Differential effects of oxytetracycline on detoxification and antioxidant defense in the hepatopancreas and intestine of Chinese mitten crab under cadmium stress.

This study aims to evaluate the effects of oxytetracycline (OTC) on detoxification and oxidative defense in the hepatopancreas and intestine of Chinese mitten crab (Eriocheir sinensis) under cadmium (Cd) stress. The crab was exposed to 0.6 µM Cd, 0.6 µM OTC, and 0.6 µM Cd plus 0.6 µM OTC for 42 days. Our results showed that in the intestine, OTC alone enhanced protein carboxylation (PC) and malondialdehyde (MDA) contents, which was associated with the increased OTC accumulation. Compared to Cd alone, Cd plus OTC increased Cd and OTC contents, and reduced detoxification (i.e., glutathione (GSH) content, gene expressions of cytochrome P450 (CYP) isoforms, 7-ethoxyresorufin O-deethylase (EROD) activity, mRNA levels and activities of glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione-S-transferase (GST)), and antioxidant defense (i.e., gene expressions and activities of catalase (CAT) and superoxide dismutase (SOD)) in the intestine, leading to the increased in PC and MDA contents, suggesting that OTC had a synergistic effect on Cd-induced oxidative damage. In the hepatopancreas, although OTC alone increased OTC accumulation, it did not affect PC and MDA contents. Compared to Cd alone, Cd plus OTC reduced MDA content, which was closely related to the improvement of detoxification (i.e., GSH content, mRNA levels of CYP isoforms, EROD activity, gene expressions and activities of GPx, GR and GST), and antioxidant defense (gene expressions and activities of CAT and SOD, metallothionein content). Aryl hydrocarbon receptor (AhR) and nuclear factor E2-related factor 2 (Nrf2) transcriptional expressions were positively correlated with most detoxification- and antioxidant-related gene expressions, respectively, indicating that AhR and Nrf2 were involved in the regulation of these gene expressions. Our results unambiguously demonstrated that OTC had tissue-specific effects on Cd-induced toxicological effect in E. sinensis, which contributed to accurately evaluating Cd toxicity modulated by TCs in crab.

Prevalence, characteristics, evaluation, and management of carotid body tumors: Systematic analysis based on available evidence.

OBJECTIVE: Although carotid body tumors (CBTs) are rare, they attract particular attention because of their propensity for malignant transformation and the high surgical risk. Because data are scarce and as it is difficult to achieve a large sample size, no study has yet comprehensively analyzed the characteristics, management, or operative complications of CBTs. Therefore, we collected and analyzed all currently available information on CBTs and used the pooled data to derive quantitative information on disease characteristics and management. METHODS: We systematically searched PubMed, Embase, the Cochrane Library, and the Web of Science up to December 1, 2022, for studies that investigated the characteristics and management of CBTs. The primary objective was to identify the prevalence of the various characteristics and the incidence of complications. The secondary objective was to compare patients who underwent preoperative embolization (PE) and those who did not (non-PE), as well as to compare patients with different Shamblin grades and those with and without succinate dehydrogenase (SDH) mutations in terms of CBT characteristics and complications. Two reviewers selected studies for inclusion and independently extracted data. All statistical analyses were performed using the standard statistical procedures of Review Manager 5.2 and Stata 12.0. RESULTS: A total of 155 studies with 9291 patients and 9862 tumors were identified. The pooled results indicated that the median age of patients with CBT was 45.72 years, and 65% were female. The proportion of patients with bilateral lesions was 13%. In addition, 16% of patients had relevant family histories, and the proportion of those with SDH gene mutations was 36%. Sixteen percent of patients experienced multiple paragangliomas, and 12% of CBTs had catecholamine function. The incidence of cranial nerve injury (CNI) was 27%, and 14% of patients suffered from permanent CNI. The incidence rates of operative mortality and stroke were both 1%, and 4% of patients developed transient ischemic attacks. Of all CBTs, 6% were malignant or associated with metastases or recurrences. The most common metastatic locations were the lymph nodes (3%) and bone (3%), followed by the lungs (2%). Compared with non-PE, PE reduced the estimated blood loss (standardized mean difference, -0.95; 95% confidence interval [CI], -1.70 to -0.20) and the operation time (standardized mean difference, -0.56; 95% CI, -1.03 to -0.09), but it increased the incidence of stroke (odds ratio, 2.44; 95% CI, 1.04-5.73). Higher Shamblin grade tumors were associated with more operative complications. Patients who were SDH gene mutation-positive were more likely to have a relevant family history and had more symptoms. CONCLUSIONS: CBT was most common in middle-aged females, and early surgical resection was feasible; there was a low incidence of serious operative complications. Routine PE is not recommended because this may increase the incidence of stroke, although PE somewhat reduced the estimated blood loss and operation time. Higher Shamblin grade tumors increased the incidence of operative complications. Patients who were SDH gene mutation-positive had the most relevant family histories and symptoms.

A new in situ magnetic method to indicate the source and seasonal diffusion of heavy metal contamination at Qingdao Beach, China.

The accumulation of heavy metals from sewage and garbage dumping can seriously impact beach tourism and thus the local economy, but it is difficult to quickly and accurately determine the pollution location and source of heavy metals and clarify their diffusion range. This study investigates a new in situ magnetic testing method to address this issue. (1) The in situ method can be used to effectively and quickly evaluate heavy metal sources and diffusion ranges based on the distribution of κ values. (2) According to chemical experiments, the specific elements polluting a beach can be determined, such as the Cr, Ni, Zn, and Fe pollution of Beach No. 3. (3) Although κ values for assessing heavy metal pollution on different beaches vary, metal pollution occurs when the higher κ value is more than 50 times the lower κ value on the same beach. (4) The κ values vary in different seasons due to the influence of natural factors and urban seasonal sewage policies.

Quantitative Measurement of Serum HBcrAg Can Be Used to Assess the Feasibility of Safe Discontinuation of Antiviral Therapy for Chronic Hepatitis B.

Hepatitis B virus (HBV) infection is a serious global health problem, and chronic HBV infection significantly increases the risk of liver fibrosis, cirrhosis, and even hepatocellular carcinoma in patients. Current first-line therapeutics such as nucleos(t)ide analogues and interferons are unable to completely clear cccDNA, so the vast majority of patients need to take long-term or even lifelong medication. However, long-term virological and biochemical responses can be achieved in some patients after drug withdrawal. Successfully screening these patients with drug withdrawal advantages is difficult. Hepatitis-B-core-related antigen (HBcrAg) is a new HBV serological marker that which can reflect the level and transcription activity of cccDNA in hepatocytes. Therefore, HBcrAg has potential value in guiding patients in drug withdrawal. This review summarizes previous reports on HBcrAg and evaluates the application value of HBcrAg in safe drug discontinuation.

Study on the High-Temperature Interaction between Coke and Iron Ores with Different Layer Thicknesses.

Coke plays a key role as the skeleton of the charge column in BF. The gas path formed by the coke layer in the BF has a decisive influence on gas permeability. At high temperatures, the interface between coke and ore undergoes a melting reaction of coke and a reduction reaction of ore. The better the reducibility of the ore, the more conducive it is to the coupling reaction of ore and coke. The melting loss reaction of coke becomes more intense, and the corresponding strength of coke will decrease, which will affect the permeability of the blast furnace and is not conducive to the smooth operation of the blast furnace. Especially with a deterioration in iron ore quality, BF operation faces severe challenges, which makes it necessary to find an effective way to strengthen BF operation. In this study, a melting-dropping furnace was used to develop and clarify the high-temperature interaction between coke and iron ores with different layer thicknesses. The influencing factors were studied by establishing a gas permeability mathematical model and observing the metallographic microscope images of samples after the coke solution loss reaction. The relationships between coke layer thickness, distribution of gas flow, and pressure drop were obtained. The results showed that, under certain conditions, the gas permeability property of a furnace burden has been improved after the coke layer thickness increased. Upon observing the size of coke particles at the interface reaction site, the degree of melting loss reaction can be determined. A smaller particle size indicates more melting loss reaction. A dripping eigenvalue for molten metal was introduced to evaluate the dynamic changes in the comprehensive dripping properties of molten metal of furnace burden, which showed that the dripping eigenvalue for the molten metal could deteriorate because of the unruly thickness and the coke layer thickness should be limited through considering the operational indicators of the blast furnace.

Characteristic changes and environmental indicators of magnetic spherules in the South Yellow Sea mud area for about 7.5 ka.

Magnetic spherules originate from anthropogenic and natural sources and can be differentiated based on morphology and composition. Using magnetic measurement, diameter measurement, scanning electron microscopy and energy dispersive spectroscopy (SEM-EDS) analysis of a 10 m sediment core in the mud area of the South Yellow Sea, we found that magnetic spherules occur at all observed depths of the core. The magnetic spherule concentrations vary from 10 spherules/0.5 g to 62 spherules/0.5 g. Here, concentrations generally less than 10 spherules/0.5 g are considered as the background value in the core. The peak value of magnetic spherules appeared at the 0.02, 0.3, 2 and 8 m, and their concentrations are 62, 52, 36, 48 spherules/0.5 g, respectively. According to the deposition age, concentration, diameter, morphology and chemical characteristics of the spherules, it is found that the spherules at 0.02 m are produced by industrial coal burning. A volcanic eruption event was the main responsible for the accumulation of spherules at 0.3 and 8 m, while the spherules located at 2 m are related to a wildfire event. Magnetic spherules are common in continental shelf regions and can well document the human activities and natural environment events.

[Soil Carbon Pool Allocation Dynamics During Soil Development in the Lower Yangtze River Alluvial Plain].

The allocation dynamics of soil carbon pools during soil development and land use are the key to revealing the carbon cycle process. To clarify the distribution of the soil carbon pool and its change trend, a soil reclamation chronosequence (0 a, 60 a, 160 a, 280 a, 1 000 a, and 1 500 a reclamation) was established in a typical alluvial plain in the Lower Yangtze River, and the content and density of soil organic carbon (SOC), soil inorganic carbon (SIC), particulate organic carbon (POC), and mineral-associated organic carbon (MAOC), along with carbon sequestration potential (CSP) indicators of topsoil under different land use types were measured and analyzed. The results showed that after approximately 1 500 a reclamation, the SOC content developed from the Yangtze River alluvial deposits generally increased by 4.9% after the initial decline, whereas the SIC content decreased to 0.2% from 25.8% of the total carbon content due to its rapid leaching. The MAOC content was normally higher than that of POC, and MAOC was contributing 48.0%-79.7% of the SOC accumulation. In this region, the soil organic carbon density (SOCD) accounted for 57.4%-100% of the total carbon density, the soil carbon sequestration levels (CSL) ranged from 18.6% to 56.1%, and CSP under paddy-dryland rotation increased by 20.8% compared to that under dryland. The C/N ratio and total nitrogen content are key factors in explaining soil carbon accumulation processes, and the reclamation year plays an important role in evaluating soil carbon sequestration levels. After long-term utilization, the cultivated soil in the Yangtze River floodplain must be carefully managed through balanced fertilization to maintain soil productivity, promote the accumulation of SOC, and avoid the decline in soil carbon sequestration capacity.

Tracking of Stem Cells in Chronic Liver Diseases: Current Trends and Developments.

Stem cell therapy holds great promise for future clinical practice for treatment of advanced liver diseases. However, the fate of stem cells after transplantation, including the distribution, viability, and the cell clearance, has not been fully elucidated. Herein, recent advances regarding the imaging tools for stem cells tracking mainly in chronic liver diseases with the advantages and disadvantages of each approach have been described. Magnetic resonance imaging is a promising clinical imaging modality due to non-radioactivity, excellent penetrability, and high spatial resolution. Fluorescence imaging and radionuclide imaging demonstrate relatively increased sensitivity, with the latter excelling in real-time monitoring. Reporter genes specialize in long-term tracing. Nevertheless, the disadvantages of low sensitivity, radiation, exogenous gene risk are inevitably present in each of these means, respectively. In this review, we aim to comprehensively evaluate the current state of methods for tracking of stem cell, highlighting their strengths and weaknesses, and providing insights into their future potential. Multimodality imaging strategies may overcome the inherent limitations of single-modality imaging by combining the strengths of different imaging techniques to provide more comprehensive information in the clinical setting.

Treatment-related gastrointestinal adverse events of nivolumab plus ipilimumab in randomized clinical trials: a systematic review and meta-analysis.

The authors used a meta-analysis to evaluate the risks of gastrointestinal adverse events in the cotreatment of malignant tumors with nivolumab and ipilimumab. The meta-analysis revealed that the most common gastrointestinal adverse event at all grades was diarrhea, followed by nausea, decreased appetite, vomiting, constipation, colitis and abdominal pain. The most common severe gastrointestinal adverse events were colitis and diarrhea. Different administration schemes differ in the risk of such events, and thus these events may be minimized by modulating the administration scheme of the cotreatment.

Different effects of continuous and pulsed Benzo[a]pyrene exposure on metabolism and antioxidant defense of large yellow croaker: Depend on exposure duration.

This study aims to compare differential effects of continuous and pulsed BaP exposures on metabolism and antioxidant defense in the liver of large yellow croaker. Fish were subjected to BaP for 4 days and 36 days in three exposure regimes with the same time-averaged concentration of BaP: 4 µg/L BaP continuously, 8 µg/L BaP for 24 h every other day or 16 µg/L BaP for 24 h every 4 days. Our results showed that compared to pulsed BaP exposures, continuous BaP exposure reduced BaP metabolism (CYP1A, CYP3A and AHR transcriptional expressions, GSH content, GSH/GSSG ratio, EROD and GST activities) and antioxidant defense (T-SOD activity) on day 4, resulting to the increases in MDA and PC contents, indicating that continuous BaP exposure induced more severe oxidative damage during the early stage of exposure. But continuous BaP exposure reduced MDA and PC contents by improving BaP metabolism and antioxidant defense during the late stage of exposure. CYP1B transcriptional expression and CAT activity were unsuitable biomarkers of both continuous and pulsed BaP exposures. In conclusion, our results demonstrated differential effects of continuous and pulsed exposures on BaP metabolism and antioxidant responses, which were depend on exposure duration.

Meta-analysis of proton pump inhibitor use and the risk of developing gastric cancer or colorectal cancer.

To evaluate the relationship between the use of proton pump inhibitors (PPI) and the risk of gastric cancer and colorectal cancer by using meta-analysis. Computer search PUBMED, EMBASE, Cochrane Library, CNKI and Wanfang database to obtain relevant literature on the use of PPI and the risk of gastric cancer and colorectal cancer, extract relevant data, and use Stata14.0 for Meta-analysis. A total of 24 articles were included, including 12 articles for gastric cancer and 12 articles for colorectal cancer. A total of 5 313 749 persons were included in the study and analysis. Meta-analysis results showed that the risk of gastric cancer in PPI users was significantly increased [risk ratio (RR) = 2.04, 95% confidence interval (CI) (1.33-2.75)], and the regional subgroup analysis results showed that in Europe [RR = 2.01, 95% CI (0.92, 3.09), P < 0.05] and Asia [RR = 2.15, 95% CI (1.16, 3.14), P < 0.05] This risk is higher, and Asia is higher than Europe. The risk of colorectal cancer is slightly increased [RR = 1. 22, 95% CI (1.03, 1.40, P < 0.05], and the regional subgroup analysis results show that in Europe [RR = 1.05 95% CI (0.98, 1.12), P < 0.05] and Asia [RR = 1.18, 95% CI (1.10, 1.27), P < 0.05]. This risk is low, but Asia is higher than Europe. The use of PPI significantly increases gastric cancer However, the risk of colorectal cancer is not significantly increased. The risk of gastric cancer and colorectal cancer in the population using PPI in Asia is higher than that in Europe.

The high level of IL-1ß in the serum of ACLF patients induces increased IL-8 expression in hUC-MSCs and reduces the efficacy of hUC-MSCs in liver failure.

BACKGROUND: Stem cells play a therapeutic role mainly through immunoregulation. However, the immunomodulatory function of stem cells may be affected by inflammation-related factors in patients' serum. Therefore, this study aims to investigate the possible mechanism by which acute-on-chronic liver failure (ACLF) patient serum influences the efficacy of hUC-MSCs. METHODS: The serum of surviving and dead ACLF patients was collected to culture hUC-MSCs in vitro, and the hUC-MSCs cultured in the serum of ACLF patients were used to treat acute liver failure (ALF) rats. The therapeutic effect on the rats was evaluated by a survival curve, the transaminase level and liver histopathology. The expression of cytokines in hUC-MSCs was detected by Q-PCR and ELISA. RESULTS: Serum pretreatment reduced the therapeutic effect of hUC-MSCs on ALF, especially pretreatment in the serum from dead ACLF patients. After hUC-MSCs were cultured in the serum of surviving or dead ACLF patients, the most differentially expressed factor was IL-8. Interfering with the expression of IL-8 in hUC-MSCs can improve the therapeutic effect of hUC-MSCs on ALF. The high level of IL-1ß in the serum of dead ACLF patients causes the increased expression of IL-8 in hUC-MSCs through the activation of the NF-κB signaling pathway. Meanwhile, we found that the neutralizing IL-1ß in serum from dead ACLF patients can improve the therapeutic effect of hUC-MSCs on ALF. CONCLUSION: The high level of IL-1ß in ACLF serum can promote the expression of IL-8 in hUC-MSCs through the NF-κB signaling pathway, thus reducing the effect of hUC-MSCs on ALF.

Improved bone and renal safety in younger tenofovir disoproxil fumarate experienced chronic hepatitis B patients after switching to tenofovir alafenamide or entecavir.

INTRODUCTION AND OBJECTIVES: Renal and bone impairment has been reported in chronic hepatitis B (CHB) patients receiving long-term tenofovir disoproxil fumarate (TDF) therapy. This study aimed to assess the incidence of renal and bone impairment in CHB patients with long-term TDF therapy and to identify the changes in bone mineral density (BMD) and renal function in these patients after switching to entecavir (ETV) or tenofovir alafenamide (TAF). MATERIALS AND METHODS: This retrospective study collected clinical data from CHB patients who received TDF monotherapy over 96 weeks. The changes in BMD and renal function were analyzed after 96 weeks of switching antiviral regimens (ETV or TAF) or maintenance TDF. RESULTS: At baseline, 154 patients receiving TDF monotherapy over 96 weeks were enrolled, with a younger median age of 36.75 years, 35.1% (54/154) of patients experienced elevated urinary ß2 microglobulin and 20.1% (31/154) of patients had reduced hip BMD (T<-1). At week 96, among the 123 patients with baseline normal BMD, patients who maintained TDF (n=85) had experienced a decrease in hip BMD, while patients who switched antiviral regimens (n=38) experienced an increase (-13.97% vs 2.34%, p<0.05). Among patients with a baseline reduced BMD (n=31), the alterations in BMD were similar in patients who maintained TDF (n=5) and those who switched antiviral regimens (n=26) (-15.81% vs 7.35%, p<0.05). Irrespective of baseline BMD status, renal function decreased significantly in patients who maintained TDF and improved in patients who switched antiviral regimens. CONCLUSIONS: Younger CHB patients on long-term TDF therapy are at high risk for bone and renal impairment, with the risk being reduced when switched to ETV or TAF.

Different cold tolerances among three strains of large yellow croaker: related to antioxidant defense and energy metabolism.

The aim of this study was to compare low-temperature tolerances in different strains of large yellow croaker. Dai Qu (DQ), Min-Yue Dong (MY), and Quan Zhou (NZ) strains of large yellow croaker were subjected to cold stress (8.6 °C) for 12 h, 24 h, 48 h, and 96 h. Survival rate, histological observation, and antioxidant and energy metabolism indicators were determined. The results showed that compared with the DQ group and MY group, NZ group aggravated hepatic structure, enhanced ROS, lactate, and anaerobic metabolism (PK gene expression and activity), while inhibited ATP, GSH, antioxidant enzymes (mRNA levels and activities of SOD, GPx, and CAT), and aerobic metabolism enzymes (mRNA levels and activities of F-ATPase, SDH, and MDH), indicating the reduction of cold tolerance in the NZ group was closely correlated with the decrement of antioxidative capacity and energy metabolism efficiency. Nrf2 and AMPK gene expressions were correlated with antioxidant and energy metabolism mRNA levels, respectively, suggesting Nrf2 and AMPK might participate in the modulation of target genes during the cold-stress adaptation. In conclusion, low temperature tolerance of fish depended on the antioxidant defense and energy metabolism efficiency, which contributes to understanding the underlying mechanisms of cold adaptation in large yellow croaker.

Mesenchymal Stem Cell Therapy in Acute Liver Failure.

Acute liver failure (ALF) is a severe liver disease syndrome with rapid deterioration and high mortality. Liver transplantation is the most effective treatment, but the lack of donor livers and the high cost of transplantation limit its broad application. In recent years, there has been no breakthrough in the treatment of ALF, and the application of stem cells in the treatment of ALF is a crucial research field. Mesenchymal stem cells (MSCs) are widely used in disease treatment research due to their abundant sources, low immunogenicity, and no ethical restrictions. Although MSCs are effective for treating ALF, the application of MSCs to ALF needs to be further studied and optimized. In this review, we discuss the potential mechanisms of MSCs therapy for ALF, summarize some methods to enhance the efficacy of MSCs, and explore optimal approaches for MSC transplantation.

The role of CSE1L silencing in the regulation of proliferation and apoptosis via the AMPK/mTOR signaling pathway in chronic myeloid leukemia.

OBJECTIVES: Chromosome segregation 1-like (CSE1L) is abundant and strongly expressed in solid tumors. However, the expression and role of CSE1L in chronic myeloid leukemia(CML) remain largely unknown. MATERIALS AND METHODS: The relative expression levels of CSE1L in bone marrow granulocytes from patients with primary CML and non-hematologic controls were measured by flow cytometry. Cell counting kit-8 analysis, DNA Content Quantitation Assay, and Annexin V-PE/7-AAD staining were applied to assess the effects of CSE1L knockdown on cell proliferation, cell cycle progression, and apoptosis. RESULTS: Elevated expression of CSE1L was detected in bone marrow granulocytes of patients with primary CML. In the CML cell line K562 cells, CSE1L knockdown impaired cell proliferation blocked the cell cycle shift from G0/G1 phase to the S phase, and promoted apoptosis. Knockdown of CSE1L reduced Bcl-2 protein expression and increased Bax protein expression. Meanwhile, knockdown of CSE1L enhanced the expression of phospho-AMPK protein and decreased the expression of phospho-mTOR protein. The expression of total AMPK and mTOR proteins was not affected. In addition, CSE1L expression levels were decreased in imatinib-treated K562 cells. CONCLUSIONS: CSE1L plays a pivotal role in K562 cell survival and growth. These functions may be partially dependent on the AMPK/mTOR signaling pathway to achieve. In addition, CSE1L may have had a future impact on the treatment of CML patients.

Upregulation of microRNA-125b-5p alleviates acute liver failure by regulating the Keap1/Nrf2/HO-1 pathway.

Background: Acute liver failure (ALF) and acute-on-chronic liver failure (ACLF) are the two most common subtypes of liver failure. They are both life-threatening clinical problems with high short-term mortality. Although liver transplantation is an effective therapeutic, its application is limited due to the shortage of donor organs. Given that both ACLF and ALF are driven by excessive inflammation in the initial stage, molecules targeting inflammation may benefit the two conditions. MicroRNAs (miRNAs) are a group of small endogenous noncoding interfering RNA molecules. Regulation of miRNAs related to inflammation may serve as promising interventions for the treatment of liver failure. Aims: To explore the role and mechanism of miR-125b-5p in the development of liver failure. Methods: Six human liver tissues were categorized into HBV-non-ACLF and HBV-ACLF groups. Differentially expressed miRNAs (DE-miRNAs) were screened and identified through high-throughput sequencing analysis. Among these DE-miRNAs, miR-125b-5p was selected for further study of its role and mechanism in lipopolysaccharide (LPS)/D-galactosamine (D-GalN) -challenged Huh7 cells and mice in vitro and in vivo. Results: A total of 75 DE-miRNAs were obtained. Of these DE-miRNAs, miR-125b-5p was the focus of further investigation based on our previous findings and preliminary results. We preliminarily observed that the levels of miR-125b-5p were lower in the HBV-ACLF group than in the HBV-non-ACLF group. Meanwhile, LPS/D-GalN-challenged mice and Huh7 cells both showed decreased miR-125b-5p levels when compared to their untreated control group, suggesting that miR-125b-5p may have a protective role against liver injury, regardless of ACLF or ALF. Subsequent results revealed that miR-125b-5p not only inhibited Huh7 cell apoptosis in vitro but also relieved mouse ALF in vivo with evidence of improved liver histology, decreased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, and reduced tumor necrosis factor-α (TNF-α) and IL-1ß levels. Based on the results of a biological prediction website, microRNA.org, Kelch-like ECH-associated protein 1 (Keap1) was predicted to be one of the target genes of miR-125b-5p, which was verified by a dual-luciferase reporter gene assay. Western blot results in vitro and in vivo showed that miR-125b-5p could decrease the expression of Keap1 and cleaved caspase-3 while upregulating the expression of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and heme oxygenase-1(HO-1). Conclusion: Upregulation of miR-125b-5p can alleviate acute liver failure by regulating the Keap1/Nrf2/HO-1 pathway, and regulation of miR-125b-5p may serve as an alternative intervention for liver failure.

Serum Pregenomic RNA Combined With Hepatitis B Core-Related Antigen Helps Predict the Risk of Virological Relapse After Discontinuation of Nucleos(t)ide Analogs in Patients With Chronic Hepatitis B.

Background and Aim: Cessation of nucleos(t)ide analogs (NAs) therapy in patients with chronic hepatitis B (CHB) is uncommon. Although criteria for discontinuation appear in some guidelines, the indicators for assessing discontinuation of NAs are limited, whether NAs can be safely ceased remains a difficult clinical issue. Our study aimed to investigate the role of serum pregenomic RNA (pgRNA) and hepatitis B core-related antigen (HBcrAg) at the end of treatment (EOT) in guiding the safe discontinuation of NAs in CHB patients. Methods: This is a retrospective study, clinical data of all CHB patients who discontinued NAs treatment at West China Hospital between June 2020 and January 2021 were collected, including EOT pgRNA, HBcrAg, hepatitis B surface antigen (HBsAg), etc. All patients should meet the Asian-Pacific guideline for discontinuation. Observing virological relapse (VR) rates during 1 year of NAs discontinuation and analyzing the relationship between EOT pgRNA, HBcrAg, and VR. Results: A total of 64 patients were enrolled in this study and 33 (51.5%) patients experienced VR in 1 year. EOT pgRNA positivity (OR = 14.59, p = 0.026) and EOT higher HBcrAg levels (OR = 14.14, p = 0.001) were independent risk factors for VR. The area under the receiver-operating characteristic (AUROC) value of EOT HBcrAg for VR was 0.817 (p < 0.001), optimal cut-off value was 3.3 log10 U/mL. Patients with EOT pgRNA positivity and EOT HBcrAg >3.3 log10 U/mL were more likely to experience VR after discontinuation of NAs (88.9 vs. 45.5%, p = 0.027). Conclusion: According to current guidelines, a higher VR rate occurs after cessation of NAs. EOT pgRNA positivity and higher HBcrAg level carries a higher risk of VR. Combining these novel markers can better help us assess whether patients can safely cease NAs treatment.

The characteristics of carotid body tumors in high-altitude region: Analysis from a single center.

OBJECTIVES: Though carotid body tumors are rare, increasing attentions have been given because of malignant transformation and high surgical risk. However, at present, the characteristics and etiology still remain unclear. Our study was designed to describe the clinical features of carotid body tumors in our institution and to compare the results with previous reports. METHODS: We retrospectively reviewed carotid body tumor patients diagnosed in our institution from January 2015 to May 2020. The demographics, comorbidities, lesion location, anatomic characteristics, complications, and postoperative outcomes were evaluated. Carotid body tumor measurements were determined from computed tomography, magnetic resonance imaging, and carotid arteriography examination. We described and compared the clinical features of carotid body tumors in our institution and other reports. RESULTS: We totally identified 122 carotid body tumor cases for the present analysis. The mean age was 50.26 years, with the majority being female (82%). The commonest presentation was a painless neck mass (68%). For the distribution of nationality, most patients were the Han nationality (69.7%). The mean altitude of habitat of patients was 2689.4 km; 19.7% patients suffered bilateral lesions. The main blood supply of carotid body tumors was from external carotid artery (54.1%). For patients who received operation, 11 (11.2%) patients experienced cranial nerve injury. The maximal diameter of tumors was 3.99 ± 1.98 cm in male and 3.38 ± 1.36 cm in female. The volume of tumors was 31.49 ± 29.76 cm3 in male and 15.27 ± 13.06 cm3 in female. The distance to base of skull of tumors was 3.39 ± 1.07 cm (3.99 ± 1.98 cm in male vs 3.38 ± 1.36 cm, P < 0.05). Two patients (2.04%) were identified as having malignant carotid body tumor. CONCLUSIONS: Though carotid body tumor had a low morbidity and multitudinous clinicopathologic features, it was apt to middle-aged women and the main blood supply was from external carotid artery. The painless neck mass was the commonest presentation of carotid body tumors. There were significant difference between male and female patients regarding platelet, hemoglobin, distance to base of skull, tumor volume, altitude of habitat, carotid body tumor location, and hypertension.