The relationship of dietary flavonoids and periodontitis in US population: a cross-sectional NHANES analysis.

OBJECTIVES: We investigated the association between dietary flavonoids intake and periodontitis. MATERIALS AND METHODS: This cross-sectional study analyzed data from the US National Health and Nutrition Examination Survey 2009-2010 on 3025 participants aged between 30 and 80 years who had full-mouth periodontal examination and dietary flavonoids intake data. This study used periodontal pocket depth (PPD) and clinical attachment loss (CAL) as periodontitis markers. Data were analyzed using multivariate linear regression. RESULTS: After adjusting confounders, the middle tertile of total dietary flavonoids was associated with decreased mean PPD (0.06 mm, P = 0.016) and mean CAL (0.13 mm, P = 0.001) and the top tertile of total dietary flavonoids was significantly associated with decreases in mean PPD (0.05 mm, P = 0.029) and mean CAL (0.11 mm, P = 0.010). Both the middle and top tertiles of total flavonoids intake were significantly related with decreased mean CAL in females, those flossing 0 days/week, overweight and non-diabetic population but not in males, smokers, those flossing 1-6 days/week and diabetic population. Higher anthocyanidins, flavones and flavonols intake was significantly associated with decreased mean PPD and mean CAL while higher flavanones intake was only significantly associated with decreased mean CAL. Higher anthocyanidins intake was particularly related with greatest decreases in mean CAL (top tertile: 0.22 mm, middle tertile: 0.17 mm, both P < 0.010). However, no significant associations were found between isoflavones and flavan_3_ols intake and mean CAL. CONCLUSIONS: Higher dietary flavonoids intake may be beneficial for periodontal health. CLINICAL RELEVANCE: Additional anthocyanidins, flavanones, flavones and flavonols intake was associated with improved periodontal health.

Characteristics of Klebsiella pneumoniae pyogenic liver abscess from 2010-2021 in a tertiary teaching hospital of South China.

OBJECTIVES: Pyogenic liver abscess (PLA) is a severe and potentially fatal infectious disease. Klebsiella pneumoniae (K. pneumoniae) is the predominant pathogen responsible for PLA. This study aims to investigate the clinical characteristics and prognostic factors of K. pneumoniae-induced pyogenic liver abscess (KP-PLA), particularly those caused by carbapenem-resistant K. pneumoniae (CRKP). METHODS: Analyses were performed on PLA patients from January 2010 to December 2021, to investigate the differences of K. pneumoniae from other etiologically infected PLA patients. Univariate and multivariate logistic regression analyses were used to compare prognostic factors between patients with carbapenem-resistant K. pneumoniae PLA (CRKP-PLA) and patients with carbapenem-sensitive K. pneumoniae PLA. RESULTS: Univariate analysis demonstrated a significant association between KP-PLA and factors including diabetes mellitus (P < 0.001), cholecystitis and cholelithiasis (P = 0.032), single abscess (P = 0.016), and abscesses with a diameter over 50 mm (P = 0.004). The CRKP group exhibited a higher prevalence of therapeutic interventions before K. pneumoniae infection, including abdominal surgery, mechanical ventilation, sputum suction, tracheal cannula, routine drainage of the abdominal cavity, and peripherally inserted central venous catheters (P < 0.05). Multivariate logistic regression analysis revealed that admission to the intensive care unit was an independent risk factor associated with CRKP-PLA (odds ratio 36; 95% confidence interval 1.77-731.56; P = 0.020). CONCLUSION: The KP-PLA patients were significantly associated with diabetes and were more likely to have single abscesses larger than 50 mm. PLA patients with a history of admission to intensive care unit or invasive therapeutic procedures should be given special consideration if combined with CRKP infection.

Tenofovir amibufenamide vs tenofovir alafenamide for treating chronic hepatitis B: A real-world study.

BACKGROUND: The efficacy and safety profile of tenofovir amibufenamide (TMF) in chronic hepatitis B (CHB) patients is not well-established. AIM: To compare the efficacy and safety of TMF and tenofovir alafenamide (TAF) over a 48-wk period in patients with CHB. METHODS: A total of 215 subjects meeting the inclusion criteria were enrolled and divided into two groups: TMF group (n = 106) and the TAF group (n = 109). The study included a comparison of virological response (VR): Undetectable hepatitis B virus DNA levels, alanine transaminase (ALT) normalization rates, renal function parameters, and blood lipid profiles. RESULTS: At 24 and 48 wk, VR rates for the TMF group were 53.57% and 78.57%, respectively, compared with 48.31% and 78.65% for the TAF group (P > 0.05). The VR rates were also similar in both groups among patients with low-level viremia, both hepatitis B e antigen (HBeAg)-positive and HBeAg-negative subgroups. The TMF cohort showed ALT normalization and renal safety profiles similar to the TAF group. There was a notable increase in total cholesterol levels in the TAF group (P = 0.045), which was not observed in the TMF group (P > 0.05). In patients with liver cirrhosis, both groups exhibited comparable VR and ALT normalization rates and renal safety profiles. However, the fibrosis 4 score at 48 wk showed a significant reduction in the TAF group as compared to the TMF group within the liver cirrhosis subgroup. CONCLUSION: Our study found TMF is as effective as TAF in treating CHB and has a comparable safety profile. However, TAF may be associated with worsening lipid profiles.

ANXA1 is identified as a key gene associated with high risk and T cell infiltration in primary sclerosing cholangitis.

BACKGROUND: Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease, with unclear pathogenesis. Although immune disorders, especially T cell infiltration, are thought to play a vital role in PSC, the specific pathogenesis mechanisms remain incompletely understood. This study evaluated the potential key gene associated with the PSC pathogenesis and analyzed the associations of the key gene with prognosis and immune cell infiltration by combining bioinformatics analysis and experimental verification. METHODS: Transcriptome data of PSC and normal human liver tissues (GSE159676) were obtained from the gene expression omnibus database. Differentially expressed genes (DEGs) were identified, and differences in biological states were analyzed. A protein-protein interaction (PPI) network was constructed. Hub genes were identified, and their expression was verified using transcriptome data of mice fed 0.1% 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) and Mdr2-/- mice (GSE179993, GSE80776), as well as by immunohistochemistry staining on clinical samples. The correlations between the key gene and other factors were evaluated by Pearson's correlation coefficient. Immune cell infiltration into human liver (GSE159676) was analyzed by xCell and verified by immunofluorescence staining on PSC liver samples. RESULTS: Of the 185 DEGs identified, 113 were upregulated and 72 were downregulated genes in PSC. Genes associated with immune cell infiltration and fibrosis were significantly enriched in PSC. PPI network showed close interactions among DEGs. A module strongly associated with immune infiltration was identified, with annexin A1 (ANXA1) being the core gene. High expression of ANXA1 in PSC was confirmed in two public datasets and by immunohistochemistry staining on clinical samples. High ANXA1 expression was strongly associated with high-risk score for PSC. Also, ANXA1 expression was positively associated with chemokines and chemokine receptors and with the infiltration of immune cells, especially T cells, into liver with PSC. Immune infiltration, fibrosis, and cancer-related processes were markedly enriched in PSC with high expression of ANXA1. CONCLUSION: ANXA1 is a key gene associated with high risk and infiltration of immune cells, especially T cells, in PSC. These findings provide new insight into the key biomarker of PSC and suggest that targeting ANXA1 may be a valuable strategy for the treatment of PSC.

Clinicopathologic characteristics of liver inflammation and fibrosis in 310 patients with chronic hepatitis B. / 310ä¾‹æ ¢æ€§ä¹™åž‹è‚ç‚Žæ‚£è€ è‚è„ç‚Žç—‡åŠçº¤ç»´åŒ–çš„ä¸´åºŠç— ç†ç‰¹å¾.

OBJECTIVES: Long-term hepatitis B virus (HBV) infection can cause recurrent inflammation in the liver, and then develop into liver fibrosis, cirrhosis, and liver cancer. The hepatic pathological change is one of the important criteria for guiding antiviral therapy in patients with chronic hepatitis B (CHB). Due to the limitations of liver biopsy, it is necessary to find valuable non-invasive indicators to evaluate the hepatic pathological changes in CHB patients and guide the antiviral therapy. This study aims to analyze the clinical characteristics of different pathological changes in CHB patients, and to explore the factors influnencing the degree of liver inflammation and fibrosis in CHB patients with normal alanine aminotransferase (ALT). METHODS: This retrospective study was conducted on 310 CHB patients. Liver biopsy was performed in all these patients. The clinical data of the patients were collected. The liver biopsy pathological results were used as the gold standard to analyze the relationship between clinical indicators and liver pathological changes. Then CHB patients with normal ALT were screened, and the independent factors influencing the degree of liver inflammation and fibrosis were explored. RESULTS: Among the 310 patients with CHB, there were 249 (80.3%) patients with significant liver inflammation [liver inflammation grade (G) ≥2] and 119 (38.4%) patients with significant liver fibrosis [liver fibrosis stage (S) ≥2]. The results of univariate analysis of total samples showed that the ALT, γ-glutamyl transferase, alkaline phosphatase, and HBV DNA were related to the significant liver pathological changes. Among the 132 CHB patients with normal ALT, the patients with liver pathology G/S≥2, G≥2, and S≥2 were 80.3% (106/132), 68.2% (90/132), and 43.2% (57/132), respectively. The results showed that the independent influencing factor of significant liver inflammation was HBV DNA>2 000 U/mL (OR=3.592, 95% CI 1.534 to 8.409), and the independent influencing factors of significant liver fibrosis were elevated alkaline phosphatase level (OR=1.022, 95% CI 1.002 to 1.043), decreased platelet count (OR=0.990, 95% CI 0.982 to 0.998), and positive in hepatitis B e antigen (HBeAg) (OR=14.845, 95% CI 4.898 to 44.995). According to the multivariate analysis, a diagnostic model for significant liver fibrosis in CHB patients with normal ALT was established, and the area under the receiver operating characteristic curve was 0.844 (95% CI 0.779 to 0.910). CONCLUSIONS: The liver pathological changes should be evaluated in combination with different clinical indicators. A considerable number of CHB patients with normal ALT still have significant liver pathological changes, which need to be identified and treated with antiviral therapy in time. Among them, HBV DNA>2 000 U/mL suggests the significant liver inflammation, and the diagnostic model for significant liver fibrosis based on alkaline phosphatase, platelet count, and HBeAg can help to evaluate the degree of liver fibrosis.

The association of severely worn dentition resulting from betel nut chewing with temporomandibular disorders: a cross-sectional study.

BACKGROUND: Most studies support parafunctions play an important role in temporomandibular disorders (TMD), whereas the association between tooth wear and TMD remains controversial. Betel nut chewing as a parafunction is popular in South and Southeast Asia. We therefore investigated the association of severely worn dentition resulting from betel nut chewing with TMD. METHODS: A cross-sectional analysis of 408 control participants (male: 380, female: 28, 43.62 ± 9.54 years) and 408 participants with betel nut chewing related severely worn dentition (male: 380, female: 28, 43.73 ± 8.93 years) who received dental and TMD checkup according to Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) in Health Management Center, Xiangya Hospital was performed. Betel nut chewing related severely worn dentition meant all the natural teeth had moderate to severe tooth wear [Tooth Wear Index (TWI) ≥ 2)] including ≥ 2 severe wear teeth (TWI ≥ 3) due to betel nut chewing. Multivariable logistic regression analysis was used. RESULTS: After adjusting for age, gender, betel nut chewing related severely worn dentition, oral submucosal fibrosis, number of missing teeth, number of dental quadrants with missing teeth, visible third molar and orthodontic history, variables of age, gender and betel nut chewing related severely worn dentition were significant for overall TMD. Multivariable analysis showed betel nut chewing related severely worn dentition was significantly associated with intra-articular TMD [odds ratio and 95% confidence intervals: 1.689 (1.271-2.244), P = 0.001] in a betel nut chewing dose-dependent manner. CONCLUSION: Betel nut chewing related severely worn dentition was associated with intra-articular TMD.

Tenofovir alafenamide versus entecavir for treating hepatitis B virus-related acute-on-chronic liver failure: real-world study.

Background and aims: Real-world data regarding hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) patients receiving tenofovir alafenamide (TAF) as an antiviral drug are limited. Hence, we evaluated the efficacy and kidney safety of TAF among this population. Methods: A total of 272 HBV-related ACLF patients hospitalized at Xiangya Hospital of Central South University were enrolled in this retrospective research. All patients received antiviral therapy with TAF (n = 100) or ETV (n = 172) and comprehensive medical treatments. Results: Through 1:1 propensity score matching, 100 patients were finally included in each group. At week 48, the survival rates without transplantation of the TAF group and ETV group were 76.00 and 58.00%, separately (P = 0.007). After 4 weeks of treatment, the TAF treatment group exhibited a significantly decline in HBV DNA viral load (P = 0.029). The mean estimated glomerular filtration rate was apparently improved in the TAF group compared with the ETV group (TAF 5.98 ± 14.46 vs. ETV 1.18 ± 18.07 ml/min/1.73 m2) (P < 0.05). There were 6 patients in TAF group and 21 patients in ETV group with chronic kidney disease (CKD) stage progression ≥ 1. By contrast, the ETV treatment group has a greater risk of renal function progression in CKD 1 stage patients (P < 0.05). Conclusion: This real-world clinical study showed that TAF is more effective than ETV in reducing viral load and improving survival rate in HBV-ACLF patients and the risk of renal function decline is lower. Clinical trial registration: https://ClinicalTrials.gov, identifier NCT05453448.

Association of severely damaged endodontically infected tooth with carotid plaque and abnormal carotid intima-media thickness: a retrospective analysis.

OBJECTIVE: We investigated the association of severely damaged endodontically infected tooth with carotid artery plaque and abnormal mean carotid intima-media thickness (CIMT) ≥ 1.0 mm. METHODS: A retrospective analysis of 1502 control participants and 1552 participants with severely damaged endodontically infected tooth who received routine medical and dental checkup in Health Management Center, Xiangya Hospital was performed. Carotid plaque and CIMT were measured with B-mode tomographic ultrasound. Data were analyzed using logistic and linear regression. RESULTS: Severely damaged endodontically infected tooth group had a significantly higher prevalence of carotid plaque (41.62%) compared to 32.22% of carotid plaque in control group. Participants with severely damaged endodontically infected tooth had a significantly higher prevalence of abnormal CIMT (16.17%) and a significantly increased level of CIMT (0.79 ± 0.16 mm) in comparison to 10.79% of abnormal CIMT and 0.77 ± 0.14 mm CIMT in control participants. Severely damaged endodontically infected tooth was significantly related with formation of carotid plaque [1.37(1.18-1.60), P < 0.001], top quartile length [1.21(1.02-1.44), P = 0.029] and top quartile thickness [1.27(1.08-1.51), P = 0.005] of carotid plaque and abnormal CIMT [1.47(1.18-1.83), P < 0.001]. Severely damaged endodontically infected tooth was significantly associated with both single [1.277(1.056-1.546), P = 0.012] and multiple carotid plaques [1.488(1.214-1.825), P < 0.001] and instable carotid plaques [1.380(1.167-1.632), P < 0.001]. Presence of severely damaged endodontically infected tooth increased 0.588 mm of carotid plaque length (P = 0.001), 0.157 mm of carotid plaque thickness (P < 0.001) and 0.015 mm of CIMT (P = 0.005). CONCLUSION: Severely damaged endodontically infected tooth was associated with carotid plaque and abnormal CIMT. CLINICAL RELEVANCE: Early treatment of endodontically infected tooth is warranted.

TRAF2 as a key candidate gene in clinical hepatitis B-associated liver fibrosis.

Objectives: Approximately 240 million individuals are infected with chronic hepatitis B virus (HBV) worldwide. HBV infection can develop into liver fibrosis. The mechanism of HBV-related liver fibrosis has not been fully understood, and there are few effective treatment options. The goal of this study was to use transcriptomics in conjunction with experimental validation to identify new targets to treat HBV-related liver fibrosis. Methods: To identify differentially expressed genes (DEGs), five liver tissues were collected from both healthy individuals and patients with chronic hepatitis B. NovoMagic and Java GSEA were used to screen DEGs and key genes, respectively. Immunocell infiltration analysis of RNA-seq data was, and the results were confirmed by Western blotting (WB), real-time quantitative polymerase chain reaction (RT-qPCR), and immunohistochemistry. Results: We evaluated 1,105 genes with differential expression, and 462 and 643 genes showed down- and upregulation, respectively. The essential genes, such as tumor necrosis factor (TNF) receptor-associated factor-2 (TRAF2), were screened out of DEGs. TRAF2 expression was abnormally high in hepatic fibrosis in patients with hepatitis B compared with healthy controls. The degree of hepatic fibrosis and serum levels of glutamate transaminase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBIL) were positively linked with TRAF2 expression. TRAF2 may be crucial in controlling T lymphocyte-mediated liver fibrosis. Conclusion: Our findings imply that TRAF2 is essential for HBV-induced liver fibrosis progression, and it may potentially be a promising target for the treatment of hepatic fibrosis in hepatitis B.

Association of congenitally missing teeth with adult temporomandibular disorders in the urban health checkup population.

BACKGROUND: Congenitally missing tooth is the most common dental abnormality which leaves spaces in the arch, leads to numerous forms of malocclusion due to the Bolton index discrepancy and is even associated with abnormal craniofacial morphology. Even though the roles of malocclusion and tooth loss in temporomandibular disorders (TMD) development remain controversial, basic researches have found some common molecules are involved in osteoarthritis and dental agenesis. However, the association of congenitally missing teeth with TMD is unknown. We hence investigated the association of congenitally missing teeth with TMD. METHODS: A cross-sectional analysis of 586 control participants (male: 287, female: 299, 38.33 ± 11.65 years) and 583 participants with non-third molar congenitally missing teeth (male: 238, female: 345, 39.13 ± 11.67 years) who consecutively received routine dental and TMD checkup according to Diagnostic Criteria for Temporomandibular Disorders Axis I in Health Management Center, Xiangya Hospital was performed. Logistic regression analysis was used to study the association of congenitally missing teeth with TMD. RESULTS: The congenitally missing teeth group included 581 hypodontia and 2 oligodontia participants. The congenitally missing anterior teeth participants, the congenitally missing posterior teeth participants and participants with both congenitally missing anterior and posterior teeth accounted for 88.34%, 8.40% and 3.26% of the congenitally missing teeth group respectively. Congenitally missing teeth group had greater ratios of females and orthodontic history. Participants with congenitally missing teeth had a significantly higher prevalence of overall TMD (67.24%) in comparison to control participants (45.90%). After adjusting age, gender, presence of congenitally missing teeth, number of congenitally missing teeth, number of non-congenitally missing teeth, number of dental quadrants with missing teeth, visible third molar and orthodontic history, the variables of age, gender, presence of congenitally missing teeth and number of dental quadrants with missing teeth were significant for overall TMD. Multivariable logistic regression analysis showed congenitally missing tooth was significantly related with overall TMD [odds ratio (OR):1.689(1.080-2.642), P = 0.022], intra-articular TMD [OR: 1.711(1.103-2.656), P = 0.017] and pain-related TMD [OR: 3.093(1.321-7.239), P = 0.009]. CONCLUSION: Congenitally missing tooth is a risk factor for TMD. When treating the congenitally missing teeth population, TMJ evaluation and multidisciplinary strategies are necessary.

Unique DUOX2+ACE2+ small cholangiocytes are pathogenic targets for primary biliary cholangitis.

Cholangiocytes play a crucial role in bile formation. Cholangiocyte injury causes cholestasis, including primary biliary cholangitis (PBC). However, the etiology of PBC remains unclear despite being characterized as an autoimmune disease. Using single-cell RNA sequencing (scRNA-seq), fluorescence-activated-cell-sorting, multiplex immunofluorescence (IF) and RNAscope analyses, we identified unique DUOX2+ACE2+ small cholangiocytes in human and mouse livers. Their selective decrease in PBC patients was associated with the severity of disease. Moreover, proteomics, scRNA-seq, and qPCR analyses indicated that polymeric immunoglobulin receptor (pIgR) was highly expressed in DUOX2+ACE2+ cholangiocytes. Serum anti-pIgR autoantibody levels were significantly increased in PBC patients, regardless of positive and negative AMA-M2. Spatial transcriptomics and multiplex IF revealed that CD27+ memory B and plasma cells accumulated in the hepatic portal tracts of PBC patients. Collectively, DUOX2+ACE2+ small cholangiocytes are pathogenic targets in PBC, and preservation of DUOX2+ACE2+ cholangiocytes and targeting anti-pIgR autoantibodies may be valuable strategies for therapeutic interventions in PBC.

Genome-wide association study using whole-genome sequencing identifies risk loci for Parkinson's disease in Chinese population.

Genome-wide association studies (GWASs) have identified numerous susceptibility loci for Parkinson's disease (PD), but its genetic architecture remains underexplored in populations of non-European ancestry. To identify genetic variants associated with PD in the Chinese population, we performed a GWAS using whole-genome sequencing (WGS) in 1,972 cases and 2,478 controls, and a replication study in a total of 8209 cases and 9454 controls. We identified one new risk variant rs61204179 (Pcombined = 1.47 × 10-9) with low allele frequency, four previously reported risk variants (NUCKS1/RAB29-rs11557080, SNCA-rs356182, FYN-rs997368, and VPS13C-rs2251086), as well as three risk variants in LRRK2 coding region (A419V, R1628P, and G2385R) with genome-wide significance (P < 5 × 10-8) for PD in Chinese population. Moreover, of the reported genome-wide significant risk variants found mostly in European ancestry populations, the correlation coefficient (rb) of effect size accounting for sampling errors was 0.91 between datasets and 63.6% attained P < 0.05 in Chinese population. Accordingly, we estimated a heritability of 0.14-0.18 for PD, and a moderate genetic correlation between European ancestry and Chinese populations (rg = 0.47, se = 0.21). Polygenic risk score (PRS) analysis revealed that individuals with PRS values in the highest quartile had a 3.9-fold higher risk of developing PD than the lowest quartile. In conclusion, the present GWAS identified PD-associated variants in Chinese population, as well as genetic factors shared among distant populations. Our findings shed light on the genetic homogeneity and heterogeneity of PD in different ethnic groups and suggested WGS might continue to improve our understanding of the genetic architecture of PD.

Demographics and Clinical Outcomes of Culture-Positive versus Culture-Negative Pyogenic Liver Abscess in an Asian Population.

Objective: Despite its high case-fatality risk, pyogenic liver abscess (PLA) lacks clear management guidelines in patients with negative microbial cultures. Our aim was to evaluate differences in clinical characteristics between patients with culture-negative liver abscess (CNLA) and those with culture-positive liver abscess (CPLA), and identify differences in the main causative pathogen. Methods: In this study, we retrospectively collected medical records of PLA patients admitted to a teaching hospital from January 2010 to December 2019. Results: In total, 324 PLA patients were enrolled in this study. Of these, 202 (62.3%) cases were confirmed cultural positive, including 109 patients (54%) and 20 (9.9%) patients infected with Klebsiella pneumoniae (K. pneumoniae) and Escherichia coli (E.coli), respectively. Patients in the CPLA group were older (p=0.029) and had higher prevalence of abscesses larger than 5 cm in diameter (p = 0.003), gas-forming rate (p = 0.016), and percutaneous drainage (p < 0.001) compared with CNLA group. Patients with CPLA had significantly longer hospitalizations than those with CNLA (p = 0.010). Nevertheless, there was no significant difference in in-hospital mortality between the two groups (p = 0.415). Compared with patients with E. coli, those with K. pneumoniae had higher incidence of diabetes mellitus (p = 0.041), solitary abscess (p < 0.001), localization in the right hepatic lobe (p = 0.033), abscess size larger than 5 cm (p < 0.001) and percutaneous drainage (p = 0.002), but mortality was not significantly different (p = 1.000). Conclusion: No significant difference in in-hospital mortality was found between patients with CNLA and those with CPLA group. However, clinical characteristics and management were different between the main causative pathogens, including K. pneumoniae and E. coli.

Identification of AKR1B10 as a key gene in primary biliary cholangitis by integrated bioinformatics analysis and experimental validation.

Background: Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease that eventually progresses to cirrhosis and hepatocellular carcinoma (HCC) in the absence of proper treatment. However, Gene expression and molecular mechanisms involved in the pathogenesis of PBC have not been completely elucidated. Methods: Microarray expression profiling dataset GSE61260 was downloaded from the Gene Expression Omnibus (GEO) database. Data were normalized to screen differentially expressed genes (DEGs) using the limma package in R. Moreover, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses were performed. A protein-protein interaction (PPI) network was constructed to identify hub genes and an integrative regulatory network of transcriptional factor-DEG-microRNA was established. Gene Set Enrichment Analysis (GSEA) was used to analyze differences in biological states for groups with different expressions of aldo-keto reductase family 1 member B10 (AKR1B10). Immunohistochemistry (IHC) analysis was performed to validate the expression of hepatic AKR1B10 in patients with PBC. The association of hepatic AKR1B10 levels with clinical parameters was evaluated using one-way analysis of variance (ANOVA) and Pearson's correlation analysis. Results: This study identified 22 upregulated and 12 downregulated DEGs between patients with PBC and healthy controls. GO and KEGG analysis revealed that DEGs were mainly enriched in immune reactions. AKR1B10 was identified as a key gene and was further analyzed by screening out hub genes from the PPI network. GSEA analysis indicated that high expression of AKR1B10 might promote PBC to develop into HCC. Immunohistochemistry results verified the increased expression of hepatic AKR1B10 in patients with PBC and demonstrated its positive correlation with the severity of PBC. Conclusion: AKR1B10 was identified as a hub gene in PBC by integrated bioinformatics analysis and clinical validation. The increase of AKR1B10 expression in patients with PBC was associated with disease severity and might promote the progression of PBC to HCC.

Efficacy and Economic Evaluation of Nonbiological Artificial Liver Therapy in Acute-on-chronic Hepatitis B Liver Failure.

Background and Aims: Nonbiological artificial liver (NBAL) is frequently used as a first-line treatment for hepatitis B virus-associated acute-on-chronic liver failure (HBV-ACLF). This study aimed to compare the therapeutic efficacy and cost-effectiveness ratio (CER) of comprehensive medical treatment, plasma exchange (PE), and double plasma molecular adsorption system (DPMAS) plus half-dose PE (DPMAS+PE) in patients with HBV-ACLF. Methods: A total of 186 patients with HBV-ACLF randomly received comprehensive medical treatment, PE, or DPMAS+PE and were prospectively evaluated. Patients were divided into four subgroups based on the pretreatment prothrombin activity (PTA): Group I (PTA>40%), group II (PTA 30-40%), group III (PTA 20-30%), and group IV (PTA<20%). The main outcome measures were 28 day effectiveness; 90 day liver transplantation-free survival; change of biochemical parameters; and CER. Results: DPMAS+PE treatment was associated with significantly higher 28 day effectiveness and 90 day liver transplantation-free survival compared with PE treatment in patients with group I liver failure. Clearance of serum total bilirubin (TBIL), AST, and creatinine (Cr) were significantly higher in the DPMAS+PE group than in the PE group. For subjects with group I liver failure, DPMAS+PE treatment had advantages of lower CER values and better cost-effectiveness. Conclusions: Compared with comprehensive medical treatment and PE alone, DPMAS with half-dose sequential PE treatment more effectively improved TBIL, AST, and Cr in HBV-ACLF patients, improved 28 day effectiveness and 90 day survival rates in patients with group I liver failure, and was more cost effective. DPMAS+PE is a viable NBAL approach for treatment of HBV-ACLF.

The involvement of homeobox-C 4 in predicting prognosis and unraveling immune landscape across multiple cancers via integrated analysis.

Background: There has been growing evidence that the aberrantly expressed Homeobox-C 4 (HOXC4) plays crucial roles in the development of some cancer types. However, it remains unclear as far as its expression patterns and prognostic significance are concerned, as is tumor immunity. Methods: To investigate the expression levels and prognostic implications of HOXC4, multiple data sources were used in conjunction with quantitative real-time polymerase chain reaction (qRT-PCR) verification. Afterward, diverse immunological-related analyses, along with anti-cancer drug sensitivity, were performed in a number of cancer types. A further exploration of the underlying mechanisms of HOXC4 in tumorigenesis and immunity was carried out using the Gene Set Enrichment Analysis (GSEA) and the Gene Set Variation Analysis (GSVA). Results: Based on extensive database mining, HOXC4 was ubiquitously expressed across 21 tumor cell lines and significantly higher than that of normal tissues in 21 tumor types. The outcome of survival analysis including overall survival (OS), disease-free interval (DFI), disease-specific survival (DSS) and progression-free interval (PFI) revealed that upregulation of HOXC4 expression in several cancers was associated with worse prognosis. Additionally, HOXC4 was observed to correlate closely with colon adenocarcinoma (COAD), head and neck squamous cell carcinoma (HNSC), lower grade glioma (LGG), liver hepatocellular carcinoma (LIHC), rectum adenocarcinoma (READ), and thyroid carcinoma (THCA) in terms of tumor immune cells infiltration. As a result of our comprehensive pan-cancer study, we have identified a significant link between the expression of HOXC4 and the efficacy of immunotherapy-related treatments, together with anti-cancer drug sensitivity. As a final note, HOXC4 was found to modulate multiple signaling pathways involved in tumorigenesis and immunity. Conclusion: HOXC4 has been implicated in our study for the first time as an oncogene in cancers with a poor prognosis, potentially laying the groundwork for promising clinical biomarkers and immunotherapy approaches.

Fluorofenidone ameliorates cholestasis and fibrosis by inhibiting hepatic Erk/-Egr-1 signaling and Tgfß1/Smad pathway in mice.

Cholestasis is characterized by intrahepatic accumulation of bile acids (BAs), resulting in liver injury, fibrosis, and liver failure. To date, only ursodeoxycholic acid and obeticholic acid have been approved for the treatment of cholestasis. As fluorofenidone (AKF-PD) was previously reported to play significant anti-fibrotic and anti-inflammatory roles in various diseases, we investigated whether AKF-PD ameliorates cholestasis. A mouse model of cholestasis was constructed by administering a 0.1 % 3,5-diethoxycarbonyl-1,4-dihydroxychollidine (DDC) diet for 14 days. Male C57BL/6 J mice were treated with either AKF-PD or pirfenidone (PD) orally in addition to the DDC diet. Serum and liver tissues were subsequently collected and analyzed. We found that AKF-PD significantly reduced the levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and total bile salts (TBA), as well as hepatic bile acids (BAs) levels. Hepatic histological analyses demonstrated that AKF-PD markedly attenuated hepatic inflammation and fibrosis. Further mechanistic analyses revealed that AKF-PD markedly inhibited expression of Cyp7a1, an enzyme key to BAs synthesis, by increasing Fxr nuclear translocation, and decreased hepatic inflammation by attenuating Erk/-Egr-1-mediated expression of inflammatory cytokines and chemokines Tnfα, Il-1ß, Il-6, Ccl2, Ccl5 and Cxcl10. Moreover, AKF-PD was found to substantially reduce liver fibrosis via inhibition of Tgfß1/Smad pathway in our mouse model. Here, we found that AKF-PD effectively attenuates cholestasis and hepatic fibrosis in the mouse model of DDC-induced cholestasis. As such, AKF-PD warrants further investigation as a candidate drug for treatment of cholestasis.

Prevalence of recurrent aphthous stomatitis, oral submucosal fibrosis and oral leukoplakia in doctor/nurse and police officer population.

BACKGROUND: The doctor/nurse and police officer population have some common typical characteristics of great professional pressure and night shift and past studies indicated oral mucosa lesions were closely associated with psychological factors and health-risking behaviors, however the prevalence of recurrent aphthous stomatitis (RAS) and the two commonly seen oral potentially malignant disorders of oral submucosal fibrosis (OSF) and oral leukoplakia in doctor/nurse and police officer in the Betel quid chewing city of Mainland China is unknown The cross-sectional study was to determine the prevalence differences of RAS, oral leukoplakia and OSF among doctor/nurse, police officer and non-doctor/nurse and non-police officer population aged 20-59 years. METHODS: RAS, OSF and oral leukoplakia were examined in doctor/nurse group (male: 659, female: 2439), police officer group (male: 839, female: 262) and non-doctor/nurse and non-police officer group (male: 7576, female: 8129) from 2020-11-01 to 2021-08-31 in Health Management Center, Xiangya Hospital in Changsha city, Hunan province. RESULTS: The prevalence rates of RAS, OSF, oral leukoplakia and oral leukoplakia combined with OSF in male and female non-doctor/nurse and non-police officer group are 8.32‰ and 10.83‰, 58.08‰ and 1.23‰, 11.75‰ and 0.25‰, 7.66‰ and 0.12‰ respectively. Compared with the non-doctor/nurse and non-police officer population, prevalence rates of RAS in male (24.27‰) and female (20.50‰) doctor/nurse population were significantly higher. Prevalence rates of OSF (21.24‰) and oral leukoplakia (3.03‰) in male doctor/nurse population were significantly less but prevalence rates of OSF (93.71‰), oral leukoplakia (20.17‰) and oral leukoplakia combined with OSF (15.42‰) for male police officer were significantly greater in comparison with male non-doctor/nurse and non-police officer group. OSF and oral leukoplakia prevalence rates were obvious lower for the female than the counterpart male group, but there were no significant differences of OSF and oral leukoplakia prevalence rates between the female non-doctor/nurse and non-police officer and female doctor/nurse group. Oral leukoplakia was not found in the female police officers. CONCLUSIONS: Doctor/nurse population have higher prevalence of RAS. Male doctors/nurses have lower prevalence of OSF and oral leukoplakia, while male police officers have higher prevalence of OSF, oral leukoplakia and oral leukoplakia combined with OSF.

The potential of CircRNA1002 as a biomarker in hepatitis B virus-related hepatocellular carcinoma.

Background: Although hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, there is a lack of effective diagnostic measures. Circular RNAs (circRNAs) can be used as biomarkers for monitoring the occurrence and development of HCC. However, a convenient and reliable serum circRNA biomarker is not currently available. Materials & Methods: CircRNA expression profiles were explored using high-throughput sequencing technology, and targeted circRNAs and mRNAs were validated by quantitative reverse transcription PCR (RT-qPCR). The biological functions of circRNAs were investigated using Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Downstream miRNAs and mRNAs of dysregulated circRNAs were predicted using TargetScan, miRanda, and miRDB; then circRNA-miRNA-mRNA interaction networks were constructed based on sequencing data and the Cancer Genome Atlas (TCGA). Results: A total of 50,327 circRNAs were identified, with 1,187 circRNAs significantly differentially expressed between hepatitis B virus (HBV)-related HCC and HBV asymptomatic carriers. Among these circRNAs, four (circRNA1002, circRNA7941, circRNA 39338, and circRNA44142) were validated by RT-qPCR as being statistically different either in HCC tissue or serum samples. circRNA1002 was significantly down-regulated in both HCC serum and tissue, indicating its reliability. Bioinformatics analysis showed that circRNA1002-associated genes were enriched in GO terms relating to hormone pathway and cell-cell interaction processes, which are involved in the progression of HCC. Conclusion: Our circRNA analysis of HCC patients and HBV asymptomatic carriers showed that circRNA1002 may be a reliable serum biomarker for HCC. These results could provide an improved assay for the early detection of HCC.