Liver Enzyme Elevation in Coronavirus Disease 2019: A Multicenter, Retrospective, Cross-Sectional Study.

INTRODUCTION: Elevated liver enzyme levels are observed in patients with coronavirus disease 2019 (COVID-19); however, these features have not been characterized. METHODS: Hospitalized patients with COVID-19 in Zhejiang Province, China, from January 17 to February 12, 2020, were enrolled. Liver enzyme level elevation was defined as alanine aminotransferase level >35 U/L for men and 25 U/L for women at admission. Patients with normal alanine aminotransferase levels were included in the control group. Reverse transcription polymerase chain reaction was used to confirm severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and patients symptomatic with SARS-CoV-2 infection were defined as patients with COVID-19. Epidemiological, demographic, clinical, laboratory, treatment, and outcome data were collected and compared. RESULTS: Of 788 patients with COVID-19, 222 (28.2%) patients had elevated liver enzyme levels (median [interquartile range {IQR}] age, 47.0 [35.0-55.0] years; 40.5% women). Being male, overweight, and smoking increased the risk of liver enzyme level elevation. The liver enzyme level elevation group had lesser pharyngalgia and more diarrhea than the control group. The median time from illness onset to admission was 3 days for liver enzyme level elevation groups (IQR, 2-6), whereas the median hospitalization time for 86 (38.7%) discharged patients was 13 days (IQR, 11-16). No differences in disease severity and clinical outcomes were noted between the groups. DISCUSSION: We found that 28.2% of patients with COVID-19 presented with elevated liver enzyme levels on admission, which could partially be related to SARS-CoV-2 infection. Male patients had a higher risk of liver enzyme level elevation. With early medical intervention, liver enzyme level elevation did not worsen the outcomes of patients with COVID-19.

Dichloroacetate induces protective autophagy in esophageal squamous carcinoma cells.

Dichloroacetate (DCA) is an inhibitor of pyruvate dehydrogenase kinase, which promotes the flux of carbohydrates into mitochondria and enhances the aerobic oxidation of glucose. DCA has previously been demonstrated to exhibit antitumor properties. The present study revealed that treatment with DCA induced increased levels of autophagy-associated proteins in esophageal squamous carcinoma cells while minimally affecting apoptosis. The present study examined the localization of light chain (LC)-3 by adenovirus infection with a green fluorescent protein (FP)-red FP-LC3 reporter construction and confirmed that DCA treatment induced significant autophagy. Furthermore, the inhibition of DCA-induced autophagy facilitated cell apoptosis and improved the drug sensitivity of esophageal squamous carcinoma cells to DCA and 5-FU (5-fluorouracil). The proliferation of TE-1 cells was markedly inhibited at low concentrations of DCA and 5-FU treatment when subjected to Atg5 mRNA interference, indicating that autophagy performed a protective role in cell survival upon DCA treatment. To determine the underlying mechanism of DCA-induced autophagy, the present study measured alterations in autophagy-associated signaling pathways. Notably, the protein kinase B (Akt)-mechanistic target of rapamycin (mTOR) signaling pathway, an important negative regulator of autophagy, was demonstrated to be suppressed by DCA treatment. These results may direct the development of novel strategies for the treatment of esophageal squamous carcinoma based on the combined use of DCA and autophagy inhibitors.

Comparison of two different size needles in endoscopic ultrasound-guided fine-needle aspiration for diagnosing solid pancreatic lesions: A meta-analysis of prospective controlled trials.

BACKGROUND: This meta-analysis aimed to provide a pooled analysis of prospective controlled trials comparing the diagnostic accuracy of 22-G and 25-G needles on endoscopic ultrasonography (EUS-FNA) of the solid pancreatic mass. METHODS: We established a rigorous study protocol according to Cochrane Collaboration recommendations. We systematically searched the PubMed and Embase databases to identify articles to include in the meta-analysis. Sensitivity, specificity, and corresponding 95% confidence intervals were calculated for 22-G and 25-G needles of individual studies from the contingency tables. RESULTS: Eleven prospective controlled trials included a total of 837 patients (412 with 22-G vs 425 with 25-G). Our outcomes revealed that 25-G needles (92% [95% CI, 89%-95%]) have higher sensitivity than 22-G needles (88% [95% CI, 84%-91%]) on solid pancreatic mass EUS-FNA (P = 0.046). However, there were no significant differences between the 2 groups in overall diagnostic specificity (P = 0.842). The pooled positive and negative likelihood ratio of the 22-G needle were 12.61 (95% CI, 5.65-28.14) and 0.16 (95% CI, 0.12-0.21), respectively. The pooled positive likelihood ratio was 12.61 (95% CI, 5.65-28.14), and the negative likelihood ratio was 0.16 (95% CI, 0.12-0.21) for the 22-G needle. The pooled positive likelihood ratio was 8.44 (95% CI, 3.87-18.42), and the negative likelihood ratio was 0.13 (95% CI, 0.09-0.18) for the 25-G needle. The area under the summary receiver operating characteristic curve was 0.97 for the 22-G needle and 0.96 for the 25-G needle. CONCLUSION: Compared to the study of 22-G EUS-FNA needles, our study showed that 25-G needles have superior sensitivity in the evaluation of solid pancreatic lesions by EUS-FNA.

[Clinical study of titanium mesh in conjunction with concentrate growth factors to rebuild severe bone defect of anterior maxilla].

PURPOSE: To evaluate the effect of overlaying titanium mesh with concentrate growth factors(CGF) for rebuilding severe buccal bone defect of anterior maxilla when used in association with dental implantation. METHODS: Twenty patients with severe buccal bone defect of maxilla were selected. A total of 25 dental implants were placed, including 5 cases in bilateral central incisor area and 15 cases in unilateral central incisor area. After implantation, the defects were treated with Bio-oss and Bio-guid in conjunction with fixation of titanium mesh and then CGF technology was used. Two-stage surgery was carried out after 6 months of submerged healing, and permanent prosthesis was used 3 months after temporary restoration. The repairs of the defect were observed at the second stage surgery. The height of margin bone around implants and the thickness of bone at implants lingual side were measured, at the time of the second stage operation, and 3, 6, 12, 18 months after permanent restoration. The differences were analyzed by SPSS 19.0 software package with multi-sample nonparametric test and Fierdman test. RESULTS: At the time of second operation, the bone plate at lingual side was completely reconstructed, and new bone was formed at the top of implants. Clinical measurements showed that the averaged thickness of bone at lingual side was (2.69±0.154) mm at that time. Three, 6, 12, 18 months after restoration, the values were (2.67±0.152) mm, (2.66±0.153) mm, (2.65±0.153) mm, (2.65±0.151) mm, respectively. Implant-abutment junction was used as a base line to assess vertical bone absorption, the marginal bone of implant neck at lingual side was all inferior to the base line, the distance was (0.02±0.048) mm, (0.69±0.085) mm，(0.87±0.019) mm, (0.87±0.013) mm, respectively. Statistical analysis showed the thickness of bone of labial side decreased significantly over time after permanent restoration (P<0.01). Likewise, the height of marginal bone was also decreased significantly (P<0.01). However, the difference between them at 12 months and 18 months was not statistically significant (P>0.05). CONCLUSIONS: The results indicate that bone augmentation at maxilla can be achieved using titanium mesh in conjunction with CGF. The height and thickness of newly formed bone at the implant neck margin will be stabilized after 1 year. This method is worthy of wide clinical application.

A serum metabolomic analysis for diagnosis and biomarker discovery of primary biliary cirrhosis and autoimmune hepatitis.

BACKGROUND: Because of the diversity of the clinical and laboratory manifestations, the diagnosis of autoimmune liver disease (AILD) remains a challenge in clinical practice. The value of metabolomics has been studied in the diagnosis of many diseases. The present study aimed to determine whether the metabolic profiles, based on ultraperformance liquid chromatography-mass spectrometry (UPLC-MS), differed between autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC), to identify specific metabolomic markers, and to establish a model for the diagnosis of AIH and PBC. METHODS: Serum samples were collected from 20 patients with PBC, 19 patients with AIH, and 25 healthy individuals. UPLC-MS data of the samples were analyzed using principal component analysis, partial least squares discrimination analysis and orthogonal partial least squares discrimination analysis. RESULTS: The partial least squares discrimination analysis model (R2Y=0.991, Q2=0.943) was established between the AIH and PBC groups and exhibited both sensitivity and specificity of 100%. Five groups of biomarkers were identified, including bile acids, free fatty acids, phosphatidylcholines, lysolecithins and sphingomyelin. Bile acids significantly increased in the AIH and PBC groups compared with the healthy control group. The other biomarkers decreased in the AIH and PBC groups compared with those in the healthy control group. In addition, the biomarkers were downregulated in the AIH group compared with the PBC group. CONCLUSIONS: The biomarkers identified revealed the pathophysiological changes in AILD and helped to discriminate between AIH and PBC. The predictability of this method suggests its potential application in the diagnosis of AILD.

[Adjuvant effect of co-stimulatory molecule CD137L on cellular responses to HBsAg DNA vaccination in mice].

OBJECTIVE: To investigate the adjuvant effect of co-stimulatory molecule CD137L on cellular responses to HBsAg DNA vaccination in mice. METHODS: Eukaryotic expression vector containing the full length of mouse CD137L cDNA sequence (pcD137L) was transfected into NIH3T3 cells, and then the expression of CD137L mRNA and protein in the transfected cells were detected by RT-PCR, flow cytometry and immunofluorescence method, respectively. The BALB/c mice were co-immunized with pcD137L and HBsAg DNA vaccine (pcDS) by intramuscular injection. HBsAg-specific activity of splenic cytotoxic T lymphocyte (CTL) in the immunized mice was measured by LDH release assay. The splenic memory CD8+ T cells, and intracellular IFN-gamma and IL-4 of splenic lymphocytes and CD8+ T cells after immunization were detected by flow cytometry. RESULTS: The NIH3T3 cells transfected with pcD137L efficiently expressed mouse CD137L mRNA and protein. HBsAg-specific CTL responses induced by the pcDS plus pcD137L group were much stronger than those induced by pcDS alone at a week after immunization (P<0.05). Compared to mice immunized with pcDS alone, CD44high and CD127(IL-7R) were all significantly up-regulated in memory CD8+ T cells from the mice immunized with pcDS combined CD137L both at a week and 12 weeks after immunization (P<0.05 and P<0.01). The pcDS plus CD137L group also elicited higher levels of IFN-gamma secreted by CD8+ T cells and splenic lymphocytes than pcDS alone at a week, 12 and 13 weeks after immunization, respectively (all P<0.01). CONCLUSION: DNA, viral/immunol; Co-stimulatory molecule CD137L can enhance the Tc1 (type I) cell-mediated immunity, HBsAg-specific CTL and memory responses induced by HBsAg DNA vaccine, and may be an efficient adjuvant in priming HBV-specific T cell response.

The roles of serum IL-18, IL-10, TNF-alpha and sIL-2R in patients with chronic hepatitis C.

OBJECTIVE: To identify the roles of serum IL-18, IL-10, TNF-alpha and sIL-2R in the pathogenesis of chronic hepatitis C and the effects of interferon on the mentioned serum cytokines. METHODS: The levels of IL-18, IL-10, TNF-alpha and sIL-2R were detected in 10 healthy controls, 24 asymptomatic HCV carriers, and 27 patients with chronic hepatitis C (before and after IFN treatment) by enzyme linked immunosorbent assay (ELISA). RESULTS: The levels of IL-18, IL-10, TNF-alpha and sIL-2R in the patients of chronic hepatitis C were higher than those in the healthy controls (P<0.05) and in asymptomatic HCV carriers (P<0.05). The values of the mentioned cytokines showed a significant positive correlation to GPT. The levels of the mentioned cytokines decreased obviously after IFN treatment (P<0.05), while the serum levels of IL-10 and sIL-2R reduced in sequence in no-response group, partial-response group and complete-response group. CONCLUSIONS: IL-18, IL-10, TNF-alpha and sIL-2R co-participate in the pathogenesis of chronic hepatitis C, and are used to evaluate the effect of IFN on the immune state of organisms, and IL-10 and sIL-2R are important for predicting the anti-viral efficacy of IFN.