Effects of Lactobacillus paracasei N1115 on gut microbial imbalance and liver function in patients with hepatitis B-related cirrhosis.

BACKGROUND: Hepatitis B cirrhosis (HBC) is a chronic disease characterized by irreversible diffuse liver damage and aggravated by intestinal microbial imbalance and metabolic dysfunction. Although the relationship between certain single probiotics and HBC has been explored, the impact of the complex ready-to-eat Lactobacillus paracasei N1115 (LP N1115) supplement on patients with HBC has not been determined. AIM: To compare the changes in the microbiota, inflammatory factor levels, and liver function before and after probiotic treatment in HBC patients. METHODS: This study included 160 HBC patients diagnosed at the General Hospital of Ningxia Medical University between October 2018 and December 2020. Patients were randomly divided into an intervention group that received LP N1115 supplementation and routine treatment and a control group that received routine treatment only. Fecal samples were collected at the onset and conclusion of the 12-wk intervention period. The structure of the intestinal microbiota and the levels of serological indicators, such as liver function and inflammatory factors, were assessed. RESULTS: Following LP N1115 intervention, the intestinal microbial diversity significantly increased in the intervention group (P < 0.05), and the structure of the intestinal microbiota was characterized by an increase in the proportions of probiotic microbes and a reduction in harmful bacteria. Additionally, the intervention group demonstrated notable improvements in liver function indices and significantly lower levels of inflammatory factors (P < 0.05). CONCLUSION: LP N1115 is a promising treatment for ameliorating intestinal microbial imbalance in HBC patients by modulating the structure of the intestinal microbiota, improving liver function, and reducing inflammatory factor levels.

Adrenomedullin, transcriptionally regulated by vitamin D receptors, alleviates atherosclerosis in mice through suppressing AMPK-mediated endothelial ferroptosis.

PURPOSE: Vitamin D receptors (VDR) play important roles in cardiovascular, immune, metabolic and other functions. Activation of VDR may help improve endothelial dysfunction, atherosclerosis, vascular calcification, and cardiac hypertrophy. However, the specific target genes and mechanisms of VDR in improving Human Umbilical Vein Endothelial Cell (HUVEC) functions remain unclear. This study aims to investigate the function and mechanism of VDR in HUVECs. METHODS: Endothelial dysfunction cell model was constructed by oxidized low-density lipoprotein (ox-LDL). An animal model of atherosclerosis was established in male homozygous Apoe-/- mice (6 weeks) on a high fat diet for 6 weeks. The relationship between VDR and adrenomedullin (ADM) was studied by bioinformatics analysis, ChIP, and luciferase reporter gene analysis. Endothelial cell function was evaluated by Transwell migration and Tube Formation tests. Ferroptosis was detected by measuring intracellular iron content, levels of oxidative stress markers, and ferroptosis related proteins. RESULTS: Overexpression of VDR in HUVECs inhibits ox-LDL-induced endothelial dysfunction and ferroptosis. VDR binds to the ADM promoter sequence and regulates the transcription of ADM. Inhibition of ADM promotes ox-LDL-induced endothelial dysfunction and ferroptosis. ADM regulates ox-LDL-induced endothelial dysfunction and ferroptosis through the AMPK signaling pathway. Overexpression of VDR in Apoe-/- mice inhibited lipid deposition and plaque area in atherosclerotic mice. CONCLUSION: VDR inhibits ox-LDL-induced endothelial dysfunction and ferroptosis by regulating ADM transcription and acting on AMPK signaling pathway. Overexpression of VDR in Apoe-/- mice reduced lipid deposition and plaque area in the thoracic aorta of atherosclerotic mice.

Compact dual-parameter sensor design based on a photonic crystal nanobeam cavity with chirped slotted annular holes.

A compact photonic crystal nanobeam cavity with a 20µm×0.8µm footprint supporting simultaneous air and dielectric resonant modes is proposed for dual-parameter sensing of refractive index and temperature. The structure consists of a row of chirped annular holes and an air-slot etched in an asymmetrical silicon slab. By tapering the lattice period and hole radius, the bands for air and dielectric modes shift in opposite directions, enabling confinement in a single cavity. Numerical simulations determine refractive index sensitivities of 173.59 nm/RIU for the air mode and 286.82 nm/RIU for the dielectric mode. Temperature sensitivities are 69.6 pm/°C and 78.7 pm/°C for the two modes, respectively. The structure demonstrates strong resistance to external interference with refractive index and temperature disturbance resistance coefficients of 2.3×10-5 and 0.07. The high sensitivities in an ultracompact footprint with resistance to crosstalk make this dual-mode nanocavity promising for on-chip biochemical sensing applications.

SIRT1 Inhibition-Induced Mitochondrial Damage Promotes GSDME-Dependent Pyroptosis in Hepatocellular Carcinoma Cells.

Hepatocellular carcinoma (HCC) is a malignant tumor that affects the liver and poses a significant threat to human health. Further investigation is necessary to fully understand the role of SIRT1, a protein linked to tumorigenesis, in HCC development. To investigate the effect of SIRT1 on HCC and elucidate the underlying mechanism. Eight pairs of HCC and paracancerous normal tissue specimens were collected. The levels of SIRT1 and GSDME in tissue samples were assessed using immunohistochemistry and western blotting. SIRT1 levels were determined in HCC (Huh7, HepG2, SNU-423, SNU-398, and HCCLM3) and L-02 cells using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting. SNU-423 and HCCLM3 cells were transfected with si-SIRT1 and/or si-GSDME to knock down SIRT1 or GSDME expression. RT-qPCR and western blotting were performed to measure the expression of SIRT1, pro-casp-3, cl-casp-3, GSDME, GSDME-N, PGC-1α, Bax, and cytochrome c (Cyto C). Cell proliferation, migration, invasion, and apoptosis were assessed using the cell counting kit-8 (CCK-8), wound healing assay, Transwell invasion assay, and flow cytometry, respectively. The release of lactate dehydrogenase (LDH) was evaluated using an LDH kit. SIRT1 was upregulated in HCC tissues and cells, and a negative correlation was observed between SIRT1 and GSDME-N. SIRT1 silencing suppressed the proliferation, migration, and invasion of HCC cells while also promoting apoptosis and inducing mitochondrial damage. Additionally, the silencing of SIRT1 resulted in the formation of large bubbles on the plasma membrane of HCC cells, leading to cellular swelling and aggravated GSDME-dependent pyroptosis, resulting in an increase in LDH release. Inhibition of GSDME reduced SIRT1 silencing-induced cell swelling, decreased LDH release rate, and promoted apoptosis. SIRT1 silencing promotes GSDME-dependent pyroptosis in HCC cells by damaging mitochondria.

Urotensin II activates the ferroptosis pathway through circ0004372/miR-124/SERTAD4 to promote the activation of vascular adventitial fibroblasts.

Both vascular adventitial fibroblasts (VAFs) and urotensin II (UII) play important roles in vascular remodeling diseases, but the mechanism of UII in VAFs is still unclear. UII inhibited miR-124 expression through up-regulating circ0004372 expression, thereby promoting SERTAD4 expression. UII significantly promoted the generation of ROS, MDA and 4-HNE, reduced the activities of SOD, GST and GR, increased Fe2+ concentration and inhibited GPX4 expression through circ0004372/miR-124/SERTAD4. Both UII and ferroptosis inducer Erastin significantly promoted the expression of α-SMA, Collagen I and TGF-ß1 in VAFs, but circ0004372 siRNA, miR-124 mimics, SERTAD4 siRNA or Ferrostatin-1 significantly inhibited the effect of UII and Erastin on cell activation. When co-transfected with circ0004372 siRNA and miR-124 inhibitors or miR-124 mimics and SERTAD4 overexpression vector, UII still significantly increased the expression of α-SMA, Collagen I and TGF-ß1. After transfection with circ0004372 overexpression vector, miR-124 inhibitors or SERTAD4 overexpression vector and then treating with UII and Ferrostatin-1, the expression of α-SMA, Collagen I and TGF-ß1 was still significant; when the circ0004372 overexpression vector and miR-124 mimics or miR-124 inhibitors and SERTAD4 siRNA were co-transfected and then UII and Ferrostatin-1 were added, the expression of α-SMA, Collagen I and TGF-ß1 was not significantly increased. Therefore, these results indicate that UII promotes the activation of VAFs through the circ0004372/miR-124/SERTAD4/ferroptosis pathway.

Lactate promotes vascular smooth muscle cell switch to a synthetic phenotype by inhibiting miR-23b expression.

Recent research indicates that lactate promotes the switching of vascular smooth muscle cells (VSMCs) to a synthetic phenotype, which has been implicated in various vascular diseases. This study aimed to investigate the effects of lactate on the VSMC phenotype switch and the underlying mechanism. The CCK-8 method was used to assess cell viability. The microRNAs and mRNAs levels were evaluated using quantitative PCR. Targets of microRNA were predicted using online tools and confirmed using a luciferase reporter assay. We found that lactate promoted the switch of VSMCs to a synthetic phenotype, as evidenced by an increase in VSMC proliferation, mitochondrial activity, migration, and synthesis but a decrease in VSMC apoptosis. Lactate inhibited miR-23b expression in VSMCs, and miR-23b inhibited VSMC's switch to the synthetic phenotype. Lactate modulated the VSMC phenotype through downregulation of miR-23b expression, suggesting that overexpression of miR-23b using a miR-23b mimic attenuated the effects of lactate on VSMC phenotype modulation. Moreover, we discovered that SMAD family member 3 (SMAD3) was the target of miR-23b in regulating VSMC phenotype. Further findings suggested that lactate promotes VSMC switch to synthetic phenotype by targeting SMAD3 and downregulating miR-23b. These findings suggest that correcting the dysregulation of miR-23b/SMAD3 or lactate metabolism is a potential treatment for vascular diseases.

Palmitic acid inhibits vascular smooth muscle cell switch to synthetic phenotype via upregulation of miR-22 expression.

Synthetic phenotype switch of vascular smooth muscle cells (VSMCs) has been shown to play key roles in vascular diseases. Mounting evidence has shown that fatty acid metabolism is highly associated with vascular diseases. However, how fatty acids regulate VSMC phenotype is poorly understood. Hence, the effects of palmitic acid (PA) on VSMC phenotype were determined in this study. The effect of the PA on VSMCs was measured by live/dead and EdU assays, as well as flow cytometry. Migration ability of VSMCs was evaluated using transwell assay. The underlying targets of miR-22 were predicted using bioinformatics online tools, and confirmed by luciferase reporter assay. The RNA and protein expression of certain gene was detected by qRT-PCR or western blot. PA inhibited VSMC switch to synthetic phenotype, as manifested by inhibiting VSMC proliferation, migration, and synthesis. PA upregulated miR-22 in VSMCs, and miR-22 mimics exerted similar effects as PA treatment, inhibiting VSMC switch to synthetic phenotype. Inhibition of miR-22 using miR-22 inhibitor blocked the impacts of PA on VSMC phenotype modulation, suggesting that PA modulated VSMC phenotype through upregulation of miR-22 expression. We found that ecotropic virus integration site 1 protein homolog (EVI1) was the target of miR-22 in regulation of VSMC phenotype. Overexpression of miR-22 or/and PA treatment attenuated the inhibition of EVI1 on switch of VSMCs. These findings suggested that PA inhibits VSMC switch to synthetic phenotype through upregulation of miR-22 thereby inhibiting EVI1, and correcting the dysregulation of miR-22/EVI1 or PA metabolism is a potential treatment to vascular diseases.

Electroacupuncture of Baihui and Shenting ameliorates cognitive deficits via Pten/Akt pathway in a rat cerebral ischemia injury model.

Cerebral ischemic stroke is a huge threat to the health and life of many people. Electroacupuncture (EA) at Baihui (GV20) and Shenting (GV24) acupoints can notably alleviate cerebral ischemia/reperfusion injury (CIRI). However, the molecular basis underlying the effectiveness of EA at the GV20 and GV24 acupoints for CIRI remains largely unknown. Our present study demonstrated that EA treatment at the GV20 and GV24 acupoints markedly alleviated middle cerebral artery occlusion/reperfusion (MCAO/R)-induced cognitive deficits and cerebral infarction in rats. Proteomics analysis revealed that 195 and 218 proteins were dysregulated in rat hippocampal tissues in the MCAO/R vs. sham group and thhhe EA vs. MCAO/R group, respectively. Moreover, 62 proteins with converse alteration trends in MCAO/R vs. sham and EA vs. MCAO/R groups were identified. These proteins might be implicated in the EA-mediated protective effect against MCAO/R-induced cerebral injury. GO enrichment analysis showed that 39 dysregulated proteins in the MCAO/R vs. sham group and 40 dysregulated proteins in the EA vs. MCAO/R group were related to brain and nerve development. Protein-protein interaction analysis of the abovementioned dysregulated proteins associated with brain and nerve development suggested that Pten/Akt pathway-related proteins might play major roles in regulating EA-mediated protective effects against MCAO/R-induced brain and nerve injury. Western blot assays demonstrated that Pak4, Akt3, and Efnb2 were expressed at low levels in the MCAO/R group vs. the sham group but at high levels in the EA group vs. the MCAO/R group. In conclusion, multiple proteins related to the protective effect of EA at the GV20 and GV24 acupoints against CIRI were identified in our study.

[Effect of electroacupuncture of Governor Vessel on expression of GAD67 and GABA-T in cerebral cortex of rats with post-stroke limb spasticity].

OBJECTIVE: To observe the effect of electroacupuncture (EA) of Governor Vessel (GV) on the expressions of glutamate decarboxylase 67 (GAD67) and γ-aminobutyric acid transaminase (GABA-T) in the cerebral cortex of rats with post-stroke limb spasticity, so as to explore its mechanism underlying improvement of limb spasticity. METHODS: Twenty four male SD rats were randomly and equally divided into control, sham operation, model, and EA groups. The cerebral ischemia model was established by occlusion of the middle cerebral artery (MCAO). EA (100 Hz, 1-3 mA) was applied to "Dazhui"(GV14), "Jizhong"(GV6) and "Houhui"( anteromedial of transverse process of the sixth lumbar vertebra) for 30 min, once daily for 7 consecutive days. The neurologic deficit score (0-5 points) was evaluated according to Zea Longa's method, and the muscular tension severity (0-5 points) was assessed according to the modified Ashworth muscle tone rating scale, and the tension signals of the quadriceps ferroris of the affected limb were recorded using tonotransducer and BL-420F electrophysiological recorder. The expression levels of GAD67 and GABA-T proteins and mRNAs in the cerebral cortex were detected by immunohistochemistry, fluorescence quantitative real-time PCR and Western blot, separately. RESULTS: After modeling, the neurological deficit score, muscle tone score, and the expression levels of GABA-T mRNA and protein in cerebral cortex were significantly increased (P<0.01, P<0.05), tension signal value and the expression levels of GAD67 mRNA and protein in cerebral cortex were significantly decreased (P<0.01) in the model group relevant to the control and sham operation groups. Following the intervention, the neurological deficit score, muscle tone score, and expression levels of GABA-T mRNA and protein in cerebral cortex were significantly decreased (P<0.01), tension signal value and the expression levels of GAD67 mRNA and protein in cerebral cortex were significantly increased (P<0.01, P<0.05) in the EA group in contrast to the model group. CONCLUSION: EA stimulation of Governor Vessel can ameliorate the limb spasticity symptom in MCAO rats, which may be associated with its functions in increasing the expressions of GAD67 protein and mRNA and inhibiting the expressions of GABA-T protein and mRNA, thereby playing the inhibitory role of GABA.

Quercetin improves atrial fibrillation through inhibiting TGF-ß/Smads pathway via promoting MiR-135b expression.

PURPOSE: To investigate the role and mechanism of quercetin in isoprenaline (ISO)-induced atrial fibrillation (AF). STUDY DESIGN: Rat cardiac fibroblasts (RCFs) models and RCFs were used to explore the effect and underlying mechanism of quercetin in isoprenaline (ISO)-induced atrial fibrillation (AF) in vivo and in vitro by a series of experiments. METHODS: Differentially expressed microRNAs were screened from human AF tissues using the GEO2R and RT-qPCR. The expressions of TGF-ß/Smads pathway molecules (TGFß1, TGFBR1, Tgfbr1, Tgfbr2, Smad2, Smad3, Smad4) in AF tissues were detected by RT-qPCR and Western blot. The relationships between miR-135b and genes (Tgfbr1, Tgfbr2, Smad2) were analyzed by Pearson correlation, TargetScan and dual-luciferase activity assay. RCFs induced by ISO were treated with quercetin (20 or 50 µM), miR-135b mimic and inhibitor, siTgfbr1 and their corresponding controls, then the cell viability was determined by MTT and the expressions of cyclin D1, α-SMA, collagen-related molecules, TGF-ß/Smads pathway molecules, and miR-135b were measured by RT-qPCR and Western blot. ISO-induced rats were treated with quercetin (25 mg/kg/day) via gavage, miR-135b antagomir, agomir and their corresponding controls. The treated rats were used for the detection of miR-135b expression by RT-qPCR, histopathological observation by HE and Masson staining, and the detection of Col1A1 and fibronectin contents by immunohistochemical technique. RESULTS: The expression of miR-135b was downregulated, and those of TGFBR1, TGFBR2, target genes of miR-135b were upregulated in human AF tissues and negatively regulated by miR-135b in RCFs. Through inhibiting TGF-ß/Smads pathway via promoting miR-135b expression, quercetin treatment inhibited proliferation, myofibroblast differentiation and collagen deposition in ISO-treated RCFs, as evidenced by reduced expressions of cyclin D1, α-SMA, collagen-related genes and proteins, and alleviated fibrosis and collagen deposition of atrial tissues in ISO-treated rats. CONCLUSION: Quercetin may alleviate AF by inhibiting fibrosis of atrial tissues through inhibiting TGF-ß/Smads pathway via promoting miR-135b expression.

Using Surface Electromyography to Evaluate the Efficacy of Governor Vessel Electroacupuncture in Poststroke Lower Limb Spasticity: Study Protocol for a Randomized Controlled Parallel Trial.

Background. Lower limb spasticity is a common complication after stroke, which seriously affects the quality of life and rehabilitation of patients. There are different treatment methods for poststroke spasticity. It has been found in clinical practice that governor vessel electroacupuncture (GV-EA) can effectively relieve poststroke upper extremity spasticity, but the efficacy of treatment of lower extremity spasticity needs to be further verified. This study aims to design a randomized controlled trial to evaluate the efficacy of GV-EA in the treatment of poststroke lower limb spasticity. Methods/Design. This is a randomized, controlled trial. Patients (N = 177) will be randomized to receive routine therapeutic drug and rehabilitation treatment plus GV-EA (experimental group) or routine therapeutic drug and rehabilitation treatment plus EA (control group 1) or routine therapeutic drug and rehabilitation treatment (control group 2). All patients will receive 20 sessions of treatment for 4 weeks. The primary outcomes are the RMS value and the Modified Ashworth Scale. Secondary outcomes include the Fugl-Meyer Assessment for Lower Extremity (FMA-LE) and the Modified Barthel Index score. All outcome measures will be evaluated at the beginning and after the intervention (4 weeks). Discussion. This trial will observe the clinical effect of GV-EA on lower extremity spasticity after stroke, especially its influence on surface electromyography characteristics, and provide high-quality experimental evidence for the clinical application of GV-EA based on surface electromyography in the treatment of poststroke lower limb spasticity. Trial Registration. China Clinical Trials Registry No. ChiCTR1900027969. Registered on 7 December 2019.

Mechanism of hysteresis in shock wave reflection.

This paper reports on the mechanism of the hysteresis in the transition between regular and Mach shock wave reflections. We disclose that, for a given inflow Mach number, a stable reflection configuration should maintain the minimal dissipation. As the wedge angle varies, the set of the minimal dissipation points forms the valley lines in the dissipation landscape, and these valley lines compose the hysteresis loop. The saddle-nodes, intersections of the ridge line, and the valley lines are actually the transition points. Additionally, the predicted reflection configurations agree well with the experimental and numerical results, validating this theory.

Glutamine switches vascular smooth muscle cells to synthetic phenotype through inhibiting miR-143 expression and upregulating THY1 expression.

AIMS: Vascular smooth muscle cells (VSMCs) are involved in the pathogenesis of many human cardiovascular diseases. They modulate their phenotype from "contractile" to "synthetic" in response to changes in local environmental cues. How glutamine regulates the differentiation of VSMCs and the underlying mechanisms remain largely unknown. MAIN METHODS: Here, we explored the effects of various doses of glutamine (0 mM, 1 mM, 2 mM, and 4 mM) on the proliferation, migration, and phenotypic switch of human VSMCs in vitro. Glutamine dose-dependently enhanced VSMC proliferation, and markedly increased VSMC migration. KEY FINDINGS: Notably, glutamine promoted the phenotypic switch of VSMCs towards a synthetic phenotype, as evidenced by significantly decreased expression of contractile markers myosin heavy chain 11 (MYH11) and calponin while increased expression of synthetic markers collagen I and vimentin. Importantly, these changes upon glutamine treatments were attenuated after additional treatments with glutamine metabolism inhibitor BPTES. Additionally, glutamine downregulated miR-143 expression, and miR-143 inactivation alone resulted in enhanced proliferation, migration, and promoted the synthetic phenotype of VSMCs. Moreover, Thy-1 cell surface antigen (THY1) was validated as a downstream target of miR-143, and THY1 expression was upregulated by glutamine in VSMCs. Furthermore, either miR-143 overexpression or THY1 silencing abolished the effect of glutamine on proliferation, migration, and phenotypic switch of VSMCs, supporting a novel glutamine-miR-143-THY1 pathway in modulating VSMC functions. SIGNIFICANCE: This study demonstrated a novel mechanism of glutamine in modulation of VSMC phenotypic switch by targeting miR-143 and THY1, and provides significant insight on targeted therapy of patients with cardiovascular diseases.

Kounis Syndrome Induced by Anisodamine: A Case Report.

Kounis syndrome is a rare type of acute coronary syndrome caused by coronary spasm with or without atherosclerotic plaque erosion or rupture due to inflammatory factors released by allergic reactions. Due to a lack of awareness, Kounis syndrome is often underdiagnosed. Here, we for the first time report a case of Kounis syndrome induced by anisodamine. A 48-year-old woman presented with upper abdominal pain and vomiting after eating. She was diagnosed with gastrointestinal spasm and intramuscularly injected with 10 mg anisodamine. The patient subsequently developed chest pain and hypotension with erythematous rash. A systemic allergic reaction was diagnosed. Saline solution, promethazine and dexamethasone were administered immediately. A 12-lead electrocardiogram indicated ST-segment elevation in II, III and aVF leads. Emergent coronary angiography was recommended. According to a preoperative electrocardiogram, the ST-segment elevation in the II, III and aVF leads had disappeared. Coronary angiograph revealed no significant coronary stenosis. The patient was diagnosed with Kounis syndrome induced by anisodamine, showing acute ST-segment elevation myocardial infarction due to allergic coronary vasospasm. During the 9-month follow-up, the patient did not receive further anisodamine injections and remained free of chest pain. In conclusion, it is essential for clinicians to be aware of Kounis syndrome because of the wide range of triggers and its potentially fatal evolution if not identified in time.

A Meta-analysis of the Value of vWF in the Diagnosis of Liver Cirrhosis with Portal Hypertension.

Background and Aims: Studies have indicated that serum von Willebrand factor (vWF) has a positive correlation with hepatic venous pressure gradient. However, information on the value of vWF in the diagnosis of liver cirrhosis with portal hypertension has been lacking. The purpose of this meta-analysis was to assess the value of vWF in the diagnosis of liver cirrhosis with portal hypertension. Methods: Studies that analyzed the sensitivity, specificity, diagnostic odds ratio combined with likelihood ratios and test for heterogeneity of vWF in the diagnosis of liver cirrhosis with portal hypertension were found in the Cochrane Library, Ovid, VOS-SCI, CNKI, PubMed, Medline, EMBASE, CMB and Wanfang databases. In the end, the data was used to draw the summary receiver operating characteristic curve and to calculate the area under the curve. Results: Four studies involving 662 patients were analyzed. The results showed that serum vWF in liver cirrhosis with portal hypertension were significantly higher than in those without portal hypertension. Sensitivity combined was 0.823 (95% CI: 0.788, 0.855). Specificity combined was 0.782 (95% CI: 0.708, 0.845). +LR combined was 3.777 (95% CI: 2.794, 5.107). -LR combined was 0.221 (95% CI: 0.180, 0.272). Diagnostic odds ratio combined was 18.347 (95% CI: 11.725, 28.708). The area under the curve was 0.8896. Conclusions: Serum vWF can be used as an effective and feasible method for noninvasive diagnosis of liver cirrhosis with portal hypertension. However, further studies are still needed to evaluate the severity of liver cirrhosis with portal hypertension.

Value of gamma-glutamyltranspeptidase-to-platelet ratio in diagnosis of hepatic fibrosis in patients with chronic hepatitis B.

AIM: To investigate the value of the gamma-glutamyltraspeptidase (GGT)-to-platelet (PLT) ratio (GPR) in the diagnosis of hepatic fibrosis in patients with chronic hepatitis B (CHB). METHODS: We included 390 untreated CHB patients in this study. The GPR, aspartate aminotransferase (AST)-to-PLT ratio index (APRI), and fibrosis-4 (FIB-4) of all patients were analysed to determine if these parameter were correlated with age, gender, medical history, liver function [total bilirubin (TBil), alanine aminotransferase (ALT), and AST], GGT, PLT count, or hepatic fibrosis stage. The GPR, APRI, and FIB-4, as well as the combination of the GPR and APRI or the GPR and FIB-4 were assessed in different cirrhosis stages using receiver operating characteristic (ROC) curve analysis to evaluate their value in diagnosing hepatic fibrosis in CHB patients. RESULTS: The GPR, APRI, and FIB-4 were not correlated with CHB patients' age, gender, or disease duration (P > 0.05), but all of these parameters were positively correlated with serum ALT, AST, GGT, and PLT count (P < 0.01). Additionally, the GPR, APRI, and FIB-4 were positively correlated with hepatic fibrosis (P < 0.01); the areas under the ROC curve for the GPR in F1, F2, F3, and F4 stages were 0.723, 0.741, 0.826, and 0.833, respectively, which were significantly higher than the respective values for the FIB-4 and APRI (F1: 0.581, 0.612; F2: 0.706, 0.711; F3: 0.73, 0.751; and F4: 0.799, 0.778). The respective diagnostic cut-off points for each stage were 0.402, 0.448, 0.548, and 0.833, respectively. The diagnostic sensitivity and specificity were, respectively, 88.8% and 87.5% in F1, 72.7% and 89.7% in F2, 81.3% and 98.6% in F3, and 80% and 97.4% in F4 when the GPR and APRI were connected in parallel; 86.6% and 90.2%, 78.4% and 96%, 78.6% and 97.4%, and 73.2% and 97.9%, respectively, when the GPR and APRI were connected in series; 80.2% and 89%, 65% and 89%, 70.3% and 98.5%, and 78.8% and 96.8%, respectively, when the GPR and FIB-4 were connected in parallel; and 83.6% and 87.9%, 76.8% and 96.6%, 72.7% and 98%, and 74.4% and 97.7%, respectively, when the GPR and FIB-4 were connected in series. CONCLUSION: The GPR, as a serum diagnostic index of liver fibrosis, is more accurate, sensitive, and easy to use than the FIB-4 and APRI, and the GPR can significantly improve the sensitivity and specificity of hepatic fibrosis diagnosis in CHB when combined with the FIB-4 or APRI.

Azelaic Acid Exerts Antileukemic Activity in Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) is an acute leukemia common in most adults; its prevalence intensifies with age. The overall survival of AML is very poor because of therapeutic resistance. Azelaic acid (AZA) is non-toxic, non-teratogenic, and non-mutagenic and its antitumor effect on various tumor cells is well established; Nonetheless, its therapeutic effects in AML cells are largely unknown. In this study, it was shown that AZA significantly inhibits the cell viability and induces apoptosis in AML cells in a dose-dependent manner. Additionally, AZA suppressed the expression of phosphorylated Akt, Jab1 and Trx, and this suppression was enhanced by treatment with Jab1 siRNA. Furthermore, AZA sensitized AML cells to Ara-c chemotherapy. The suppressive effect of AZA on tumor growth was examined in vivo by subcutaneously inoculated AML cells in a tumor model using nude mice. These findings indicate that AZA is useful as an effective ingredient in antineoplastic activity.

Assessment of high-sensitivity C-reactive protein tests for the diagnosis of hepatocellular carcinoma in patients with hepatitis B-associated liver cirrhosis.

Hepatocellular carcinoma (HCC) is a common malignant tumor worldwide, with high morbidity and mortality. Chronic infection with hepatitis B virus (HBV) is a major risk factor for the development of hepatocellular carcinoma and the majority (~80%) of hepatocellular carcinoma patients in China exhibit co-morbidity with HBV-associated liver cirrhosis. The goal of reliable early diagnostic and prognostic techniques for HBV-associated HCC remains unrealized. The aim of the present study was to explore the efficacy of serum high-sensitivity C-reactive protein (hs-CRP) tests in the early diagnosis of HCC in patients with HBV-associated liver cirrhosis. A cohort of 493 patients with HBV-associated liver disease was divided into three groups: Chronic HBV (CHB) group; liver cirrhosis without HCC (LC) group; and liver cirrhosis with HCC (HCC) group. A further 47 healthy individuals comprised the healthy control (CN) group. Comparative analyses of clinical symptoms, histopathology, ultrasound imagery, computed tomography, magnetic resonance imaging, biochemistry [α-fetoprotein (AFP) and liver function enzymes], and hs-CRP tests were conducted across these four groups. Immunohistochemical analysis showed that CRP is strongly expressed in HCC tumor tissue, but is not expressed elsewhere. Analyses of the correlations between serum hs-CRP levels and HCC clinical parameters indicated that there was no correlation between serum hs-CRP levels, tumor Edmondson grade, tumor-node-metastasis stage and AFP status. Serum hs-CRP and AFP levels were found to be significantly elevated in the HCC group compared to those in the LC, CHB and CN groups (P<0.01). Receiver operator characteristic analysis showed that measurement of serum hs-CRP could differentiate HCC from HBV-associated liver cirrhosis, as well as increase the accuracy of HCC diagnoses. Additionally, measurement of hs-CRP and AFP together improved diagnostic accuracy for HCC compared with either test alone. Serum hs-CRP could have potential as an effective diagnostic tool to complement AFP in diagnosing HCC and improving the identification of AFP-negative HCC in patients with HBV-associated liver cirrhosis. The present findings may facilitate the earlier diagnosis of hepatocellular carcinoma, permitting more effective treatment and a broader spectrum of treatment modalities for patients with advanced hepatic disease.

[Clinical significance of high-sensitivity C-reactive protein in development of chronic hepatitis B].

OBJECTIVE: To explore the clinical significance of high-sensitivity C-reactive protein (hsCRP) in the development of chronic hepatitis B (CHB). METHODS: A total of 182 patients with untreated CHB and 50 healthy individuals (controls) participated in the study. Correlation analysis was performed to determine the association of serum hs-CRP with the age,sex,medical history,serum hepatitis B virus (HBV) DNA, liver function parameters,liver stiffness measure (LSM) and hepatic fibrosis; in addition, correlation analysis was carried out for the associations of degree of liver damage with grade of hepatic fibrosis, LSM and the serum levels of hs-CRP. RESULTS: CHB patients showed significantly higher serum hs-CRP levels than healthy controls (2.38 ± 2.79 vs.0.78 ± 1.07; t =2.495, P < 0.05). Serum hs-CRP levels were significantly correlated with HBV DNA (r = 0.159), liver function parameters (total bilirubin, r = 0.271; alanine aminotransferase, r = 0.298; aspartate aminotransferase, r = 0.389), and LSM, r = 0.562) (all P < 0.05). The correlations with liver function (r = 0.340), LSM (r = 0.292) and hepatic fibrosis grade were positive (r = 0.434) (all P < 0.01). CONCLUSION: Serum hs-CRP levels in CHB patients can reflect degree of liver damage and of liver fibrosis.

Serum high-sensitivity C-reactive protein are associated with HBV replication, liver damage and fibrosis in patients with chronic hepatitis B.

BACKGROUND/AIMS: The aim of this study was to explore the potential role of serum high-sensitivity C-reactive protein (hs-CRP) in the pathogenic process of chronic hepatitis B. METHODOLOGY: A total of 380 patients with chronic hepatitis B were included in this study. All patients received the concentrations of serum hs-CRP, Hepatitis B sero-markers, serum HBV-DNA loads, liver function parameters and liver stiffness were measured, and in which 172 patients undertaken liver biopsy and immunohistochemistry analysis. RESULTS: Serum hs-CRP concentration in patients with the chronic hepatitis B (2.38 ± 5.52) was significantly higher than healthy controls (0.60 ± 0.53), P < 0.05. The area under ROC curve in fibrosis S4 and S3 is 0.826 and 0.78. The sensitivity and specificity of hs-CRP for fibrosis S3 and S4 diagnosis were 81.8%, 80% and 73.4%, 76.2% respectively (cut off: 1.01 mg/ml, 1.11 mg/l). CONCLUSIONS: C-reactive Protein are associated with HBV replication, liver damage and fibrosis in patients with chronic hepatitis B, and serum High-sensitivity C-reactive Protein may be a marker for diagnosing significant fibrosis in patients with chronic hepatitis B, and can reflect the severity of liver damage.