Protein phosphatase 2A deficiency in hippocampal CA1 inhibits priming effect of morphine on conditioned place preference in mice.

Studies have shown that protein phosphorylation plays an important role in morphine abuse. However, the neurobiological mechanism of protein phosphatase 2A (PP2A) underlying the morphine-priming process is still unclear. Here we constructed T29-2-Cre; PP2Afl/fl conditional knockout mice (KO) and investigated the role of hippocampal PP2A in morphine priming. We observed that the deficit of PP2A inhibited the priming behavior of morphine and blocked the priming-induced long-term potentiation (LTP) in the hippocampus of KO mice. Moreover, the expression levels of Rack1 and the membrane GluN2B were significantly reduced in the nucleus accumbens of KO mice compared with those in the control mice, which may be attributed to the decreased HDAC4 in the hippocampus of KO mice. Consistent with it, the similar inhibited priming effects were also observed in the wild-type mice treated with sodium butyrate (NaB)-a nonspecific inhibitor of histone deacetylases-3 h after morphine administration. Taken together, our results suggest that hippocampal PP2A may be involved in morphine priming through the PP2A/HDAC4/Rack1 pathway.

PDK1 Regulates the Maintenance of Cell Body and the Development of Dendrites of Purkinje Cells by pS6 and PKCγ.

3-Phosphoinositide-dependent protein kinase-1 (PDK1) plays a critical role in the development of mammalian brain. Here, we investigated the role of PDK1 in Purkinje cells (PCs) by generating the PDK1-conditional knock-out mice (cKO) through crossing PV-cre or Pcp2-cre mice with Pdk1fl/fl mice. The male mice were used in the behavioral testing, and the other experiments were performed on mice of both sexes. These PDK1-cKO mice displayed decreased cerebellar size and impaired motor balance and coordination. By the electrophysiological recording, we observed the reduced spontaneous firing of PCs from the cerebellar slices of the PDK1-cKO mice. Moreover, the cell body size of PCs in the PDK1-cKO mice was time dependently reduced compared with that in the control mice. And the morphologic complexity of PCs was also decreased after PDK1 deletion. These effects may have contributed to the reduction of the rpS6 (reduced ribosomal protein S6) phosphorylation and the PKCγ expression in PDK1-cKO mice since the upregulation of pS6 by treatment of 3-benzyl-5-((2-nitrophenoxy) methyl)-dihydrofuran-2(3H)-1, the agonist of mTOR1, partly rescued the reduction in the cell body size of the PCs, and the delivery of recombinant adeno-associated virus-PKCγ through cerebellar injection rescued the reduced complexity of the dendritic arbor in PDK1-cKO mice. Together, our data suggest that PDK1, by regulating rpS6 phosphorylation and PKCγ expression, controls the cell body maintenance and the dendritic development in PCs and is critical for cerebellar motor coordination.SIGNIFICANCE STATEMENT Here, we show the role of 3-phosphoinositide-dependent protein kinase-1 (PDK1) in Purkinje cells (PCs). The ablation of PDK1 in PCs resulted in a reduction of cell body size, and dendritic complexity and abnormal spontaneous firing, which attributes to the motor defects in PDK1-conditional knock-out (cKO) mice. Moreover, the ribosomal protein S6 (rpS6) phosphorylation and the expression of PKCγ are downregulated after the ablation of PDK1. Additionally, upregulation of rpS6 phosphorylation by3-benzyl-5-((2-nitrophenoxy) methyl)-dihydrofuran-2(3H)-1 partly rescued the reduction in cell body size of PCs, and the overexpression of PKCγ in PDK1-KO PCs rescued the reduction in the dendritic complexity. These findings indicate that PDK1 contributes to the maintenance of the cell body and the dendritic development of PCs by regulating rpS6 phosphorylation and PKCγ expression.

PDK1 Deficit Impairs the Development of the Dentate Gyrus in Mice.

3-Phosphoinositide-dependent protein kinase-1 (PDK1) is crucial for the development of the dentate gyrus (DG), the first gateway receiving afferent inputs from the entorhinal cortex. However, the role of PDK1 in DG development is unclear. In the present study, by crossing Pdk1fl/fl mice with the Emx1-cre line, we identified that the ablation of PDK1 disrupted the development of DG via decreasing the proliferation, and increasing the differentiation of dentate neural progenitor cells, downregulating AKT activity and upregulating GSK3ß signaling. Moreover, PDK1 deletion disrupted the distribution of Reelin+ cells and decreased the level of Reelin mRNA which may contribute to the defective migration of progenitor cells and the disrupted radial glial scaffolds. Furthermore, the inhibition of GSK3ß activity partially restored the decreased proliferation of primary neural stem cells in vitro. Taken together, our data indicated that the ablation of PDK1 affected the proliferation and differentiation of dentate neural progenitor cells in mice.

Hippocampal Wdr1 Deficit Impairs Learning and Memory by Perturbing F-actin Depolymerization in Mice.

WD repeat protein 1 (Wdr1), known as a cofactor of actin-depolymerizing factor (ADF)/cofilin, is conserved among eukaryotes, and it plays a critical role in the dynamic reorganization of the actin cytoskeleton. However, the function of Wdr1 in the central nervous system remains elusive. Using Wdr1 conditional knockout mice, we demonstrated that Wdr1 plays a significant role in regulating synaptic plasticity and memory. The knockout mice exhibited altered reversal spatial learning and fear responses. Moreover, the Wdr1 CKO mice showed significant abnormalities in spine morphology and synaptic function, including enhanced hippocampal long-term potentiation and impaired long-term depression. Furthermore, we observed that Wdr1 deficiency perturbed actin rearrangement through regulation of the ADF/cofilin activity. Taken together, these results indicate that Wdr1 in the hippocampal CA1 area plays a critical role in actin dynamics in associative learning and postsynaptic receptor availability.

Colorimetric determination of ascorbic acid using a polyallylamine-stabilized IrO2/graphene oxide nanozyme as a peroxidase mimic.

The authors describe a peroxidase-mimicking nanozyme composed of IrO2 and graphene oxide (GO). It was synthesized from monodisperse IrO2 nanoparticles with an average diameter of 1.7 ± 0.3 nm that were prepared by pulsed laser ablation in ethanol. The nanoparticles were then placed on polyallylamine-modified GO nanosheets through electrostatic interaction. The peroxidase-like activity of the resulting nanocomposites was evaluated by catalytic oxidation of 3,3',5,5'-tetramethylbenzidine in the presence of H2O2. Kinetic results demonstrated that the catalytic behavior of the nanocomposites follows Michaelis-Menten kinetics. Experiments performed with terephthalic acid and cytochrome C confirmed that the peroxidase-like activity originated from the electron transfer mechanism rather than from generation of hydroxy radicals. The peroxidase-like activity is inhibited in the presence of ascorbic acid (AA). Based on this property, a colorimetric assay was developed for the determination of AA by exploiting the peroxidase-like activity of IrO2/GO nanocomposites. The linear relationship between absorbance at 652 nm and the concentration of AA was acquired. The limit of detection for AA is 324 nM. Further applications of the method for AA detection in real samples were also successfully demonstrated. Graphical abstractSchematic of the preparation of polyallylamine (PAH)-stabilized IrO2/GO nanocomposites and the colorimetric detection of AA based on the peroxidase-like activity of IrO2/GO nanocomposites.

HLA-DQB1*03 and DRB1*07 alleles increase the risk of cervical cancer among Uighur and Han women in Xinjiang, China.

AIM: To explore the association between the determinant factors including HLA-DQB1*03, DRB1-*07, -*13 and high-risk HPV infection, the cervical squamous cell carcinoma (CSCC) pathogenesis among Chinese Uighur and Han population. MATERIALS & METHODS: HLA alleles were genotyped by PCR sequence-specific primers. RESULTS: HPV16 infection rate was significantly higher among the Uighurs and Hans with CSCC as compared with healthy controls, respectively. HLA-DQB1*03 significantly increased among Uighurs with CSCC, while HLA-DRB1*07 significantly increased among Hans with CSCC. Similar tendencies were observed for DQB1*03 with HPV16-positive Uighurs CSCC and DRB1*07 with HPV16-positive Hans CSCC. CONCLUSION: This study suggests that HLA-DQB1*03 and DRB1*07 alleles may influence the immune response to HPV16 infection and increase the risk of CSCC among the Uighurs and Hans in China.

Excellent peroxidase mimicking property of CuO/Pt nanocomposites and their application as an ascorbic acid sensor.

Due to low cost and high stability, the applications of inorganic nanomaterials as efficient alternatives to natural enzymes are drawing much attention. In this work, novel CuO/Pt nanocomposites with high peroxidase-like activity were designed and applied for the colorimetric detection of ascorbic acid (AA). The nanocomposites were prepared by decorating Pt NPs on the surface of CuO nanosheets, which displayed good uniformity and showed improved distribution and stability. The catalytic activity of the prepared CuO/Pt nanocomposites was tested against various chromogenic substrates in the presence of H2O2, which displayed efficient peroxidase-like activity and high catalytic stability against temperature. The catalytic mechanism of the CuO/Pt nanocomposites was investigated by hydroxyl radical detection. The peroxidase-like activity decreased significantly in the presence of AA. On the basis of the inhibition property, a colorimetric biosensor was constructed by using the CuO/Pt nanocomposites for the detection of AA. It showed a high selectivity against amino acids, carbohydrates and normal ions. Thus, this work provides new insights into the application of inorganic nanocomposite-based nanozymes in the biosensing field.

Synergistically enhanced photocatalytic and chemotherapeutic effects of aptamer-functionalized ZnO nanoparticles towards cancer cells.

Today cancer is one of the most life-threatening diseases in the world. The conventional cancer therapies, including surgery, chemo- and radiation therapies, have some disadvantages, such as limited efficiency and significant side effects. It is necessary to develop new therapeutic treatments. Herein, we integrated the targeted photocatalytic and chemotherapy in a multifunctional drug-delivery platform. The aptamer-functionalized ZnO nanoparticles (NPs) were successfully synthesized. The anti-cancer drug was loaded in the aptamer-ZnO NP system. In vitro cell cytotoxicity experiments showed that combined therapy had a higher rate of death of cancer cells compared to that of single photocatalytic or chemotherapy. Furthermore, aptamer-functionalization could greatly increase the accumulation of nanoparticles within cancer cells and lead to better therapeutic effects. The results suggest that aptamer-functionalized semiconductor nanoparticles may have potential in the development of targeted photocatalytic and chemotherapy against cancer.

Fluorescence light-up probe for parallel G-quadruplexes.

Putative G-quadruplex-forming sequences (PQS) are highly prevalent in human genome; however, the structures and functions of most PQSs in genome are poorly understood. Therefore, selective recognition of certain types of G-quadruplexes (G4s) is important for the study of G4s. A new light up fluorescent probe, BPBC composed of benzimidazole and carbazole moieties was designed and synthesized. BPBC possesses a crescent-shaped π-conjugated planar core that is slightly larger than the dimension of the G-quartet plane in G4s. This structure endows BPBC with excellent selectivity to parallel G4s. BPBC exhibits almost no fluorescence in the aqueous buffer condition, its fluorescence increases approximately 330-1800-fold in the presence of parallel G4s but only about 30-fold in the presence of single/double-stranded (ss/ds) DNA and 30-110-fold in the presence of antiparallel G4s. Binding studies indicate that the highly selective fluorescent response of BPBC arises from end-stack binding model to G-quartet.

Development of macrophage-associated genes prognostic signature predicts clinical outcome and immune infiltration for sepsis.

Sepsis is a major global health problem, causing a significant burden of disease and death worldwide. Risk stratification of sepsis patients, identification of severe patients and timely initiation of treatment can effectively improve the prognosis of sepsis patients. We procured gene expression datasets for sepsis (GSE54514, GSE65682, GSE95233) from the Gene Expression Omnibus and performed normalization to mitigate batch effects. Subsequently, we applied weighted gene co-expression network analysis to categorize genes into modules that exhibit correlation with macrophage activity. To pinpoint macrophage-associated genes (MAAGs), we executed differential expression analysis and single sample gene set enrichment analysis. We then established a prognostic model derived from four MAAGs that were significantly differentially expressed. Functional enrichment analysis and immune infiltration assessments were instrumental in deciphering the biological mechanisms involved. Furthermore, we employed principal component analysis and conducted survival outcome analyses to delineate molecular subgroups within sepsis. Four novel MAAGs-CD160, CX3CR1, DENND2D, and FAM43A-were validated and used to create a prognostic model. Subgroup classification revealed distinct molecular profiles and a correlation with 28-day survival outcomes. The MAAGs risk score was developed through univariate Cox, LASSO, and multivariate Cox analyses to predict patient prognosis. Validation of the risk score upheld its prognostic significance. Functional enrichment implicated ribonucleoprotein complex biogenesis, mitochondrial matrix, and transcription coregulator activity in sepsis, with an immune infiltration analysis indicating an association between MAAGs risk score and immune cell populations. The four MAAGs exhibited strong diagnostic capabilities for sepsis. The research successfully developed a MAAG-based prognostic model for sepsis, demonstrating that such genes can significantly stratify risk and reflect immune status. Although in-depth mechanistic studies are needed, these findings propose novel targets for therapy and provide a foundation for future precise clinical sepsis management.

Exosomes from Hypoxia-treated Mesenchymal Stem Cells: Promoting Neuroprotection in Ischemic Stroke Through miR-214-3p/PTEN Mechanism.

Stroke stands as the second leading cause of death globally, surpassed only by ischemic heart disease. It accounts for 9% of total worldwide deaths. Given the swiftly evolving landscape, medical professionals and researchers are devoting increased attention to identifying more effective and safer treatments. Recent years have witnessed a focus on exosomes derived from mesenchymal stem cells cultivated under hypoxic conditions, referred to as Hypo-Exo. These specialized exosomes contain an abundance of components that facilitate the restoration of ischemic tissue, surpassing the content found in normal exosomes. Despite advancements, the precise role of Hypo-Exo in cases of cerebral ischemia remains enigmatic. Therefore, this study was designed to shed light on the potential efficacy of Hypo-Exo in stroke treatment. Our investigations unveiled promising outcomes, as the administration of Hypo-Exo led to improved behavioral deficits and reduced infarct areas in mice affected by ischemic conditions. Notably, these positive effects were hindered when Hypo-Exo loaded with anti-miR-214-3p were introduced, implying that the neuroprotective attributes of Hypo-Exo are reliant on miR-214-3p. This conclusion was substantiated by the high levels of miR-214-3p detected within Hypo-Exo. Furthermore, our examination of the ischemic penumbra zone revealed a gradual and sustained escalation in PTEN expression, a phenomenon effectively countered by Hypo-Exo treatment. Collectively, our findings suggest the existence of a regulatory pathway centered on miR-214-3p within Hypo-Exo. This pathway exerts a downregulating influence on the PTEN/Akt signaling pathway, thereby contributing to the amelioration of neurological function subsequent to ischemia-reperfusion events.

Resveratrol improves learning and memory in normally aged mice through microRNA-CREB pathway.

Resveratrol (RSV) is a natural compound found in grapes and red wine. It has been well known for its beneficial effects as a dietary supplement in prevention of cardiovascular diseases and cancer. Recently, in vitro studies have reported the neuroprotective role of RSV in neurodegenerative process in Alzheimer's disease (AD). However, in vivo effects of RSV on the decline of brain function accompanying the aging process, especially those on cognitive loss, have not been not investigated. Here we report that, after intraventricular injection of RSV for one week in 8-9 month-old mice, the long-term memory formation and the LTP induction from hippocampus CA1 were improved. The RSV enhancement effects were blocked in SIRT1 mutant mice. Additional experiments suggest that RSV effects are likely to be mediated through reduced expressions of miR-134 and miR-124, which may in turn up-regulate CREB levels to subsequently promote BDNF synthesis. These findings demonstrate a role for RSV in cognition and a microRNA-CREB-BDNF mechanism by which RSV regulates these processes, demonstrating its value as a potential therapeutic target against CNS disorders in aging.

Distribution characteristics of non-point source pollution of TP and identification of key source areas in Nanyi Lake (China) Basin: based on InVEST model and source list method.

The Nanyi Lake basin, located in the middle and lower reaches of the Yangtze River, is a crucial component of the Yangtze River ecosystem. Excessive phosphorus levels lead to eutrophication in rivers and lakes. This study aims to enhance the identification efficiency of key source areas for non-point source pollution of total phosphorus (TP) in the Nanyi Lake Basin and improve decision-making regarding the treatment of these areas. The study employs the InVEST model and utilizes GIS spatial hot spot analysis to identify key source areas of agricultural TP non-point source pollution. The accuracy of the InVEST model's simulation results was verified using the source list method. The findings indicate that paddy fields serve as the primary pollution source. TP non-point source pollution in Nanyi Lake is influenced by pollution sources, pollution load filtration rate, and potential TP runoff mass concentration. Different pollution sources correspond to distinct key source areas, and the pollution generated by these sources in different administrative regions, ultimately affecting the lake, varies as well. The InVEST model demonstrates great applicability in regions where agricultural TP is the primary pollution source. For the Nanyi Lake basin, which predominantly experiences agricultural TP non-point source pollution, a combination of the InVEST model and the source list method is recommended. The InVEST model serves as the primary tool, while the source list method supplements it. This approach not only compensates for any limitations of the InVEST model's simulation results but also avoids unnecessary economic waste. The outcomes of this study contribute to a deeper scientific understanding of TP pollution in the Nanyi Lake Basin. They also aid in effectively identifying key source areas and formulating appropriate measures based on the pollution characteristics, thereby providing guidance for non-point source pollution control in the basin.

The role of molecular subtypes and immune infiltration characteristics based on disulfidptosis-associated genes in lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is the most common type of lung cancer which accounts for about 40% of all lung cancers. Early detection, risk stratification and treatment are important for improving outcomes for LUAD. Recent studies have found that abnormal accumulation of cystine and other disulfide occurs in the cell under glucose starvation, which induces disulfide stress and increases the content of disulfide bond in actin cytoskeleton, resulting in cell death, which is defined as disulfidptosis. Because the study of disulfidptosis is in its infancy, its role in disease progression is still unclear. In this study, we detected the expression and mutation of disulfidptosis genes in LUAD using a public database. Clustering analysis based on disulfidptosis gene was performed and differential genes of disulfidptosis subtype were analyzed. 7 differential genes of disulfidptosis subtype were used to construct a prognostic risk model, and the causes of prognostic differences were investigated by immune-infiltration analysis, immune checkpoint analysis, and drug sensitivity analysis. qPCR was used to verify the expression of 7 key genes in lung cancer cell line (A549) and normal bronchial epithelial cell line (BEAS-2B). Since G6PD had the highest risk factor of lung cancer, we further verified the protein expression of G6PD in lung cancer cells by western blot, and confirmed through colony formation experiment that interference with G6PD was able to significantly inhibit the proliferation ability of lung cancer cells. Our results provide evidence for the role of disulfidptosis in LUAD and provide new ideas for individualized precision therapy of LUAD.

The deficiency of Maged1 attenuates Parkinson's disease progression in mice.

Melanoma-associated antigen D1 (Maged1) has critical functions in the central nervous system in both developmental and adult stages. Loss of Maged1 in mice has been linked to depression, cognitive disorder, and drug addiction. However, the role of Maged1 in Parkinson's disease (PD) remains unclear. In this study, we observed that Maged1 was expressed in the dopaminergic (DA) neurons of the substantia nigra in mice and humans, which could be upregulated by the in vivo or in vitro treatment with 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or 1-Methyl-4-phenylpyridinium iodide (MPP+). Genetic ablation of Maged1 in mice attenuated motor deficits, the loss of DA neurons, and disease progression induced by MPTP. Moreover, Maged1 deficiency protected DA neurons against MPP+-induced toxicity in primary cultured cells. Mechanistically, loss of Maged1 upregulated the Akt signaling pathway and downregulated the mTOR signaling pathway in SH-SY5Y cells, which may in turn attenuate the cell apoptosis and impairment of autophagy. Consistent with it, the degeneration of midbrain and striatum among elderly Maged1 knockout mice was relatively mild compared to those in wild-type mice under physiological conditions. Taken together, this study suggested that Maged1 deficiency inhibited apoptosis and enhanced autophagy, which may provide a new potential target for the therapy of PD.

Functional-group specific aptamers indirectly recognizing compounds with alkyl amino group.

Aptamers are usually generated against a specific molecule. Their high selectivity makes them only suitable for studying specific targets. Since it is nearly impossible to generate aptamers for every molecule, it can be of great interest to select aptamers recognizing a common feature of a group of molecules in many applications. In this paper, we describe the selection of aptamers for indirect recognition of alkyl amino groups. Because amino groups are small and positive charged, we introduced a protection group, p-nitrobenzene sulfonyl (p-nosyl) to convert them into a form suitable for aptamer selection. Taking N(ε)-p-nosyl-L-lysine (PSL) as a target, we obtained a group of aptamers using the SELEX technique. Two optimized aptamers, M6b-M14 and M13a exhibit strong affinity to PSL with the K(d) values in the range of 2-5 µM. They also show strong affinity to other compounds containing p-nosyl-protected amino groups except those also possessing an α-carboxyl group. Both aptamers adopt an antiparallel G-quadruplex structure when binding to targets. An aptamer beacon based on M6b-M14 showed good selectivity toward the reaction mixture of p-nosyl-Cl and alkyl amino compounds, and could recognize lysine from amino acid mixtures indirectly, suggesting that aptamers against a common moiety of a certain type of molecules can potentially lead to many new applications. Through this study, we have demonstrated the ability to select aptamers for a specific part of an organic compound, and the chemical conversion approach may prove to be valuable for aptamer selection against molecules that are generally difficult for SELEX.

Specific interactions between adenosine and streptavidin/avidin.

The screening of ligands against proteins plays important role in drug discovery and biological research. Using a dye labelled Streptavidin binding aptamer (SBA) as a competitive reporter probe, we found that adenosine bound to streptavidin specifically. Fluorescence spectral analysis showed that adenosine bound to both avidin and streptavidin with the K(ds) in the range of 0.1-0.2 mM, and these bindings can be blocked by biotin. Although streptavidin and avidin are well-known and widely used in bioanalysis, their biological role is still a riddle so far. Since adenosine is a ubiquitous physiological regulator present in cells, our finding provides new clues for the understanding of the functions of both proteins.

Valproic acid enhances neurosphere formation in cultured rat embryonic cortical cells through TGFß1 signaling.

This study aimed to investigate the effect and mechanism of valproic acid (VPA) on the neurosphere formation in rat embryonic cortical cells. We used free-floating neurosphere formation as a model system to evaluate the VPA on the proliferation of neural stem cells (NSCs). We found a time- and dose-dependent increase in neurosphere formation and NSC proliferation after VPA treatment. Further RNA-seq analysis demonstrated that the upregulated TGFß1 signaling might attribute to the effect of VPA on the neurosphere formation and NSC proliferation. Consistently, the neurosphere formation and NSC proliferation were blocked by the treatment with SB431542, an inhibitor of TGFß1 receptor. Moreover, in a coculture system, NSCs treated with VPA significantly reduced the oxygen-glucose deprivation-induced neuronal apoptosis. Taken together, our results showed that VPA could enhance neurosphere formation and NSC proliferation by activating TGFß1, which might be a novel therapeutic strategy for neurological disorders.

Interleukin-1ß inhibits voltage-gated sodium currents in a time- and dose-dependent manner in cortical neurons.

Interleukin-1ß (IL-1ß) is a multifunctional proinflammatory cytokine that plays a key role in the injuries and diseases of the central nervous system (CNS). A voltage-gated Na(+) channel is essential for the excitability and electrical properties of neurons. However, it is not known whether IL-1ß directly affects the central Na(+) channels. In the present study, we examined the effects of IL-1ß on Na(+) currents in cultured cortical neurons using patch-clamp recording. Our results showed that IL-1ß suppressed Na(+) currents through its receptor in a time- and dose-dependent manner, but did not alter the voltage-dependent activation and inactivation. PKC and then p38 MAPK were involved in this inhibition. The spike amplitude was also inhibited by IL-1ß in the doses that decreased the Na(+) currents. Our findings revealed the inhibition of chronic IL-1ß treatment on voltage-gated Na(+) channels in the CNS, and showed that the action potential (AP) amplitude was reduced by IL-1ß due to a decrease of Na(+) currents.

Laparoscopic versus open appendectomy for acute appendicitis: a metaanalysis.

BACKGROUND: Currently, laparoscopic appendectomy (LA) provides a safe and effective alternative to open appendectomy (OA), but its use remains controversial. This study aimed to evaluate the efficiency and safety of LA through a metaanalysis. METHODS: Randomized controlled trials (RCTs) comparing LA and OA published between January 1992 and February 2010 were included in this study. Strict literature appraisal and data extraction were carried out independently by two reviewers. A metaanalysis then was performed to evaluate operative time, hospital cost, postoperative complications, length of analgesia, bowel function recovery, day liquid diet began, hospital stay, and return to work and normal activity. RESULTS: The metaanalysis comprised 25 RCTs involving 4,694 patients (2,220 LA and 2,474 OA cases). No significant differences were found between the LA and OA groups in terms of age, gender, body mass index (BMI), or type of appendiceal inflammation. Compared with OA, LA showed advantages of fewer postoperative complications (odds ratio [OR], 0.74; 95% confidence interval [CI], 0.55-0.98; p = 0.04), less pain (length of analgesia: weighted mean difference [WMD], -0.53; 95% CI, -0.91 to -0.15; p = 0.007), earlier start of liquid diet (WMD, -0.51; 95% CI, -0.75 to -0.28; p < 0.0001), shorter hospital stay (WMD, -0.68; 95% CI, -1.02 to -0.35; p < 0.0001), and earlier return to work (WMD, -3.09; 95% CI, -5.22 to -0.97; p = 0.004) and normal activity (WMD, -4.73; 95% CI, -6.54 to -2.92; p < 0.00001), but a comparable hospital cost (WMD of LA/OA ratio, 0.11; 95% CI, -0.18 to 0.40; p = 0.47) and a longer operative time (WMD, 10.71; 95% CI, 6.76-14.66; p < 0.00001). CONCLUSION: Despite the longer operative time, LA results in less postoperative pain, faster postoperative rehabilitation, a shorter hospital stay, and fewer postoperative complications than OA. Therefore, LA is worth recommending as an effective and safe procedure for acute appendicitis.