Monocyte Chemoattractant Protein-Induced Protein 1 Targets Hypoxia-Inducible Factor 1α to Protect Against Hepatic Ischemia/Reperfusion Injury.

Sterile inflammation is an essential factor causing hepatic ischemia/reperfusion (I/R) injury. As a critical regulator of inflammation, the role of monocyte chemoattractant protein-induced protein 1 (MCPIP1) in hepatic I/R injury remains undetermined. In this study, we discovered that MCPIP1 downregulation was associated with hepatic I/R injury in liver transplant patients and a mouse model. Hepatocyte-specific Mcpip1 gene knockout and transgenic mice demonstrated that MCPIP1 functions to ameliorate liver damage, reduce inflammation, prevent cell death, and promote regeneration. A mechanistic study revealed that MCPIP1 interacted with and maintained hypoxia-inducible factor 1α (HIF-1α) expression by deubiquitinating HIF-1α. Notably, the HIF-1α inhibitor reversed the protective effect of MCPIP1, whereas the HIF-1α activator compensated for the detrimental effect of MCPIP1 deficiency. Thus, we identified the MCPIP1-HIF-1α axis as a critical pathway that may be a good target for intervention in hepatic I/R injury. (Hepatology 2018; 00:000-000).

Caspase Recruitment Domain Protein 6 Protects Against Hepatic Steatosis and Insulin Resistance by Suppressing Apoptosis Signal-Regulating Kinase 1.

The rapidly increasing prevalence of metabolic disorders associated with nonalcoholic fatty liver disease (NAFLD) warrants further study of the underlying mechanisms to identify key regulators as targets for the development of therapeutic interventions. Caspase recruitment domain protein 6 (Card6), as a member of the CARD family that regulates cell death and immunity, may potentially control this process. Indeed, Card6 down-regulation was found to be closely associated with the fatty livers observed in NAFLD patients, obese mice, and a palmitate-treated hepatocyte model. Gain-of-function and loss-of-function Card6 mouse models demonstrated that Card6 protected mice from insulin resistance, hepatic steatosis, and inflammatory responses upon high-fat diet administration. Mechanistically, Card6 interacted with and inhibited apoptosis signal-regulating kinase 1 (Ask1) and its subsequent downstream c-Jun N-terminal kinase/p38 signaling. Furthermore, Ask1 was sufficient to mediate Card6 function, and the interaction between Ask1 and Card6 was absolutely required for Card6 function in vivo. Adenovirus-mediated Card6 overexpression in the liver effectively ameliorated insulin resistance and hepatic steatosis in ob/ob mice. Therefore, we identified Card6 as an important negative regulator in NAFLD. Conclusion: Targeting Ask1 by Card6 may be a good strategy to develop a therapeutic method against NAFLD.

The long noncoding RNA, EGFR-AS1, a target of GHR, increases the expression of EGFR in hepatocellular carcinoma.

LncRNA has provided an important new perspective regarding gene regulation. Both the expression and activation of EGFR have been proven to be under the tight control of the GHR pathway. EGFR-AS1 has been found to inhibit the expression of EGFR. GHR-siRNA and EGFR-AS1-siRNA were transfected into HCC cell lines, and a series of WB, q-PCR, and IF experiments was conducted to evaluate whether EGFR-AS1 participated in the regulation of GHR and EGFR. We found that impeded expression of GHR decreased the expression of EGFR and EGFR-AS1 in vivo and in vitro. Then, it was verified that EGFR and EGFR-AS1 were relatively upregulated in HCC tissue, and they were significantly related to some clinical characteristics and patient prognosis. Furthermore, EGFR-AS1 was determined to promote HCC development by improving the ability of invasion and proliferation of HCC cells in vitro, and it was also found to affect the cell cycle. Our study identified that EGFR-AS1 may promote HCC genesis and development. EGFR-AS1 may act as a prognostic factor in HCC. More importantly, we observed that the inhibition of EGFR-AS1 in HCC cells significantly impeded cell proliferation and invasion in vivo, which might provide a potential possibility for targeted therapy of HCC.

A combined pre- and intra-operative nomogram in evaluation of degrees of liver cirrhosis predicts post-hepatectomy liver failure: a multicenter prospective study.

Background: Adequate evaluation of degrees of liver cirrhosis is essential in surgical treatment of hepatocellular carcinoma (HCC) patients. The impact of the degrees of cirrhosis on prediction of post-hepatectomy liver failure (PHLF) remains poorly defined. This study aimed to construct and validate a combined pre- and intra-operative nomogram based on the degrees of cirrhosis in predicting PHLF in HCC patients using prospective multi-center's data. Methods: Consecutive HCC patients who underwent hepatectomy between May 18, 2019 and Dec 19, 2020 were enrolled at five tertiary hospitals. Preoperative cirrhotic severity scoring (CSS) and intra-operative direct liver stiffness measurement (DSM) were performed to correlate with the Laennec histopathological grading system. The performances of the pre-operative nomogram and combined pre- and intra-operative nomogram in predicting PHLF were compared with conventional predictive models of PHLF. Results: For 327 patients in this study, histopathological studies showed the rates of HCC patients with no, mild, moderate, and severe cirrhosis were 41.9%, 29.1%, 22.9%, and 6.1%, respectively. Either CSS or DSM was closely correlated with histopathological stages of cirrhosis. Thirty-three (10.1%) patients developed PHLF. The 30- and 90-day mortality rates were 0.9%. Multivariate regression analysis showed four pre-operative variables [HBV-DNA level, ICG-R15, prothrombin time (PT), and CSS], and one intra-operative variable (DSM) to be independent risk factors of PHLF. The pre-operative nomogram was constructed based on these four pre-operative variables together with total bilirubin. The combined pre- and intra-operative nomogram was constructed by adding the intra-operative DSM. The pre-operative nomogram was better than the conventional models in predicting PHLF. The prediction was further improved with the combined pre- and intra-operative nomogram. Conclusions: The combined pre- and intra-operative nomogram further improved prediction of PHLF when compared with the pre-operative nomogram. Trial Registration: Clinicaltrials.gov Identifier: NCT04076631.

Dysregulated microRNAs as a biomarker for diagnosis and prognosis of hepatitis B virus-associated hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a malignancy with a high incidence and fatality rate worldwide. Hepatitis B virus (HBV) infection is one of the most important risk factors for its occurrence and development. Early detection of HBV-associated HCC (HBV-HCC) can improve clinical decision-making and patient outcomes. Biomarkers are extremely helpful, not only for early diagnosis, but also for the development of therapeutics. MicroRNAs (miRNAs), a subset of non-coding RNAs approximately 22 nucleotides in length, have increasingly attracted scientists' attention due to their potential utility as biomarkers for cancer detection and therapy. HBV profoundly impacts the expression of miRNAs potentially involved in the development of hepatocarcinogenesis. In this review, we summarize the current progress on the role of miRNAs in the diagnosis and treatment of HBV-HCC. From a molecular standpoint, we discuss the mechanism by which HBV regulates miRNAs and investigate the exact effect of miRNAs on the promotion of HCC. In the near future, miRNA-based diagnostic, prognostic, and therapeutic applications will make their way into the clinical routine.

[Analysis of pigments from Rhodotorula glutinis by Raman spectroscopy and thin layer chromatography].

The pigments from Rhodotorula glutinis were separated by using thin layer chromatography, and the result showed that Rhodotorula glutinis cells could synthesize at least three kinds of pigments, which were beta-carotene, torulene, and torularhodin. The Raman spectra based on the three pigments were acquired, and original spectra were preprocessed by background elimination, baseline correction, and three-point-smoothing, then the averaged spectra from different pigments were investigated, and the result indicated that Raman shift which represents C-C bond was different, and the wave number of beta-carotene demonstrated the largest deviation, finally torulene and torularhodin in Rhodotorula glutinis had more content than beta-carotene. Quantitative analysis of Raman peak height ratio revealed that peak height ratio of pigments showed little difference, which could be used as parameters for further research on living cells, providing reference content of pigments. The above results suggest that Raman spectroscopy combined with thin layer chromatography can be applied to analyze pigments from Rhodotorula glutinis, provides abundant information about pigments, and serves as an effective method to study pigments.

Unexpected discovery of intrahepatic cholangiocarcinoma during follow-up in two cases of liver cysts: case report.

Background: The liver cyst is commonly treated by hepatobiliary surgery. Generally, most patients show no apparent symptoms and often get diagnosed accidentally during the imaging examinations. In addition, most patients with liver cysts follow a benign course, with fewer severe complications and rare occurrences of malignant changes. Therefore, based on disease characteristics and healthcare costs, long-term regular follow-up of liver cysts are rarely performed clinically. Case Description: Here, we reported two previously treated or observed cases for liver cysts, where intrahepatic neoplastic lesions were found unexpectedly at the liver cyst during follow-up. These two patients' clinical manifestations and laboratory examinations lacked specificity with unclear pre-operative diagnosis, whereas the post-operative pathology confirmed cholangiocarcinoma. One of the patients was a 64-year-old female with right upper abdominal distension. She underwent cyst fenestration for a liver cyst 3 years ago. In the latest admission, imaging examination revealed a tumor in the left inner lobe of the liver. The tumor was located in the exact fenestration location, and the pathological diagnosis of cholangiocarcinoma was made after surgical resection. The patient received Lenvatinib post-operatively and had no recurrence during the follow-up. Another patient, a 68-year-old woman, was asymptomatic, but the liver margin was palpable under the ribs on her physical examination. She had a previous diagnosis of liver cysts and was on regular yearly follow-up. In the last follow-up, a tumor was found close to a cyst. It was diagnosed as intrahepatic cystadenocarcinoma before surgery; however, the pathological features after surgical resection were more consistent with the cholangiocarcinoma. The patient had lung metastases 2 months after the surgery, but her condition improved after receiving targeted therapy and immunotherapy. Moreover, she is alive to this day. Conclusions: We reported 2 cases of intrahepatic cholangiocarcinoma discovered accidentally during the follow-up of hepatic cysts. The location of the malignant tumor coincided with the location of the cyst, making the clinical differential diagnosis problematic. Therefore, it is necessary to be vigilant about the possibility of combined malignant tumors for the follow-up of complex cysts, as early detection and treatment may help improve the prognosis of these patients. After surgery, multimodal therapy, including chemotherapy, immunotherapy, and targeted therapy, is helpful.

[Raman tweezers-based analysis of carotenoid synthesis in Rhodotorula glutinis].

Carotenoid synthesis in Rhodotorula glutinis was investigated with Raman tweezers in order to find the effect of nitrogen and carbon resource on carotenoid yield. The cells in fermentation terminus were harvested, and then divided into two parts, one for UV analysis, the other for Raman tweezers detection. Original spectra were preprocessed by carrying out background elimination and baseline correction, and the averaged spectra of cells cultivated in different fermentation medium were analyzed qualitatively. The results showed that the Raman intensity of carotenoid were obviously different. There was a high correlation between UV results and Raman peak height data, the correlation coefficients of fitted parameters were 0.907 8 and 0.912 1, respectively. Quantitative analysis of 1 508 cm(-1) peak height indicated that the appropriate nitrogen and carbon resources for the growth of Rhodotorula glutinis cells and synthesis of carotenoid were yeast extract + tryptone, and glucose, respectively. The above results suggest that Raman tweezers can provide information about carotenoids in Rhodotorula glutinis cells and serve as an effective tool for real time measurement of carotenoid synthesis and optimization of fermentation medium.

[Identification of Cortex Phellodendri by Fourier-transform infrared spectroscopy and principal component analysis].

Fourier transform infrared spectrometer was used to collect infrared spectra of Cortex Phellodendri from six different regions. Original spectra were preprocessed by carrying out appropriate baseline correction and five-points smoothing, and the averaged spectra of Cortex Phellodendri from the six origins were analyzed. As a result, the averaged spectra looked quite similar. The normalized spectra were selected to construct principal component analysis model in the range of fingerprint region 1800 - 500 cm(-1), and according to the model, the first three principal components accounted for 98% of the variance information in the fingerprint region, and each sample was able to form distinct cluster in the principal component space, then the identification of Cortex Phellodendri from the six regions was basically achieved; besides, to some extent, the sparse density of the samples distribution reflected the genetic relationship. The loading factors of the model were analyzed, and the results indicated that the differences between Cortex Phellodendri samples mostly depended on the contents of protein, carbohydrates, lipids, alkaloids, sterols, obaculactone, oba-cunone, and obacunonlc acid. On the whole, combined with principal component analysis, FTIR provides an effective way to evaluate the herbal Cortex Phellodendri rapidly and nondestructively, which also reflects the content difference of material composition.

Extracorporeal Membrane Oxygenation Therapy for Critically Ill Coronavirus Disease 2019 Patients in Wuhan, China: A Retrospective Multicenter Cohort Study.

Currently, little in-depth evidence is known about the application of extracorporeal membrane oxygenation (ECMO) therapy in coronavirus disease 2019 (COVID-19) patients. This retrospective multicenter cohort study included patients with COVID-19 at 7 designated hospitals in Wuhan, China. The patients were followed up until June 30, 2020. Univariate and multivariate logistic regression analyses were performed to identify the risk factors associated with unsuccessful ECMO weaning. Propensity score matching was used to match patients who received veno-venous ECMO with those who received invasive mechanical ventilation (IMV)-only therapy. Of 88 patients receiving ECMO therapy, 27 and 61 patients were and were not successfully weaned from ECMO, respectively. Additionally, 15, 15, and 65 patients were further weaned from IMV, discharged from hospital, or died during hospitalization, respectively. In the multivariate logistic regression analysis, a lymphocyte count ≤0.5×109/L and D-dimer concentration >4× the upper limit of normal level at ICU admission, a peak PaCO2 >60 mmHg at 24 h before ECMO initiation, and no tracheotomy performed during the ICU stay were independently associated with lower odds of ECMO weaning. In the propensity score-matched analysis, a mixed-effect Cox model detected a lower hazard ratio for 120-day all-cause mortality after ICU admission during hospitalization in the ECMO group. The presence of lymphocytopenia, higher D-dimer concentrations at ICU admission and hypercapnia before ECMO initiation could help to identify patients with a poor prognosis. Tracheotomy could facilitate weaning from ECMO. ECMO relative to IMV-only therapy was associated with improved outcomes in critically ill COVID-19 patients.

HOXD9 Activates the TGF-ß/Smad Signaling Pathway to Promote Gastric Cancer.

BACKGROUND: Gastric cancer (GC) is the most common malignant tumor of the digestive tract and its molecular mechanism is not clear. HOXD9 plays an important role in tumor progression as transcription factor. In the current study, we explored the role of HOXD9 in GC. METHODS: We predicted the expression and potential mechanism of HOXD9 in GC through an online database. The expression of HOXD9 was detected in GC and adjacent tissues, and then we analyzed the relationship between HOXD9 and the prognosis of patients with GC. In vitro, we investigated the effects of HOXD9 on malignant biological behaviors such as proliferation, migration, and invasion of the GC cell line MCG-803. In addition, we have initially studied the underlying mechanism by Western blot. RESULTS: High expression of HOXD9 in GC was predicted by online database prediction and implied poor prognosis. In the clinical sample, we confirmed the above predictions. In vitro, we found that knockdown of HOXD9 could effectively inhibit the proliferation, migration, and invasion of GC cells. In terms of mechanism, HOXD9 may activate the TGF-ß/Smad signaling pathway. CONCLUSION: HOXD9 promotes the malignant biological process of GC, which may be a potential therapeutic target for GC.

Perceived infection transmission routes, infection control practices, psychosocial changes, and management of COVID-19 infected healthcare workers in a tertiary acute care hospital in Wuhan: a cross-sectional survey.

BACKGROUND: Many healthcare workers were infected by coronavirus disease 2019 (COVID-19) early in the epidemic posing a big challenge for epidemic control. Hence, this study aims to explore perceived infection routes, influencing factors, psychosocial changes, and management procedures for COVID-19 infected healthcare workers. METHODS: This is a cross-sectional, single hospital-based study. We recruited all 105 confirmed COVID-19 healthcare workers in the Zhongnan Hospital of Wuhan University from February 15 to 29, 2020. All participants completed a validated questionnaire. Electronic consent was obtained from all participants. Perceived causes of infection, infection prevention, control knowledge and behaviour, psychological changes, symptoms and treatment were measured. RESULTS: Finally, 103 professional staff with COVID-19 finished the questionnaire and was included (response rate: 98.1%). Of them, 87 cases (84.5%) thought they were infected in working environment in hospital, one (1.0%) thought their infection was due to the laboratory environment, and 5 (4.9%) thought they were infected in daily life or community environment. Swab of throat collection and physical examination were the procedures perceived as most likely causing their infection by nurses and doctors respectively. Forty-three (41.8%) thought their infection was related to protective equipment, utilization of common equipment (masks and gloves). The top three first symptoms displayed before diagnosis were fever (41.8%), lethargy (33.0%) and muscle aches (30.1%). After diagnosis, 88.3% staff experienced psychological stress or emotional changes during their isolation period, only 11.7% had almost no emotional changes. Arbidol (Umifenovir; an anti-influza drug; 69.2%) was the drug most commonly used to target infection in mild and moderate symptoms. CONCLUSION: The main perceived mode of transmission was not maintaining protection when working at a close distance and having intimate contact with infected cases. Positive psychological intervention is necessary.

A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version).

In December 2019, a new type viral pneumonia cases occurred in Wuhan, Hubei Province; and then named "2019 novel coronavirus (2019-nCoV)" by the World Health Organization (WHO) on 12 January 2020. For it is a never been experienced respiratory disease before and with infection ability widely and quickly, it attracted the world's attention but without treatment and control manual. For the request from frontline clinicians and public health professionals of 2019-nCoV infected pneumonia management, an evidence-based guideline urgently needs to be developed. Therefore, we drafted this guideline according to the rapid advice guidelines methodology and general rules of WHO guideline development; we also added the first-hand management data of Zhongnan Hospital of Wuhan University. This guideline includes the guideline methodology, epidemiological characteristics, disease screening and population prevention, diagnosis, treatment and control (including traditional Chinese Medicine), nosocomial infection prevention and control, and disease nursing of the 2019-nCoV. Moreover, we also provide a whole process of a successful treatment case of the severe 2019-nCoV infected pneumonia and experience and lessons of hospital rescue for 2019-nCoV infections. This rapid advice guideline is suitable for the first frontline doctors and nurses, managers of hospitals and healthcare sections, community residents, public health persons, relevant researchers, and all person who are interested in the 2019-nCoV.

Chemoprophylaxis, diagnosis, treatments, and discharge management of COVID-19: An evidence-based clinical practice guideline (updated version).

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, coronavirus disease 2019 (COVID-19), affecting more than seventeen million people around the world. Diagnosis and treatment guidelines for clinicians caring for patients are needed. In the early stage, we have issued "A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version)"; now there are many direct evidences emerged and may change some of previous recommendations and it is ripe for develop an evidence-based guideline. We formed a working group of clinical experts and methodologists. The steering group members proposed 29 questions that are relevant to the management of COVID-19 covering the following areas: chemoprophylaxis, diagnosis, treatments, and discharge management. We searched the literature for direct evidence on the management of COVID-19, and assessed its certainty generated recommendations using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Recommendations were either strong or weak, or in the form of ungraded consensus-based statement. Finally, we issued 34 statements. Among them, 6 were strong recommendations for, 14 were weak recommendations for, 3 were weak recommendations against and 11 were ungraded consensus-based statement. They covered topics of chemoprophylaxis (including agents and Traditional Chinese Medicine (TCM) agents), diagnosis (including clinical manifestations, reverse transcription-polymerase chain reaction (RT-PCR), respiratory tract specimens, IgM and IgG antibody tests, chest computed tomography, chest x-ray, and CT features of asymptomatic infections), treatments (including lopinavir-ritonavir, umifenovir, favipiravir, interferon, remdesivir, combination of antiviral drugs, hydroxychloroquine/chloroquine, interleukin-6 inhibitors, interleukin-1 inhibitors, glucocorticoid, qingfei paidu decoction, lianhua qingwen granules/capsules, convalescent plasma, lung transplantation, invasive or noninvasive ventilation, and extracorporeal membrane oxygenation (ECMO)), and discharge management (including discharge criteria and management plan in patients whose RT-PCR retesting shows SARS-CoV-2 positive after discharge). We also created two figures of these recommendations for the implementation purpose. We hope these recommendations can help support healthcare workers caring for COVID-19 patients.

Ultra-small bimetallic iron-palladium (FePd) nanoparticle loaded macrophages for targeted tumor photothermal therapy in NIR-II biowindows and magnetic resonance imaging.

Nanoparticles working in the NIR-II biowindows possess larger maximum permissible exposure (MPE) and desirable penetration depth to the laser. However, most NIR-II responsive nanomaterials lack tumor targeting and Magnetic Resonance Imaging (MRI) ability. This greatly limits their applications. This study reported ultra-small bimetallic iron-palladium (FePd) nanoparticle loaded macrophages for targeted tumor photothermal therapy in NIR-II biowindows and magnetic resonance imaging. The crystal phase, morphology, absorption spectrum and photothermal performance of the synthesized samples were systematically characterized. The effects of photothermal therapy and nuclear magnetic imaging (MRI) were studied both in vitro and in vivo. Since FePd nanoparticles have both iron and palladium elements, it had a good MRI imaging capability and high photothermal conversion efficiency (36.7%). After binding to macrophages, FePd nanoparticles@macrophages (FePd@M) showed a good tumor targeting ability and were used for targeting NIR-II photothermal therapy and MRI imaging of tumors. The results of photothermal treatment showed that the tumor volume decreased by 90% compared to the control group, and no significant organ toxicity was observed. The results of MRI imaging showed that the FePd@M has the best imaging effect. The nanoparticles with the excellent NIR-II PTT ability and MRI effect have overcome the problem of tumor targeting and avoid the rapid removal of ultra-small nanoparticles. The FePd@M delivery system provides new ideas for material construction in the NIR-II region and has great clinical application potential.

Pterostilbene inhibits MTA1/HDAC1 complex leading to PTEN acetylation in hepatocellular carcinoma.

PURPOSE: The aim of this study is to investigate the inhibition of cancer growth by pterostilbene through Metastasis-Associated Protein 1 (MTA1) and the histone deacetylase 1 (HDAC1) complex in hepatocellular carcinoma (HCC). METHODS: We investigate the antitumor effects of pterostilbene (PTER) in HCC. The SMMC-7721 hepatoma cell line was cultured and treated with PTER for different time depending on the experiment. After treatment, we tested the cellular expression of proteins by Western blot and the expression of MTA1 mRNA by real-time PCR. And the immunoprecipitation was performed to confirm the acetylation in PTEN. Animal models have been established to confirm the anti-cancer effects of PTER. RESULTS: PTER treatment could downregulate the expression of MTA1, and HDAC1 and elevates the Ac-PTEN ratio in tumors. The results suggest that PTER can decrease the expression of MTA1 and destabilize the MTA1/HDAC1 complex allowing acetylation/activation of PTEN on Lys402 site. The expression of MTA1 may be linked to cell apoptosis and invasion in HCC. CONCLUSION: We demonstrated that PTER suppressed the growth, and invasion of HCC and was effective in regulating the levels of the MTA1/HDAC1/NuRD complex, promoting PTEN acetylation and apoptosis in HCC. Our findings suggest that the novel epigenetic nature of PTER anticancer activity opens up new avenues for primary chemoprevention, as well as anticancer and antimetastatic treatment.

Clinicopathologic Significance and Prognostic Value of Programmed Cell Death Ligand 1 (PD-L1) in Patients With Hepatocellular Carcinoma: A Meta-Analysis.

Background: There is still a dispute over an issue of the clinical pathology and prognostic of programmed cell death ligand 1 (PD-L1) in hepatocellular carcinoma (HCC) patients. Here, we undertook this meta-analysis to survey the conceivable role of PD-L1 in HCC. Method: We searched databases like MEDLINE, EMBASE, and Google Scholar for relevant studies published in English up to February 13, 2018. We implemented the appraisal of the eligible studies according to the choice criterion. We used Hazard ratio (HR) and its 95% confidence interval (95% CI) to evaluate the prognostic role of PD-L1 for overall survival (OS), disease-free survival (DFS), and recurrence-free survival (RFS). Odds ratio (OR) and the corresponding 95% CI were calculated to evaluate the connection between PD-L1 and clinicopathological features. Publication bias was tested. Results: 13 studies, which published range from 2009 to 2017 were contained in this meta-analysis, involving 1,843 patients with HCC. The results indicated that high PD-L1 could predict shorter OS (HR = 1.57, 95% CI: 1.09-2.27, P < 0.00001) as well as poorer DFS (HR = 2.07, 95% CI: 1.20-3.58, P = 0.009). Additionally, high PD-L1 expression was correlated to liver cirrhosis (OR = 1.66, 95% CI: 1.10-2.50, P = 0.02), poorer tumor Barcelona Clinical Liver Cancer (BCLC) stage (OR = 0.30, 95% CI: 0.10-0.88, P = 0.03) and portal vein invasion (OR = 1.96, 95% CI: 1.04-3.68, P = 0.04), but had no correlation with age, gender, tumor size, number of tumors, AFP, vascular invasion, HBVs-Ag, Anti-HCV, differentiation or TNM stage. Besides, no significant publication bias was found among these identified studies. Conclusion: The meta-analysis suggested that PD-L1 overexpression could foresee worse OS and DFS in HCC. Moreover, the PD-L1 expression has to bear on liver cirrhosis, portal vein invasion, and BCLC stage.

Hepatogenic differentiation from human adipose-derived stem cells and application for mouse acute liver injury.

Adipose-derived stem cells (ADSCs) derived from adipose tissue have the capacity to differentiate into endodermal, mesoderm, and ectodermal cell lineages in vitro, which are an ideal engraft in tissue-engineered repair. In this study, human ADSCs were isolated from subcutaneous fat. The markers of ADSCs, CD13, CD71, CD73, CD90, CD105, CD166, CYP3A4, and ALB were detected by immunofluorescence assays. Human ADSCs were cultured in a specific hepatogenesis differentiation medium containing HGF, bFGF, nicotinamide, ITS, and oncostatin M for hepatogenic differentiation. The hepatocyte markers were analyzed using immunofluorescence and real-time PCR after dramatic changes in morphology. Hepatocytes derived from ADSCs or ADSCs were transplanted into the mice of liver injury for observation cells colonization and therapy in liver tissue. The result demonstrated that human ADSCs were positive for the CD13, CD71, CD73, CD90, CD105, and CD166 but negative for hepatocyte markers, ALB and CYP3A4. After hepatogenic differentiation, the hepatocytes were positive for liver special markers, gene expression level showed a time-lapse increase with induction time. Human ADSCs or ADSCs-derived hepatocyte injected into the vein could improve liver function repair and functionally rescue the CCl4-treated mice with liver injury, but the ADSCs transplantation was better than ADSCs-derived hepatocyte transplantation. In conclusion, our research shows that a population of hepatocyte can be specifically generated from human ADSCs and that cells may allow for participation in tissue-repair.

[Role of bFGF and TGF-beta1 in primary cultured prostatic stromal cells].

OBJECTIVE: To study the role of the basic fibroblast growth factor (bFGF) and transforming growth factor beta1 (TGF-beta1) in benign prostatic hyperplasia (BPH). METHODS: The human stromal cells of BPH were isolated and cultured. The proliferation of the stromal cells cultured in serum-free medium was detected by MTT method, the phenotype changes of smooth muscle cells detected by immunohistochemical method, and the effect of different concentrations of bFGF and TGF-beta1 on the cultured stromal cells of BPH observed. RESULTS: bFGF stimulated the cultured BPH stromal cell proliferation (P < 0.05, P < 0.01) and decreased the expression of smooth muscle cell (SMC) phenotype in higher concentration (10 microg/L). TGF-beta1 (> 1 microg/L) inhibited stromal cell proliferation and increased the expression of SMC phenotype (P < 0.05, P < 0.01). 5 microg/ml bFGF and TGF-beta1 (0.001 microg/L, 0.01 microg/L) promoted stromal cell proliferation (P < 0.01), while 5 microg/L bFGF and TGF-beta1 (0.1 microg/L, 1 microg/L, 10 microg/L) inhibited it, slightly in 0.1 microg/L (P > 0.05) and significantly in 1 microg/L and 10 microg/L (P < 0.01), and increased the expression of SMC phenotype in higher concentration (> 1 microg/L, P < 0.01). CONCLUSION: bFGF stimulates the proliferation of the prostatic stromal cells of BPH in a time- and dose-dependent fashion and decreases the expression of SMC phenotype, TGF-beta1 inhibits the growth of stromal cells and induces the differentiation of stromal cells to SMC, both playing an important role in the mechanism of BPH.

Comparative Efficacy of Interventional Therapies for Early-stage Hepatocellular Carcinoma: A PRISMA-compliant Systematic Review and Network Meta-analysis.

There are several interventional therapies that improve the prognosis and increase the survival rate of early-stage hepatocellular carcinoma (early-stage HCC), but it is uncertain about whether one is superior to others, and available researches investigating the comparative effects of different treatments are limited. The main objective of this Bayesian network meta-analysis was to compare the efficacy of these different treatment strategies for early-stage HCC and rank these interventions for practical consideration. We performed an electronic search of PubMed, Embase, and Cochrane Library, and extracted data from randomized controlled trials that compared different interventional therapies for early-stage HCC. Direct comparison and network meta-analyses were conducted with Aggregate Data Drug Information System software. Consistency models were created to determine whether there was a significant difference between any 2 therapies, and cumulative probability was used to rank different treatments. Twenty-one randomized controlled trials involving 2691 patients were included. In our network meta-analysis, the combination therapy of transcatheter arterial chemoembolization (TACE) and radiofrequency ablation (RFA) was associated with better 1-year survival rate, as compared with hepatic resection alone (P < 0.05, odds ratio [OR] 0.25, 95% confidence interval [CI] 0.06-0.83), percutaneous ethanol injection (PEI) alone (P < 0.05, OR 0.13, 95% CI 0.03-0.45), and RFA alone (P < 0.05, OR 0.23, 95% CI 0.07-0.70). TACE + RFA had a higher 3-year survival rate than PEI alone (P < 0.05, OR 0.32, 95% CI 0.15-0.72) and RFA alone (P < 0.05, OR 0.45, 95% CI 0.24-0.87). And there was a statistical difference between RFA + PEI and PEI alone (P < 0.05, OR 0.33, 95% CI 0.12-0.93) for 3-year survival rate. The results of rank test and cumulative probability showed that TACE + RFA ranked highest on the evaluation of 1-year, 3-year, and 5-year survival rate. Based on Bayesian network meta-analysis combining direct and indirect comparisons, the combination therapy of TACE and RFA seemed to be the most effective strategy for early-stage HCC.