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To standardize the effective prevention, surveillance, and diagnosis of primary liver cancer, the Chinese Society of Hepatology, Chinese Medical Association, invited clinical experts and methodologists to develop the Consensus on the Secondary Prevention of Primary Liver Cancer, which was based on the clinical and scientific advances on hepatocellular carcinoma. The purpose is to provide a current basis for the prevention, surveillance, and early diagnosis of primary liver cancer in patients with chronic liver diseases.

Oncolytic viruses can effectively unwrap a multimodal anti-tumor activity, encompassing a selective tumor cell killing and promoting a systemic anti-tumor immunity, making them a formidable foe against cancer. Among these, several members of the Rhabdoviridae family are particularly attractive as oncolytic agents due to their natural tumor selectivity and non-pathogenicity in humans. In this study, we demonstrated that intratumorally (IT) administration of Jurona virus (JURV), a novel oncolytic Rhabdovirus, induces dynamic tumor regression in human HCC xenograft and syngeneic models. Our data shows that IT injections of JURV trigger the recruitment and activation of cytotoxic T (CTLs) and decrease the tumor-associated macrophages (TAM) infiltration leading to tumor growth delay in both local and distant murine HCC tumors in a syngeneic model. Moreover, when administered concomitantly, JURV and anti-PD-1 therapy profoundly modulate the tumor microenvironment (TME) via enhanced infiltration of CTLs, suggesting that immune checkpoint blockade therapy could potentiate the immunomodulatory effect of JURV and potentially provide durable anti-tumor immunity. Our analysis of the molecular and cellular mechanism of JURV-medicated anti-cancer activity unveiled that JURV and anti-PD-1 antibodies activate different effectors of the immune system but have complementary anti-tumor activities. Furthermore, our results indicate that the abscopal effect induced by JURV is likely mediated by the mechanism regulating the T helper cell responses. Our work supports the further development of JURV as a novel immunovirotherapy platform for hepatocellular carcinoma.

Dandan Zhao,1,2 Xiaoxiao Zhang,1,2 Yuhui Tang,1,2 Peilin Guo,1,2 Rong Ai,1,2 Mengmeng Hou,1,2 Yiqi Wang,1,2 Xiwei Yuan,1,2 Luyao Cui,1,2 Yuguo Zhang,1,2 Suxian Zhao,1,2 Wencong Li,1,2 Yang Wang,1,2 Xiaoye Sun,1,2 Lingdi Liu,1,2 Shiming Dong,1,2 Lu Li,1,2 Wen Zhao,1,2 Yuemin Nan1,2 1Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 2Hebei Provincial Key Laboratory of Liver Fibrosis in Chronic Liver Diseases, Shijiazhuang, Hebei, People’s Republic of ChinaCorrespondence: Yuemin Nan, Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, No. 139 Ziqiang Road, Shijiazhuang, Hebei Province, 050051, People’s Republic of China, Tel +86 311-66781227, Fax +86 311-66781289, Email nanyuemin@163.comPurpose: The aim of this study was to identify and validate novel biomarkers for distinguishing among hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), liver fibrosis/liver cirrhosis (LF/LC) and chronic hepatitis B (CHB).Patients and Methods: Transcriptomic sequencing was conducted on the liver tissues of 5 patients with HCC, 5 patients with LF/LC, 5 patients with CHB, and 4 healthy controls. The expression levels of selected mRNAs and proteins were assessed by quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemical (IHC) staining, and were verified in validation set (n=200) and testing set (n=400) via enzyme-linked immunosorbent assay (ELISA).Results: A total of 9 hub mRNAs were identified by short time-series expression miner and weighted gene co-expression network analysis. Of note, the results of qRT-PCR and IHC staining demonstrated that SHC adaptor protein 1 (SHC1), SLAM family member 8 (SLAMF8), and interleukin-32 (IL-32) exhibited gradually increasing trends in the four groups. Subsequent ELISA tests on the validation cohort indicated that the plasma levels of SHC1, SLAMF8 and IL-32 also gradually increased. Furthermore, a diagnostic model APFSSI (age, PLT, ferritin, SHC1, SLAMF8 and IL-32) was established to distinguish among CHB, LF/LC and HCC. The performance of APFSSI model for discriminating CHB from healthy subjects (AUC=0.966) was much greater compared to SHC1 (AUC=0.900), SLAMF8 (AUC=0.744) and IL-32 (AUC=0.821). When distinguishing LF/LC from CHB, APFSSI was the most outstanding diagnostic parameter (AUC=0.924), which was superior to SHC1, SLAMF8 and IL-32 (AUC=0.812, 0.684 and 0.741, respectively). Likewise, APFSSI model with the greatest AUC value displayed an excellent performance for differentiating between HCC and LF/LC than other variables (SHC1, SLAMF8 and IL-32) via ROC analysis. Finally, the results in the test set were consistent with those in the validation set.Conclusion: SHC1, SLAMF8 and IL-32 can differentiate among patients with HCC, LF/LC, CHB and healthy controls. More importantly, the APFSSI model greatly improves the diagnostic accuracy of HBV-associated liver diseases.Keywords: HBV-associated liver diseases, transcriptome sequencing technology, SHC adaptor protein 1, SLAM family member 8, interleukin-32

Background and Aim. Heme oxygenase-1 (HO-1) has been verified to play an important role in nonalcoholic steatohepatitis (NASH), but the mechanism remains unclear. In this study, we aimed to clarify whether induction of HO-1 reverses steatofibrosis via suppression of the Wnt signaling pathway and to explore the potential mechanism of HO-1 on NASH-related liver fibrosis. Methods. Mice were fed with a methionine-choline-deficient (MCD) diet for 8 weeks to induce steatohepatitis-related liver fibrosis and were treated with HO-1 inducer Hemin and inhibitor ZnPP. Mouse sera were collected for the biochemical analysis, and livers were obtained for further histological observation and gene expression analysis. HSC-T6 cells were cultured for the in vitro study and were administrated with Hemin and si-HO-1 to induce or inhibit the expression of HO-1. qPCR and Western blot were used to assess the mRNA and protein levels of genes. Results. MCD-fed mice developed marked macrovesicular steatosis, focal necrosis, and inflammatory infiltration and pericellular fibrosis in liver sections. Administration of Hemin could significantly ameliorate the severity of steatosis, inflammation, and fibrosis and also could decrease the serum ALT and AST. We demonstrated that HO-1 induction was able to downregulate the key regulator of the canonical Wnt pathway Wnt1 and the noncanonical Wnt pathway Wnt5a. The downstream factors of the Wnt pathway β-catenin and NFAT5 were inhibited by Hemin, but GSK-3β was upregulated compared to the MCD group, which were consistent with the in vitro study. Hemin markedly inhibited the TGF-β1/Smad signaling pathway in both in vivo and in vitro studies. Conclusion. Our study demonstrated that HO-1 inhibited the activation of canonical and noncanonical Wnt signaling pathways in NASH-related liver fibrosis. Thus, these results may suggest a new therapeutic strategy for NASH-related liver fibrosis.

In this paper, the demand for value transfer and traceability in the quantitative measurement of infrared radiation characteristics in the field environment is analyzed, and the necessity and significance of value transfer and traceability are expounded. According to the requirements of infrared radiation quantity transfer and traceability in the field environment, the development of infrared radiation quantity transfer radiometer is completed, which mainly includes athermalized optical system, diaphragm module, chopper, reference blackbody module, infrared detection module, signal acquisition system and so on. It is applied in the field environment. By comparing the measurement method with the standard blackbody radiation source, the quantity transfer of a certain type of field target characteristic measurement equipment is carried out, and the relevant data are analyzed. The analysis results show that the measurement uncertainty is better than 1 % by traceability in the field environment. Therefore, the measurement uncertainty of the infrared radiation characteristics in the field can be effectively improved by transmitting the infrared radiometer through this value and cooperating with the standard blackbody radiation source, and the traceability chain of the infrared radiation value in the field environment can be improved, which has good application value.

BackgroundAt present, there are no accurate diagnostic biomarkers for distinguishing among hepatitis B virus (HBV)-related liver diseases. This research aimed to identify and validate a novel biomarker panel in patients with HBV-related hepatocellular carcinoma (HCC), liver fibrosis/liver cirrhosis (LF/LC) and chronic hepatitis B (CHB).MethodsTranscriptomics sequencing was conducted on a total of 19 liver tissues of the four groups. The hub mRNAs were identified using weighted gene co-expression network analysis (WGCNA) and short time-series expression miner (STEM) method. The expression levels of selected mRNAs and proteins were assessed by quantitative real-time polymerase chain reaction (qRT-PCR) using both liver tissues and peripheral blood mononuclear cells (PBMCs) and immunohistochemical (IHC) staining in liver tissues, respectively. Then, the expression activities of the screened targets were detected by enzyme-linked immunosorbent assay (ELISA) using the plasma samples from 200 and 400 subjects in the validation and testing sets, respectively. Finally, receiver operating characteristic (ROC) curve analysis was carried out to evaluate the diagnostic performance of each mRNA biomarker.ResultsSTEM analysis revealed 25 mRNAs exhibited an increasing trend in the four groups; while 9 hub mRNAs were identified by using WGCNA. Of note, the results of qRT-PCR and immunohistochemical analyses demonstrated that SHC adaptor protein 1 (SHC1), SLAM family member 8 (SLAMF8), and interleukin-32 (IL-32) exhibited a gradually increasing trend in the four groups. Subsequent ELISA tests on the validation cohort demonstrated that the plasma levels of SHC1, SLAMF8 and IL-32 were remarkably elevated in HCC group compared to the remaining three groups. Furthermore, a diagnostic model APFSSI (age, PLT, ferritin, SHC1, SLAMF8 and IL-32) was established to distinguish HCC from LF/LC (AUC=0.904), LF/LC from CHB (AUC=0.924), and CHB from healthy controls (AUC=0.966). Finally, the results in the test set were consistent with those in the validation set. ConclusionsSHC1, SLAMF8 and IL-32 can differentiate among HCC patients, LF/LC patients, CHB patients and healthy controls. More importantly, the combination of age, PLT, ferritin, SHC1, SLAMF8, and IL-32 (APFSSI model) greater improves the diagnostic accuracy of HBV-associated liver diseases.

The Yiqi Huoxue (YQHX) recipe has been shown to attenuate liver fibrosis, but precise mechanisms have not yet been elucidated. Recently, Yes-associated protein (YAP)/transcriptional coactivator with PDZ-binding motif (TAZ) signaling has been implicated in liver fibrogenesis. This study investigated whether the YAP/TAZ signaling is involved in the therapeutic effect of YQHX on hepatic fibrosis.Wistar rats were used to generate a model of carbon tetrachloride (CCl₄)-induced liver fibrosis. Chronic hepatitis B (CHB) patients with liver fibrosis were enrolled and assigned to receive either nucleoside/nucleotide analogues (NAs) or NAs plus YQHX. Histology, immunohistochemistry, qRT-PCR, and western blotting were conducted to mechanistically assess the therapeutic effects of YQHX on liver fibrosis.YQHX markedly alleviated morphological alterations in CCl₄-induced liver fibrosis and decreased markers of hepatic fibrosis in rats. Furthermore, YQHX significantly suppressed CCl₄-meidated activation of the transforming growth factor-beta (TGF-β)/Smad signaling pathway. Notably, CCl₄ induced up-regulation of YAP, TAZ, and connective tissue growth factor (CTGF), which were significantly abrogated by YQHX. Consistent with the above major findings in rats, CHB patients treated with NAs plus YQHX had greater improvement in liver fibrosis than those given NAs alone (71.4% vs. 28.6%; P = 0.057). In addition, hepatic and plasma levels of YAP were significantly decreased after YQHX treatment in CHB patients with liver fibrosis.YAP/TAZ signaling plays a role, at least in part, in the anti-fibrotic activity of YQHX. The findings may help to better understand the mechanisms of YQHX in the treatment of liver fibrosis.

MicroRNAs (miRNAs or miRs) have been found to participate in the development and malignant progression of human cancers by negatively mediating the expression of their target genes. Recently, miR‑33b has been reported to be involved in multiple types of human cancer, including hepatocellular carcinoma (HCC). However, the underlying regulatory mechanisms of miR‑33b in HCC cell growth and metastasis remain largely unclear. In the present study, RT-qPCR revealed that miR‑33b was significantly downregulated in HCC tissues compared to their matched adjacent normal tissues. Moreover, the miR‑33b level was significantly lower in advanced-stage HCC (stages T3-T4) compared to early-stage HCC (stages T1-T2). Furthermore, it was also downregulated in the HCC cell lines, LH86, HepG2, LMH and PLHC-1, when compared with the THLE-3 normal human liver cells. We further demonstrated that the overexpression of miR‑33b led to a significant decrease in the proliferation, migration and invasion of HepG2 and LH86 cells. Luciferase reporter assay identified Sal-like protein 4 (SALL4) as a target gene of miR‑33b, and its protein expression was negatively regulated by miR‑33b in HepG2 and LH86 cells. Moreover, the restoration of SALL4 expression markedly reversed the inhibitory effect of miR‑33b overexpression on the proliferation, migration and invasion of HepG2 and LH86 cells, indicating that SALL4 is involved in miR‑33b-mediated malignant phenotypes of HCC cells. Furthermore, we found that SALL4 was significantly upregulated in HCC tissues compared to their matched adjacent normal tissues, and its increased expression was significantly associated with the advanced malignancy of HCC. Moreover, SALL4 was also upregulated in HCC cell lines compared to the THLE-3 normal human liver cells. Finally, we found that the SALL4 expression inversely correlated with the miR‑33b level in HCC tissues. On the whole, the findings of our study demonstrate that miR‑33b suppresses the proliferation and metastasis of HCC cells through the inhibition of SALL4 expression. Therefore, miR‑33b/SALL4 may become a potential therapeutic target for the treatment of HCC.

Primary biliary cholangitis (PBC) is an autoimmune disease characterized by chronic destruction of the bile ducts. A major unanswered question regarding the pathogenesis of PBC is the precise mechanisms of small bile duct injury. Emperipolesis is one of cell-in-cell structures that is a potential histological hallmark associated with chronic hepatitis B. This study aimed to clarify the pathogenesis and characteristics of emperipolesis in PBC liver injury. Sixty-six PBC patients, diagnosed by liver biopsy combined with laboratory test, were divided into early-stage PBC (stages I and II, n = 39) and late-stage PBC (stages III and IV, n = 27). Emperipolesis was measured in liver sections stained with haematoxylin-eosin. The expressions of CK19, CD3, CD4, CD8, CD20, Ki67 and apoptosis of BECs were evaluated by immunohistochemistry or immunofluorescence double labelling. Emperipolesis was observed in 62.1% of patients with PBC, and BECs were predominantly host cells. The number of infiltrating CD3+ and CD8+ T cells correlated with the advancement of emperipolesis (R2 = 0.318, P

Non-alcoholic steatohepatitis (NASH) has no approved therapy. The farnesoid X nuclear receptor (FXR) agonist obeticholic acid (OCA) has shown promise as a drug for NASH, but can adversely affect plasma lipid profiles. Therefore, the present study aimed to investigate the effects and underlying mechanisms of OCA in combination with simvastatin (SIM) in a high-fat diet (HFD)-induced model of NASH. C57BL/6J mice were fed with a HFD for 16 weeks to establish the NASH model. The mice were randomly divided into the following five groups: HFD, HFD + OCA, HFD + SIM, HFD + OCA + SIM and control. After 16 weeks, the mice were sacrificed under anesthesia. The ratios of liver weight to body weight (Lw/Bw) and of abdominal adipose tissue weight to body weight were calculated. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol, triglycerides and low-density lipoprotein were measured. Liver sections were stained with hematoxylin and eosin. The protein levels of FXR, small heterodimeric partner (SHP) and cytochrome P450 family 7 subfamily A member 1 (CYP7A1) in the liver were detected by western blotting, while the mRNA levels of FXR, SHP, CYP7A1, bile salt export pump, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), sterol regulatory element binding protein-1 (SREBP1) and fatty acid synthase (FASN) were examined by reverse transcription-quantitative polymerase chain reaction. The administration of OCA with or without SIM reduced the liver inflammation score compared with those of the HFD and HFD + SIM groups, with no significant difference between the HFD + OCA and HFD + OCA + SIM groups. The steatosis score followed similar trends to the inflammation score. In HFD-fed mice, OCA combined with SIM prevented body weight gain compared with that in HFD and HFD + OCA groups, and reduced the Lw/Bw ratio compared with that in the HFD and HFD + SIM groups. In addition to preventing HFD-induced increases of ALT and AST, the combination of OCA and SIM reduced the mRNA levels of IL-6, TNF-α, SREBP1 and FASN. On the basis of these results, it may be concluded that the strategy of combining OCA with SIM represents an effective pharmacotherapy for NASH.

Objective: To evaluate the clinical effects of general anesthesia and intraspinal anesthesia on total hip arthroplasty. Methods: A total of 110 patients who underwent unilateral total hip arthroplasty in our hospital were randomly divided into the observation group and the control group, with 55 patients in each group. The observation group was given intraspinal anesthesia, while the control group was given general anesthesia. The excellent anesthesia rate, intraoperative blood pressure, intraoperative heart rate, observation time in the postoperative recovery room, the incidence of complications and hospitalization time were observed and compared between the two groups. Results: Compared with the control group, the excellent anesthesia rate of the observation group increased (P

Fatty liver disease associated with metabolic dysfunction is of increasing concern in mainland China, the world's most populous country. The incidence of fatty liver disease is highest in China, surpassing the incidence in European countries and the USA. An international consensus panel recently published an influential report recommending a novel definition of fatty liver disease associated with metabolic dysfunction. This recommendation includes a switch in name from non-alcoholic fatty liver disease (NAFLD) to metabolic (dysfunction)-associated fatty liver disease (MAFLD) and adoption of a set of positive criteria for disease diagnosis that are independent of alcohol intake or other liver diseases. Given the unique importance of this proposal, the Chinese Society of Hepatology (CSH) invited leading hepatologists and gastroenterologists representing their respective provinces and cities to reach consensus on alternative definitions for fatty liver disease from a national perspective. The CSH endorses the proposed change from NAFLD to MAFLD (supported by 95.45% of participants). We expect that the new definition will result in substantial improvements in health care for patients and advance disease awareness, public health policy, and political, scientific and funding outcomes for MAFLD in China.

Severe dynamic disturbance in extrathick coal seam mining has become one of the main factors threatening the stability of roadway surrounding rock. In this article, the #6 thick coal seam of Buliangou mine in Inner Mongolia, China, is taken as the engineering background. A mechanical model of the roadway roof structure is established to obtain an analytic formula of the key block subsidence. A three-dimensional discrete element model is established and used to verify the field measurement results. The fracture characteristics of the main roof above the F6104 transport roadway and the deformation and damage evolution law of the surrounding rock during thick coal seam mining are analyzed. The results show that because of the long-term breaking and falling of the roof rocks during extrathick coal seam mining, the F6104 transport roadway will undergo two severe mining disturbances at the locations of 10∼30 m and 50∼70 m ahead of the F6103 working face. During the two disturbance periods, the roadway roof displacement settles to 300∼350 mm and 750∼800 mm, and the deformation of the solid coal wall reaches 650∼700 mm and 1350∼1450 mm, respectively. The energy change curve of the total length of the fractured key roof is obtained, and when mining at 50 m, the basic roof is close to its tensile strength, and the strain energy can reach the peak value of 5.2 × 10 4 kJ, which easily leads to rock burst. The plastic damage zones on both sides of the roadway develop to the roof central area and eventually coalesce, and the deformation of the surrounding rock is obvious. When mining at 50∼70 m, the basic roof breaks and unloads, and elastic strain energy of 3.57 × 10 4 kJ is instantaneously released. These two dynamic disturbances are the main reasons for the instability of the roadway surrounding rock. The results clarify that the failure mechanism investigation of roadways in thick coal seam mining conditions can be effectively applied to control the stability of the roadway surrounding rock under strong mining disturbance.

Aims To explore the potential regulatory mechanism of differentially expressed mRNAs in Hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC). Main methods Patients with HCV-related HCC and age- and gender-matched healthy subjects were enrolled. Differentially expressed mRNAs in the plasma were detected by digital gene expression (DGE) profile analysis. HepG2 and SMMC7721 cells stably transfected with HCV-core protein and the control plasmid were established. And small interfering RNA (siRNA) was used to knockdown the target gene in HCV core-expressing HCC cell lines. mRNA expression was determined by qRT-PCR. Protein expression was measured by Western blot and immunohistochemistry staining. Key findings DGE profile data showed aberrant mRNA expression contributed to the progression of HCV-HCC, and clusterin (CLU), which was significantly highly expressed, was chosen as a candidate gene. Further evidence showed CLU was highly expressed in tumor tissues of HCV-HCC patients and HCV core-expressing HCC cell lines, accompanied with enhanced autophagy and upregulation of pro-autophagy genes. And knockdown of CLU in HCC cell lines suppressed cell autophagy, which was indicated by decreased expression of autophagy marker light chain 3B (LC3B) ІІ/І ratio, and downregulated pro-autophagy genes like Beclin1, autophagy-related protein 7 (Atg7) and Lamp2. On the other hand, anti-autophagy genes or regulators, including p62 and phosphorylated mammalian target of rapamycin (p-mTOR), were notably upregulated. Significance CLU could promote the progression of HCV-related HCC by regulating autophagy, which might be a potential therapeutic target of HCV-HCC.

The liver is the only visceral organ that exhibits a remarkable capability of regenerating in response to partial hepatectomy (PH) or chemical injury. Improving liver regeneration (LR) ability is the basis for the favourable treatment outcome of patients after PH, which can serve as a potential indicator for postoperative survival. The present study aimed to investigate the protective effects of Yiqi Huoxue recipe (YQHX) on LR after PH in rats and further elucidate its underlying mechanism. A two-thirds PH rat model was used in this study. Wistar rats were randomly divided into four groups: sham-operated, PH, YQHX + PH, and Fuzheng Huayu decoction (FZHY) + PH groups. All rats were sacrificed under anesthesia at 24 and 72 h after surgery. The rates of LR were calculated, and the expression levels of cyclin D1 and c-jun were determined by immunohistochemical staining. The protein levels of p-JNK1/2, JNK1/2, p-c-jun, c-jun, Bax, and Bcl-2 were detected by Western blotting, while the mRNA levels of JNK1, JNK2, c-jun, Bax, and Bcl-2 were examined by real-time polymerase chain reaction (RT-PCR). At the corresponding time points, YQHX and FZHY administration dramatically induced the protein levels of p-JNK1/2 compared to the PH group p<0.05, while FZHY + PH group showed prominently increase in p-JNK1/2 protein levels compared to the YQHX + PH group p<0.05. A similar trend was observed for the expression levels of p-c-jun. Compared to the PH group, YQHX and FZHY markedly reduced the mRNA and protein expression levels of Bax at 24 h after PH, while those in the FZHY + PH group decreased more obviously p<0.05. Besides, in comparison with the PH group, YQHX and FZHY administration predominantly upregulated the mRNA and protein expression levels of Bcl-2 at 24 and 72 h after PH p<0.05. In conclusion, YQHX improves LR in rats after PH by inhibiting hepatocyte apoptosis via the JNK signaling pathway.

Zero-energy states in tunnel spectra, an important manifestation of topological superconductivity, have been the focus of the field of topological phases of matter. However, experimentally creating and controlling the zero-energy states is difficult, e.g., it requires a large magnetic field in the case of topological superconductivity. Here, we report on an effective approach to generate controllable zero-energy states in the superconducting Rashba oxide heterostructure by in-plane magnetic field cooling. A pronounced zero-bias conductance peak emerging below a threshold magnetic field down to zero after in-plane magnetic field cooling of a Rashba perovskite oxide heterostructure connecting to an s-wave superconductor. We further demonstrate the high tunability of the zero-energy states between a zero-bias conductance peak and a zero-bias conductance valley by electrical gating at a zero magnetic field. Our theoretical analysis indicates that the in-plane magnetic field or magnetization could lead to finite center-of-mass momentum pairing that supports topological zero-energy states in the Rashba system and provides an opportunity to manipulate topological zero-energy states through gating.

MicroRNA (miRNA) play a pivotal role in the development of liver fibrosis. However, the functions of miRNA in hepatitis C virus (HCV)-related liver fibrosis remain unclear. In this study, we systematically analyzed the microarray data of the serum miRNA in patients with HCV-induced hepatic fibrosis. Among 41 dysregulated miRNA, miR-1273g-3p was the most significantly upregulated miRNA and correlated with the stage of liver fibrosis. Overexpression of miR-1273g-3p could inhibit translation of PTEN, increase the expression of α-SMA, Col1A1, and reduce apoptosis in HSCs. Hence, we conclude that miR-1273g-3p might affect the activation and apoptosis of HSCs by directly targeting PTEN in HCV-related liver fibrosis.

Objective To investigate the regulation mechanism of T cell immunoglobulin and mucin domain-3 (Tim-3) combined with toll-like receptor 3 (TLR3) or TLR4 on antiviral immune and inflammatory response in patients with chronic hepatitis C virus (HCV) infection. Methods Patients with chronic HCV infection and healthy control subjects were recruited. Patients received interferon (IFN)-α based therapy. Plasma galectin-9 (Gal-9) was quantitated. Peripheral blood mononuclear cells (PBMCs) were cultured with TLR3 or TLR4 agonists, alone or in combination with Tim-3 antagonist. Levels of IFN-α, TNF-α, and 2′-5′ oligoadenylate synthetase (2′-5′OAS), myxovirus resistance protein A (MxA) and suppressor of cytokine 1 (SOCS1) RNA in PBMC cultures were evaluated. Results Plasma Gal-9 levels were increased in patients ( n = 52) compared with controls ( n = 20) and significantly declined at treatment week 12 and 24 weeks post-treatment. IFN-α, 2′-5′OAS, MxA, TNF-α and SOCS1 were upregulated by TLR3 and TLR4 agonists. TNF-α and SOCS1 levels were suppressed by the addition of Tim-3 antagonist. Conclusions Tim-3 blockade in combination with TLR activation induces the expression of antiviral molecules without a significant increase in TNF-α or SOCS1.

It has been reported that treatment with telbivudine might be associated with a significant improvement of renal function in patients with chronic hepatitis B. To confirm this finding, a systematic literature review was conducted. Four online databases (PubMed, CNKI/FMJS, Ovid and SpringerLink) were searched. Serum creatinine, glomerular filtration rate and estimated glomerular filtration rate changes from baseline to the end of the treatment were analyzed. A total of seven full-text articles and 13 abstracts with sample sizes ranging from 15 to 689 patients fulfilled the selection criteria for review. The results showed that long-term treatment with telbivudine, either as monotherapy or combined with other nucleos(t)ide analogs, can significantly improve renal function in chronic hepatitis B patients, particularly those at high risk of renal impairment.

Activation of the innate immune system is involved in the development of chronic liver diseases, including nonalcoholic steatohepatitis. Toll‑like receptor 4 (TLR4) is one of the sensors of the innate immune system. The aim of the present study was to elucidate the role of the TLR4‑dependent signaling pathway, and examine the effect of pioglitazone on hepatic fibrosis, through modulation of the TLR4 pathway in a mouse model of nutritional fibrotic steatohepatitis. Male C57BL/6J mice were fed a methionine‑choline deficient (MCD) diet for 8 weeks to induce nonalcoholic fibrotic steatohepatitis. The PPARγ agonist, pioglitazone, and PPARγ inhibitor, GW9662, were administered to the mice, respectively. The effects of the induction of PPARγ on liver biochemistry and histology, the modulation of TLR4 and its downstream pathway, and the expression levels of inflammatory and fibrogenic genes were assessed using reverse transcription‑quantitative polymerase chain reaction and Western blot analyses. The MCD‑fed mice exhibited progressive hepatic steatosis, necrotic inflammation and fibrosis, along with increase levels of serum alanine aminotransferase and aspartate aminotransferase, accompanied by the upregulation of TLR4, the TLR4‑myeloid differentiation primary response gene 88‑dependent pathway and downstream genes, and proinflammatory and profibrotic genes; and downregulation of basic membrane protein and activin membrane‑bound inhibitor. The administration of pioglitazone was found to reverse hepatic nutritional fibrosis via restoration of the expression levels of proinflammatory and profibrotic genes in the MCD‑fed mice. The results of the present study provide novel evidence supporting the protective role of pioglitazone in ameliorating nutritional fibrotic steatohepatitis, through modulation of the TLR4‑mediated signaling pathway.

Hepatic fibrosis is a crucial pathological process involved in the development of chronic hepatitis C (CHC) and may progress to liver cirrhosis and hepatocellular carcinoma. Activated peripheral blood monocytes and intrahepatic macrophages further promote hepatic fibrogenesis by releasing proinflammatory and profibrogenic cytokines. The present study aimed to investigate the role of peripheral CD14+ monocytes and intrahepatic CD163+ macrophages in hepatitis C virus (HCV)-associated liver fibrosis and clarify whether serum soluble CD163 (sCD163) may serve as a fibrosis marker in patients with CHC. A total of 87 patients with CHC and 20 healthy controls were recruited. Serum sCD163 levels were measured by ELISA. Frequencies of peripheral CD14+ monocytes and inflammatory cytokines expressed by CD14+ monocytes were analyzed by flow cytometry. The degree of fibrosis in human liver biopsies was graded using the Metavir scoring system and patients were stratified into two groups based on those results (F

To investigate the expression of thrombospondin 2 (THBS2) in colorectal cancer (CRC) and its relationship with clinicopathological features and prognosis.THBS2 expression was evaluated with tissue microarrays (TMAs) immunohistochemistry (IHC) staining in 100 CRC samples.High THBS2 expression was found in 73 patients (45 male and 28 female). THBS2 expression was significantly correlated to TNM stages (p=4.1×10-5), T classification (p=0.005), lymph node metastasis (p=3×10-4) and AJCC stages (p=0), while no significant association was found in gender, age, distant metastasis or tumor size. In both univariate and multivariate analyses, THBS2 showed statistically prognostic significance [p0.001, HR (hazard ratio) = 0.237, 95% CI (0.101-0.557) and p0.001, HR=0.158, 95% CI (0.062-0.401)]. Kaplan-Meier survival analysis further confirmed that THBS2 expression was significantly correlated with clinical outcomes (p0.001).All the results indicated THBS2 expression might become a prognostic marker for CRC.

Previous studies using microRNA (miRNA or miR) microarrays have demonstrated that miR-1273g-3p is upregulated in patients with hepatitis C virus (HCV)-associated fibrosis. As miRNAs have been suggested to be promising non-invasive biomarkers, the aim of the present study was to assess whether miR-1273g-3p may be useful as a potential indicator of fibrosis progression in patients with HCV. Liver biopsies were performed on 112 patients with chronic hepatitis C (CHC) and liver stiffness measurements (LSM) were performed using FibroTouch. Liver fibrosis was determined based on Meta-analysis of Histological Data in Viral Hepatitis classification, and the aspartate aminotransferase (AST)-to-platelet count (PLT) ratio index (APRI) and Fibrosis-4 score (FIB-4) were calculated. The diagnostic performance of miR-1273g-3p, LSM, APRI and FIB-4 in predicting fibrosis stage were evaluated and compared by receiver operating characteristic (ROC) analysis. It was demonstrated that miR-1273g-3p levels were significantly positively correlated with the liver fibrosis stage (r=0.657, P

The BIC signal of the Chinese Beidou III navigation system brings new features compared to the previous civilian signals, such as new modulation technique (i.e. Binary Offset Carrier BOC), data/pilot channels, secondary code and so on. These innovations are able to enhance the signal tracking robustness, but require adapted special techniques to track this new signal. In this paper, two joint data/pilot tracking techniques are introduced to enable the dual channel (i.e. data and pilot) tracking, which are called semi-joint data/pilot and joint data/pilot respectively. Both methods can realize signal tracking and enable data extraction at the same time, while the later one results in less power loss but needs additional computational resources. Furthermore, the bump-jump method is brought in to resolve the side peak issue caused by BOC modulation. The experiment results demonstrated that the proposed tracking methods could enable the BIC signal tracking process without locking on the side peaks, while the tracking sensitivity of the joint method was around 1.1dB higher than the one of the semi-joint method, but required additional 90% correlations.

The modern signals of the Chinese Beidou III navigation system bring new features compared to the previous civilian signals, such as longer spreading code, involving secondary code, new modulation technique (i.e. Binary Offset Carrier BOC), data/pilot channels and so on. These innovations are able to enhance the signal acquisition robustness, but they also require specific acquisition techniques to handle the large data stream, deal with the problem of sign transition and side peaks caused by the secondary code and the BOC modulation respectively. This paper proposes a novel two-stage acquisition technique for realizing efficient acquisition of the B1C signal in the engineering implementation of the modern receiver. The first stage employs an extended parallelized Averaging Correlation (AC) search structure, which can cope with the sign transition problem, to coarsely capture the signal with high efficiency. At the second stage, a fine-search process is completed within a reduced searching range to provide high precision result. The involving of the later stage aims to avoid the side peaks effect in the tracking stage that can easily cause a false lock. In addition, both of the single and channel combining acquisition techniques are introduced, which give designers an option of implementing the acquisition with higher sensitivity but more resources. The experiment results demonstrate that the proposed method allows to use much cheaper FFT blocks and enables fast acquisition by parallel process. The proposed method can reduce the number of multiplications by at least 61% when the sampling frequency is over 50MHz while providing quite similar acquisition precisions with the conventional method.