IRE1α inhibits osteogenic differentiation of mouse embryonic fibroblasts by limiting Shh signaling.

OBJECTIVES: This study aimed to investigate the effect of endoplasmic reticulum (ER) stress sensor inositol-requiring enzyme 1α (IRE1α) on the sonic hedgehog N-terminus (N-Shh)-enhanced-osteogenic differentiation process in mouse embryonic fibroblasts (MEFs). MATERIALS AND METHODS: Osteogenesis of MEFs was observed by alkaline phosphatase (ALP) staining, alizarin red staining, and Von Kossa staining assays. Activation of unfolded protein response and Shh signaling were examined using real-time quantitative PCR and western blot assays. IRE1α-deficient MEFs were used to explore the effect of IRE1α on N-Shh-driven osteogenesis. RESULTS: N-Shh increased ALP activity, matrix mineralization, and the expression of Alp and Col-I in MEFs under osteogenic conditions; notably, this was reversed when combined with the ER stress activator Tm treatment. Interestingly, the administration of N-Shh decreased the expression of IRE1α. Abrogation of IRE1α increased the expression of Shh pathway factors in osteogenesis-induced MEFs, contributing to the osteogenic effect of N-Shh. Moreover, IRE1α-deficient MEFs exhibited elevated levels of osteogenic markers. CONCLUSIONS: Our findings suggest that the IRE1α-mediated unfolded protein response may alleviate the ossification of MEFs by attenuating Shh signaling. Our research has identified a strategy to inhibit excessive ossification, which may have clinical significance in preventing temporomandibular joint bony ankylosis.

Analysis of Factors Influencing the Prognosis of Periodontal Disease Treated with Host Modulation and the Development of a Predictive Model.

Objective: To explore the effect of host regulation (HMT) therapy on periodontal disease and construct prognosis prediction model. Methods: The clinical data of 106 patients who received HMT treatment in our hospital from January 2020 to January 2023 were retrospectively analyzed. The changes of plaque index (PLI), periodontal pocket depth (PD), tooth looseness (TM), attachment loss (AL) and gingival bleeding index (BI) were observed before and after treatment. According to the clinical efficacy of patients after treatment, they were divided into effective group and ineffective group. Multivariate Logistic regression model was used to analyze the relevant factors affecting the prognosis of patients., and a predictive model of the factors affecting the prognosis of periodontal disease was constructed to predict the diagnostic value of the prognostic outcome of periodontal disease using the relative operating characteristic (ROC) curve. Results: After HMT treatment, PLI, PD, AL and BI were significantly reduced in all patients, while TM(grade II and III) patients were decreased (P < .05). After 4 weeks of treatment, a total of 74 patients were included in the effective group. Univariate and multivariate analysis showed that oral hygiene, early use of broad-spectrum antibiotics, periodontal bone loss shape, gingival flap thickness and alveolar bone resorption type were independent factors influencing the prognosis of HMT (P < .001). ROC results showed that the area under the curve (AUC), sensitivity and specificity of the above independent influencing factors combined to predict the clinical efficacy of HMT in patients with periodontal disease were higher. Conclusion: HMT has a good clinical effect in the treatment of periodontal disease, but there are still cases of poor prognostic effect. The combination of independent factors affecting the prognosis of HMT has a good predictive value for the clinical efficacy of patients with periodontal disease after HMT treatment.

Gearbox Compound Fault Diagnosis in Edge-IoT Based on Legendre Multiwavelet Transform and Convolutional Neural Network.

The application of edge computing combined with the Internet of Things (edge-IoT) has been rapidly developed. It is of great significance to develop a lightweight network for gearbox compound fault diagnosis in the edge-IoT context. The goal of this paper is to devise a novel and high-accuracy lightweight neural network based on Legendre multiwavelet transform and multi-channel convolutional neural network (LMWT-MCNN) to fast recognize various compound fault categories of gearbox. The contributions of this paper mainly lie in three aspects: The feature images are designed based on the LMWT frequency domain and they are easily implemented in the MCNN model to effectively avoid noise interference. The proposed lightweight model only consists of three convolutional layers and three pooling layers to further extract the most valuable fault features without any artificial feature extraction. In a fully connected layer, the specific fault type of rotating machinery is identified by the multi-label method. This paper provides a promising technique for rotating machinery fault diagnosis in real applications based on edge-IoT, which can largely reduce labor costs. Finally, the PHM 2009 gearbox and Paderborn University bearing compound fault datasets are used to verify the effectiveness and robustness of the proposed method. The experimental results demonstrate that the proposed lightweight network is able to reliably identify the compound fault categories with the highest accuracy under the strong noise environment compared with the existing methods.

Drug delivery strategy in hepatocellular carcinoma therapy.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide, with high rates of recurrence and death. Surgical resection and ablation therapy have limited efficacy for patients with advanced HCC and poor liver function, so pharmacotherapy is the first-line option for those patients. Traditional antitumor drugs have the disadvantages of poor biological distribution and pharmacokinetics, poor target selectivity, high resistance, and high toxicity to nontargeted tissues. Recently, the development of nanotechnology has significantly improved drug delivery to tumor sites by changing the physical and biological characteristics of drugs and nanocarriers to improve their pharmacokinetics and biological distribution and to selectively accumulate cytotoxic agents at tumor sites. Here, we systematically review the tumor microenvironment of HCC and the recent application of nanotechnology in HCC. Video Abstract.

Continuous elevation of procalcitonin in cirrhosis combined with hepatic carcinoma: a case report.

BACKGROUND: Serum levels of procalcitonin (PCT) are considered a useful biomarker for the diagnosis of bacterial infection or inflammation. There are few reports of high PCT levels in end-stage liver disease regardless of bacterial infection. Here, we present a case of extremely high PCT levels (> 100 ng/mL) in a patient with severe cirrhosis combined with hepatic carcinoma. CASE PRESENTATION: A 65-year-old man developed end-stage cirrhosis with hepatic carcinoma. Radiographic imaging showed a massive hepatocellular carcinoma with multiple loci lack of indications of resection. Hence, transcatheter hepatic arterial chemoembolization was performed three times over a period of 4 months. Before and after interventional therapies, the biochemistry laboratory results were only slightly abnormal except for persistently high PCT concentrations (> 100 ng/mL), irrespective of the evidence for bacterial infection or sepsis. CONCLUSIONS: This case suggests that continuously high levels of PCT (> 100 ng/mL) may be present in advanced liver disease, particularly in complex situations such as decompensated cirrhosis and liver cancer, in the absence of severe infection or sepsis. This knowledge could expand the significance of PCT in liver disease.

In vitro antibiofilm activity of resveratrol against avian pathogenic Escherichia coli.

BACKGROUND: Avian pathogenic Escherichia coli (APEC) strains cause infectious diseases in poultry. Resveratrol is extracted from Polygonum cuspidatum, Cassia tora Linn and Vitis vinifera, and displays good antimicrobial activity. The present study aimed to investigate the antibiofilm effect of resveratrol on APEC in vitro. The minimum inhibitory concentration (MIC) of resveratrol and the antibiotic florfenicol toward APEC were detected using the broth microdilution method. Then, the effect of resveratrol on swimming and swarming motility was investigated using a semisolid medium culture method. Subsequently, the minimum biofilm inhibitory concentration (MBIC) and the biofilm eradication rate were evaluated using crystal violet staining. Finally, the antibiofilm activity of resveratrol was observed using scanning electron microscopy (SEM). Meanwhile, the effects of florfenicol combined with resveratrol against biofilm formation by APEC were evaluated using optical microscopy (OM) and a confocal laser scanning microscopy (CLSM). RESULTS: The MICs of resveratrol and florfenicol toward APEC were 128 µg/mL and 64 µg/mL, respectively. The swimming and swarming motility abilities of APEC were inhibited in a resveratrol dose-dependent manner. Furthermore, resveratrol showed a significant inhibitory activity against APEC biofilm formation at concentrations above 1 µg/mL (p < 0.01). Meanwhile, the inhibitory effect of resveratrol at 32 µg/mL on biofilm formation was observed using SEM. The APEC biofilm was eradicated at 32 µg/mL of resveratrol combined with 64 µg/mL of florfenicol, which was observed using CLSM and OM. Florfenicol had a slight eradication effect of biofilm formation, whereas resveratrol had a strong biofilm eradication effect toward APEC. CONCLUSION: Resveratrol displayed good antibiofilm activity against APEC in vitro, including inhibition of swimming and swarming motility, biofilm formation, and could eradicate the biofilm.

Epidemiological, clinical and virological characteristics of 74 cases of coronavirus-infected disease 2019 (COVID-19) with gastrointestinal symptoms.

OBJECTIVE: The SARS-CoV-2-infected disease (COVID-19) outbreak is a major threat to human beings. Previous studies mainly focused on Wuhan and typical symptoms. We analysed 74 confirmed COVID-19 cases with GI symptoms in the Zhejiang province to determine epidemiological, clinical and virological characteristics. DESIGN: COVID-19 hospital patients were admitted in the Zhejiang province from 17 January 2020 to 8 February 2020. Epidemiological, demographic, clinical, laboratory, management and outcome data of patients with GI symptoms were analysed using multivariate analysis for risk of severe/critical type. Bioinformatics were used to analyse features of SARS-CoV-2 from Zhejiang province. RESULTS: Among enrolled 651 patients, 74 (11.4%) presented with at least one GI symptom (nausea, vomiting or diarrhoea), average age of 46.14 years, 4-day incubation period and 10.8% had pre-existing liver disease. Of patients with COVID-19 with GI symptoms, 17 (22.97%) and 23 (31.08%) had severe/critical types and family clustering, respectively, significantly higher than those without GI symptoms, 47 (8.14%) and 118 (20.45%). Of patients with COVID-19 with GI symptoms, 29 (39.19%), 23 (31.08%), 8 (10.81%) and 16 (21.62%) had significantly higher rates of fever >38.5°C, fatigue, shortness of breath and headache, respectively. Low-dose glucocorticoids and antibiotics were administered to 14.86% and 41.89% of patients, respectively. Sputum production and increased lactate dehydrogenase/glucose levels were risk factors for severe/critical type. Bioinformatics showed sequence mutation of SARS-CoV-2 with m6A methylation and changed binding capacity with ACE2. CONCLUSION: We report COVID-19 cases with GI symptoms with novel features outside Wuhan. Attention to patients with COVID-19 with non-classic symptoms should increase to protect health providers.

Hepatitis B and hepatitis C prevalence among people living with HIV/AIDS in China: a systematic review and Meta-analysis.

BACKGROUND: There has been little published data on estimates of HBV and/or HCV coinfection in HIV-positive patients in China or an understanding of how this coinfection varies with different factors. Therefore, this study aimed to determine, through a systematic review and meta-analysis, the prevalence of HBV and/or HCV in HIV-positive patients in China and explore variations in prevalence. METHODS: The Medicine, Web of Science, Chinese Web of Knowledge, and Wanfang databases were searched using a search strategy combining key words and related disease-specific subject terms to identify relevant cohort or cross-sectional studies published up to April 2019. Included articles were assessed for quality. Pooled prevalence and 95% confidence intervals (CIs) were calculated according to study region and other specific characteristics. RESULTS: Our searches identified 7843 records, but only 66 studies were included in our meta-analysis. The pooled HBsAg prevalence in HIV-positive patients was 13.7% (95% CI 12.3-15.3%), with variations found in terms of age and geographic region. The meta-HCV prevalence was 24.7% (95% CI 19.3-30.5%), which varied over the study period and age. The pooled HBV-HCV coinfection prevalence was 3.5% (95% CI 2.4-4.8%), with variations found in terms of age and geographic region. CONCLUSION: Given the high burden of HBV and HCV coinfections in HIV-positive patients, the incorporation of comprehensive screening, treatment, prevention, and vaccination programs into general HIV management in China is imperative.

Efficacy and cost-effectiveness of antiviral regimens for entecavir-resistant hepatitis B: A systematic review and network meta-analysis.

BACKGROUND: Chronic hepatitis B (CHB) patients who had exposed to lamivudine (LAM) and telbivudine (LdT) had high risk of developing entecavir (ETV)-resistance after long-term treatment. We aimed to conduct a systematic review and a network meta-analysis on the efficacy and cost-effectiveness on antiviral regimens in CHB patients with ETV-resistance. DATA SOURCES: We searched PubMed, EMBASE and Web of Science for studies on nucleos(t)ide analogues (NAs) treatment [including tenofovir disoproxil fumarate (TDF)-based rescue therapies, adefovir (ADV)-based rescue therapies and double-dose ETV therapy] in CHB patients with ETV-resistance. The network meta-analysis was conducted for 1-year complete virological response (CVR) and biological response (BR) rates using GeMTC and ADDIS. A cost-effective analysis was conducted to select an economic and effective treatment regimen based on the 1-year CVR rate. RESULTS: A total of 6 studies were finally included in this analysis. The antiviral efficacy was estimated. On network meta-analysis, the 1-year CVR rate in ETV-TDF [odds ratio (OR)  = 22.30; 95 % confidence interval (CI): 2.78-241.93], LAM-TDF (OR  = 70.67; 95 % CI: 5.16-1307.45) and TDF (OR  = 16.90; 95 % CI: 2.28-186.30) groups were significantly higher than that in the ETV double-dose group; the 1-year CVR rate in the LAM-TDF group (OR  = 14.82; 95 % CI: 1.03-220.31) was significantly higher than that in the LAM/LdT-ADV group. The 1-year BR rate of ETV-TDF (OR = 28.68; 95 % CI: 1.70-1505.08) and TDF (OR = 21.79; 95 % CI: 1.43-1070.09) therapies were significantly higher than that of ETV double-dose therapy. TDF-based therapies had the highest possibility to achieve the CVR and BR at 1 year, in which LAM-TDF combined therapy was the most effective regimen. The ratio of cost/effectiveness for 1-year treatment was 8 526, 17 649, 20 651 Yuan in the TDF group, TDF-ETV group, and ETV-ADV group, respectively. CONCLUSIONS: TDF-based combined therapies such as ETV-TDF and LAM-TDF therapies were the first-line treatment if financial condition is allowed.

Establishment and development of national community-based collaborative innovation demonstration areas to achieve the control target of hepatitis B in China.

BACKGROUND: The major infectious diseases of hepatitis B has constituted an acute public health challenge in China. An effective and affordable HBV control model is urgently needed. A national project of Community-based Collaborative Innovation HBV (CCI-HBV) demonstration areas has optimized the existing community healthcare resources and obtained initial results in HBV control. METHODS: Based on the existing community healthcare network, CCI-HBV project combined the community health management and health contract signing service for long-staying residents in hepatitis B screening. Moreover, HBV field research strategy was popularized in CCI-HBV areas. After screening, patients with seropositive results were enrolled in corresponding cohorts and received treatment at an early stage. And the uninfected people received medical supports including health education through new media, behavior intervention and HBV vaccinations. In this process, a cloud-based National Information Platform (NIP) was established to collect and store residents' epidemiological data. In addition, a special quality control team was set up for CCI project. RESULTS: After two rounds of screening, HBsAg positive rate dropped from 5.05% (with 5,173,003 people screened) to 4.57% (with 3,819,675 people screened), while the rate of new HBV infections was 0.28 per 100 person-years in the fixed cohorts of 2,584,322 people. The quality control team completed PPS sampling simultaneously and established the serum sample database with 2,800,000 serum samples for unified testing. CONCLUSIONS: CCI-HBV project has established a large-scale field research to conduct whole-population screening and intervention. We analyzed the HBsAg prevalence and new infection rate of HBV in the fixed population for the epidemic trend and intervention effect. The purpose of CCI-HBV project is to establish and evaluate a practical model of grid management and field strategy, to realize the new goal to control hepatitis B in China. To provide policymakers with a feasible model, our results are directly applicable. TRIAL REGISTRATION: The project was funded by the Major Projects of Science Research for the 11th and 12th five-year plans of China, entitled "The prevention and control of AIDS, viral hepatitis and other major infectious diseases", Grant Nos. 2009ZX10004901, 2011ZX10004901, 2013ZX10004904, 2014ZX10004007 and 2014ZX10004008.

Effect of probiotic treatment on cirrhotic patients with minimal hepatic encephalopathy: A meta-analysis.

BACKGROUND: Minimal hepatic encephalopathy (MHE) is an early and reversible form of hepatic encephalopathy. The documentations on the treatment with probiotics are inconsistent. The present meta-analysis was to verify the role of probiotics in the treatment of cirrhotic patients with MHE. DATA SOURCES: Seven electronic databases were searched for relevant randomized controlled trials (RCTs) published until July 2015. The effects of probiotics on serum ammonia, endotoxin, and MHE were evaluated. RESULTS: A total of 14 RCTs (combined n = 1132) were included in the meta-analysis. When probiotics were compared to placebo or no treatment, probiotics were more likely to reduce values in the number connection test (NCT; week 4: MD = -30.25, 95% CI: -49.85 to -10.66), improve MHE (week 4: OR = 0.18, 95% CI: 0.07 to 0.47; week 12: OR = 0.15, 95% CI: 0.07 to 0.32), and prevent overt HE progression (week 4: OR = 0.22, 95% CI: 0.07 to 0.67) in patients with liver cirrhosis. When probiotics was compared to lactulose, probiotics tended to reduce serum ammonia levels (week 4: MD = -0.33 µmol/L, 95% CI: -5.39 to 4.74; week 8: MD = 6.22 µmol/L, 95% CI: -24.04 to 36.48), decrease NCT (week 8: MD = 3.93, 95% CI: -0.72 to 8.58), improve MHE (week 4: OR = 0.93, 95% CI: 0.45 to 1.91; week 12: OR = 0.73, 95% CI: 0.35 to 1.51) and prevent the development of overt HE (week 4: OR = 0.96, 95% CI: 0.17 to 5.44; week 12: OR = 2.7, 95% CI: 0.50 to 14.64) in patients with liver cirrhosis. However, lactulose appears to be more effective in reducing NCT values as compared to probiotics (week 4: MD = 6.7, 95% CI: 0.58 to 12.82). CONCLUSION: Probiotics can decrease serum ammonia and endotoxin levels, improve MHE, and prevent overt HE development in patients with liver cirrhosis.

Systemic transcriptome analysis of hepatocellular carcinoma.

Liver cancer is one of the most common malignant tumors, and most of which is hepatocellular carcinoma (HCC). We aim to study the characteristic changes of numerous genes and their roles in HCC through systematical analysis of the characteristics of expression spectrum of HCC. Firstly, we made systematic clustering of the HCC samples according to the RNAseq data from TCGA (The Cancer Genome Atlas) and newly classified HCC. Then the characteristic genes in different molecular subtypes were found out and further analyzed combing with methylation and SNP 6.0 chip. Finally, these genes were subjected to do functional annotation and abnormal signaling pathways of HCC in various molecular subtypes and were screened out. There were 3843 differential genes screened; among which, 689 genes were enriched into 13 KEGG-related pathways, and the expression of 27 and 924 genes showed positive and negative correlation to methylation level, respectively, while the expression of 43 genes showed positive correlation to variation level of copy number. The methylation degree of ZSCAN18 may be considered as a marker for prognosis evaluation, and ABHD6 could be a potential anti-oncogene.

Tissue transglutaminase 2 exerts a tumor-promoting role in hepatitis B virus-related hepatocellular carcinoma.

Hepatitis B virus (HBV) infection is a major risk factor which can lead to development of hepatocellular carcinoma (HCC). Tissue transglutaminase-2 (TG2) has been shown to be critical for cancer progression. However, how TG2 promotes the progression of HBV-related HCC remains unknown. In this study, we aimed to explore the expression and function of TG2 on HBV-related HCC progression. The expression levels of TG2 were examined in a series of HBV-related HCC tissues and a panel of HCC cell lines. The effects of TG2 knockdown on the proliferation and migration of HBV-related cells were determined. TG2 expression was found to be significantly upregulated in HBV-related HCC tissues. TG2 expression was higher in HBV-related HCC cell lines than HBV-unrelated HCC cell lines. Moreover, inhibition of TG2 in HCC cell lines HepG2.2.15 and Hep3B could inhibit cell proliferation, migration, and invasion in vitro. Our results indicated that TG2 could serve as a promising target for treatment of HBV-related HCC patients.

Effects of Salmonella infection on hepatic damage following acute liver injury in rats.

BACKGROUND: Acute liver injury is a common clinical disorder associated with intestinal barrier injury and disturbance of intestinal microbiota. Probiotic supplementation has been reported to reduce liver injury; however, it is unclear whether enteropathogen infection exacerbates liver injury. The purpose of this study was to address this unanswered question using a rat model. METHODS: Oral supplementation with Salmonella enterica serovar enteritidis (S. enteritidis) was given to rats for 7 days. Different degrees of acute liver injury were then induced by intraperitoneal injection of D-galactosamine. The presence and extent of liver injury was assayed by measuring the concentrations of serum alanine aminotransferase, aspartate aminotransferase, and total bilirubin. Histology was used to observe liver tissue damage. Additionally, we measured the changes in plasma endotoxin, serum cytokines and bacterial translocation to clarify the mechanisms underlying intestinal microbiota associated liver injury. RESULTS: The levels of liver damage and endotoxin were significantly increased in the Salmonella infected rats with severe liver injury compared with the no infection rats with severe liver injury (P<0.01); The peyer's patch CD3+ T cell counts were increased significantly when the Salmonella infection with severe injury group was compared with the normal group (P<0.05). S. enteritidis pretreatment enhanced intestinal barrier impairment and bacterial translocation. CONCLUSIONS: Oral S. enteritidis administration exacerbates acute liver injury, especially when injury was severe. Major factors of the exacerbation include inflammatory and oxidative stress injuries induced by the translocated bacteria and associated endotoxins, as well as over-activation of the immune system in the intestine and liver.

[Effect of shift rotation culture on formation and activity of encapsulated hepatocytes aggregates].

Objective: To observe the effect of uniform and shift rotation culture on the formation and activity of the alginate-chitosan (AC) microencapsulated HepLL immortalized human hepatocytes and HepG2 cells aggregates. Methods: AC microcapsulated HepG2 and HepLL cells were randomly divided into two groups. Each group was divided into 3 subgroups according to uniform and shift rotation culture.The size and number of aggregates were observed and measured under laser confocal microscopy and inverted microscope dynamically. The amount of albumin synthesis was detected by ELISA, the clearance of ammonia was detected by colorimetry, and diazepam conversion function was detected by high performance liquid chromatography (HPLC). Results: On day 6, 8, 10, 12, 14 and 16, the number and size of the aggregates, albumin synthesis, diazepam clearance and ammonium clearance increased significantly in shift rotation culture group than in uniform group (all P<0.01). The albumin synthesis, diazepam clearance, and ammonium clearance in the microencapsulated HepLL groups were significantly higher than those of HepG2 cells at any time (all P<0.01). Conclusion: Shift rotation culture can significantly promote the formation and increase the activity of AC microencapsulated HepLL and HepG2 aggregates, and HepLL cells may be more suitable for bioartificial liver than HepG2.

Fine mapping analysis of HLA-DP/DQ gene clusters on chromosome 6 reveals multiple susceptibility loci for HBV infection.

Recent genome-wide association studies have revealed the HLA region on chromosome 6p21 as a susceptibility locus for hepatitis B virus (HBV) infection, a finding subsequently replicated in independent samples. However, only limited single nucleotide polymorphisms (SNPs) were analyzed in most of these studies, and it remains to be determined which SNPs contribute to the detected association. After genotyping 140 SNPs within this genomic region in a total of 1657 HBV-positive patients and 1456 HBV-negative controls, we conducted a series of genetic epidemiological and bioinformatics analysis, including individual SNP-based association analysis, haplotype-based association analysis, and conditional analysis. We identified 76 SNPs and 5 LD blocks in HLA-DP/DQ clusters that are significantly associated with HBV infection, with the smallest P value being 3.88 × 10(-18) for rs9277535 in HLA-DPB1. With conditional analysis, we further revealed that the genes contributing to the effects of variants in HLA-DP/DQ on infection are independent of each other, and the LD block 5 in the 3'-UTR region of HLA-DPB1 had a predominant effect in the association of HLA-DP with HBV infection. We also found that the SNPs in the 3'-UTR region of HLA-DPB1 were significant between the subgroups of inactive HBV carrier, chronic hepatitis B, or hepatic cirrhosis from the case group and the spontaneous HBV-clearance subgroup from the control group. Finally, we did further association analysis of SNPs in this region with different subgroups from the case group, which revealed no association of these SNPs with the progression of HBV-related diseases. In sum, we showed, for the first time, that the HLA-DP/DQ clusters contribute independently to HBV infection, and the 3'-UTR region of HLA-DPB1 represents an important functional region involved in HBV infection.

The serum IL-23 level predicts the response to pegylated interferon therapy in patients with chronic hepatitis B.

BACKGROUND & AIMS: This study investigated the possible use of interleukin (IL)-23 and IL-17 serum levels as indicators for anti-hepatitis B virus (HBV) therapy. METHODS: A total of 127 patients with chronic hepatitis B (CHB) who received pegylated interferon (PegIFN) therapy, 20 chronic asymptomatic HBV carriers (AsCs) and 32 healthy controls were recruited. The serum levels of IL-23 and IL-17 were detected by ELISA. The predictive value of baseline and early on-treatment changes in the levels of IL-23 and IL-17 for therapeutic response were evaluated by receiver operating characteristic analysis. Multivariate logistic regression models were generated to identify independent factors that affect the clearance of hepatitis B e antigen (HBeAg) and the decline in hepatitis B surface antigen (HBsAg). RESULTS: The baseline serum levels of IL-23 and IL-17 were higher in patients with CHB than in normal controls and in AsCs. High levels of pre-treatment IL-23 and IL-17 and more significant on-treatment reductions in IL-23 and IL-17 levels were observed in patients with CHB who achieved HBeAg clearance or a decline in HBsAg >1 log10  IU/ml compared with patients who were persistently HBeAg-positive or who experienced a decline in HBsAg <1 log10  IU/ml. The predictive cut-off value of IL-23 for HBeAg clearance was 135 pg/ml, and the specificity and sensitivity were 71.4% and 70% respectively. A high pre-treatment level of IL-23 was an independent factor for the prediction of the therapeutic response in patients with HBeAg-positive CHB. Early on-treatment changes of IL-23 and IL-17 showed no predictive value. CONCLUSIONS: A high pre-treatment serum IL-23 level predicts the therapeutic response in HBeAg-positive CHB patients during PegIFN therapy.

Effects of plasma exchange combined with continuous renal replacement therapy on acute fatty liver of pregnancy.

BACKGROUND: Acute fatty liver of pregnancy (AFLP) in the third trimester or early postpartum period can lead to fatal liver damage. Its traditional therapy is not very effective in facilitating hepatic recovery. The safety and effect of plasma exchange (PE) in combination with continuous renal replacement therapy (CRRT) (PE+CRRT) for AFLP still needs evaluation. METHODS: Five AFLP patients with hepatic encephalopathy and renal failure were subjected to PE+CRRT in our department from 2007 to 2012. Their symptoms, physical signs and results were observed, and all relevant laboratory tests were compared before and after PE+CRRT. RESULTS: All the 5 patients were well tolerated to the therapy. Four of them responded to the treatment and showed improvement in clinical symptoms/signs and laboratory results, and they were cured and discharged home after the treatment. One patient succeeded in bridging to transplantation for slowing down hepatic failure and its complications process after 2 treatment sessions. Intensive care unit stay and hospital stay were 9.4 (range 5-18) and 25.0 days (range 11-42), respectively. CONCLUSION: PE+CRRT is safe and effective and should be used immediately at the onset of hepatic encephalopathy and/or renal failure in patients with AFLP.

IRE1α pathway: A potential bone metabolism mediator.

Osteoblasts and osteoclasts collaborate in bone metabolism, facilitating bone development, maintaining normal bone density and strength, and aiding in the repair of pathological damage. Endoplasmic reticulum stress (ERS) can disrupt the intracellular equilibrium between osteoclast and osteoblast, resulting in dysfunctional bone metabolism. The inositol-requiring enzyme-1α (IRE1α) pathway-the most conservative unfolded protein response pathway activated by ERS-is crucial in regulating cell metabolism. This involvement encompasses functions such as inflammation, autophagy, and apoptosis. Many studies have highlighted the potential roles of the IRE1α pathway in osteoblasts, chondrocytes, and osteoclasts and its implication in certain bone-related diseases. These findings suggest that it may serve as a mediator for bone metabolism. However, relevant reviews on the role of the IRE1α pathway in bone metabolism remain unavailable. Therefore, this review aims to explore recent research that elucidated the intricate roles of the IRE1α pathway in bone metabolism, specifically in osteogenesis, chondrogenesis, osteoclastogenesis, and osteo-immunology. The findings may provide novel insights into regulating bone metabolism and treating bone-related diseases.