RIPK1 inhibition contributes to lysosomal membrane stabilization in ischemic astrocytes via a lysosomal Hsp70.1B-dependent mechanism.

Receptor-interacting protein kinase 1 (RIPK1) contributes to necroptosis. Our previous study showed that pharmacological or genetic inhibition of RIPK1 protects against ischemic stroke-induced astrocyte injury. In this study, we investigated the molecular mechanisms underlying RIPK1-mediated astrocyte injury in vitro and in vivo. Primary cultured astrocytes were transfected with lentiviruses and then subjected to oxygen and glucose deprivation (OGD). In a rat model of permanent middle cerebral artery occlusion (pMCAO), lentiviruses carrying shRNA targeting RIPK1 or shRNA targeting heat shock protein 70.1B (Hsp70.1B) were injected into the lateral ventricles 5 days before pMCAO was established. We showed that RIPK1 knockdown protected against OGD-induced astrocyte damage, blocked the OGD-mediated increase in lysosomal membrane permeability in astrocytes, and inhibited the pMCAO-induced increase in astrocyte lysosome numbers in the ischemic cerebral cortex; these results suggested that RIPK1 contributed to the lysosomal injury in ischemic astrocytes. We revealed that RIPK1 knockdown upregulated the protein levels of Hsp70.1B and increased the colocalization of Lamp1 and Hsp70.1B in ischemic astrocytes. Hsp70.1B knockdown exacerbated pMCAO-induced brain injury, decreased lysosomal membrane integrity and blocked the protective effects of the RIPK1-specific inhibitor necrostatin-1 on lysosomal membranes. On the other hand, RIPK1 knockdown further exacerbated the pMCAO- or OGD-induced decreases in the levels of Hsp90 and the binding of Hsp90 to heat shock transcription factor-1 (Hsf1) in the cytoplasm, and RIPK1 knockdown promoted the nuclear translocation of Hsf1 in ischemic astrocytes, resulting in increased Hsp70.1B mRNA expression. These results suggest that inhibition of RIPK1 protects ischemic astrocytes by stabilizing lysosomal membranes via the upregulation of lysosomal Hsp70.1B; the mechanism underlying these effects involves decreased Hsp90 protein levels, increased Hsf1 nuclear translocation and increased Hsp70.1B mRNA expression.

SARS-CoV-2 BA.2 (Omicron) variant infection in pediatric liver transplanted recipients and cohabitants during 2022 Shanghai outbreak: a prospective cohort.

BACKGROUND: The Omicron variant BA.2 was the dominant variant in the COVID-19 outbreak in Shanghai since March 2022. We aim to investigate the characteristics of SARS-CoV-2 Omicron variant infection in pediatric liver-transplanted recipients. METHODS: We conducted a single-center, prospective, observational, single-arm study. We enrolled pediatric liver-transplanted patients infected with the Omicron variant BA.2 from March 19th to October 1st, 2022 and analyzed their demographic, clinical, laboratory, and outcome data. The management of COVID-19 was conducted according to the 9th trial edition of the Chinese guideline. The immunosuppressive therapy was tailored considering the patients' infection developments and liver functions. RESULTS: Five children were included. The primary diseases included Niemann-Pick disease, propionic acidemia, decompensated cirrhosis, biliary atresia, and Crigler-Najjar syndrome type I. All of the patients were onset with fever before or when getting RNA-positive results at the age of 3 (Range: 1-13) years. The infection duration was 29 (Range: 18-40) days. Three and two children were diagnosed with mild and moderate COVID-19 respectively. Two patients were tested RNA-positive within 14 days after having been tested negative. The immunosuppressants were paused or extenuated in four patients. Eight of all nine cohabitants were injected with at least two doses of inactivated SARS-CoV-2 vaccine. The disease courses were significantly longer than the patients (P < 0.05). CONCLUSIONS: Post-transplant immunosuppression slows down the virus clearance and increases the risk of relapse but does not affect symptom duration or infection severity in pediatric patients. Patients can usually gain a favorable outcome and prognosis by extenuating immunosuppressants.

Pure laparoscopic versus open left lateral hepatectomy in pediatric living donor liver transplantation: a review and meta-analysis.

PURPOSE: The meta-analysis was conducted to evaluate the safety and feasibility of pure laparoscopic left lateral hepatectomy in comparison with open approach for pediatric living donor liver transplantation (LDLT). METHODS: A systemic literature survey was performed by searching the PubMed, EMBASE and Cochrane Library databases for articles that compared pure laparoscopic left lateral living donor hepatectomy (LLDH) and open left lateral living donor hepatectomy (OLDH) by November 2021. Meta-analysis was performed to assess donors' and recipients' perioperative outcomes using RevMan 5.3 software. RESULTS: A total of five studies involving 432 patients were included in the analysis. The results demonstrated that LLDH group had significantly less blood loss (WMD = -99.28 ml, 95%CI -152.68 to -45.88, p = 0.0003) and shorter length of hospital stay (WMD = -2.71d, 95%CI -3.78 to -1.64, p < 0.00001) compared with OLDH group. A reduced donor overall postoperative complication rate was observed in the LLDH group (OR = 0.29, 95%CI 0.13-0.64, p = 0.002). In the subgroup analysis, donor bile leakage, wound infection and pulmonary complications were similar between two groups (bile leakage: OR = 1.31, 95%CI 0.43-4.02, p = 0.63; wound infection: OR = 0.38, 95%CI 0.10-1.41, p = 0.15; pulmonary complications: OR = 0.24, 95%CI 0.04-1.41, p = 0.11). For recipients, there were no significant difference in perioperative outcomes between the LLDH and OLDH group, including mortality, overall complications, hepatic artery thrombosis, portal vein and biliary complications. CONCLUSION: LLDH is a safe and effective alternative to OLDH for pediatric LDLT, reducing invasiveness and benefiting postoperative recovery. Future large-scale multi-center studies are expected to confirm the advantages of LLDH in pediatric LDLT.

Design, Synthesis, Insecticidal Activities and Molecular Docking of Sulfonamide Derivatives Containing Propargyloxy or Pyridine Groups.

The discovery of new highly active molecules from natural products is a common method to create new pesticides. Celangulin V targeting Mythimna separate (M. separate) midgut V-ATPase  H subunit, has received considerable attention for its excellent insecticidal activity and unique mechanism of action. Therefore, combined with our preliminary work, thirty-seven sulfonamide derivatives bearing propargyloxy or pyridine groups were systematically synthesized to search for insecticidal candidate compounds with low cost and high efficiency on the  H subunit of V-ATPase. Bioactive results showed that compounds A2-A4 and A6-A7 exhibited a better bioactivity with median effective concentration (LC50 ) values (2.78, 3.11, 3.34, 3.54 and 2.48 mg/mL, respectively) against third-instar larvae of M. separate than Celangulin V (LC50 =18.1 mg/mL). Additionally, molecular docking experiments indicated that these molecules may act on the H subunit of V-ATPase. Based on the above results, these compounds provide new ideas for the discovery of insecticides.

Design, synthesis and insecticidal activity of benzenesulfonamide derivatives containing various alkynyl, alkenyl and cyclopropyl groups in para position.

Celangulin V is a natural ß-dihydrofuran sesquiterpene polyester with anti Mythimna separate activity and unique mechanism of action. Further study showed that its target was the H subunit of V-ATPase in the midgut of M. separate. Thus, combined with the previous work, thirty-two benzene sulfonamide derivatives were systematically synthesised to discover efficient and low-budget insecticidal candidates for the H subunit of V-ATPase. Screening results showed that compounds C2, C4, C5, C6 and C8 could significantly cause death of tested third-instar larvae of M. separate, and provided the corresponding LC50 values of 0.844, 0.953, 0.705, 0.599 and 0.887 mg/mL, which were extremely better than Celangulin V (LC50 = 11.5 mg/mL). The docking results indicated that this novel framework might target H subunit of V-ATPase. Given these excellent bioactivity results, this kind of sulfonamide framework could provide a suitable point for exploring highly efficient insecticidal agents.

Design, Synthesis, and Biological Profiles of Novel 1,3,4-Oxadiazole-2-carbohydrazides with Molecular Diversity.

To unceasingly expand the molecular diversity of 1,3,4-oxadiazole-2-carbohydrazides, herein, small fragments (including -CH2-, -OCH2-, and -SCH2-) were incorporated into the target compounds to screen out the potential succinate dehydrogenase inhibitors (SDHIs). The bioassay results showed that the antifungal effects (expressed by EC50) against Sclerotinia sclerotiorum, Botryosphaeria dothidea, Fusarium oxysporum, and Colletotrichun higginsianum could reach 1.29 (10a), 0.63 (8h), 1.50 (10i), and 2.09 (10i) µg/mL, respectively, which were slightly lower than those of carbendazim (EC50 were 0.69, 0.13, 0.55, and 0.80 µg/mL, respectively). Especially, compound 10h was extremely bioactive against Gibberella zeae (G. z.) with an EC50 value of 0.45 µg/mL. This outcome was better than that of fluopyram (3.76 µg/mL) and was similar to prochloraz (0.47 µg/mL). In vivo trials against the corn scab (infected by G. z.) showed that compound 10h had control activity of 86.8% at 200 µg/mL, which was better than that of boscalid (79.6%). Further investigations found that compound 10h could inhibit the enzymatic activity of SDH in the G. z. strain with an IC50 value of 3.67 µM, indicating that potential SDHIs might be developed. Additionally, the other biological activities of these molecules were screened simultaneously. The anti-oomycete activity toward Phytophthora infestans afforded a minimal EC50 value of 3.22 µg/mL (10h); compound 4d could strongly suppress the growth of bacterial strains Xanthomonas axonopodis pv. citri and Xanthomonas oryzae pv. oryzae with EC50 values of 3.79 and 11.4 µg/mL, respectively; and compound 10a displayed some insecticidal activity toward Plutella xylostella. Given their multipurpose features, these frameworks could be actively studied as potential pesticide leads.

Computed tomography-guided chemical renal sympathetic nerve modulation in the treatment of resistant hypertension: A case report.

BACKGROUND: Resistant hypertension (RH) has always been a difficult problem in clinical diagnosis and treatment. At present, there is no recognized safe and effective minimally invasive treatment. CASE SUMMARY: An 80-year-old woman was admitted to hospital due to trigeminal neuralgia (TN). The patient had a history of RH for more than 10 years and her blood pressure (BP) was not well-controlled. Before the treatment for TN, we decided to perform chemical renal sympathetic denervation with ethanol in the Pain Department of our hospital. One year after the operation, she stopped taking antihypertensive drugs, and her BP was satisfactorily controlled within 4 years after surgery. CONCLUSION: Computed tomography-guided chemical renal sympathetic modulation may be a feasible method for the treatment of RH.

Fabrication of Versatile Pyrazole Hydrazide Derivatives Bearing a 1,3,4-Oxadiazole Core as Multipurpose Agricultural Chemicals against Plant Fungal, Oomycete, and Bacterial Diseases.

Developing multipurpose agricultural chemicals is appealing in crop protection, thus eventually realizing the reduction and efficient usage of pesticides. Herein, an array of versatile pyrazole hydrazide derivatives bearing a 1,3,4-oxadiazole core were initially synthesized and biologically evaluated the antifungal, antioomycetes, and antibacterial activities. In addition, the pyrazole ring was replaced by the correlative pyrrole, thiazole, and indole scaffolds to extend the molecular diversity. The results showed that most of these hybrid compounds were empowered with multifunctional bioactivities, which are exemplified by compounds a1-a6, b1-b3, b7, b10, b13, and b18. For the antifungal activity, the minimal EC50 values could afford 0.47 (a2), 1.05 (a2), 0.65 (a1), and 1.32 µg/mL (b3) against the corresponding fungi Gibberella zeae (G. z.), Fusarium oxysporum, Botryosphaeria dothidea, and Rhizoctonia solani. In vivo pot experiments against corn scab (caused by G. z.) revealed that the compound a2 was effective with protective and curative activities of 90.2 and 86.3% at 200 µg/mL, which was comparable to those of fungicides boscalid and fluopyram. Further molecular docking study and enzymatic activity analysis (IC50 = 3.21 µM, a2) indicated that target compounds were promising succinate dehydrogenase inhibitors. Additionally, compounds b2 and a4 yielded superior anti-oomycete and antibacterial activities toward Phytophora infestins and Xanthomonas oryzae pv. oryzae with EC50 values of 2.92 and 8.43 µg/mL, respectively. In vivo trials against rice bacterial blight provided the control efficiency within 51.2-55.3% (a4) at 200 µg/mL, which were better than that of bismerthiazol. Given their multipurpose characteristics, these structures should be positively explored as agricultural chemicals.

Rational Optimization of 1,2,3-Triazole-Tailored Carbazoles As Prospective Antibacterial Alternatives with Significant In Vivo Control Efficiency and Unique Mode of Action.

Plant bacterial diseases can potentially damage agricultural products around the world, and few effective bactericides can manage these infections. Herein, to sequentially explore highly effective antibacterial alternatives, 1,2,3-triazole-tailored carbazoles were rationally fabricated. These compounds could suppress the growth of three main intractable pathogens including Xanthomonas oryzae pv oryzae (Xoo), X. axonopodis pv citri (Xac), and Pseudomonas syringae pv actinidiae (Psa) with lower EC50 values of 3.36 (3p), 2.87 (3p), and 4.57 µg/mL (3r), respectively. Pot experiments revealed that compound 3p could control the rice bacterial blight with protective and curative efficiencies of 53.23% and 50.78% at 200 µg/mL, respectively. Interestingly, the addition of 0.1% auxiliaries such as organic silicon and orange oil could significantly enhance the surface wettability of compound 3p toward rice leaves, resulting in improved control effectiveness of 65.50% and 61.38%, respectively. Meanwhile, compound 3r could clearly reduce the white pyogenic exudates triggered by Psa infection and afforded excellent control efficiencies of 79.42% (protective activity) and 78.74% (curative activity) at 200 µg/mL, which were quite better than those of commercial pesticide thiodiazole copper. Additionally, a plausible apoptosis mechanism for the antibacterial behavior of target compounds was proposed by flow cytometry, reactive oxygen species detection, and defensive enzyme (e.g., catalase and superoxide dismutase) activity assays. The current work can promote the development of 1,2,3-triazole-tailored carbazoles as prospective antibacterial alternatives bearing an intriguing mode of action.

Study on effects of co-solvents on the structure of DhaA by molecular dynamics simulation.

With the increasing application of enzymes in various research fields, the choices of co-solvents in enzymatic preparations which directly related to the catalytic activity have been attracted attention. Thus, researching on the stabilization or destabilization behaviors of enzymes in different solvents is extremely essential. In this study, the structural changes of DhaA in two typical aprotic co-solvents (acetonitrile and tetrahydrofuran) were firstly investigated by molecular dynamics (MD) simulation. The simulation results revealed the strong van der Waals force between co-solvents and DhaA which could induce the structural change of enzyme. Interestingly, the differences of molecular size and the electrostatic force with enzyme of two co-solvents led to quite different influences on DhaA. As for acetonitrile, solvent molecules could penetrate into the catalytic site of DhaA which promoted by the electrostatic interaction. On the contrary, tetrahydrofuran molecules were mainly distributed around the catalytic site due to the relative weak electrostatic interaction and steric resistance effect. It can be concluded that different co-solvent can affect the key domains, substrate pathway and catalytic pocket of DhaA.Communicated by Ramaswamy H. Sarma.

Production technology, nutritional, and microbiological investigation of traditionally fermented mare milk (Chigee) from Xilin Gol in China.

Mare milk originated from female horses, known as mares, to feed their foals during lactation. The health-promoting characteristics of traditionally fermented mare milk (Chigee) are well known for the function of clinic treatment in the traditional Mongolian medicine. This study was conducted to investigate the production technology of Chigee and to evaluate the nutritional and microbiological characteristics of mare milk and Chigee based on 188 samples. The nutritional analysis of mare milk and Chigee indicated that lactose significantly decreased from 6.95 ± 0.45% to 2.82 ± 1.65% and acidity and alcoholic content significantly increased to 136.72 ± 57.88°T and 1.22 ± 0.7%, respectively, after spontaneous fermentation of mare milk. The microbiological analysis of Chigee showed that the total lactic acid bacteria (LAB) count varied from 5.32 to 8.56 log cfu/ml and total yeast count varied from 2.41 to 6.98 log cfu/ml. Moreover, the acidity of Chigee rose with the increase in LAB count within limits, and high acidity (≥178°T) inhibited the growth of coliforms. These findings provide an understanding of traditional production technology, nutrition, and microbiology that is fundamental for establishing the food standard of Chigee in China and will contribute to standardize the fermentation process for the industrial production of Chigee in the future.

SAP102 contributes to hyperalgesia formation in the cancer induced bone pain rat model by anchoring NMDA receptors.

The pathogenesis of cancer induced bone pain (CIBP) is extremely complex, and glutamate receptor dysfunction plays an important role in the formation of CIBP. Synapse-associated protein 102 (SAP102) anchors glutamate receptors in the postsynaptic membrane. However, its effect on hyperalgesia formation in CIBP has not been clarified. This study investigated the role of SAP102 in the formation of hyperalgesia in rats with CIBP SAP102 is present in spinal dorsal horn neurons, but not in astrocytes or microglia. NMDAR-NR2B is localized with neurons. In addition, SAP102 and NMDAR-NR2B expression levels in spinal dorsal horn tissues were detected by Western blot and co-immunoprecipitation. Intrathecal injection of lentiviral vector of RNAi to knockdown SAP102 expression in the spinal dorsal horn significantly attenuated abnormal mechanic pain when compared to non-coding lentiviral vector. These findings indicate that SAP102 can anchor NMDA receptors to affect hyperalgesia formation in bone cancer pain.

Novel 1,3,4-Oxadiazole-2-carbohydrazides as Prospective Agricultural Antifungal Agents Potentially Targeting Succinate Dehydrogenase.

A novel simple 1,3,4-oxadiazole-2-carbohydrazide was reported to discover low-cost and versatile antifungal agents. Bioassay results suggested that a majority of the designed compounds were extremely bioactive against four types of fungi and two kinds of oomycetes. This extreme bioactivity was highlighted by the applausive inhibitory effects of compounds 4b, 4h, 5c, 5g, 5h, 5i, 5m, 5p, 5t, and 5v against Gibberella zeae, affording EC50 values ranging from 0.486 to 0.799 µg/mL, which were superior to that of fluopyram (2.96 µg/mL) and comparable to those of carbendazim (0.947 µg/mL) and prochloraz (0.570 µg/mL). Meanwhile, compounds 4g, 5f, 5i, and 5t showed significant actions against Fusarium oxysporum with EC50 values of 0.652, 0.706, 0.813, and 0.925 µg/mL, respectively. Pharmacophore exploration suggested that the N'-phenyl-1,3,4-oxadiazole-2-carbohydrazide pattern is necessary for the bioactivity. Molecular docking of 5h with succinate dehydrogenase (SDH) indicated that it can completely locate the inside of the binding pocket via hydrogen-bonding and hydrophobic interactions, revealing that this novel framework might target SDH. This result was further verified by the significant inhibitory effect on SDH activity. In addition, scanning electron microscopy patterns were performed to elucidate the anti-G. zeae mechanism. Given these features, this type of framework is a suitable template for future exploration of alternative SDH inhibitors against plant microbial infections.

Investigation of physicochemical composition and microbial communities in traditionally fermented vrum from Inner Mongolia.

Mongolian traditionally fermented vrum is known for its functional characteristics, and indigenous microbial flora plays a critical role in its natural fermentation. However, studies of traditionally fermented vrum are still rare. In this study, we investigated the artisanal production of traditionally fermented vrum from Inner Mongolia. In general, its physicochemical composition was characterized by 34.5 ± 8% moisture, 44.9 ± 12.1% fat, 10.6 ± 3.2% protein, and 210 ± 102°T. The total lactic acid bacteria and yeast counts ranged from 50 to 2.8 × 108 cfu/g and from 0 to 1.1 × 106 cfu/g, respectively. We studied bacterial and fungal community structures in 9 fermented vrum; we identified 5 bacterial phyla represented by 11 genera (an average relative abundance >1%) and 8 species (>1%), and 3 fungal phyla represented by 8 genera (>1%) and 8 species (>1%). Relative abundance values showed that Lactococcus and Lactobacillus were the most common bacterial genera, and Dipodascus was the predominant fungal genus. This scientific investigation of the nutritional components, microbial counts, and community profiles in Mongolian traditionally fermented vrum could help to develop future functional biomaterials and probiotics.

[Effect of cultivation substrate on growth and active component contents of Anoectochilus roburghii from three different origins].

Three different origins of Anoectochilus roburghii were used as experimental materials to study the effect of three different substrate( peat soil-river sand-peanut shell) radio on survival rate,plant height,stem diameter,plant fresh weight,root number,the longest root length,root diameter,and the contents of polysaccharide,flavonoids,and polyphenol. The results showed that when the substrate ratio was 4 ∶2 ∶2,the survival rate of A. roburghii from different origins was the highest,and the plant height,stem diameter,plant fresh weight,the longest root length and root diameter were also the largest. The cultivation substrate had no significant effect on the polysaccharide content of A. roxburghii and A. formosanus. When the substrate ratio was 4 ∶ 2 ∶ 2,the polysaccharide content of A.chapaensis was significantly lower than that of the other two combinations. When the substrate ratio was 4 ∶2 ∶1,the flavonoid content of A. formosanus was higher than that of the other two combinations. When the substrate ratio was 4 ∶2 ∶2,A. formosanus and A. chapaensis had higher polyphenol content.

Study of bacterial and fungal community structures in traditional koumiss from Inner Mongolia.

Koumiss is notable for its nutritional functions, and microorganisms in koumiss determine its versatility. In this study, the bacterial and fungal community structures in traditional koumiss from Inner Mongolia, China, were investigated. Our results demonstrated that 6 bacterial phyla represented by 126 genera and 49 species and 3 fungal phyla represented by 59 genera and 57 species were detected in 11 samples of artisanal koumiss. Among them, Lactobacillus was the predominant genus of bacterium, and Kluyveromyces and Saccharomyces dominated at the fungal genus level. In addition, there were no differences in the bacterial and fungal richness and diversity of koumiss from 3 neighboring administrative divisions in Inner Mongolia, and the bacterial and fungal community structures (the varieties and relative abundance of bacterial and fungal genera and species) were clearly distinct in individual samples. This study provides a comprehensive understanding of the bacterial and fungal population profiles and the predominant genus and species, which would be beneficial for screening, isolation, and culture of potential probiotics to simulate traditional fermentation of koumiss for industrial and standardized production in the future.

Four-Subtest Index-based Short Form of WAIS-IV: Psychometric Properties and Clinical Utility.

Short form of the Wechsler Adult Intelligence Scale is often needed to quickly estimate intelligence for time-saving or screening in clinical practice. The present study aims to examine the psychometric properties of Chinese version of the four-subtest index-based short form (SF4) of WAIS-IV (FS) and to confirm its clinical application. 1,757 adults from the WAIS-IV Chinese version standardization sample and 239 mixed clinical samples including patients with schizophrenia or schizoaffective disorder (SCH), obsessive-compulsive disorder (OCD), and mild or moderate intellectual disability (ID) were used. Demographic data were collected and intelligence was assessed with WAIS-IV. The SF4 split-half reliability, test-retest stability coefficients and corrected SF4-FS correlations were good to excellent. The result of the Bland-Altman plot showed that the difference fell within 2SD was 95% and indicated a random error. The sensitivity, specificity positive predictive value (PPV), and negative predictive value (NPV) of the stepwise screening were good. There was an interaction (p < .001) between the IQ level (≥111) and gender on the accuracy of SF4, SF4 might get underestimated on females with the IQ level (≥111) than on males. In conclusion, SF4 is a valid and reliable instrument for use in the clinic, and its clinical application, stepwise screening and influencing factors in clinical use are discussed herein.

Blood Lactate or Lactate Clearance: Which Is Robust to Predict the Neurological Outcomes after Cardiac Arrest? A Systematic Review and Meta-Analysis.

AIMS: Lactate and lactate clearance were supposed to be associated with cardiac arrest outcomes, but studies obtained different results. Thus, we conducted this meta-analysis to investigate the association between lactate or lactate clearance and neurological outcomes and their usefulness for prediction of neurological outcomes. METHODS: We conducted a systematic search in PubMed, Web of science, EMBASE, Medline, and Google Scholar until May 1, 2018, for relevant studies. Studies reporting lactate, lactate clearance on admission, or other time points after admission associated with neurological outcomes were included in our analysis. Pooled effect date was shown as weighed mean difference (WMD) and 95% confidence interval (CI). To measure the usefulness of lactate on admission to predict neurological outcomes, we also pooled the data of diagnostic test. RESULTS: 23 studies involving 6720 cardiac arrest (CA) patients were included. Results from our analysis indicated that patients with good neurological outcomes tended to have a lower lactate level on admission (WMD: -2.66 mmol/L, 95%CI: -3.39 to -1.93) and 12h, 24h, and 48h after admission (P<0.001). Furthermore, the pooled AUC for lactate level on admission to predict neurological outcomes was 0.77 (95%CI: 0.73-0.80). However, a significant association between lactate clearance and neurological outcomes was only found in 24h but not 12h lactate clearance rate. CONCLUSIONS: Lactate levels on admission and all time points up to 48h were associated with neurological outcomes after CA, whereas the association between lactate clearance and neurological outcomes was not so stable. Lactate was a more robust surrogate marker than lactate clearance to predict neurological outcomes after CA.

miR-124 inhibits progression of hepatocarcinoma by targeting KLF4 and promises a novel diagnostic marker.

Hepatocarcinoma is one of the most lethal malignancy haunting the Chinese population, which is partially due to the difficulties in diagnosis at an early stage. The search for a biomarker that could signify the presence and progress of hepatocarcinoma is never ended. MicroRNAs are 22-nt RNAs that could bind to 3' UTR of target mRNAs, mediating degradation of mRNAs or inhibiting the translation. Although much has been investigated, the role of miR-124 in hepatocarcinoma remained elusive. We first detected aberrant expression level of miR-124 in HCC tissues of 112 patients. By exploring the clinical parameters, we found a significantly inverse correlation between miR-124 level and TNM stages. Consistent with this, the survival analysis indicated the association of low miR-124 with longer survival time. Subsequent forced expression miR-124 resulted in reduced cell viability of Hep3B and SMMC-7221, which cell lines have high and low background expression of miR-124, respectively. TargetScan prediction rendered a subset of target candidates, which were selected for experimental validation, KLF4 was subject to luciferase assay. Ectopic expression of KLF4 increased the sphere formation ability and CD44/133-positive cell numbers, which can be reversed by abundant expression of miR-124, suggesting that KLF4 is a functional target of miR-124 in tumourigenesis and cancer progression of HCC.