Metallic nanoparticles and photosynthesis organisms: Comprehensive review from the ecological perspective.

This review presents a comprehensive analysis of the ecological implications of metallic nanoparticles (MNPs) on photosynthetic organisms, particularly plants and algae. We delve into the toxicological impacts of various MNPs, including gold, silver, copper-based, zinc oxide, and titanium dioxide nanoparticles, elucidating their effects on the growth and health of these organisms. The article also summarizes the toxicity mechanisms of these nanoparticles in plants and algae from previous research, providing insight into the cellular and molecular interactions that underpin these effects. Furthermore, it discusses the reciprocal interactions between different types of MNPs, their combined effects with other metal contaminants, and compares the toxicity between MNPs with their counterpart. This review highlights the urgent need for a deeper understanding of the environmental impact, considering their escalating use and the potential risks they pose to ecological systems, especially in the context of photosynthetic organisms that are vital to ecosystem health and stability.

Sodium thiosulfate ameliorates atopic dermatitis via inhibiting the activation of NLRP3 inflammasome.

Atopic dermatitis (AD) is a common disease with a considerable impact on the patient's quality of life and limited treatment options. Sodium thiosulfate (STS) is a traditional medicine used in the rescue of cyanide poisoning, and some pruritus dermatosis. However, the exact efficacy and mechanism of its application on AD are not clear. In this work, comparing to other traditional therapy, STS was found to effectively improve the severity of skin lesions and the quality of life in AD patients with a dose-dependent manner. Mechanically, STS downregulated the expression of IL-4, IL-13, IgE in the serum of AD patients, as well as reduce the concentration of eosinophils. Furthermore, in the AD-like mice model triggered by ovalbumin (OVA) and calcitriol, STS was found to reduce the epidermal thickness, scratching times, and the infiltration of dermal inflammatory cells in AD mice, as well as the reactive oxygen species (ROS) production and the expression levels of inflammatory cytokines in the skin tissue. In HacaT cells, STS inhibited the accumulation of ROS and activation of NLRP3 inflammasome and its downstream IL-1ß expression. Therefore, this study revealed that STS plays an important therapeutic role in AD, and the mechanism may be that STS inhibits the activation of NLRP3 inflammasome and the subsequent release of inflammatory cytokines. Thus, the role of STS in treating AD was clarified and the possible molecular mechanism was revealed.

Influence of the COVID-19 Pandemic on the Prevalence Pattern of Allergens.

INTRODUCTION: The effect of the COVID-19 pandemic on allergic diseases is not certain, as people's living habits and the environment have been affected by the pandemic. The present study described the influence of the COVID-19 pandemic on the allergen sensitization rate in patients with allergic diseases in central China. The results provide reliable epidemiological data for the prevention and control of allergic diseases during the COVID-19 epidemic. METHODS: Data were collected from a total of 6,915 patients with symptoms of allergic diseases who visited the Third Xiangya Hospital of Central South University in China for allergen testing from January 1, 2018, to December 31, 2021. Patients were divided into a children group (<14 years old), youth group (15∼44 years old), middle-aged group (45∼59 years old), and elderly group (>60 years old). Immunoblotting was used to detect 20 serum allergen-specific IgE (sIgE) antibodies in patient serum samples. We compared the positive rates of various allergens in different age and sex groups before and during the COVID-19 epidemic, and the prevalence data of sIgE sensitization were analysed. RESULTS: Among the 6,915 patients with symptoms of allergic diseases, 2,838 (41.04%) patients were positive for at least one of the allergens. The top three positive rates of inhaled allergens were Dermatophagoides farinae (1,764 cases, 25.51%), Dermatophagoides pteronyssinus (1,616 cases, 23.37%), and house dust (645 cases, 9.33%). The top three positive rates of food allergens were eggs (686 cases, 9.92%), milk (509 cases, 7.36%), and crabs (192 cases, 2.78%). The total positive rate of allergens was higher in men (46.99%) than in women (37.30%). Compared to 2 years before the COVID-19 epidemic, the rate of sensitization to indoor inhalant allergens increased, but outdoor inhalant allergens showed no significant change. The positive rates of milk and eggs peaked during the outbreak of COVID-19 (2020) then declined in 2021. The total positive rate of allergens was higher in males than females before and during the COVID-19 epidemic, but more allergens were different between males and females during the pandemic. Compared to middle-aged and older adults, the children and youth groups were more susceptible to allergic diseases, and they exhibited an increasing positive rate for most common allergens, especially indoor inhalant allergens, during the COVID-19 epidemic than before the pandemic. CONCLUSION: D. pteronyssinus and D. farinae are the most common allergens in South China. Under the background of normalization of epidemic prevention, indoor inhaled allergens should be first in the prevention and control of allergic diseases, and a combination of various indoor cleaning measures should be used to improve the efficiency of interventions.

Real-world study on HBsAg loss of combination therapy in HBeAg-negative chronic hepatitis B patients.

Combination therapy with pegylated interferon (PEG-IFN) and nucleos(t)ide analogues (NAs) can enhance hepatitis B surface antigen (HBsAg) clearance. However, the specific treatment strategy and the patients who would benefit the most are unclear. Therefore, we assessed the HBsAg loss rate of add-on PEG-IFN and explored the factors associated with HBsAg loss in chronic hepatitis B (CHB) patients. This was a real-world cohort study of adults with CHB. Hepatitis B e antigen (HBeAg)-negative NAs-treated patients with baseline HBsAg ≤1500 IU/ml and HBV DNA < the lower limit of detection, or 100 IU/ml, received 48 weeks of add-on PEG-IFN. The primary outcome of the study was the rate of HBsAg loss at 48 weeks of combination treatment. Using multivariable logistic regression analysis, we determined factors associated with HBsAg loss. HBsAg loss in 2579 patients (mean age: 41.2 years; 80.9% male) was 36.7% (947 patients) at 48 weeks. HBsAg loss was highest in patients from south-central and southwestern China (40.0%). Factors independently associated with HBsAg loss included: increasing age (odds ratio = 0.961); being male (0.543); baseline HBsAg level (0.216); HBsAg decrease at 12 weeks (between 0.5 and 1.0 log10 IU/ml [2.405] and >1.0 log10 IU/ml [7.370]); alanine aminotransferase (ALT) increase at 12 weeks (1.365); haemoglobin (HGB) decrease at 12 weeks (1.558). There was no difference in the primary outcomes associated with the combination regimen. In conclusion, HBsAg loss by combination therapy was higher in patients from southern China than those from the north. An increased chance of HBsAg loss was associated with baseline characteristics and dynamic changes in clinical indicators.

Dysregulated behaviour of hair follicle stem cells triggers alopecia and provides potential therapeutic targets.

Due to a steady increase in the number of individuals suffering from alopecia, this condition has recently received increasing attention. Alopecia can be caused by various pathological, environmental or psychological factors, eventually resulting in abnormalities in hair follicle (HF) structures or HF regeneration disorders, especially dysregulated hair follicle stem cell (HFSC) behaviour. HFSC behaviour includes activation, proliferation and differentiation. Appropriate HFSC behaviour sustains a persistent hair cycle (HC). HFSC behaviour is mainly influenced by HFSC metabolism, ageing and the microenvironment. In this review, we summarize recent findings on how HFSC metabolism, ageing and the microenvironment give rise to hair growth disorders, as well as related genes and signalling pathways. Recent research on the application of stem cell-based hair tissue engineering and regenerative medicine to treat alopecia is also summarized. Determining how dysregulated HFSC behaviour underlies alopecia would be helpful in identifying potential therapeutic targets.

Factors associated with prolonged hospital stay of imported malaria cases in Chengdu, China: a retrospective study.

BACKGROUND: Although China has entered the post-malaria-elimination era, imported cases remain a public health concern in China. METHODS: We retrospectively analyzed data from cases of imported malaria from January 2017 to December 2020 in Chengdu Public Health Clinical Center. We assessed potential clinical, epidemiological, geographical, and seasonal effects on duration of hospital stay. Cox proportional hazards model was used to identify predictive factors for prolonged hospital stay. Multivariate logistic regression was used to assess the potential risk factors associated with severe cases. RESULTS: The highest number of imported cases of malaria were from the Democratic Republic of the Congo (23%, 34/150) and most patients (74%, 26/34) were infected by Plasmodium falciparum. The Edwards test indicated no significant seasonality in imported cases of malaria (χ2 = 2.51, p = 0.28). Bacterial infection (adjusted hazard ratio [aHR] for discharge = 0.58, p = 0.01) and thrombocytopenia (aHR = 0.66, p = 0.02) were risk factors for prolonged hospital stay. The C-reactive protein (OR = 1.02, p = 0.01) and procalcitonin (OR = 1.03, p = 0.01) were risk factors for severe cases. CONCLUSIONS: Bacterial infection and thrombocytopenia are risk factors for prolonged hospital stay among imported malaria cases. The C-reactive protein and procalcitonin level were risk factors for severe cases.

Dynamic changes of viral load and the duration of viral shedding in patients with hand, foot and mouth disease: a protocol for longitudinal study.

BACKGROUND: The duration of virus shedding is necessary for determining the infectious period. But there were few quantitative studies on the changes of viral load and the law of the viral shedding in hand foot and mouth disease (HFMD) patients has not yet been clarified. METHODS: This study will prospectively recruit coxsackievirus A10 (CV-A10), coxsackievirus A16 (CV-A16) and coxsackievirus A6 (CV-A6) infected inpatients from January 2022 to December 2022. A series of samples and questionnaire information will be collected regularly to establish the dynamic function relationship between time and viral load changes and a Bayesian multilevel model will be constructed to clarify the evolvement rules which reflect the dynamic changes of viral load and the duration of viral shedding in patients with HFMD. DISCUSSION: The results of this study is expected to further clarify the evolvement rules which reflect the dynamic changes of viral load and the duration of viral shedding in HFMD patients under the influence of related factors. It can also provide important evidence for the scientific definition of the infectious period and isolation period of HFMD in China.

Performance of noninvasive tools for identification of minimal liver fibrosis in patients with hepatitis B virus infection.

BACKGROUND: Various noninvasive liver fibrosis assessment tools are available. Here, we evaluated the performance of the asparagine aminotransferase-to-platelet ratio index (APRI), the fibrosis-4 index (FIB-4), transient elastography (TE), and the globulin-platelet (GP) ratio for identifying liver fibrosis in patients with hepatitis B virus (HBV) infection. METHODS: A total of 146 patients were assessed using TE, FIB-4, APRI, the GP ratio, and liver biopsy. Three patient grouping methods were applied: any fibrosis (AF; F0 vs. F1/2/3/4); moderate fibrosis (MF; F0/1 vs. F2/3/4); and severe fibrosis (SF; F0/1/2 vs. F3/4). Receiver operating characteristic (ROC) curve analysis, univariate analyses, and multivariate logistic regression were conducted. RESULTS: Regardless of patient-grouping method, the area under the curve (AUC) of TE and the GP ratio were similar. Using the AF grouping method, the GP ratio showed superior performance compared with APRI and FIB-4: the AUCs for the GP ratio, TE, APRI, and FIB-4 were 0.76, 0.75, 0.70, and 0.66, respectively. Using the MF grouping method, the GP ratio also showed superior performance compared with APRI and FIB-4: the AUCs for the GP ratio, TE, APRI, and FIB-4 were 0.66, 0.68, 0.57, and 0.53, respectively. Using the SF grouping method, the AUCs for the GP ratio, TE, APRI, and FIB-4 were not significantly different. CONCLUSION: Compared with FIB-4 and APRI, the GP ratio had higher accuracy for identifying liver fibrosis, especially early-stage fibrosis, in patients with HBV infection.

Vitamin D signaling maintains intestinal innate immunity and gut microbiota: potential intervention for metabolic syndrome and NAFLD.

A lack of sunlight exposure, residence in the northern latitudes, and dietary vitamin D insufficiency are coprevalent with metabolic syndrome (MetS), Type 2 diabetes (T2D), and nonalcoholic fatty liver diseases (NAFLD), implying a potential causality and underlying mechanism. Whether vitamin D supplementation or treatment can improve these disorders is controversial, in part, because of the absence of large-scale trials. Experimental investigations, on the other hand, have uncovered novel biological functions of vitamin D in development, tumor suppression, and immune regulation, far beyond its original role as a vitamin that maintained calcium homeostasis. While the large intestine harbors massive numbers of microbes, the small intestine has a minimal quantity of bacteria, indicating the existence of a gating system located in the distal region of the small intestine that may restrain bacterial translocation to the small intestine. Vitamin D receptor (VDR) was found to be highly expressed at the distal region of small intestine, where the vitamin D signaling promotes innate immunity, including the expression of α-defensins by Paneth cells, and maintains the intestinal tight junctions. Thus, a new hypothesis is emerging, indicating that vitamin D deficiency may impair the intestinal innate immunity, including downregulation of Paneth cell defensins, leading to bacterial translocation, endotoxemia, systemic inflammation, insulin resistance, and hepatic steatosis. Here, we review the studies for vitamin D for innate immunity and metabolic homeostasis, and we outline the clinical trials of vitamin D for mitigating MetS, T2D, and NAFLD.

Continuous thrombocytopenia after SARS-CoV-2 nucleic acid negative in a non-severe COVID-19 patient for several months.

BACKGROUND: Thrombocytopenia was common in the coronavirus disease (Covid-19) patients during the infection, especially in severe COVID-19 patients, but was less in the non-severe Covid-19 patients. However, the platelet count would be restored after antivirus treatment. In this paper, we report continuous thrombocytopenia in a non-severe Covid-19 case after a negative nucleic acid test for Covid-19. CASE PRESENTATION: A non-severe COVID-19 patient had the platelet continuous decrease for several months after the SARS-CoV-2 nucleic acid turning negative, and without well response to the glucocorticoid. The dynamic change of platelet count followed that of the lymphocyte count. After excluding the medicines possibility, immune system disorders, other specific virus infection and specific antibody of platelet, the thrombocytopenia continuously lasted for several months. The upward trend did not begin until June 2020 and she took the tapering dose of prednisone under the instruction of the hematologist. CONCLUSION: Excluding other potentialities inducing thrombocytopenia, we highly hypothesized the SARS-CoV-2 may cause thrombocytopenia by disturbing the immune system to induce the thrombocytopenia in our report,, which needs longer time to restore the immune system and platelet count via the glucocorticoid. We firstly reported this case in order to contribute the clinician to better deal with the patients like this.

Cathepsin H-Mediated Degradation of HDAC4 for Matrix Metalloproteinase Expression in Hepatic Stellate Cells: Implications of Epigenetic Suppression of Matrix Metalloproteinases in Fibrosis through Stabilization of Class IIa Histone Deacetylases.

In three-dimensional extracellular matrix, mesenchymal cells including hepatic stellate cells (HSCs) gain the ability to express matrix metalloproteinases (MMPs) on injury signals. In contrast, in myofibroblastic HSCs in fibrotic liver, many MMP genes are silenced into an epigenetically nonpermissive state. The mechanism by which the three-dimensional extracellular matrix confers the MMP genes into an epigenetically permissive state has not been well characterized. In continuation of previous work, we show here that the up-regulation of MMP genes is mediated through degradation of class IIa histone deacetylases (HDACs) by certain cysteine cathepsins (Cts). In three-dimensional extracellular matrix culture, CtsH, among other cysteine cathepsins, was up-regulated and localized as puncta in the nuclear and cytoplasmic compartments in a complex with HDAC4 for its degradation. Conversely, along with HSC trans-differentiation, CtsH and CtsL were progressively down-regulated, whereas HDAC4 was concurrently stabilized. The inhibition of cysteine cathepsins by specific proteinase inhibitors or chloroquine, which raises cellular pH, restored HDAC4. Recombinant CtsH could break down HDAC4 in the transfected cells and in vitro at acidic pH. In human cirrhotic liver, activated HSCs express high levels of class IIa HDACs but little CtsH. We propose that cysteine cathepsin-mediated degradation of class IIa HDACs plays a key role in the modulation of MMP expression/suppression and HSC functions in tissue injury and fibrosis.

[Difference of Liver Enzymes in Different Metabolism States of Chronic Hepatitis B].

OBJECTIVE: To analyze the difference of liver enzymes in different metabolism state groups of chronic hepatitis B (CHB). METHODS: We use prospective cross-sectional study to analyze the difference of liver enzymes in different metabolism state groups in 110 cases of CHB, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and glutamyl transferase (GGT). RESULTS: Regardless of the presence or absence of fatty liver, the levels of ALP and GGT were increased along with the deterioration of glucose metabolism (P<0.05).The levels of ALP and GGT in the presence of fatty liver group were higher than those in the absence of fatty liver group (P<0.05). The levels of AST, ALP and GGT showed the trend of increasing along with the increase of HOMA-IR and the decrease of HOMA-ß. There was no difference of liver enzymes among the groups with or without other metabolism disorder (P>0.05). CONCLUSION: In CHB, abnormal glucose metabolism and fatty liver can lead to the increase of ALP and GGT. The increase of HOMA-IR and the decrease of HOMA-ß may lead to the increase of AST, ALP and GGT. Other metabolism disorder did not show any effect on the level of liver enzymes.

Efficacy of L-ornithine L-aspartate for minimal hepatic encephalopathy in patients with cirrhosis: A meta-analysis of randomized controlled trials.

BACKGROUND AND STUDY AIMS: Minimal hepatic encephalopathy (MHE) is an early stage of hepatic encephalopathy (HE) and is highly prevalent. The efficacy of L-ornithine L-aspartate (LOLA) for the treatment of HE is well known but its role in MHE remains uncertain. The objectives of the current study were to evaluate the efficacy of LOLA for the treatment of MHE in patients with cirrhosis. METHODS: The Cochrane Library, PubMed, EMBASE, Web of Science and Ovid databases were searched. Only randomized controlled trials (RCTs) that compared the efficacy of LOLA with placebo or no intervention for the treatment of MHE in patients with cirrhosis were included from inception to January 2023. The primary outcomes were reversal of MHE and development of overt hepatic encephalopathy (OHE). RESULTS: Overall, six RCTs comprising 292 patients were included. Compared with placebo or no intervention, LOLA was more effective in reversing MHE (RR = 2.264, 95 % CI = 1.528, 3.352, P = 0.000, I2 = 0.0 %) and preventing progression of OHE (RR = 0.220, 95 % CI = 0.076, 0.637, P = 0.005, I2 = 0.0 %). Based on subgroup analyses, oral LOLA treatment appeared more likely to reverse MHE (RR = 2.648, 95 % CI = 1.593, 4.402, P = 0.000, I2 = 0.0 %), intravenous LOLA treatment yielded a similar probability of reversing MHE (RR = 1.669, 95 % CI = 0.904, 3.084, P = 0.102, I2 = 0.0 %). LOLA did not show a superior possibility in reducing mortality (RR = 0.422, 95 % CI = 0.064, 2.768, P = 0.368, I2 = 0.0 %) and ammonia levels (SMD = 0.044, 95 % CI = -0.290, 0.379, P = 0.795, I2 = 0.0 %) compared with placebo or no intervention. CONCLUSIONS: LOLA has significant beneficial effects on reversal of MHE and prevention of OHE in patients with cirrhosis compared with placebo or no intervention.

TDF and TAF inhibit liver cancer cell migration, invasion via p7TP3.

Tenofovir disoproxil fumarate (TDF) seems to prevent hepatocellular carcinoma (HCC) in patients with chronic hepatitis B virus (HBV). However, the mechanism is still little known. This study aimed to investigate the the roles and mechanisms of TDF, tenofovir alafenamide fumarate (TAF), and entecavir (ETV) on the malignant characteristics of liver cancer cells. Using the wound-healing assays, transwell assays, matrigel transwell assays, and cell counting kit-8 (CCK-8) assays, it was possible to identify that TDF/TAF, inhibited migration, invasion, and proliferation of HepG2 cells and Huh7 cells. To investigate the mechanisms, we performed TOP/FOP-Flash system, Western blot, and RT-qPCR assays of liver cancer cells cultured with TDF/TAF and found a lower activity of Wnt/ß-catenin signaling pathway compared with control cells. Finally, Hepatitis C virus p7 trans-regulated protein 3 (p7TP3), a tumor suppressor in liver cancers, was significantly increased in HepG2 cells and Huh7 cells that treated with TDF/TAF. However, entecavir (ETV)-treated liver cancer cells showed no significant difference in the malignant characteristics of liver cancer cells, activity of Wnt/ß-catenin signaling pathway, and expression of p7TP3, compared with the control groups. To conclude, TDF/TAF maybe novel promising therapeutic strategy for liver cancers, including HCC and hepatoblastoma, via Wnt/ß-catenin signaling pathway, by up-regulating expression of the tumor suppressor, p7TP3.

Interim analysis of the PARADISE study: Benefits of add-on peginterferon-α in NA-treated patients with CHB.

This study aimed to investigate whether peginterferon-α (IFN) add-on nucleos(t)ide analogs(NAs) can further reduce hepatocellular carcinoma(HCC) risk compared with NAs monotherapy in NA-treated patients with chronic hepatitis B(CHB). In this multi-center randomized controlled trial "PARADISE study" (NCT05671315), CHB patients with intermediate to high risk of HCC after more than 24-week NAs pretreatment were recruited, randomized to two groups at a ratio of 1:2 and followed up for 240 weeks. NAs group maintained NAs monotherapy, while IFN + NAs group received IFN add-on NAs therapy for 48 weeks, then switched to NAs monotherapy. Totally, 196 patients were included in interim analysis (NAs group 68, IFN + NAs group 128). The 96-week cumulative HCC incidence was lower in IFN + NAs group than NAs group (0% vs. 4.5%, p < 0.05). Compared with NAs group, IFN + NAs group had significantly higher rates of HBsAg loss at week 48 and 96 (22.7% vs. 0%; 16.7% vs. 0%, both p < 0.05). A new scoring system was established to predict HBsAg decline >2log10 IU/ml, HBsAg <10 IU/ml or HBsAg loss at the end of 48-week IFN treatment. The area under ROC curve was 0.914, 0.922 or 0.905 in the original cohort (n = 128) and 0.896, 0.896 or 0.864 in the external validation cohort (n = 162) for the aforementioned three outcomes, respectively. IFN add-on NAs therapy may suggest the dual benefits of reducing HCC development and facilitating HBsAg loss among NA-treated CHB patients with intermediate to high risk of HCC. The new scoring system helps to make the most of IFN treatment for a higher cost-effectiveness in healthcare.

2D TiO2 Nanosheets Decorated Via Sphere-Like BiVO4: A Promising Non-Toxic Material for Liquid Phase Photocatalysis and Bacterial Eradication.

An in-depth investigation was conducted on a promising composite material (BiVO4/TiO2), focusing on its potential toxicity, photoinduced catalytic properties, as well as its antibiofilm and antimicrobial functionalities. The preparation process involved the synthesis of 2D TiO2 using the lyophilization method, which was subsequently functionalized with sphere-like BiVO4 through wet impregnation. Finally, we developed BiVO4/TiO2 S-scheme heterojunctions which can greatly promote the separation of electron-hole pairs to achieve high photocatalytic performance. The evaluation of concentration- and time-dependent viability inhibition was performed on human lung carcinoma epithelial A549 cells. This assessment included the estimation of glutathione levels and mitochondrial dehydrogenase activity. Significantly, the BiVO4/TiO2 composite demonstrated minimal toxicity towards A549 cells. Impressively, the BiVO4/TiO2 composite exhibited notable photocatalytic performance in the degradation of rhodamine B (k=0.135 min-1) and phenol (k=0.016 min-1). In terms of photoinduced antimicrobial performance, the composite effectively inactivated both gram-negative E. coli and gram-positive E. faecalis bacteria upon 60 minutes of UV-A light exposure, resulting in a significant log 6 (log 10 CFU/mL) reduction in bacterial count. In addition, a 49 % reduction of E. faecalis biofilm was observed. These promising results can be attributed to the unique 2D morphology of TiO2 modified by sphere-like BiVO4, leading to an increased generation of (intracellular) hydroxyl radicals, which plays a crucial role in the treatments of both organic pollutants and bacteria. This research has significant potential for various applications, particularly in addressing environmental contamination and microbial infections.

Effectiveness of enterovirus A71 vaccine against pediatric HFMD and disease profile of post-vaccination infection.

BACKGROUND: Vaccination has been proven effective against infection with enterovirus A71 (EV-A71) in clinical trials, but vaccine effectiveness in real-world situations remains incompletely understood. Furthermore, it is not clear whether previous vaccination will result in symptom attenuation among post-vaccinated cases. METHODS: Based on long-term data extracted from the only designed referral hospital for infectious diseases, we used a test-negative case-control design and multivariate logistic regression models to analyze the effectiveness of EV-A71 vaccine against hand, foot and mouth disease (HFMD). And then, generalized linear regression models were used to evaluate the associations between prior vaccination and disease profiles. RESULTS: We selected 4883 inpatients for vaccine efficacy estimations and 2188 inpatients for disease profile comparisons. Vaccine effectiveness against EV-A71-induced HFMD for complete vaccination was 63.4 % and 51.7 % for partial vaccination. The vaccine effectiveness was higher among cases received the first dose within 12 months. No protection was observed against coxsackievirus (CV) A6-, CV-A10- or CV-A16-associated HFMD among children regardless of vaccination status. Completely vaccinated cases had shorter hospital stay and disease course compared to unvaccinated cases (P < 0.05). CONCLUSIONS: These findings reiterate the need to continue the development of a multivalent vaccine or combined vaccines, and have implications for introducing optimized vaccination strategies.

Efficacy of pegylated interferon α-2b plus entecavir therapy and predictors of treatment success in children with chronic hepatitis B.

Introduction: Interferon therapy, used in the treatment of chronic hepatitis B (CHB), is one of the means by which patients can achieve a functional cure. Pegylated interferon is currently used in the treatment of CHB. There are two main types of pegylated interferon: α-2b and α-2a. Methods: This study explored the efficacy, safety, and predictors of treatment response for α-2b plus entecavir among children in a real-world setting. Results: The study included 76 patients aged 3-18 years, all of whom were treated with interferon α-2b plus entecavir. The mean duration of treatment was 401.99 days, and 31.6% (24/76) of patients achieved HBsAg clearance. Competing risk model analyses showed that children with baseline HBsAg <1500 IU/mL (subdistribution hazard ratio [sHR]=2.643, P=0.022) and a higher baseline alanine aminotransferase (ALT) level (sHR=1.005, P=0.000) had a higher probability of achieving HBsAg clearance during treatment. Conversely, children with a higher hepatitis B virus loading level (sHR=0.835, P=0.043) and age ≥10 years (sHR=0.243, P=0.002) had a lower probability of achieving HBsAg clearance during treatment. A decrease of >1 log10 in HBsAg level (sHR=3.479, P=0.001) at 12 weeks of treatment was associated with a higher probability of achieving surface antigen clearance. Discussion: These results indicated that interferon plus entecavir therapy is a promising means of achieving HBsAg clearance in children with CHB. Moreover, HBsAg, ALT, virus loading, and age are indicators of treatment success probability.

MALAT1-mediated EZH2 Recruitment to the GFER Promoter Region Curbs Normal Hepatocyte Proliferation in Acute Liver Injury.

Background and Aims: The goal of this study was to investigate the mechanism by which the long noncoding RNA MALAT1 inhibited hepatocyte proliferation in acute liver injury (ALI). Methods: Lipopolysaccharide (LPS) was used to induce an ALI cellular model in HL7702 cells, in which lentivirus vectors containing MALAT1/EZH2/GFER overexpression or knockdown were introduced. A series of experiments were performed to determine their roles in liver injury, oxidative stress injury, and cell biological processes. The interaction of MALAT1 with EZH2 and enrichment of EZH2 and H3K27me3 in the GFER promoter region were identified. Rats were treated with MALAT1 knockdown or GFER overexpression before LPS induction to verify the results derived from the in vitro assay. Results: MALAT1 levels were elevated and GFER levels were reduced in ALI patients and the LPS-induced cell model. MALAT1 knockdown or GFER overexpression suppressed cell apoptosis and oxidative stress injury induced cell proliferation, and reduced ALI. Functionally, MALAT1 interacted directly with EZH2 and increased the enrichment of EZH2 and H3K27me3 in the GFER promoter region to reduce GFER expression. Moreover, MALAT1/EZH2/GFER was activated the AMPK/mTOR signaling pathway. Conclusion: Our study highlighted the inhibitory role of reduced MALAT1 in ALI through the modulation of EZH2-mediated GFER.

The Role of VD/VDR Signaling Pathway in Autoimmune Skin Diseases.

BACKGROUND: Immune-related cutaneous diseases are a series of disorders, such as alopecia areata, psoriasis, atopic dermatitis, systemic lupus erythematosus and autoimmune bullous dermatoses. Vitamin D is a fat-soluble vitamin, which is known for its classical pleiotropic effect. Recent studies have found that vitamin D, after catalyzed into its biologically active form [1,25(OH) 2D], correlated with its receptor, vitamin D receptor, plays a vital role in multiple pathophysiological processes, including immune-related dermatoses. This review mainly summarizes evidence on the role of vitamin D/vitamin D receptor in immune-related cutaneous diseases and the potential therapeutic targets for skin disorders. METHODS: We have carried out a comprehensive literature search in PubMed and Google Scholar databases using keywords like "vitamin D", "vitamin D receptor", "immune", "psoriasis", "atopic dermatitis", "skin", "systemic lupus erythematosus", "alopecia areata" and "autoimmune bullous dermatoses". Only articles related to the topic were included in this review. Conference, patent, graduation thesis and articles without available full text were excluded. RESULTS: Vitamin D/vitamin D receptor is critical for skin in regulating the proliferation and differentiation of keratinocytes, keeping the integrity of the skin barrier as well as maintaining the homeostasis of the "skin's immune system". Vitamin D deficiency/vitamin D receptor mutations are potential risk factors for some immune-related cutaneous diseases. CONCLUSION: Vitamin D is a pleiotropic hormone, which is important in the homeostasis of human body. Many studies have revealed vitamin D deficiency in several skin diseases. Thus, vitamin D supplementation may be a useful therapeutic option for immune-related skin diseases.