Clinical and histological features of patients with chronic hepatitis B virus infection in the grey zone.

Chronic HBV infection patients who do not conform to any of the usual immune states are regarded as 'grey zone' patients. We aimed to investigate the proportion of chronic HBV infection patients in the grey zone, and evaluate the clinical characteristics and liver pathological changes in grey zone patients. Clinical data of 1391 treatment-naive chronic HBV infection patients with liver biopsy were collected. Natural history of HBV infection was determined based on European Association for the Study of the Liver (EASL) 2017, American Association for the Study of Liver Diseases (AASLD) 2018 and Chinese 2019 guidelines for the prevention and treatment of chronic HBV infection. Significant liver histological changes and associated risk factors of normal ALT grey zone patients were analysed. According to EASL, AASLD and Chinese criteria, there were 50.0%, 28% and 37.4% chronic HBV infection patients in the grey zone. Among the 353 grey zone patients with normal ALT, 72.4% had significant liver histological changes. ALT (optimal cut-off value 25 IU/L) and HBV DNA (optimal cut-off value 18,000 IU/mL) were independent risk factors of significant liver histological abnormalities. In conclusion, a substantial proportion of grey zone patients with normal ALT have significant liver histological changes that can be predicted by levels of serum ALT and HBV DNA. These results provide guidance of antiviral treatment in grey zone patients.

LncRNA HOTAIR Promotes LPS-Induced Inflammation and Apoptosis of Cardiomyocytes via Lin28-Mediated PDCD4 Stability.

Sepsis is one of the primary causes of death in intensive care units. Recently, increasing evidence has identified lncRNA HOTAIR is involved in septic cardiomyopathy. However, the potential mechanism underlying HOTAIR on septic cardiomyopathy is still unknown. H9C2 cells were treated with lipopolysaccharide (LPS) after transfection with sh-HOTAIR, sh-Lin28, pcDNA3.1-HOTAIR, and pcDNA3.1-PDCD4. qRT-PCR was used to examine the level of HOTAIR, Lin28, PDCD4, and sepsis-related inflammatory cytokines. Flow cytometric analysis was applied to detect cell apoptosis. The interaction between Lin28 and HOTAIR or PDCD4 was verified by RNA pull-down and RIP assay. HOTAIR levels were interfered by AAV9-sh-HOTAIR in LPS-induced septic cardiomyopathy mice. ELISA analysis was used to evaluate TNF-α, IL-6, and IL-1ß level. Western blot was used to detect the expression of LIN28 and PDCD4 in mouse cardiomyocytes. Echocardiography was used to evaluate the cardiac function. In our study, knockdown of HOTAIR inhibited LPS-induced inflammation and H9C2 cells apoptosis. HOTAIR promoted LPS-induced inflammatory response and apoptosis of H9C2 cells by enhancing PDCD4 stability. RNA pull-down and RIP assay exhibited that Lin28, a highly conserved RNA-binding protein, was combined with HOTAIR and PDCD4. The in vivo experiments verified that the HOTAIR knockdown alleviated the cardiac function injury and secretion of inflammatory factors caused by sepsis. In conclusion, our findings supported that the HOTAIR/Lin28/PDCD4 axis serves as a critical regulator of sepsis, which may open a new direction for the development of sepsis therapeutic.

Prognostic Values of Platelet-Associated Indicators in Resectable Lung Cancers.

BACKGROUND: Lung cancer is the leading cause of cancer death. Platelet-related indictors, including platelet count, plateletcrit, mean platelet volume, and platelet distribution width, not only associate with morphology and functions of platelet but also correlate with tumor development and metastasis. In the present study, we investigated the values of platelet-related indictors in the prognosis evaluation of resectable lung cancers. METHODS: In total, 101 patients with resectable lung cancer were recruited in this study. Patients were divided into 2 groups according to the median pretreatment values. To evaluate the individual value changes after treatment, we introduced the concept of post-/pretreatment ratio (≤1 indicated value was not increased after treatment, while >1 suggested increased value). RESULTS: The high pretreatment platelet count level was correlated with larger tumor size. High pretreatment plateletcrit level was associated with more lymph nodes metastasis. Patients with high pretreatment plateletcrit level had worse overall survival, whereas pretreatment platelet count, mean platelet volume, and platelet distribution width levels were not correlated with outcomes. Surgery had no impact on the values of platelet count, plateletcrit, mean platelet volume, or platelet distribution width. Adjuvant chemotherapy significantly decreased the values of platelet count and plateletcrit, whereas it had no effect on the values of mean platelet volume or platelet distribution width. Whole course of treatment (surgery combined with adjuvant chemotherapy) significantly decreased the values of platelet count and platelet distribution width, whereas it had no effect on the values of plateletcrit or mean platelet volume. Post-/pretreatment platelet count, plateletcrit, mean platelet volume, and platelet distribution width ratios were not correlated with outcomes. Univariate analyses demonstrated that American Joint Committee on Cancer stage and pretreatment plateletcrit level were significant risk factors for prognosis. Cox regression analysis revealed that no factor independently associated with worse survival. CONCLUSION: Pretreatment plateletcrit level could be a potential prognostic factor in resectable lung cancers.

The values of applying classification and counts of white blood cells to the prognostic evaluation of resectable gastric cancers.

BACKGROUND: The classifications and counts of white blood cells (WBCs) have been proved to be able to be used as prognostic markers in cancer cases. The present study investigated the potential values of the classifications and counts of WBC, including lymphocyte (LY), monocyte (MO), neutrophil (NE), eosinophil (EO), and basophil (BA) in the prognosis of resectable gastric cancers (GCs). METHODS: This retrospective study recruited 104 resectable GC cases which were pathologically confirmed. The patients were divided into two groups according to the median pre-treatment values. To evaluate the changes in WBC counts and classification after treatment, we introduced the concept of post/pre-treatment ratios (≤ 1 indicated count was not increased after therapy, while > 1 suggested increased count). RESULTS: Pre-treatment NE and total WBC counts were negatively correlated with overall survival (OS). Surgery significantly decreased the level of NE count, but increased the level of EO, whereas had no effect on the levels of LY, MO, BAor total WBC. Adjuvant chemotherapy significantly decreased the level of BA. Whole course of treatment (surgery combined with adjuvant chemotherapy) had no significant effect on the counts of LY, MO, NE, EO, BA or total WBC. Post/pre-treatment ratios of LY, MO NE, EO, BA and total WBC levels had no effects on OS. Univariate analysis indicated that AJCC stage (III) and higher level of pre-treatment total WBC count were prognostic factors affecting OS. Multivariate Cox regression analysis revealed that AJCC stage (III) and higher level of pre-treatment total WBC count were independent prognostic factors. CONCLUSIONS: Pre-treatment NE count and pre-treatment total WBC count may be potential prognostic factors for the prognostic evaluation of GCs.

Preventive and therapeutic effects of Danhong injection on lipopolysaccharide induced acute lung injury in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Danhong injection (DHI), a Chinese Materia Medica standardized product extracted from Radix et Rhizoma Salviae Miltiorrhizae (Salvia miltiorrhiza Bge., Labiatae, Danshen in Chinese) and Flos Carthami (Carthamus tinctorius L., Compositae, Honghua in Chinese), has been reported to have anti-inflammatory, anti-oxidative and anti-fibrinolytic properties, which is used extensively for the treatment of cardiovascular diseases in clinic. AIM OF THIS STUDY: The present study aimed to investigate the preventive and therapeutic effects of DHI on lipopolysaccharide (LPS) induced acute lung injury (ALI) in mice. MATERIALS AND METHODS: Lung injury was induced by intranasal instillation with 10 µg LPS. Mice were randomly divided into four groups: Control group; LPS group; LPS+5 ml/kg DHI group and LPS+10 ml/kg DHI group. The effects of DHI on LPS-induced neutrophils influx, inflammatory cytokines release, protein leakage, myeloperoxidase (MPO) and superoxide dismutase (SOD) activities, malondialdehyde (MDA) level were examined. In addition, the NF-κB activation in lung tissues was detected by Western blot. RESULTS: In LPS challenged mice, DHI significantly reduced the infiltration of activated neutrophils and decreased the levels of TNF-α and IL-6 in bronchoalveolar lavage fluid (BALF). DHI also inhibited protein extravasation in BALF, attenuated edema and the pathological changes in the lung. In addition, DHI markedly prevented LPS-induced elevation of MDA and MPO levels, as well as reduction of SOD activity. Further study demonstrated that DHI effectively inhibited the NF-κB activation in lung tissues. CONCLUSION: DHI has been demonstrated to protect mice from LPS induced acute lung injury by its anti-inflammatory and anti-oxidant activities.

CYP3A4*1B polymorphism and cancer risk: a HuGE review and meta-analysis.

CYP450 3A4 (CYP3A4), encoded by the CYP3A4 gene, is a major enzyme catalyzing the metabolism of both endogenous and exogenous agents that may play a role in the etiology of carcinogenesis. Several potentially functional polymorphisms of the CYP3A4 gene have been implicated in cancer risk, but individually published studies have shown inconclusive results. The aim of this Human Genome Epidemiology (HuGE) review and meta-analysis was to investigate the association between CYP3A4*1B (rs2740574 A > G) polymorphism and cancer risk. Eleven studies were included with a total of 3,810 cancer patients and 3,173 healthy controls. We found that the G allele and GG genotype of CYP3A4*1B polymorphism were associated with increased risk of cancers using the fixed effects model (allele model: odds ratio (OR) = 1.24, 95 %CI: 1.09-1.42, P = 0.001; recessive model: OR = 1.77, 95 %CI: 1.30-2.41, P < 0.001; homozygous model: OR = 1.72, 95 %CI: 1.19-2.47, P = 0.004). Subgroup analyses by cancer type showed that the G allele and G carrier (AG + GG) of CYP3A4*1B polymorphism had significant associations with increased risk of prostate cancer, but not with breast cancer, leukemia, or other cancers. With further subgroup analysis based on different ethnicities, the results indicated that the GG genotype of CYP3A4*1B polymorphism might increase the risk of cancer among African populations. However, similar associations were not observed among Caucasian and Asian populations. Results from the current meta-analysis indicate that the G allele and GG genotype of CYP3A4*1B polymorphism might be associated with increased cancer risk, especially for prostate cancer among African populations.

[Prevalence and clinical characteristics of orthostatic hypotension in the elderly and retired population].

OBJECTIVE: To determine the prevalence and clinical characteristics of orthostatic hypotension (OH) in the elderly and retired population. METHODS: A total of 1174 elderly and retired people underwent health screening physical examination in Guangzhou military region were included. The orthostatic blood pressure and heart rate were measured in supine position after resting for more than 5 minutes and at 0 and 2 min after standing. Subjects were divided into OH positive group and OH negative group. Orthostatic hypotension was defined as 20 mm Hg (1 mm Hg = 0.133 kPa) or greater decrease in SBP and/or 10 mm Hg or greater decrease in DBP after standing. RESULTS: The prevalence of OH in this cohort was 25.6% at either 0 or 2 min after standing (21.6% or 20.7% respectively). Incidence of hypertension, myocardial infarction (MI), heart failure (HF), ischemic stroke and diabetes was significantly higher in OH positive group than in OH negative group (all P < 0.05), however, antihypertensive medication was similar between the two groups. CONCLUSIONS: Orthostatic hypotension is common in the elderly and retired population and is associated with increased risk of hypertension, diabetes mellitus and cardiovascular disease.

[Correlation between orthostatic hypotension and cardiovascular risks in elderly population].

OBJECTIVE: To investigate the correlation between orthostatic hypotension and cardiovascular risks and hospitalization rate in the elders. METHODS: A total of 1174 people over 65 years old underwent health screening physical examination through a self-made questionnaire at our hospital. Their clinical data were collected. The orthostatic blood pressure and heart rate were measured in supine position after resting for over 5 minutes and at 0 and 2 min after standing. Orthostatic hypotension was defined as 20 mm Hg or greater decrease in SBP or/and 10 mm Hg or greater decrease in DBP after standing. All cases were followed up by telephone or hospitalization medical records for a mean period of 315.8 days. The primary endpoint was the occurrence of such cardiovascular or cerebrovascular events as angina, fatal or nonfatal myocardial infarction (MI), congestive heart failure, sudden cardiac death, ischemic and hemorrhagic stroke. RESULTS: The prevalence of OH was 25.6% in this cohort. Significant differences could be found in the rate of all-cause and cardiovascular-related hospitalization between OH positive and OH negative (45.1% vs 32.5%; 19.1% vs 7.4%); the rates of angina and myocardial infarction in the OH positive group were significantly higher than those in the OH negative group (7.5% vs 3.7%: 4.8% vs 0.5%, P < 0.05); after adjusting for age, supine blood pressure, heart rate and cerebrovascular history by logistic regression, statistical differences could also be observed between OH and angina [P = 0.011, HR (hazard ratio): 2.122, 95%CI (confidence interval): 1.184-3.802 and MI (P < 0.001, HR: 8.995, 95%CI: 2.909 - 27.819)]. CONCLUSION: Orthostatic hypotension may increase the rates of all-cause and cardiovasular-related hospitalization. And it is a robust predictor of angina and myocardial infarction in the elders.

[A clinical analysis of morning blood pressure surge in middle and old aged male hypertensive patients].

OBJECTIVE: To investigate the morning blood pressure surge (MBPS) and its relationship with 24-hour blood pressure variability and anti-hypertensive drugs in middle-aged and elderly hypertensive patients. METHODS: A total of 521 middle-age and elderly men were surveyed with ambulatory blood pressure monitoring and ambulatory electrocardiograms recordings as well as questionnaire investigation from January 2009 to December 2010. Subjects were divided into MBPS positive group and MBPS negative group according to the level of MBPS [> 35 mm Hg (1 mm Hg = 0.133 kPa) or ≤ 35 mm Hg]. RESULTS: In all the cases, the prevalence of MBPS was 19.4%, of which the elderly and very elderly had higher prevalences (18.9% and 21.8%, respectively) than the middle-aged (5.6%, both P < 0.01). Significant differences could be found in age[(81.6 ± 6.4) years vs (78.7 ± 9.7) years], day mean systolic blood pressure [(132.8 ± 13.3) mm Hg vs (128.8 ± 13.3) mm Hg], fasting blood glucose [(5.96 ± 1.59) mmol/L vs (5.68 ± 1.22) mmol/L] and 24-hour blood pressure variability between the two groups (all P < 0.05). Significant difference could be observed in the prevalence of MBPS between the diuretics-taking group and non-taking group (27.4% vs 17.6%, P < 0.05). CONCLUSIONS: The elderly hypertensive patients are prone to appear MBPS phenomenon. Fasting blood glucose level, 24-hour blood pressure variability may be associated with MBPS. Diuretic antihypertensive treatment may not be conductive for MBPS control.

Electrochemical determination of 6-mercaptopurine at silver microdisk electrodes.

The electrochemical behaviour of 6-mercaptopurine (6-MP) at a microdisk electrode is investigated by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). The results indicate that 6-MP can be strongly adsorbed on the surface of the static mercury drop electrode (SMDE) and reacts with Ag+ ions which are produced at positive potentials. 6-MP yields a well-defined cathodic stripping signal during the negative scan at about -0.812 V (vs. SCE) in pH 9.0 phosphate buffer solution. The electrode has hence been used for the determination of 6-MP by differential pulse voltammetry (DPV). The linear range is between 2.0x10(-7) and 5.0x10(-5) mol/l, with the calculated detection limit (S/N=3) of 8.0x10(-8) mol/l. The relative standard deviation is 3.0% for eight successive determinations of 4.0x10(-5) mol/l 6-MP. The determination of 6-MP in tablets has also been carried out and satisfactory results have been obtained.