Engeletin alleviates depression-like phenotype by increasing synaptic plasticity via the BDNF-TrkB-mTORC1 signalling pathway.

Major depressive disorder (MDD) is a severe mental disorder associated with high rates of morbidity and mortality. Current first-line pharmacotherapies for MDD are based on enhancement of monoaminergic neurotransmission, but these antidepressants are still insufficient and produce significant side-effects. Consequently, the development of novel antidepressants and therapeutic targets is desired. Engeletin, a natural Smilax glabra rhizomilax derivative, is a compound with proven efficacy in treating ischemic stroke, yet its therapeutic effects and mechanisms for depression remain unexplored. The effects of engeletin were assessed in the forced swimming test (FST) and tail suspension test (TST) in mice. Engeletin was also investigated in the chronic restraint stress (CRS) mouse model of depression with fluoxetine (FLX) as the positive control. Changes in prefrontal cortex (PFC) spine density, synaptic plasticity-linked protein expressions and the brain-derived neurotrophic factor (BDNF)-tyrosine kinase B (TrkB)- mammalian target of rapamycin complex 1 (mTORC1) signalling pathway after chronic stress and engeletin treatment were then investigated. The TrkB and mTORC1 selective inhibitors, ANA-12 and rapamycin, respectively, were utilized to assess the engeletin's antidepressive mechanisms. Our data shows that engeletin exhibited antidepressant-like activity in the FST and TST in mice without affecting locomotor activity. Furthermore, it exhibited efficiency against the depression of CRS model. Moreover, it enhanced the BDNF-TrkB-mTORC1 pathway in the PFC during CRS and altered the reduction in dendritic spine density and levels of synaptic plasticity-linked protein induced by CRS. In conclusion, engeletin has antidepressant activity via activation of the BDNF-TrkB-mTORC1 signalling pathway and upregulation of PFC synaptic plasticity.

Construction and validation of a prognostic model based on autophagy-related genes for hepatocellular carcinoma in the Asian population.

BACKGROUND AND OBJECTIVE: Hepatocellular carcinoma (HCC), which has a complex pathogenesis and poor prognosis, is one of the most common malignancies worldwide. Hepatitis virus B infection is the most common cause of HCC in Asian patients. Autophagy is the process of digestion and degradation, and studies have shown that autophagy-associated effects are closely related to the development of HCC. In this study, we aimed to construct a prognostic model based on autophagy-related genes (ARGs) for the Asian HCC population to provide new ideas for the clinical management of HCC in the Asian population. METHODS: The clinical information and transcriptome data of Asian patients with HCC were downloaded from The Cancer Genome Atlas (TCGA) database, and 206 ARGs were downloaded from the human autophagy database (HADB). We performed differential and Cox regression analyses to construct a risk score model. The accuracy of the model was validated by using the Kaplan-Meier (K-M) survival curve, receiver operating characteristic (ROC) curve, and univariate and multivariate Cox independent prognostic analyses. The results Thirteen ARGs that were significantly associated with prognosis were finally identified by univariate and multivariate Cox regression analyses. The K-M survival curves showed that the survival rate of the low-risk group was significantly higher than that of the high-risk group (p < 0.001), and the multi-indicator ROC curves further demonstrated the predictive ability of the model (AUC = 0.877). CONCLUSION: The risk score model based on ARGs was effective in predicting the prognosis of Asian patients with HCC.

Multi-omics analysis identifies rare variation in leptin/PPAR gene sets and hypermethylation of ABCG1 contribute to antipsychotics-induced metabolic syndromes.

Antipsychotic-induced metabolic syndrome (APs-induced Mets) is the most common adverse drug reaction, which affects more than 60% of the psychiatric patients. Although the etiology of APs-induced Mets has been extensively investigated, there is a lack of integrated analysis of the genetic and epigenetic factors. In this study, we performed genome-wide, whole-exome sequencing (WES) and epigenome-wide association studies in schizophrenia (SCZ) patients with or without APs-induced Mets to find the underlying mechanisms, followed by in vitro and in vivo functional validations. By population-based omics analysis, we revealed that rare functional variants across in the leptin and peroxisome proliferator-activated receptors (PPARs) gene sets were imbalanced with rare functional variants across the APs-induced Mets and Non-Mets cohort. Besides, we discovered that APs-induced Mets are hypermethylated in ABCG1 (chr21:43642166-43642366, adjusted P < 0.05) than Non-Mets, and hypermethylation of this area was associated with higher TC (total cholesterol) and TG (triglycerides) levels in HepG2 cells. Candidate genes from omics studies were furtherly screened in C. elegans and 17 gene have been verified to associated with olanzapine (OLA) induced fat deposit. Among them, several genes were expressed differentially in Mets cohort and APs-induced in vitro/in vivo models compared to controls, demonstrating the validity of omics study. Overexpression one of the most significant gene, PTPN11, exhibited compromised glucose responses and insulin resistance. Pharmacologic inhibition of PTPN11 protected HepG2 cell from APs-induced insulin resistance. These findings provide important insights into our understanding of the mechanism of the APs-induced Mets.

Altered microRNAs in C3H10T1/2 cells induced by p.E95K mutant IHH signaling.

BACKGROUND: Indian Hedgehog (IHH), an important cell signaling protein, plays a key regulatory role in development of cartilage and chondrogenesis. Earlier studies have shown that heterozygous missense mutations in IHH gene may cause brachydactyly type A1 (BDA1), an autosomal dominant inheritance disease characterized by apparent shortness or absence of the middle phalanges of all digits. MicroRNAs (miRNAs) have been found to be significant post-transcriptional regulators of gene expression and significantly influence the process of bone-development. Therefore, it is possible that miRNAs are involved in the mechanism underlying the development of BDA1. However, the relationship between miRNAs and the pathogenesis of BDA1 remains unclear. METHODS: In this study, we used microarray-based miRNA profiling to investigate the role of miRNAs in BDA1 by characterization of differentially expressed miRNAs in C3H10T1/2 cell line induced by wild type (WT) and p.E95K mutant (MT) IHH signaling. RESULTS: Our results identified 6 differentially expressed miRNAs between WT and control (CT) group and 5 differentially expressed miRNAs between MT and CT groups. In particular, miR-135a-1-3p was found to be a significantly differentially expressed miRNA between WT and CT group. Results of dual-luciferase reporter gene experiment successfully discovered Hoxd10 was one of the target gene of miR-135a-1-3p. Additionally, our pathway analysis revealed that the targets of these miRNAs of interest were highly involved with Runx1/2, Notch and collagen-related pathways. CONCLUSIONS: Taken together, our findings provided important clue for future study of the process of miRNA-regulation in IHH signaling and novel insights into the regulatory role of miRNA in pathogenesis of BDA1.

Cytochrome P450 Enzymes and Drug Metabolism in Humans.

Human cytochrome P450 (CYP) enzymes, as membrane-bound hemoproteins, play important roles in the detoxification of drugs, cellular metabolism, and homeostasis. In humans, almost 80% of oxidative metabolism and approximately 50% of the overall elimination of common clinical drugs can be attributed to one or more of the various CYPs, from the CYP families 1-3. In addition to the basic metabolic effects for elimination, CYPs are also capable of affecting drug responses by influencing drug action, safety, bioavailability, and drug resistance through metabolism, in both metabolic organs and local sites of action. Structures of CYPs have recently provided new insights into both understanding the mechanisms of drug metabolism and exploiting CYPs as drug targets. Genetic polymorphisms and epigenetic changes in CYP genes and environmental factors may be responsible for interethnic and interindividual variations in the therapeutic efficacy of drugs. In this review, we summarize and highlight the structural knowledge about CYPs and the major CYPs in drug metabolism. Additionally, genetic and epigenetic factors, as well as several intrinsic and extrinsic factors that contribute to interindividual variation in drug response are also reviewed, to reveal the multifarious and important roles of CYP-mediated metabolism and elimination in drug therapy.

Homology Modeling-Based in Silico Affinity Maturation Improves the Affinity of a Nanobody.

Affinity maturation and rational design have a raised importance in the application of nanobody (VHH), and its unique structure guaranteed these processes quickly done in vitro. An anti-CD47 nanobody, Nb02, was screened via a synthetic phage display library with 278 nM of KD value. In this study, a new strategy based on homology modeling and Rational Mutation Hotspots Design Protocol (RMHDP) was presented for building a fast and efficient platform for nanobody affinity maturation. A three-dimensional analytical structural model of Nb02 was constructed and then docked with the antigen, the CD47 extracellular domain (CD47ext). Mutants with high binding affinity are predicted by the scoring of nanobody-antigen complexes based on molecular dynamics trajectories and simulation. Ultimately, an improved mutant with an 87.4-fold affinity (3.2 nM) and 7.36 °C higher thermal stability was obtained. These findings might contribute to computational affinity maturation of nanobodies via homology modeling using the recent advancements in computational power. The add-in of aromatic residues which formed aromatic-aromatic interaction plays a pivotal role in affinity and thermostability improvement. In a word, the methods used in this study might provide a reference for rapid and efficient in vitro affinity maturation of nanobodies.

Phase behaviour and temperature-responsive properties of a gemini surfactant/Brij-30/water system.

The phase behaviour of a ternary system composed of cationic gemini surfactant 2-hydroxypropyl-1,3-bis(myristyldimethylammonium chloride) (14-3(OH)-14(2Cl)), nonionic surfactant polyoxyethylene laurel ether (C12H25(OCH2CH2)10OH, Brij-30) and H2O was studied and its phase diagram was determined. In several different phase regions identified in the phase diagram, the viscoelastic worm-like micellar solution region was investigated. The focus of the investigation was the increase in the viscosity of the micellar solution with the temperature and the Brij-30 content, as suggested by a partial region of the triangular phase diagram. With an increase in the Brij-30 content or temperature, one-dimensional micellar growth occurred, and a maximum appeared in the zero-shear viscosity, η0, versus Brij-30 content or temperature curves; this was true for mixed solutions containing 14-3(OH)-14(2Cl) and Brij-30 in different mass ratios (WBrij-30/W14-3(OH)-14(2Cl)). After the maximum point, the decrease in viscosity is the result of the micellar shortening in the size with Brij-30 content and of the micellar branching in the network structure with temperature. This rheological analysis was performed to investigate the structural changes in different solutions as well as the effects of various factors on micellar growth. Various techniques were used to study the phase-transition processes occurring in this system, including cryogenic transmission electron microscopy, small-angle X-ray scattering measurements, and differential scanning calorimetry. The transition mechanisms of the aggregates were analysed on the basis of the obtained results.

Efficacy and safety of gemcitabine plus raltitrexed or S-1 versus standard third-line therapies in metastatic colorectal cancer: a retrospective cohort study.

Background: After the failure of standard first- and second-line treatments, including oxaliplatin, irinotecan, and 5-fluorouracil (5-FU) combined with targeted drugs, the currently recommended third-line regimens for metastatic colorectal cancer (mCRC) include TAS-102, regorafenib, and fruquintinib. However, these regimens have the drawbacks of mediocre efficacy, substantive side effects, and high cost. Therefore, more effective, economical regimens with fewer side effects are needed in clinical practice. In this study, we assessed the efficacy and safety of gemcitabine plus raltitrexed or S-1 as a third- or later-line treatment in comparison to those of standard third-line therapies for patients with mCRC. Methods: Patients with previous failures of at least two lines of standard therapy with oxaliplatin, 5-FU, irinotecan, or capecitabine combined with targeted drugs were included. The participants received standard third-line therapies (including TAS-102, regorafenib, and fruquintinib) or gemcitabine plus raltitrexed or S-1 until disease progression, death, or intolerable toxicity arose. Imaging follow-up was performed every 3 months during their treatment. Progression-free survival (PFS) and overall survival (OS) were recorded. Cox regression analysis was used to investigate the potential predictors of survival. Results: From April 2018 to October 2022, 60 patients with mCRC were enrolled in our study. The numbers of patients in the chemotherapy, fruquintinib, regorafenib, and TAS-102 groups were 13, 15, 17, and 15, respectively; the median OS of the four groups was 7.4, 6.1, 8.3, and 6.7 months (P=0.384), respectively; the median PFS was 4.1, 3.4, 4.4, and 2.3 months (P=0.656), respectively; the overall response rate was 7.69%, 6.67%, 0.00%, and 13.33%, respectively; and the disease control rate was 61.54%, 60.00%, 70.59%, and 60.00%, respectively. Additionally, multivariate analysis revealed that primary lesion located in the rectum was adverse independent prognostic factors for OS. A typical case is presented in this article. Conclusions: The gemcitabine plus raltitrexed or S-1 regimen is a potential regimen with tolerable adverse reactions and low cost for patients with mCRC.

Molecular, biological characterization and drug sensitivity of chidamide-resistant MCF7 cells.

Background: Chidamide (CHI) is a subtype-selective histone deacetylase inhibitor (HDACI) developed in China and approved as a second-line treatment combined with the aromatase inhibitor for hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer. However, drug resistance is commonly occurred after a long period of medication. This study aimed to investigate the characterization of induced resistance to CHI and explore the potential cross-resistance to chemotherapeutic agents. Methods: CHI with gradually increasing concentrations was added to breast cancer MCF7 cells to establish a CHI-resistant MCF7 (MCF7-CHI-R) cell line. Cell counting kit-8 (CCK-8) assays were performed to detect half-maximal inhibitory concentration (IC50) of CHI. Colony formation was used to determine the proliferation inhibition rate. Western blot analysis was conducted to detect expressions of protein related with cell cycle, apoptosis, ferroptosis, and histone deacetylase (HDAC). Flow cytometry was used to analyze apoptosis and cell cycle. Results: The IC50 value of CHI of MCF7-CHI-R cells was increased in comparison with MCF7 cells. And CHI led to cell cycle arrest and ferroptosis, which were not exhibited in MCF7-CHI-R cells. Moreover, HDAC activity decreased in MCF7-CHI-R cells in comparison with MCF7 cells, and HDAC1 and HDAC10 might be involved in the resistance to CHI. In addition, MCF7-CHI-R cells were resistant to gemcitabine (GEM), doxorubicin (ADM), docetaxel (DXT), albumin-bound paclitaxel (nab-PTX) and paclitaxel (PTX). Conclusions: The MCF7-CHI-R was established and the anti-ferroptosis pathway activation was involved in the resistance of MCF-CHI-R cells. Also, MCF7-CHI-R cells were resistant to GEM, ADM, DXT, nab-PTX and PTX.

Changes in blood lactate levels after major elective abdominal surgery and the association with outcomes: a prospective observational study.

BACKGROUND: Prolonged elevated blood lactate levels strongly correlate with poor outcomes in a variety of critically ill patients. We hypothesized that the dynamic postoperative changes in blood lactate levels during the first 24 h were significantly associated with postoperative morbidity and mortality in patients undergoing elective major abdominal surgery. MATERIALS AND METHODS: We performed a single-center prospective observational study of 114 consecutive patients undergoing elective major abdominal surgery from September 2009 to December 2010. Blood lactate was determined postoperatively at 6 h intervals during the first 24 h. In-hospital complications and deaths occurring within 30 d of enrollment were included in the data analysis. RESULTS: A total of 88 postoperative complications were recorded in 51 patients (44.7%). There was a significant difference in blood lactate levels among patients with no, minor, and major complications (ANOVA, Groups, P < 0.001; time, P < 0.001; groups × time interaction, P = 0.014). The accuracy of lactate levels to predict both overall and major complications increased postoperatively from 0 h to 24 h. Using a multivariate analysis, the time-weighted average lactate was independently predictive of both overall (OR 7.108, 95% CI 2.271-22.249, P = 0.001) and major (OR 3.277, 95% CI 1.363-7.877, P = 0.008) postoperative complications, and lactate clearance at 0-24 h (OR 0.217, CI 0.077-0.616, P = 0.004) was independently predictive of major postoperative complications. The optimal time-weighted average lactate cutoff value for complication prediction was 1.46 mmol/L; below this level, both overall and major complication rates were significantly reduced, which was true even after adjusting for potential confounding factors. CONCLUSIONS: The dynamic changes in blood lactate levels during the first 24 postoperative h were significantly associated with complications after major elective abdominal surgery. This result warrants a "golden hour and silver day" perspective of early resuscitation in this patient cohort.

Establishment and verification of a prognostic risk score model based on immune genes for hepatocellular carcinoma in an Asian population.

Background: Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide, with the highest incidence in East Asia, and hepatitis B virus (HBV) infection is the most common cause of HCC in Asian population. The immune system is closely related to the development of HCC and plays an important role in the treatment of this disease. In this study, we analyzed the data of HCC from The Cancer Genome Atlas (TCGA) database and constructed a risk-score prognostic model based on immune genes of an Asian HCC population, aiming to provide new perspectives for clinical treatment and management of HCC in Asian population. Methods: Data concerning clinical attributes and transcriptomic profiles of individuals in the Asian population diagnosed with HCC were retrieved from the TCGA database. Concurrently, immune-related genes were sourced from the Immport database for incorporation into our analysis. A total of 265 immune-related genes displaying differential expression were identified through wilcoxTest analysis in R. Further refinement using univariate and multivariate Cox regression analysis led to the identification of 15 genes that exhibited strong associations with prognosis. MICB/PSMD14/TRAF3/SP1/NDRG1/HDAC1/HRAS/NRAS/SEMA5B/GMFB/ACVR2B/BRD8/MMP12/KITLG/DCK, and a prognostic risk score model was constructed based on the above genes. Results: The findings demonstrated notable differences in survival rates between the low-risk and high-risk groups, as depicted by the Kaplan-Meier (K-M) survival curves (P<0.001). Furthermore, the model's predictive capability was evidenced by receiver operating characteristic (ROC) curves, with area under the curve (AUC) =0.901. Finally, the relationship of the model with each clinical trait and immune cells was assessed by correlation analysis. Conclusions: The prognostic risk score model constructed by immune genes based on the Asian HCC population has certain predictive capacity.

Plasma metabolomics for the assessment of the progression of non-small cell lung cancer.

OBJECTIVES: Non-small cell lung cancer (NSCLC) is a leading type of lung cancer with a high mortality rate worldwide. Although many procedures for the diagnosis and prognosis assessment of lung cancer exist, they are often laborious, expensive, and invasive. This study aimed to develop an ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS)-based analysis method for the plasma biomarkers of NSCLC with the potential to indicate the stages and progression of this malignancy conveniently and reliably. METHODS: A total of 53 patients with NSCLC in early stages (I-III) and advanced stage (IV) were classified into the early and advanced groups based on the tumor node metastasis staging system. A comprehensive metabolomic analysis of plasma from patients with NSCLC was performed via UPLC-MS/MS. Principal component analysis and partial least squares-discriminant analysis were conducted for statistical analysis. Potential biomarkers were evaluated and screened through receiver operating characteristic analyses and correlation analysis. Main differential metabolic pathways were also identified by utilizing metaboanalyst. RESULTS: A total of 129 differential metabolites were detected in accordance with the criteria of VIP ≥ 1 and a P-value of ≤ 0.05. The receiver operating characteristic curves indicated that 11 of these metabolites have the potential to be promising markers of disease progression. Apparent correlated metabolites were also filtered out. Furthermore, the 11 most predominant metabolic pathways with alterations involved in NSCLC were identified. CONCLUSION: Our study focused on the plasma metabolomic changes in patients with NSCLC. These changes may be used for the prediction of the stage and progression of NSCLC. Moreover, we discussed the metabolic pathways wherein the altered metabolites were mainly enriched.

Anatomical Laparoscopic Orchiopexy and Hybrid Transscrotal Orchiopexy for High Inguinal Undescended Testis: A Novel and Interfascial Technique.

Background: In traditional laparoscopic orchiopexy for inguinal undescended testis (UDT) surgery, the testicles are pulled back into the abdominal cavity by grasping and cephalad retracting the testicle and the cord. If this fails, a subsequent open inguinal incision is made to complete orchiopexy. To improve the orchiolysis and avoid extra open inguinal incision, we describe our early experience with and illustrate the surgical procedure of a novel anatomical laparoscopic orchiopexy (ALO) and hybrid transscrotal orchiopexy as required in high palpable UDT. Methods: From March 2018 to April 2020, ALO was performed in 140 consecutive patients (158 testes) with high inguinal UDT. After blunt and bloodless dissection of the inter-tunica vaginalis-cremasteric fascia plane, tunica vaginalis enveloping the testis was brought into the abdominal cavity as a whole. When the tunica vaginalis was unable to be brought into the abdominal cavity, given that the orchiolysis had already been partially carried out, the testis could be brought out of the external ring and descended when converting to transscrotal surgery. Results: The mean age in this study was 1.88 years (standard deviation ±1.95). The position of the testis assessed at surgery was peeping (58, 36.7%) and canalicular (100, 63.3%). In 128 testes (81.1%), ALO brought the UDT into the abdominal cavity; the remaining 30 testes (18.9%) required a hybrid transscrotal technique. All testes were descended without conversion to open inguinal procedure. The mean operative time was 43.9 ± 9.2 minutes. All patients had follow-up within a median of 17.8 months, with satisfactory results in relation to viability and location of the testis. Conclusions: ALO was shown to be not only safe, feasible, and effective for high inguinal UDT but also facilitated subsequent hybrid transscrotal orchiopexy; when the testis failed to be pulled into the abdominal cavity, the conversion to open inguinal orchiopexy could be obviated.

Protective effects of Radix Codonopsis on ischemia-reperfusion injury in rats after kidney transplantation.

PURPOSE: Kidney ischemia-reperfusion injury (IRI) after kidney transplant remains a major problem, separate from immune rejection that can lead to kidney transplant failure and graft function loss. Free radicals, disturbance of microcirculation and the inflammatory cascade appear to be the main contributors. Radix Codonopsis, a traditional Chinese drug used in vascular diseases, is an antioxidant and free radical scavenger. This study investigates the protective effect and underlying mechanisms of Radix Codonopsis extract saponins on kidney transplantation. METHODS: Renal transplantation was performed after rat kidneys had been stored for 1 h at 4°C. Blood urea nitrogen (BUN), serum creatinine (Scr), superoxide dismutase (SOD) and malondialdehyde (MDA) were assayed; bcl-2 and bax mRNA expression was detected using RT-PCR; bcl-2 and bax protein expression was detected by immunohistochemistry (IHC). Terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) was used to detect apoptotic cells and determine the apoptosis index (AI). Analysis of variance (ANOVA) followed by Dunnett's test was used when more than two groups were compared. RESULTS: Saponin-treated animals showed increased SOD levels accompanied by decreased MDA, Scr and BUN levels (p < 0.05 vs. untreated controls); bcl-2 mRNA and protein levels were increased in transplanted kidney from treated animals, while bax mRNA and protein levels were decreased (p < 0.05 vs. untreated controls). AI was significantly decreased in transplanted kidneys from treated animals relative to untreated controls (p < 0.05 vs. untreated controls). CONCLUSION: This study clearly demonstrates the protective effects on IRI after kidney transplantation, which may be explained by decreased lipid peroxidation and inhibition of apoptosis.

[Value of microalbuminuria in fluid balance after abdominal surgery].

OBJECTIVE: To evaluate the relationship among the microalbuminuria, surgical stress and postoperative fluid balance after abdominal surgery. METHODS: A total of 191 patients undergoing an elective abdominal operation were studied. According to the extent of operative trauma, all patients were divided into 4 groups. GroupI: laparoscopic cholecystectomy (n=64); Group II: laparotomy of cholecyst and biliary tract (n=36); Group III: radical surgery of colorectal cancer (n=43); Group IV: distal subtotal gastrectomy (D2) or total gastectomy (D3) or pancreaticoduodenectomy (n=48). The operative severities were predicated by surgical stress score (SSS). Urine albumin-creatinine ratio (ACR) was measured at both pre- and post-operation. The levels of ACR were compared by ANOVA among these 4 groups. The correlation of ACR and SSS was analyzed. In Groups III and IV, body weight was measured by weight-bed simultaneously. The correlation of variation of ACR at 0 and 6 hours post-operation (ΔACR) and the volume of positive fluid balance in the first 24 hour post-operation were studied. We also compared the varied durations of ACR levels returning to normal or the pre-operative level and body weight reaching peak values. RESULTS: The levels of ACR increased in all groups. The level of ACR was the highest in Group IV and the lowest in Group I, significantly different from the levels of group II and III. There was a significant positive correlation between the increase in ACR and the severity of surgical trauma as measured by SSS. A positive correlation was observed between the volume of positive fluid balance in the first 24 hour post-operation and ΔACR at 0 and 6 hours post-operation. The varied duration of ACR levels returning normal or the pre-operative level was earlier than that of reaching the peak values. CONCLUSION: ACR has a positive correlation with the extent of surgical stress and volume of positive fluid balance. The fact that the ACR comes earlier than the change of body weight indicates that the change of ACR is a more sensitive and simpler parameter than body weight to predict the onset of negative fluid balance.

[Application of B type natriuretic peptide in fluid therapy after major abdominal operations].

OBJECTIVE: To evaluate the values of serum level of B type natriuretic peptide level (BNP) in the prediction of fluid overloading after major abdominal operations. METHODS: The levels of BNP were dynamically monitored in 105 patients during peri-operative period from February 2009 to November 2010. Then comparisons were made with age and the volume of positive fluid balance. RESULTS: A post-operative elevation of BNP was observed in all cases. Among them, the peak level of BNP exceeded 100 ng/L in 32 patients while a normal peak level of BNP was found in 73 patients. Congestive heart failure (CHF) was diagnosed in 5 patients. At every single time point, the volume of positive fluid balance showed no significant difference among the peak level of BNP < 100 ng/L, ≥ 100 ng/L and CHF patients (all P > 0.05). In the group of peak level of BNP ≥ 100 ng/L, the patients received post-operative diuretic and the urine volume increased significantly [(280 ± 55) ml/h vs (82 ± 22) ml/h, P < 0.05]. However, in the group of the peak level of BNP < 100 ng/L, the urine volume showed no difference after dosing of diuretic [(95 ± 18) ml/h vs (89 ± 24) ml/h, P > 0.05]. Single variance analysis showed that the elevated level of BNP was associated with age and concurrent cardiopulmonary diseases (R = 0.87, P = 0.006) but not with the volume of positive fluid balance (R = 0.43, P = 0.080). And multiple variance analysis showed the similar results (R = 0.59, P = 0.020, R = 0.38, P = 0.120). In all cases, the levels of BNP peaked at 12 hours post-operation. However, body weight and the volume of positive fluid balance peaked at 18 - 24 hours post-operation. CONCLUSION: The post-operative level of BNP is associated with age. And a highly elevated level of BNP may predict the occurrence of fluid overloading. An early peak of BNP value may be used as a cut-off point of positive and negative fluid balances.

[The study of hypertonic saline and hydroxyethyl starch treating severe sepsis].

OBJECTIVE: To evaluate the effect of 7.5% hypertonic saline (HS) and 6% hydroxyethyl starch (HES) 130/0.4 on early fluid resuscitation for severe sepsis. METHODS: Prospective randomized control trial was carried out in intensive care unit (ICU) of the Affiliated Hospital of Jianghan University. One hundred and thirty five patients with severe sepsis were randomly divided into three groups, each group consisted of 45 patients. Patients in HS+HES group received lactated Ringer solution following 4 ml/kg of 7.5% HS and 6% HES 130/0.4 500 ml, those in HES group received lactated Ringer solution following 6% HES 130/0.4 500 ml, and those in the lactated Ringer group (RL group) received lactated Ringer solution only.Mean arterial pressure (MAP), oxygenation index (PaO2/FiO2),arterial lactate (Lac),lactate clearance rate, acute physiology and chronic health evaluation II(APACHEII) score,fluid infusion volume, urine output as well as incidence of multiple organ dysfunction syndrome (MODS), and mortality were compared among three groups at 6 hours and 24 hours after ICU admission. RESULTS: At 6 hours after ICU admission,MAP[mm Hg (1 mm Hg=0.133 kPa): 68.7 ± 3.0], PaO2/FiO2(mm Hg: 262.2 ± 17.4), lactate clearance rate [(21 ± 4)%] in HS+HES group were significantly higher than those in HES group [MAP: 63.8 ± 3.5,PaO(2)/FiO(2): 252.0 ± 21.2, lactate clearance rate: (11 ± 2)%] and RL group [MAP: 62.6 ± 3.6, PaO2/FiO2:248.4 ± 17.0,lactate clearance rate: (9 ± 1)%, all P <0.01]. Arterial Lac in HS+HES group (mmol/L: 3.5 ± 0.7) was significantly lower than that in HES group (4.1 ± 0.7) and RL group (4.0 ± 0.7, both P <0.01). There was no significant difference in APACHE II score between HS+HES group (13.2 ± 1.9) and HES group (14.0 ± 1.6), and the APACHEII score in HS+HES group was significantly lower than that in RL group (15.2 ± 1.7, P <0.01). At 24 hours after ICU admission, PaO2/FiO2 (mm Hg: 303.3 ± 17.3) was significantly higher in HS+HES group than that in HES group (282.9 ± 21.1) and RL group (268.9 ± 15.2, both P <0.01). There was no significant difference in MAP, arterial Lac, lactate clearance rate and APACHEII score among three groups. At 6 hours and 24 hours after ICU admission, fluid infusion volume in HS+HES group (ml, 6 hours: 1 877.8 ± 215.2, 24 hours: 5 475.6 ± 208.8) was markedly less than that in HES group (6 hours: 2 505.6 ± 276.2, 24 hours: 6 383.3 ± 287.4) and RL group (6 hours: 3 496.7 ± 325.5,24 hours: 7 439.6 ± 229.6), yet urine output in HS+HES group (ml, 6 hours: 294.2 ± 36.9, 24 hours : 2 793.8 ± 37.1) was significantly higher than that in HES group (6 hours: 248.9 ± 25.3, 24 hours : 2 248.9 ± 25.3) and RL group (6 hours: 178.9 ± 14.8, 24 hours: 2 000.4 ± 147.0, all P <0.01). The incidence of MODS in HS+HES group (6.7%) was statistically lower than that in RL group (28.9%, P <0.05), while no obvious difference was found between HS+HES group and HES group (17.8%, P >0.05). There was no significant difference in mortality among three groups (HS+HES group: 2.2%, HES group: 4.4%, RL group: 8.9%, all P >0.05). CONCLUSION: 7.5%HS and 6%HES 130/0.4 could improve the effect of early fluid resuscitation on severe sepsis, and it could lower the incidence of MODS.

Prognostic value of platelet-to-lymphocyte ratio in neoadjuvant chemotherapy for solid tumors: A PRISMA-compliant meta-analysis.

INTRODUCTION: Previous research indicates that the platelet-to-lymphocyte ratio (PLR) may be an indicator of poor prognosis in many tumor types. However, the PLR is rarely described in patients undergoing neoadjuvant chemotherapy (NAC) for solid tumors. Thus, we performed a meta-analysis to investigate the prognostic value of this ratio for patients with solid tumors treated by NAC. METHODS: A comprehensive search of the literature was conducted using the PubMed, EMBASE, Cochrane Library, and Web of Science databases, followed by a manual search of references from the retrieved articles. Pooled hazard ratios (HRs) with 95% confidence interval (CIs) were used to evaluate the association between PLR and 3 outcomes, namely, overall survival, disease-free survival, and pathological complete response rate after NAC. RESULTS: Eighteen studies published no earlier than 2014 were included in our study. A lower PLR was associated with better overall survival (HR = 1.46, 95% CI, 1.11-1.92) and favorable disease-free survival (HR = 1.81, 95% CI, 1.27-2.59). A PLR that was higher than a certain cutoff was associated with a lower pathological complete response rate in patients with cancer who received NAC (Odds ratio = 1.93, 95% CI, 1.40-2.87). CONCLUSION: Elevated PLR is associated with poor prognosis in various solid tumors. PLR may be a useful biomarker in delineating those patients with poorer prognoses who may benefit from neoadjuvant therapies.

Edge/Defect-Rich, Metallic, and Oxygen-Heteroatom-Doped WS2 Superstructure with Superior Electrocatalytic Performance for Green Solar Energy Conversion.

Two-dimensional tungsten sulfide is widely applied in electrocatalysis. However, WS2 possesses catalytic active sites located at the layer edge and an inert surface for catalysis. Therefore, increasing the exposure of active sites at the edge and effectively activating the inert sites on the surface is an important challenge. Here, an edge/defect-rich and oxygen-heteroatom-doped WS2 (ED-O-WS2 ) superstructure was synthesized. The power-conversion efficiency (PCE) of dye-sensitized solar cells (DSCs) based on an ED-O-WS2 counter electrode reached 10.36 % (under 1 sun, AM 1.5, 100 mW cm-2 ) and 11.19 % (under 40 mW cm-2 ). These values are, to our knowledge, the highest reported efficiency for DSCs based on Pt-free counter electrodes in I3 - /I- electrolytes. Analysis of the micro/nano structure and the electrocatalytic mechanism indicate that ED-O-WS2 exhibits metallic properties in the electrolyte, and that abundant edges and defects as well as oxygen doping in ED-O-WS2 play an important role in improving the catalytic activity of WS2 . Moreover, ED-O-WS2 displays better catalytic reversibility for I3 - /I- electrolytes than Pt.

[Initial serum lactate level as predictor of morbidity after major abdominal surgery].

OBJECTIVE: To evaluate the value of immediate postoperative arterial lactate level to predict morbidity after major abdominal surgery. METHODS: 139 patients, 73 males and 66 females, aged (64 +/- 14) (26 - 87), who underwent major abdominal surgery had their levels of arterial lactate, blood routine, blood gas and electrolytes measured after they were sent to the ICU. The physiological and operative severity score for the enumeration of mortality and morbidity (POSSUM) and the simplified acute physiology score II (SAPSII) levels in the first 24-hour postoperative period were calculated Multivariate logistic regression analysis was utilized to examine the independent relationship of the initial lactate, blood gas values, and anion gap with the morbidity. RESULTS: Sixty-one cases of postoperative complications were recorded in the 47 patients (34%). The median initial lactate level of the patients with postoperative complications was 1.7 mmol/L, significantly higher than that of the patients without complication (1.2 mmol/L, P = 0.001). Multivariate analysis showed that lactate level (odds ratio: 1.81, 95% confidence interval: 1.14 - 2.89; P = 0.013) and Simplified Acute Physiology Score II (SAPSII (odds ratio:1.14; 95% confidence interval:1.08-1.21, P < 0.001) were significantly predictive of postoperative morbidity. The optimal value of lactate to discriminate between the patients who did or did not develop postoperative complications was 2.7 mmol/L as associated with the highest sum of sensitivity and specificity (29.8% and 95.7% respectively). The lactate level more than 2.7 mmol/L was associated with 9.3-fold-higher odds for postoperative complications (95% confidence interval: 2.9 - 30.4, P < 0.001). After adjustment for SAPII, the lactate level > 2.7 mmol/L remained strongly associated with morbidity (odds ratio: 5.9; 95% confidence interval: 1.6 - 21.7; P = 0.007). CONCLUSION: Initial serum lactate level is significantly associated with postoperative complications and can independently predict in-hospital morbidity after major abdominal surgery. When hyperlactatemia means the presence of oxygen debt, strategies to resuscitate patients during surgery should include reversing ongoing tissue hypoxia by increasing oxygen delivery.