关系相关文献,提取数据并计算与癌症或总体生存时间对应的危险比及其95%可信区间。重要结论:HER-2高表达可能与结直肠癌患者术后生存时间无关(见图2)。

The ATP Level in the mPFC Mediates the Antidepressant Effect of Calorie Restriction

Food deprivation can rescue obesity and overweight-induced mood disorders,and promote mood performance in normal subjects.Animal studies and clinical research have revealed the antidepressant-like effect of calorie restriction,but little is known about the mechanism of calorie restriction-induced mood modification.Previous studies have found that astrocytes modulate depressive-like behaviors.Inositol 1,4,5-trisphosphate receptor type 2(IP3R2)is the predominant isoform in mediating astrocyte Ca2+signals and its genetic knockout mice are widely used to study astrocyte function in vivo.In this study,we showed that deletion of IP3R2 blocked the antidepressant-like effect induced by calorie restriction.In vivo microdialysis experiments demonstrated that calorie restriction induced an increase in ATP level in the medial prefrontal cortex(mPFC)in naïve mice but this effect disappeared in IP3R2-knockout mice,suggesting a role of astrocytic ATP in the calorie restriction-induced antidepressant effect.Further experiments showed that systemic administration and local infusion of ATP into the mPFC induced an antidepressant effect,whereas decreasing ATP by Apyrase in the mPFC blocked calorie restriction-induced antidepressant regulation.Together,these findings support a role for astrocytic ATP in the antidepressant–like effect caused by calorie restriction.

Chimera states in Gaussian coupled map lattices

We study chimera states in one-dimensional and two-dimensional Gaussian coupled map lattices through simulations and experiments. Similar to the case of global coupling oscillators, individual lattices can be regarded as being controlled by a common mean field. A space-dependent order pa- rameter is derived from a self-consistency condition in order to represent the collective state.