Antibiotics in urine of the general population: Exposure, health risk assessment, and food factors.

Diet is known to be one of the main sources from which human intake many environmental contaminants, for example, antibiotics. To determine the effect of dietary factors on antibiotic intake, we identified the levels of antibiotics present in the urine of the general population from two regions of Shanghai. Moreover, we assessed the amount of exposure to these substances and the health risks they posed. There were a total of 18 antibiotics, which were sorted into five categories. Based on the above, we used the Food Frequency Questionnaire (FFQ) and demographic data to evaluate the effects of food consumption and demographic factors on levels of the antibiotics in urine. The results found that food sourced from animals had a direct relation to the level of veterinary antibiotics or preferred veterinary antibiotics (VAs/PVAs) detected in urine. Those who regularly consumed, for example, meat, milk and eggs, had considerably more VAs/PVAs in their urine compared to those who didn't. These results demonstrated that animal-derived foods are the main causes of unintentional exposure to antibiotics in human. Our study, therefore, evidenced that more attention must be paid to the residues of unneeded VAs/PVAs derived from animal-sourced food.

Direct antiviral agent treatment leads to rapid and significant fibrosis regression after HCV eradication.

Limited data are currently available regarding fibrosis progression after hepatitis C virus (HCV) eradication. The goal of the present study was to evaluate the effects of HCV eradication on liver stiffness measurements (LSMs), aspartate aminotransferase/platelet ratio index (APRI) scores, fibrosis-4(FIB-4) scores, chitinase-3-like protein 1 (CHI3L1) levels and Golgi protein 73 (GP73) levels in patients with chronic hepatitis C (CHC). One hundred and two patients who received direct antiviral agents (DAAs) therapy at Peking University First Hospital participated in the present study. Clinical information and serum samples were collected at baseline, at the end of treatment (EOT), and at the weeks 12, 24 and 48 after treatment (W12, W24 and W48, respectively). Of the 102 patients, 51 had mild-to-moderate fibrosis (F1/F2), and 51 had advanced fibrosis (F3/F4). The LSMs improved for all patients at the EOT, with observed changes of 2.85 kPa, and the decrease continued to W12. However, a more pronounced improvement was noted for the advanced fibrosis (F3/F4) patients, with a change of 3.6 kPa from baseline to the EOT. Significant decreases between the baseline and EOT measurements were observed in the APRI and FIB-4 scores [0.64 (0.39-1.21) vs. 0.35 (0.26-0.52), p<0.001; 2.53 (1.30-3.91) vs. 1.87 (0.89-2.5), p<0.001], after which the values decreased until W12, with no significant difference observed. Serum CHI3L1 and GP73 levels were profoundly decreased at the EOT compared with those at baseline [134.07 (154.49) vs. 103.75 (98.04), p=0.025; 98.24 (64.76) vs. 88.91 (50.89), p=0.002]. DAA treatments could significantly improve liver fibrosis of CHC patients as evidenced by decreased liver stiffness, APRI scores and FIB-4 scores. Improvements in liver fibrosis markers (especially serum CHI3L1 and GP73) were prominent in patients with advanced fibrosis, indicating that serum CHI3L1 and GP73 could be noninvasive markers for monitoring fibrosis in CHC patients. Significance Statement The prospective cohort evaluated the effect of direct antiviral agents (DAAs) on fibrosis regression after hepatitis C virus (HCV) eradication of Chinese people in the real-world study. This study highlighted that rapid and significant fibrosis regression rather than reduction in inflammation was achieved with DAA treatment, and this regression could be detected as early as the end of treatment. We found the serum CHI3L1 and GP73 levels can be used to monitor changes in fibrosis in CHC patients.

Hepatitis B virus pregenomic RNA status can reveal the long-term prognoses of chronic hepatitis B patients treated with nucleos(t)ide analogues.

We examined whether the hepatitis B virus (HBV) pregenomic RNA (pgRNA) status after nucleos(t)ide (NA) treatment can predict the long-time prognoses of chronic hepatitis B patients. Patients with chronic hepatitis B (98) who were treatment-naïve and had begun a 7-year NA therapy regimen were enrolled in this study. Biochemical indicators and serological markers of HBV infection were performed during therapy. HBV pgRNA was quantified by real-time quantitative PCR with specific primers. During treatment, HBV DNA undetectable rates increased. The aminotransferase (ALT) normalization (ALT < 50 IU/L) and HBeAg-negative rates also increased. After 48 weeks' NA treatment, 48.28% (28/58) of HBV DNA undetectable patients still had HBV pgRNA-positive. After 7 years of treatment, more HBV pgRNA-negative patients (n = 35) achieved HBeAg clearance than the patients who were HBV pgRNA-positive (n = 63) (19/23 vs 19/56, P < .00). HBV pgRNA-positive patients also had an increased risk of failing to achieve HBeAg clearance (OR = 9.25, 95% CI: 2.75-31.08). The median time to HBeAg clearance in the HBV pgRNA-positive patients was longer than that of the HBV pgRNA-negative patients (152 weeks vs 72 weeks). The HBV pgRNA-positive patients also required more time to achieve HBV DNA undetectable (124 weeks, 95% CI: 103.33-144.67 vs 48 weeks, 95% CI: 34.80-61.20). The HBV pgRNA status after NA treatment can predict the long-term prognoses of patients with chronic HBV. Patients who remain HBV pgRNA-positive after 48 weeks of NA treatment have an increased risk of not achieving HBeAg clearance, need more time to achieve HBeAg clearance and undetectable HBV DNA load.

High-density lipoprotein cholesterol is a predictor of survival in cirrhotic patients with acute gastrointestinal bleeding: a retrospective study.

BACKGROUND: Lipid profiles are declined in patients with viral liver cirrhosis and correlated with severity of liver disease. Hepatitis B virus (HBV) is the leading cause of liver cirrhosis in China. Our primary aim was to investigate whether serum lipids and lipoproteins associate with survival in patients with HBV-related cirrhosis and acute gastrointestinal bleeding, and develop a 6-week mortality risk score that incorporates it. METHODS: From January 2008 to December 2015, consecutive cirrhotic patients with acute gastrointestinal bleeding admitted to our hospital were evaluated and randomly divided into the derivation (n = 629) and validation (n = 314) cohorts. A logistic regression model was established to confirm the association between lipoprotein cholesterol and mortality. Accuracy to predict mortality were assessed by area under the receiver operating characteristic curves (AUROCs) and compared using the Hanley and McNeil test. RESULTS: Among study subjects, the 6-week mortality rate was 10.6%. High-density lipoprotein cholesterol (HDL-C) level was found to correlate most strongly with prognostic scores. On ROC analysis, HDL-C showed excellent diagnostic accuracy for 6-week mortality. Logistic regression analysis provided a simple algorithm based on the combined use of 4 variables (total bilirubin (TBIL), HDL-C, International normalized ratio, and hemoglobin), allowing accurate discrimination of 3 distinct prognostic subgroups with 1.7% (low risk), 12.3% (intermediate risk), and 56.9% (high risk) mortality. Its accuracy was significantly better than that of Child-Pugh, model of end-stage liver disease, albumin-bilirubin score, D'Amico model, Augustin model, AIMS65 score and Glasgow-Blatchford score. Baseline HDL-C values ≤ 0.54 mmol/L were associated with markedly lower 6-week survival. Comparable results were found in the validation set. CONCLUSION: HDL-C is a potential indicator for the prognosis of patients with cirrhosis and acute gastrointestinal bleeding. The new algorithm based on HDL-C allowed an accurate predictive assessment of 6-week mortality after bleeding attack.

PI3K/Akt pathway-mediated enhancement of bone and vascular regeneration by gelatin/hyaluronic acid/exosome composite scaffold in bone tissue engineering.

Tissue engineering (TE) is commonly suggested as a promising remedy for the worldwide shortage of organ donors required for transplantation. Scholars are investigating organic and biocompatible materials as the principal options for regeneration to replicate the natural extracellular matrix. Hydrogels exhibit swift gel formation and outstanding biocompatibility, thus presenting considerable promise in tissue regeneration. The objective of this study was to investigate the role of a novel biomaterial complex, comprising gelatin (Gel), hyaluronic acid (HA) and exosomes (Exo), in promoting bone regeneration and elucidate its underlying molecular mechanism. The experimental results demonstrated that the Gel/HA/Exo complex could significantly enhance the proliferation and differentiation of osteoblasts, as well as the deposition and mineralization of bone matrix. Further mechanistic studies demonstrated that TGF-ß in exosomes enhanced the biological activity of osteoblasts by activating the PI3K/Akt pathway, thus promoting the fracture healing process. The results of in vivo experiments indicated that the application of Gel/HA/Exo complexes significantly accelerated the fracture healing rate and improved the quality of healing, exhibiting good biocompatibility and controlled degradation properties. Consequently, the present study concluded that the Gel/HA/Exo complex not only has potential clinical applications, but also provides an important theoretical and experimental basis for the development of novel bone regeneration therapeutic strategies.

Bacterial meningitis in children with an abnormal craniocerebral structure.

Background: We studied the causative pathogens, clinical characteristics, and outcome of bacterial meningitis in children with an abnormal craniocerebral structure. Methods: A retrospective single-center study was conducted on children aged in the range of 29 days to 14 years by using data obtained from the pediatric intensive care unit in Shengjing Hospital between January 2014 and August 2021. All children were diagnosed with bacterial meningitis. They were divided into complex and simple groups by taking into account the presence of an abnormal craniocerebral structure before they contracted bacterial meningitis. We collected data on demographics, clinical presentations, laboratory results, imaging studies, treatments, and outcomes. Results: A total of 207 patients were included in the study (46 in the complex group and 161 in the simple group). Patients in the complex group had a lower mortality rate (6.5% vs. 11.2%, p < 0.05), positive blood culture (13.0% vs. 34.8%; p < 0.05), multiple organ dysfunction syndrome (0% vs. 9.3%; p < 0.05), and shock (2.2% vs. 9.3%; p = 0.11). These patients were more often detected with neurological sequelae (80.4% vs. 53.4%; p < 0.05), cerebrospinal fluid drainage (50% vs. 15.5%; p < 0.05), nosocomial infection (54.3% vs. 3.1%; p < 0.05), and multidrug-resistant bacteria (62.5% vs. 55.6%, p = 0.501). In patients in the simple group, infection was mostly confined to the nervous system. Conclusion: Bacterial meningitis patients with an abnormal craniocerebral structure had fewer bloodstream infections, lower mortality rates, and higher incidence rates of neurological sequelae. Pathogens were more likely to be nosocomial and multidrug-resistant bacteria.

Enhanced decomplexation of Cu-EDTA and simultaneous removal of Cu(II) by electron beam irradiation accompanied with autocatalytic fenton-like reaction: Synergistic performance and mechanism.

Widely existing heavy metal complexes with high stability and poor biodegradability are intractable to be eliminated by conventional methods. In this study, electron beam (EB) irradiation characterized by rapidly producing strong oxidizing radicals was employed to effectively decompose Cu-ethylenediaminetetraacetic acid (Cu-EDTA) with almost complete elimination at 5 kGy. In terms of heavy metal removal, EB irradiation at relatively low doses was insufficient to remove copper ions, which was only 17.2% under 15 kGy. However, with the extra addition of 8 mM H2O2, such an irradiation dose could result in 99.0% copper ions removal. Mechanism analysis indicated that EB irradiation combined with spontaneously induced Fenton-like reactions were responsible for its excellent performance. The prime function of EB irradiation was to destroy the structure of Cu-EDTA with in-situ produced ·OH, and the subsequent released Cu-based intermediates could activate H2O2 to initiate autocatalytic chain reactions, correspondingly accelerating the degradation of complexes and the liberation of metal ions. Highly oxidative ·OH and O2·- were demonstrated as main active species acted on different positions of Cu-EDTA to realize gradual decarboxylation, synchronously generating low molecular weight compounds. XRD and XPS analysis showed that the released copper ions were mainly precipitated in the form of CuO, Cu(OH)2 and Cu2(OH)2CO3. In general, EB/H2O2 was an adoptable strategy for the disposal of such refractory heavy metal complexes.

CaCl2 treatment effectively delays postharvest senescence of passion fruit.

This study aimed to systematically investigate the changes in peel color, physicochemical characteristics, textural properties, and peel ultrastructure between CaCl2-treated and water-soaked passion fruit under short-term storage at room temperature (20 °C) for eight days. The fruit peel was further analyzed and compared for the differences in calmodulin (CaM) gene expression between the two groups. The data were analyzed using principal component analysis. The results confirmed that CaCl2 treatment effectively maintained the appearance and color of passion fruit, inhibited peel browning, and improved fruit quality. The treatment had an effect on maintaining the physiological properties of passion fruit parenchyma, effectively delayed the passion fruit senescence, and kept the structural integrity of the fruit peel. The relative expression of PeCaM gene in the CaCl2-treated fruit peels was higher than that of the control peels. The Ca2+ stimulated the relative expression of the PeCaM gene, which delayed the senescence of passion fruit.

The characteristics and alteration of peripheral immune function in patients with multiple system atrophy.

Objective: Multiple system atrophy (MSA) is a degenerative disease. Immune dysfunction found to play a crucial role in the pathogenesis of this disease in the literature, while the characteristics of peripheral immune function remain unclear. This study aimed to investigate the characteristics and alterations of peripheral immune function in patients with MSA. Methods: A case-control study was conducted between January 2021 to December 2022 at SanBo Brain Hospital, Capital Medical University, Beijing, China. A total of 74 participants were recruited, including 47 MSA patients and 27 non-MSA participants. Peripheral blood samples were collected from each participant. A total of 29 types of immune cells were measured using the flow cytometry analysis technology. Single-factor analysis and multiple-factor analysis (multiple linear regression models) were performed to determine the differences and risk factors in immune cells between the MSA and non-MSA groups. Results: Alterations of the count or percentage of CD19+ B lymphocytes and CD3-CD56+ B lymphocytes in MSA patients were found in this study. The reductions of the count and percentage of CD19+ B lymphocytes were still robust after adjusting for variables of age, gender, body mass index, albumin, and hemoglobin. Furthermore, the reductions in the count and percentage of CD19+ B lymphocytes in the MSA patients were more significant in women and individuals aged 60 years old or above than in the non-MSA participants. Conclusion: Our findings suggested that MSA patients may be influenced by B lymphocytes, particularly CD19+ cells. Therefore, the reductions in immune cells should be considered in the diagnosis and treatment of MSA. Further studies are warranted to confirm and expand upon these findings.

Self-assembled iRGD-R7-LAHP-M nanoparticle induced sufficient singlet oxygen and enhanced tumor penetration immunological therapy.

The generation of singlet oxygen (1O2) using photodynamic therapy (PDT) is limited by the hypoxia of the tumor microenvironment and the depth of external light penetration because it depends on the precise cooperation between the photosensitizers, oxygen, and light. Herein, we report a self-sufficient 1O2 nanoreactor with enhanced penetration into deep tumors for cancer therapy. Linoleic acid hydroperoxide (LAHP) is coordinated with transition metal ions (Cu2+/Fe3+) to prepare linoleic acid hydroperoxide metal complex nanoparticles (LAHP-M NPs). iRGD combined with R7 decoration endows the nanoparticles with tumor targeting and penetration ability. We show that the polypeptide carries the nanoparticles into deep tumors, and thereafter the nanoparticles are disassembled into LAHP and catalytical metal ions to produce 1O2 based on the Russell mechanism under the stimulation of acidic pH. The elevated ROS induces necrotic cell death in vitro and in vivo, and further causes immunogenic cell death (ICD). This study demonstrates the effectiveness of exploiting biochemical reactions as a spatial-temporal strategy to overcome the current limitations of photodynamic therapy.

Melatonin treatment improves postharvest quality and regulates reactive oxygen species metabolism in "Feizixiao" litchi based on principal component analysis.

Postharvest quality of litchi reduces rapidly during storage at room temperature. This study aimed to investigate the effect of melatonin treatment on postharvest quality and oxidative stress markers of litchi fruit during cold storage. The "Feizixiao" litchi was treated with melatonin solution concentrations of 0.2 and 0.6 mmol·L-1 and then stored at 4°C for 12 days. The results confirmed that the melatonin treatment effectively maintained the appearance and color of the litchi fruit, suppressed the peel browning, and improved the litchi quality. The treatment also significantly enhanced the levels of endogenous melatonin, antioxidant components (total phenolics, flavonoids, and anthocyanin), and antioxidant enzyme activities of the fruit. It also inhibited the other oxidative stress markers, such as O 2 - , H2O2, MDA, and protein carbonyl content, and upregulated the expressions of antioxidant and Msr-related genes. Correlation and principal component analyses further confirmed that the melatonin treatment effectively delayed the fruit senescence by enhancing the antioxidant enzyme activities and modulating peel browning and reactive oxygen species metabolism of the litchi fruit via regulating gene expression of the related enzymes (SOD and PPO). These findings suggested that the exogenous application of melatonin to litchi during the postharvest is an ideal way to preserve the fruit quality and delay fruit senescence.

High levels of soluble programmed death-1 are associated with virological response in chronic hepatitis B patients after antiviral treatment.

BACKGROUND: Soluble programmed cell death protein-1 (sPD-1) plays an important role in chronic hepatitis B virus (HBV) infection by counteracting the inhibitory effect of programmed death ligand-1 (PD-L1) on immune cells. Here, we investigated the ability of sPD-1 to predict the virological response (VR) in chronic hepatitis B (CHB) patients undergoing Nucleos(t)ide analogue (NA) therapy. METHODS: CHB patients [hepatitis B surface antigen (HBsAg) positive ≥6 months] who initiated NA therapy in March 2007 at Peking University First Hospital (China) were enrolled in this study. Eighty-nine CHB patients were followed-up every 12 weeks for 96 weeks. RESULTS: Serum sPD-1 levels at baseline were negatively correlated with hepatitis B surface antigen (HBsAg) and HBV DNA. Immune-active CHB patients exhibited higher serum sPD-1 levels at baseline. Patients with VR during the antiviral treatment exhibited higher sPD-1 levels and lower HBsAg levels at baseline. Receiver operating characteristic (ROC) curves were generated to determine the predictive value of sPD-1 and HBsAg for VR in patients who received first-line therapy (entecavir, ETV). The area under ROC (AUROC) values of sPD-1 and HBsAg at baseline were 0.850 (95%CI:0.729-0.971, P = 0.0005) and 0.785 (95%CI: 0.642-0.929, P = 0.005), respectively, and the optimal cut-off values were 459.46 pg/mL and 14,710 IU/mL, respectively. The combination of sPD-1 and HBsAg exhibited a higher AUROC value (0.870,95% CI: 0.748-0.983, P = 0.001) than did sPD-1 or HBsAg alone. In patients administered second-line therapy (lamivudine, LAM/adefovir divipoxil, ADV), baseline sPD-1 levels above 677.2 pg/mL were significantly associated with higher incidence of VR after 96 weeks of antiviral therapy. It is 7.956 times the level of ≤677.2 pg/mL. CONCLUSIONS: By combining sPD-1 and HBsAg, we obtained a biomarker significantly associated with VR in CHB patients. The sPD-1 levels could be used to screen out patients with poor prognosis of antiviral therapy.

Dynamics of Hepatitis B Virus Pregenomic RNA in Chronic Hepatitis B Patients With Antiviral Therapy Over 9 Years.

Serum hepatitis B virus pregenomic RNA (HBV pgRNA) is a potential biomarker that is correlated with covalently closed circular DNA. The long-term dynamics of HBV pgRNA in patients with chronic hepatitis B need to be explored. One hundred naïve nucleos(t)ide analog-treated patients with chronic hepatitis B were enrolled to analyze the dynamics of HBV pgRNA over 9 years. The positive rates of HBV pgRNAs declined gradually and showed biphasic kinetics. Serum HBV pgRNA levels in patients treated with entecavir became negative later than those treated with adefovir or lamivudine. Patients who remain positive for HBV pgRNA after 9 years of treatment may have higher viral transcription efficiencies. The reverse transcription efficiency of hepatitis B e-antigen (HBeAg)-positive patients was higher than that of HBeAg-negative patients at baseline and showed no difference after 24-week nucleos(t)ide analog treatment. The trajectory of serum HBV pgRNA-negative transformation differs in patients with different characteristics. Long-term dynamic monitoring of serum HBV pgRNA levels has significance in hepatitis B treatment.

Prognosis and Risk Factors of Recurrence in HBV-Related Small Hepatocellular Carcinoma After Stereotactic Body Radiation Therapy.

Objective: The role of stereotactic body radiation therapy (SBRT) for treating small hepatocellular carcinoma (sHCC) has gained increasing recognition. However, the prognosis and risk factors for recurrence in patients with sHCC remain unclear. This study investigated the risk factors for the recurrence of hepatitis B virus (HBV)-related sHCC after SBRT. Methods: A total of 240 HBV-related sHCC patients treated with SBRT between March 2011 and March 2020 were retrospectively analyzed. The cumulative probability of recurrence was calculated according to the Kaplan-Meier method. Univariate and multivariate analyses were performed with Cox proportional hazard models. Results: Recurrent hepatocellular carcinoma developed in 134 (55.8%) patients at a median time of 27 months after SBRT. The one- and two-year rates of recurrence were 20.9 and 45.0%, respectively. The median follow-up time was 30 months. The Cox multivariate analysis indicated that age (P = 0.029, HR [1.019, 1.002-1.037]), tumor size (P = 0.012, HR [1.227, 1.045-1.440]), and aspartate aminotransferase-to-platelet ratio index (APRI) (P = 0.005, HR [1.911, 1.221-2.989]) were independent risk factors for recurrence. Conclusion: Patients receiving SBRT for HBV-related sHCC may be at greater risk of recurrence if they have a high APRI score combined with advanced age and large tumor size.

Exploration of immune infiltration and feature genes in viral hepatitis-associated liver fibrosis using transcriptome data.

Background: Immune cells play an essential role in virus-induced liver fibrosis. However, the underlying mechanisms remain unclear. In this study, we systematically explored immune cell infiltration and feature genes to provide new insights into viral hepatitis-associated liver fibrosis. Methods: The expression datasets GSE14323, GSE33650, GSE6764 (for testing), and GSE84044 (for validation) were downloaded from the Gene Expression Omnibus (GEO) database. Immune cell infiltration was assessed using the CIBERSORT algorithm, and characteristic subgroups were obtained using least absolute shrinkage and selection operator (LASSO) regression and Wilcoxon test. The association between feature genes and immune-infiltrating cells was explored using Spearman's correlation analysis. R software and IBM SPSS Statistics were utilized for data analysis and visualization. Results: We identified 10 differential immune cells between viral hepatitis-associated liver fibrosis and non-fibrosis, including naive B cells, plasma cells, resting CD4+ memory T cells, T follicular helper (Tfh) cells, regulatory T (Treg) cells, M0-M2 macrophages, and resting and activated mast cells. Six feature genes were identified: STAT1, CXCL10, PTPRC, IFIT3, OAS2, and MX1. They also differed significantly in the subgroups of non-fibrosis, mild to moderate fibrosis and severe fibrosis. Both the feature genes and immune cells were verified in the validation group. All the genes were positively associated with macrophages M1 and negatively associated with macrophages M2. Conclusions: The six feature genes may be involved in viral hepatitis-associated liver fibrosis by promoting the polarization of macrophages from M0 to M1 and inhibiting their conversion to M2. Thus, these genes may serve as potential therapeutic targets.

A Multicenter Real-World Study Evaluating the Hepatoprotective Effect of Polyene Phosphatidylcholine Against Chronic Hepatitis B.

Background: Polyene phosphatidylcholine (PPC) has been widely used to treat liver diseases in China. However, there is a lack of post-marketing evidence demonstrating its liver-protective efficiency among patients infected with hepatitis B virus (HBV). This study analyzed the multicenter real-world data to compare the effectiveness of PPC with those of magnesium isoglycyrrhizinate (IsoMag) and glutathione (GSH) in patients with liver injury. Methods: This study comprised the real-world data analysis of a multicenter, retrospective observational cohort. The data were retrieved from the Cooperative Registry of the Hospital Prescription in China between 1 October 2018, and 30 September 2019. A growth curve analysis was performed to compare the effects of different treatments on liver function longitudinally for up to 30 days after treatment commencement. In addition, the dose effect of the PPC treatment was investigated. Results: The final cohort included 6,052 patients with approximately 8% infected with HBV (N = 471). There were 1,649, 1,750, and 2,653 patients in the PPC, GSH, and IsoMag groups, respectively, with an average age of 53.9 years. In patients with HBV infection, the PPC treatment was associated with a significant decline in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels (slopes: -3.7, 95% CI, -6.0 to -1.5 U/L/day; -2.4, 95% CI, -4.5 to -0.3 U/L/day, respectively). However, there were no significant differences in the effects among the three groups. In patients without HBV infection, the PPC treatment decreased ALT, AST, γ-glutamyl transferase (GGT), and albumin levels (-5.2, 95% CI, -5.8 to -4.5 U/L/day; -3.5, 95% CI, -4.2 to -2.7 U/L/day; -4.9, 95% CI, -6.2 to -3.7 U/L/day, -0.07, 95% CI, -0.09 to -0.04 g/L/day, respectively) and showed a stronger effect on lowering ALT levels than GSH (-2.6, 95% CI, -3.3 to -1.8 U/L/day, p < 0.05), as well as a stronger effect on lowering GGT levels than IsoMag (-1.4, 95% CI, -2.4 to -0.4 U/L/day, p < 0.05). PPC had no impact on prothrombin activity levels in patients with or without HBV infection. High-dose PPC exhibited a stronger effect on lowering ALT and AST levels than low-dose PPC. Conclusion: This was the first real-world multicenter study to demonstrate that PPC efficiently lowers ALT and AST levels in patients with liver diseases regardless of the status of HBV infection. PPC treatment showed a comparable or better effect compared with GSH and IsoMag treatments. High-dose PPC resulted in a stronger effect than low-dose PPC.

Resistant-Associated Substitutions Do Not Affect HCV RNA and HCV Core Antigen Clearance During Direct-Acting Antiviral Agent Treatment in a Real-World Setting.

Background: Since oral direct-acting antiviral agents (DAAs) became available, the global hepatitis C treatment situation has undergone tremendous changes. However there are still many issues worthy of attention in treatment. Methods: We selected 53 HCV-infected patients who were treated and followed up in the Peking University First Hospital from December 2017 to January 2021 to detect the RASs in HCV. Pearson correlation analysis was used to analyze HCV RNA and HCV cAg, the Fisher exact test and chi-square test was used to compare the effects of RASs on the rate of decline of HCV RNA and HCV core antigen (cAg) during DAA treatment. Results: The RASs and its prevalence on the NS3 are mainly Y56F 2.56% (1/39), Q80K 23.08% (9/39), S122G 71.79% (28/39), and V170I 38.46% (15/39). On the NS5A were R30Q 10.53% (4/38), P32A 5.26% (2/38), P58S 2.63% (1/39), and Y93H 21.05% (8/38). On NS5B were C316N 71.05% (27/38), C451H 2.63% (1/38), and I585C 2.63% (1/38). There was no significant correlation between the RASs (Y93H, V179I, Q80K, S122G, C316N) and HCV genotype (p > 0.05). The baseline serum HCV RNA and HCV cAg had a significant medium-degree correlation (r = 0.601, p = 0.002). After 1 week of DAA treatment was weak correlation (r = 0.413, p = 0.032). Q80K, S122G, V170I, Y93H, and C316N had no effect on the clearance of HCV RNA and HCV cAg within the first week of DAA treatment (p>0.05). Conclusion: The HCV genotype may have a limited impact on the presence of the five RASs (Y93H, V179I, Q80K, S122G, and C316N) as shown in this study. HCV RNA and HCV cAg have a correlation, especially at baseline is the highest; the appearance of some RASs has no effect on DAA treatment in most chronic hepatitis C patients.

Evaluation of the association of a variant in PNPLA3 and TM6SF2 with fibrosis progression in patients with chronic hepatitis C infection after eradication: A retrospective study.

The relationship of single nucleotide polymorphisms (SNPs) in patatin-like phospholipase domain containing 3 (PNPLA3) rs738409, transmembrane 6 superfamily member 2 (TM6SF2) rs58542926, and membrane bound O-acyltransferase domain containing 7 (MBOAT7) rs641738 with outcomes in patients with hepatitis C infection (HCV) is unclear. This study aimed to evaluate the association of PNPLA3, TM6SF2, and MBOAT7 with the baseline fibrosis stage and progression of liver fibrosis after HCV eradication with direct antiviral agents (DAAs). A total of 171 patients who received the DAAs at the Peking University First Hospital between June 2015 and June 2020 were included in the retrospective cohort. Transient elastography was used to determine liver stiffness measurements (LSMs) at the baseline, the end of treatment (EOT), 24 weeks after treatment (W24), and the last follow-up (LFU) visit. We used the QIAamp Blood Mini Kit (Qiagen) for whole blood genomic DNA extraction and polymerase chain reaction for PNPLA3, TM6SF2, and MBOAT7 amplification of the target gene. The PNPLA3 rs738409 SNP was associated with the baseline fibrosis stage in multivariate logistic regression analysis adjusted for other factors, and the adjusted odds ratio (OR) for advanced fibrosis (≥F3) at baseline was 2.52 (95% confidence interval[CI] = 1.096-5.794, p = 0.03). The G and GG alleles were predictive of advanced fibrosis (OR = 1.98, 95% CI = 1.021-4.196, p = 0.015; OR = 3.12, 95% CI = 1.572-6.536, p = 0.005). Similarly, the OR of TM6SF2 rs58542926 at baseline was 2.608 (95% CI = 1.081-6.29, p = 0.033). T and TT alleles were predictive of advanced fibrosis (OR = 2.3, 95% CI = 1.005-5.98, p = 0.007; OR = 3.05, 95% CI = 1.32-6.87, p = 0.001). After adjustment, the MBOAT7 rs641738 T plus TT alleles were not independently associated with the baseline fibrosis stage (95% CI = 0.707-2.959, p = 0.312). At the EOT, there were 35 patients and 136 patients in the fibrosis improvement and fibrosis non-improvement group, respectively. Logistic regression analysis showed that the G allele in PNPLA3 rs738409 was associated with fibrosis progression (OR = 2.47, 95% CI = 1.125-5.89, p = 0.003). The GG alleles were predictive of fibrosis progression (OR = 2.95, 95% CI = 1.35-6.35, p = 0.005). Similarly, the ORs of the T and TT alleles in TM6SF2 rs58542926 for fibrosis progression were 1.82 and 2.21, respectively (95% CI = 1.006-5.373, p = 0.045; 95% CI = 1.18-5.75, p = 0.01). At the W24 visit, we found that there was an association between the G allele in PNPLA3 rs738409 and fibrosis progression (OR = 2.218, 95% CI = 1.095-5.631, p = 0.015). Moreover, GG alleles were also predictive for fibrosis progression (OR = 2.558, 95% CI = 1.252-5.15, p = 0.008). Similarly, the OR of T allele and TT alleles in TM6SF2 rs58542926 for fibrosis progression was 2.056 and 2.652 (95% CI = 1.013-5.592, p = 0.038; 95% CI = 1.25-5.956, p = 0.015). For additional affirmation, we surveyed fibrosis progression utilizing the Cox proportional hazards model. G and GG alleles in PNPLA3 rs738409 were associated with an increased risk of progression to advanced fibrosis in multivariate model (hazard ratio [HR]1.566, 95% CI = 1.02-2.575, p = 0.017; and HR2.109, 95% CI = 1.36-3.271, p = 0.001, respectively). Besides, T and TT alleles in TM6SF2 rs58542926 were associated with an increased risk of progression to advanced fibrosis in multivariate model (HR = 1.322, 95% CI = 1.003-1.857, p = 0.045; and HR = 1.855, 95% CI = 1.35-2.765, p = 0.006, respectively). In contrast, rs641738 in MBOAT7 did not show a significant trend in the univariate and multivariate models. The PNPLA3 CG/GG SNP at rs738409 and TM6SF2 CT/TT SNP at rs58542926 were associated with the baseline fibrosis stage and fibrosis progression after HCV eradication with DAAs.

Clinical characteristics of COVID-19 in family clusters: a systematic review.

BACKGROUND: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread around the world and reports of children during early epidemic period showed features of family clusters. The aim of this study is to assess clinical profiles of COVID-19 in family clusters with children. METHODS: We performed a systematic literature review of English database (PubMed, Web of Science) and Chinese database (" www.cnki.net ", " www.cqvip.com " and " www.Wanfangdata.com.cn ") to identify papers on family clusters of COVID-19 with children and their family members. RESULTS: Eighteen studies involving 34 children and 98 adults from 28 families were included. Fever, cough and ground-grass opacity change of chest computed tomography (CT) were the dominant features, whereas proportion of asymptomatic infections for children was higher than adults with statistical significance (32.4% and 13.3%, respectively, P < 0.05). Median time of longer incubation period (10 days) and shorter duration of pharyngeal swab nucleic acid test positive period (11 days) were seen in children than adults (7 and 17 days, respectively) with statistical significance (P < 0.05). There were statistically significant differences in lymphopenia, increased C-reactive protein and abnormal chest CT between children and adult patients (P < 0.05). Twenty-seven families reported adults as first case of COVID-19 in family clusters. CONCLUSIONS: The same virus strain can cause milder disease in children compared with their caregivers. Children of COVID-19 were infected by adults in family during the early epidemic period. Asymptomatic patients can transmit the virus.

Predictive Nomograms for Clinical Outcomes in Hepatitis B-Related Cirrhosis Patients Receiving Antiviral Therapy.

OBJECTIVE: Many scores have been constructed to predict liver-related events in chronic hepatitis B, while most of them are based on baseline clinical parameters. The objective of this study was to develop nomograms based on on-treatment improvement in established scores to predict clinical outcomes in patients with hepatitis B virus (HBV)-related cirrhosis who are receiving antiviral therapy. METHODS: The Cox proportional hazards regression model was used. Nomograms were constructed for the prediction of liver-related events, hepatocellular carcinoma (HCC), and liver-related mortality risk during long-term antiviral therapy. RESULTS: A total of 277 treatment-naive patients with HBV-associated cirrhosis were enrolled from January 2010 to December 2013. After a median follow-up of 63.3 months, 95 patients developed liver-related events, including 59 patients with liver-related death. Multivariate Cox analysis showed that the albumin-bilirubin score at year 1 was an independent predictor of liver-related events, liver-related mortality, and HCC. Age, decompensation, and delayed virological remission were independent factors for liver-related mortality. Age was also a risk factor for liver-related events. The concordance index values of event-nomogram, mortality-nomogram, and HCC-nomogram were 0.742 (95% confidence interval [CI], 0.691~0.793), 0.799 (95% CI, 0.748~0.850), and 0.613 (95% CI, 0.540~0.686), respectively. The calibration plots showed an agreement between the predicted and observed incidences, which indicates good calibration of the model of event-nomogram and mortality-nomogram. CONCLUSION: The nomograms achieved an optimal preoperative prediction of liver-related events, mortality, and HCC development in patients with HBV-related cirrhosis receiving antiviral therapy. These findings may help to identify high-risk patients for further optimal surveillance and intervention strategies.