The prognostic role of platelet-to-lymphocyte ratio on overall survival in gastric cancer: a systematic review and meta-analysis.

BACKGROUND: This study aimed to summarize the previously published literature on the role of platelet-to-lymphocyte ratio (PLR) on overall survival (OS) in patients with gastric cancer. METHODS: We systematically searched PubMed, EmBase, and the Cochrane library to identify eligible studies to review. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using the random-effects model. Sensitivity and subgroup analyses were performed, and publication bias was assessed. RESULTS: A total of 28 studies comprising 15,617 patients with gastric cancer were included in this meta-analysis. The pooled results indicated that elevated PLR was associated with poor OS (HR: 1.37; 95% CI: 1.24-1.51; P < 0.001). A significant publication bias was observed (Egger test, P = 0.036; Begg test, P = 0.017). After adjusting for publication bias using the trim and fill method, an adjusted pooled HR of 1.19 (95% CI: 1.08-1.33; P = 0.001) was observed. Subgroup analyses indicated an elevated PLR in retrospective studies. Studies conducted in Turkey, the UK, the USA, and Costa Rica; studies with a sample size of < 1000, with < 70% male patients, and with patients treated with chemotherapy; studies with PLR cutoff value of ≥200; and studies with lower quality as determined by the Newcastle-Ottawa Scale all showed greater harmful effects on OS than their corresponding subsets (P < 0.05). CONCLUSIONS: An elevated PLR was associated with poor OS in patients with gastric cancer. These results might differ between studies due to differences in design, country of origin, sample size, sex proportion, treatment strategy, PLR cutoff value, and study quality.

Prognostic role of pretreatment thrombocytosis on survival in patients with cervical cancer: a systematic review and meta-analysis.

BACKGROUND: This meta-analysis summarized the prognostic role of an elevated platelet count before treatment on survival outcomes in patients with cervical cancer. METHODS: The PubMed, Embase, and Cochrane library electronic databases were systematically searched for studies reporting the effect estimates with 95% confidence intervals (CIs) of pretreatment thrombocytosis on survival from the database inceptions to December 2018. The pooled hazard ratios (HRs) with 95% CIs for overall survival (OS), progression-free survival (PFS), and recurrence-free survival (RFS) were calculated using random-effects models. RESULTS: Nineteen retrospective studies that recruited 6521 patients with cervical cancer were eligible for this study. The summary results indicated that an elevated platelet count was significantly associated with a poor OS (HR 1.50; 95% CI 1.19-1.88; P = 0.001), PFS (HR 1.33; 95% CI 1.07-1.64; P = 0.010), and RFS (HR 1.66; 95% CI 1.20-2.28; P = 0.002). Sensitivity analysis indicated that the pooled PFS was variable after sequential exclusion of individual studies. The predictive value of pretreatment thrombocytosis on OS differed according to the publication year (P = 0.039), country (P = 0.013), and sample size (P = 0.029), and the role of pretreatment thrombocytosis on PFS could be affected by the study quality (P = 0.046). CONCLUSION: The findings of this study indicated that an elevated platelet count before treatment was associated with poor OS, PFS, and RFS. These results require further verification in large-scale prospective studies.

[A study of risk factors of psychiatric symptoms occurring in treating Sheehan's syndrome patients].

OBJECTIVE: To investigate the risk factors of psychiatric symptoms in the process of the treatment of Sheehan's Syndrome (SS). METHODS: We collected the clinical data of 119 inpatients diagnosed of SS in Department of Endocrinology, the Second Xiangya Hospital, Central South University from January 2002 to November 2014. Logistic regression analyses were applied to investigate the risk factors of psychoses during the treatment of SS. RESULTS: We found that among all the 119 subjects, 64 (54%) out of the pathients developed into pituitary crisis over the course of treatment for SS. And, 42 (35%) of the patients had psychiatric symptoms. SS patients with psychiatric symptoms had lower levels of hemoglobin [(96 ± 16) g/L vs (104 ± 23) g/L, (P < 0.05)], sodium [(117 ± 12) mmol/L vs (127 ± 12) mmol/L, (P < 0.01)], free serum T3 (FT3) [(1.4 ± 1.0) pmol/L vs (2.1 ± 1.3) pmol/L, (P < 0.01)] and free serum T4 (FT4) [(4.1 ± 2.8) pmol/L vs (6.5 ± 4.9) pmol/L, (P < 0.05)], but higher levels of daily dosage of hydrocortisone for the first three days (P < 0.05) compared to the group without the same. Upon occurrence of psychiatric symptoms, the daily dosage of hydrocortisone for the first three days was 165 mg. Among them, patients also with pituitary crisis had a higher requirement of hydrocortisone, that is, daily dosage of hydrocortisone for the first three days was 208 mg. Logistic regression analysis showed that sodium (P < 0.05, OR < 1) and hydrocortisone dosage of the first day (P < 0.01, OR > 1) were included in the logistic regression equation, suggesting that serum sodium, is a protective factor against psychiatric symptoms (OR = 0.950). And the dosage of glucocorticoid required on the first day (OR = 1.008) is a risk factor for psychiatric symptoms. CONCLUSION: SS patients with severe anterior pituitary dysfuncthion, especially those with pituitary crisis are susceptible to have psychiatric symptoms during glucocorticoid treatment. The dosage of glucocorticoid, especially the first day dosage is one of the risk factors for psychiatric symptoms.

Nasal Administration of bFGF-Loaded Nanoliposomes Attenuates Neuronal Injury and Cognitive Deficits in Mice with Vascular Dementia Induced by Repeated Cerebral Ischemia‒Reperfusion.

Introduction: Basic fibroblast growth factor (bFGF) shows great potential for preventing vascular dementia (VD). However, the blood‒brain barrier (BBB) and low bioavailability of bFGF in vivo limit its application. The present study investigated how nasal administration of bFGF-loaded nanoliposomes (bFGF-lips) affects the impaired learning and cognitive function of VD mice and the underlying mechanism involved. Methods: A mouse model of VD was established through repeated cerebral ischemia‒reperfusion. A Morris water maze (MWM) and novel object recognition (NOR) tests were performed to assess the learning and cognitive function of the mice. Hematoxylin and eosin (HE) staining, Nissl staining and TUNEL staining were used to evaluate histopathological changes in mice in each group. ELISA and Western blot analysis were used to investigate the molecular mechanism by which bFGF-lips improve VD incidence. Results: Behavioral and histopathological analyses showed that cognitive function was significantly improved in the bFGF-lips group compared to the VD and bFGF groups; in addition, abnormalities and the apoptosis indices of hippocampal neurons were significantly decreased. ELISA and Western blot analysis revealed that bFGF-lips nasal administration significantly increased the concentrations of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), bFGF, B-cell lymphoma 2 (Bcl-2), phosphorylated protein kinase B (PAKT), nuclear factor erythroid 2-related factor 2 (Nrf2), NAD(P)H quinone oxidoreductase 1 (NQO1) and haem oxygenase-1 (HO-1) in the hippocampus of bFGF-lips mice compared with the VD and bFGF groups. Furthermore, the concentrations of malondialdehyde (MDA), caspase-3 and B-cell lymphoma 2-associated X (Bax) were clearly lower in the bFGF-lips group than in the VD and bFGF groups. Conclusion: This study confirmed that the nasal administration of bFGF-lips significantly increased bFGF concentrations in the hippocampi of VD mice. bFGF-lips treatment reduced repeated I/R-induced neuronal apoptosis by regulating apoptosis-related protein concentrations and activating the phosphatidylinositol-3-kinase (PI3K)/(AKT)/Nrf2 signaling pathway to inhibit oxidative stress.

A cuproptosis-related lncRNA signature for predicting prognosis and immune response in hepatocellular carcinoma.

Background: Hepatocellular carcinoma (HCC) has a high incidence and poor prognosis. Cuproptosis is a novel type of cell death, which differs from previously reported types of cell death such as apoptosis, autophagy, proptosis, ferroptosis, necroptosis, etc. Long non-coding RNAs (lncRNAs) play multiple roles in HCC. Methods: We downloaded information from The Cancer Genome Atlas (TCGA) database, and obtained cuproptosis-related genes from published studies. The cuproptosis-related lncRNAs were obtained by correlation analysis, and subsequently used to construct a prognostic cuproptosis-related lncRNA signature. Analyses of overall survival (OS), progression-free survival (PFS), receiver operating characteristic (ROC) curve with the area under the curve (AUC) values and the index of concordance (c-index) curve were used to evaluate the signature. The tumor microenvironment (TME) was analyzed by ESTIMATE algorithm. The immune cell data was downloaded from the Tumor Immune Estimation Resource (TIMER) 2.0 database. Immune-related pathways were analyzed by single-sample gene set enrichment analysis (ssGSEA) algorithm. Immunophenoscore (IPS) scores from The Cancer Immunome (TCIA) database were used to evaluate immunotherapy response. The "pRRophetic" was employed to screen drugs for high-risk patients. The candidate lncRNA expression levels were detected by Real Time Quantitative PCR. Results: We constructed a cuproptosis-related lncRNA signature containing seven lncRNAs: AC125437.1, PCED1B-AS1, PICSAR, AP001372.2, AC027097.1, LINC00479, and SLC6A1-AS1. This signature had excellent accuracy, and was independent of the stratification of clinicopathological features. Further study showed that high-risk tumors under this signature had higher TMB, fewer TME components and higher tumor purity. The tumors with high risk were not enriched in immune cell infiltration or immune process pathways, and high-risk patients had a poor response to immunotherapy. Moreover, 29 drugs such as sorafenib, dasatinib and paclitaxel were screened for high-risk HCC patients to improve their prognosis. The expression levels of the candidate lncRNAs in HCC tissue were significantly increased (except PCED1B-AS1). Conclusions: Our prognostic cuproptosis-related lncRNA signature was accurate and effective for predicting the prognosis of HCC. The immunotherapy was unsuitable for high-risk HCC patients with this signature.

[Effect of acupuncture on analgesia and sedation in elderly patients with severe pneumonia during invasive mechanical ventilation].

OBJECTIVE: To observe the analgesic and sedative effects of acupuncture in elderly patients with severe pneumonia during invasive mechanical ventilation. METHODS: A total of 188 elderly patients with severe pneumonia were randomly divided into an observation group and a control group, 94 cases in each group. Both groups were treated with routine nursing and treatment of severe pneumonia such as invasive mechanical ventilation, analgesia and sedation. Based on these, the observation group was treated with acupuncture at Neiguan (PC 6), Hegu (LI 4), Yintang (GV 29) and Baihui (GV 20), twice a day until the mechanical ventilation was offline. The critical care pain observation tool (CPOT) score and Richmond agitation-sedation score (RASS) were observed before treatment and 0.5 h after analgesia and sedation; the average time of reaching the standard, the reaching standard rate of shallow sedation and analgesia within 0.5 h and 72 h as well as the dosage of analgesic and sedative drugs and compilations were compared between the two groups. The mean arterial pressure (MAP), heart rate (HR), respiratory rate (RR) and blood oxygen saturation (SpO2) were observed before treatment and 0.5 h, 1 h and 2 h after analgesia and sedation. The levels of partial pressure of blood oxygen (PaO2), partial pressure of carbon dioxide (PaCO2) and lactic acid (Lac) were observed before treatment and 12 h, 24 h, 48 h, 72 h, 96 h, 120 h and 144 h after analgesia and sedation. The white blood cell (WBC), neutrophil percentage (NEUT%), high-sensitivity C-reactive protein (hs-CRP), aspartate aminotransferase (AST), alanine aminotransferase (ALT) and creatinine (Cr) were observed before treatment and 72 h after analgesia and sedation. The tracheal intubation time and ICU hospitalization time were compared between two groups. RESULTS: At the time point of 0.5 h after treatment, the CPOT and RASS scores in the two groups were lower than those before treatment (P<0.05); the average time of reaching the standard in the observation group was shorter than that in the control group (P<0.01); the 30 min reaching standard rates of CPOT and RASS scores as well as the rate of reaching the shallow sedation and analgesia within 72 h in the observation group were higher than those in the control group (P<0.01, P<0.05). The dosage and duration of dexmedetomidine, propofol and butorphanol in the observation group were less than those in the control group (P<0.05), and the occurrence times of hypotension, respiratory depression, bradycardia, constipation as well as average tracheal intubation time and average ICU hospitalization time in the observation group were less than those in the control group (P<0.05). After 0.5 h, 1 h and 2 h of treatment, the HR and RR were lower than those before treatment in the two groups (P<0.05), MAP and SpO2 were higher than those before treatment in the two groups (P<0.05); the MAP 0.5 h after treatment in the observation group was higher than that in the control group (P<0.05); the HR after 1 h and 2 h of treatment in the observation group was lower than that in the control group (P<0.05). Compared before treatment, the levels of PaCO2 and Lac were reduced and the levels of PaO2 were increased 12 h, 24 h, 48 h, 72 h, 96 h, 120 h and 144 h after treatment in both groups (P<0.05); compared before treatment, the WBC, NEUT%, hs-CPR, ALT and Cr were reduced 72 h after treatment in the two groups (P<0.05), and the hs-CRP in the observation group was lower than that in the control group (P<0.05). CONCLUSION: Acupuncture has analgesic and sedative effect in elderly patients with severe pneumonia during invasive mechanical ventilation, which could reduce the dosage of sedative and analgesic drugs and the occurrence of complications, improve blood oxygen, and has good safety.

Association of ALOX5, LTA4H and LTC4S gene polymorphisms with ischemic stroke risk in a cohort of Chinese in east China.

BACKGROUND: Genetic variations of the 5-lipoxygenase activating protein and leukotriene A4 hydrolase genes that confer an increased risk of ischemic stroke have implicated the family of leukotrienes as potential mediators of ischemic stroke. This study aimed to explore the association of ALOX5, LTA4H and LTC4S gene polymorphisms with ischemic stroke risk in a cohort of Chinese in east China. METHODS: This case-control study consisted of 690 patients with ischemic stroke and 690 controls. Polymorphisms of ALOX5 rs2029253 A/G, LTA4H rs6538697 T/C, and LTC4S rs730012 A/C were genotyped by the polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) analysis. The multivariate logistic regression model was used to exclude the effects of conventional risk factors on ischemic stroke. RESULTS: Carriers of C allele in rs730012 were more susceptible to ischemic stroke (OR: 1.37; 95%CI: 1.08-1.73; P=0.009). The rs2029253 GG genotype showed a risk-reducing effect on ischemic stroke (OR: 0.72; 95%CI: 0.55-0.93; P=0.013) while the rs6538697 CC genotype had an increased risk of ischemic stroke (OR: 1.77; 95%CI: 1.09-2.89; P=0.022). The rs730012 variant was not associated with ischemic stroke risk after adjusting confounding factors (P>0.05). CONCLUSION: The present study suggested that gene polymorphisms in the leukotrienes pathway may exert influences, with independent genetic effects, on ischemic stroke susceptibility in a cohort of Chinese in east China.

Genetic variation in members of the leukotrienes biosynthesis pathway confers risk of ischemic stroke in Eastern Han Chinese.

This study was aimed to explore the association of genetic variation in members of the leukotrienes biosynthesis pathway as potential mediators with ischemic stroke (IS) risk in Eastern Han Chinese. A case-control study of was conducted with five selected single nucleotide polymorphisms (SNPs). In the single-locus analysis, carriers of C allele of rs730012 in LTC4S were more susceptible to IS (OR, 1.28; 95% CI, 1.02-1.60; P=0.033). Under the recessive genetic model, ALOX5 rs2029253 variant reduced IS risk (adjusted OR, 0.78; 95% CI, 0.60-1.00; P=0.048) while LTA4H rs6538697 and LTC4S rs730012 variants increased (adjusted OR, 1.66; 95% CI, 1.04-2.64; P=0.032 and adjusted OR, 3.63; 95% CI, 1.01-13.05; P=0.048, respectively). However, there was no evidence of association between all five SNPs and IS risk after correction for multiple testing. In combined analysis of multiple genes and loci, individuals with ALOX5AP rs12429692 T allele, ALOX5 rs2029253 A allele, and LTA4H rs6538697 C allele suggested a significantly increased susceptibility to IS (adjusted OR, 1.70; 95% CI, 1.07-2.69; P=0.024). The present study suggested gene-gene interactions in leukotrienes pathway could exert influences on the risk of IS.

Variants of the arachidonate 5-lipoxygenase-activating protein (ALOX5AP) gene and risk of ischemic stroke in Han Chinese of eastern China.

Variants of the arachidonate 5-lipoxygenase-activating protein (ALOX5AP) gene have been suggested to play an important role in the pathogenesis of atherosclerosis and ischemic stroke. This study was aimed to explore the association of ALOX5AP variants with ischemic stroke risk in Han Chinese of eastern China. A total of 690 ischemic stroke cases and 767 controls were recruited. The subjects were further subtyped according to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria. On the basis of that, two polymorphisms of the ALOX5AP gene (rs10507391 and rs12429692) were determined by TaqMan genotyping assay. In addition, plasma leukotriene B4 (LTB4) levels were analyzed in these subjects. There was no evidence of association between the two variants of ALOX5AP and the risk of ischemic stroke or its TOAST-subtypes. Haplotype analysis and stratification analysis according to sex, age, body mass index, hypertension, and diabetes also showed negative association. Analysis of LTB4 levels in a subset of cases and controls revealed that LTB4 levels were significantly higher in ischemic stroke cases than in the controls (70.06±14.75 ng/L vs 57.34±10.93 ng/L; P = 0.000) and carriers of the T allele of the rs10507391 variant were associated with higher plasma LTB4 levels (P = 0.000). The present study suggests there is no association of the two polymorphisms in the ALOX5AP gene with ischemic stroke risk in Han Chinese of eastern China.