Clinical, pathological and genetic characteristics of 17 unrelated children with Alagille Syndrome.

BACKGROUND: Alagille syndrome (ALGS) is a multisystem genetic disorder frequently characterized by hepatic manifestations. This study analyzed the clinical, pathological, and molecular genetic features of ALGS to improve the efficiency of clinical diagnosis. METHODS: We retrospectively analyzed the clinical manifestations, pathological examination findings, and genetic testing results of 17 children diagnosed with ALGS based on the revised criteria and hospitalized at our center from January 2012 to January 2022. RESULTS: The clinical manifestations are as follows: Cholestasis (16/17, 94%), characteristic facies (15/17, 88%), heart disease (12/16, 75%), butterfly vertebrae (12/17, 71%) and posterior embryotoxon (7/12, 58%). Among the 15 patients who underwent liver pathology examination, 13 (87%) were found to have varying degrees of bile duct paucity. Genetic testing was performed on 15 children, and pathogenic variants of the jagged canonical Notch ligand 1 (JAG1) gene were identified in 13 individuals, including 4 novel variants. No pathogenic variant in the notch homolog 2 (NOTCH2) gene were identified, and 2 children exhibited none of the aforementioned gene pathogenic variants. The median follow-up duration was 7 years. Of the remaining 15 patients (excluding 2 lost to follow-up), 11 remained stable, 4 deteriorated, and no patient died during the follow-up period. CONCLUSIONS: Among children diagnosed with ALGS, cholestasis stands as the most common feature. To minimize the risk of misdiagnosis, genetic testing should be performed on children exhibiting cholestasis, followed by the application of the revised diagnostic criteria for ALGS. While pharmacological therapy has shown effectiveness for ALGS patients, liver transplantation may be considered in instances of severe pruritus.

Characteristics analysis of hepatitis B core-related antigen in children with hepatitis B e antigen-positive chronic viral hepatitis B infection.

BACKGROUND: The objective of antiviral therapy for chronic viral hepatitis B infection (CHB) is to achieve a functional cure. An important viral marker in the serum of patients with CHB is the serum hepatitis B core-related antigen (HBcrAg). However, there is limited research on HBcrAg in juvenile patients with CHB. In this study, we aimed to investigate the correlation between serum HBcrAg and other hepatitis B virus (HBV) markers in children with CHB and its predictive significance for prognosis during antiviral therapy. METHODS: A single-center retrospective study was conducted involving 79 children with CHB, aged between 0 and 16 years. All the children were treated with interferon [or combined nucleos(t)ide analogs] for 48 weeks. HBcrAg, hepatitis B surface antigen (HBsAg), and HBV DNA were measured before treatment, and at 12 and 48 weeks after treatment. The enrolled children were classified into the seroclearance group and the nonseroclearance group based on the therapeutic outcome. RESULTS: HBsAg seroclearance was observed in 28 out of 79 patients and hepatitis B e antigen seroconversion without HBsAg seroclearance was observed in 14 out of 79 patients following the conclusion of the treatment, with baseline HBcrAg titer levels showing no statistical significance in both the seroclearance and nonseroclearance groups (P = 0.277). HBsAg and HBV DNA were positively correlated with HBcrAg in children with CHB (R2 = 0.3289, 0.4388). The area under the receiver operating characteristic curve of the decrease in HBcrAg at 12 weeks of treatment as a predictor of seroclearance at 48 weeks of treatment, exhibited a value of 0.77. CONCLUSION: A decrease in serum HBcrAg levels in children with hepatitis B serves as a prognostic indicator.

Clinical and genetic study of ABCB4 gene-related cholestatic liver disease in China: children and adults.

BACKGROUND: ABCB4 gene-related cholestatic liver diseases have a wide spectrum of clinical and genetic variations. The correlation between genotype and clinical phenotype still unclear. This study retrospectively analyzed the clinical and pathological characteristics of 23 patients with ABCB4 gene-related cholestatic liver diseases. Next-generation sequencing was used to identify the genetic causes. RESULTS: The 23 included patients (15 children and 8 adults) were diagnosed as progressive familial intrahepatic cholestasis type 3 (PFIC3), drug-induced liver injury (DILI), cirrhosis cholestasis, cirrhosis, and mild liver fibrosis. Nineteen patients underwent liver pathological examination of the liver, exhibiting fibrosis, small bile duct hyperplasia, CK7(+), Cu(+), bile duct deletion, and cirrhosis. Thirty ABCB4 variants were identified, including 18 novel variants. CONCLUSION: ABCB4 gene-related cholestatic liver diseases have a wide spectrum of clinical and genetic variations. Biallelic ABCB4 mutation carriers tended to severe PFIC3, which mostly occurs in children; while ABCB4 non-biallelic variants can lead to milder ICP, LACP, DILI or overlapping, mostly in adults. Thus, the ABCB4 genotype has a specific correlation with the phenotype, but there are exceptions. Non-biallelic null mutations can cause severe diseases. The mechanisms underlying this genetic phenotype require further investigation.

Functional cure is associated with younger age in children undergoing antiviral treatment for active chronic hepatitis B.

BACKGROUND AND AIMS: Functional cure is difficult to achieve using current antiviral therapies; moreover, limited data are available regarding treatment outcomes in children. This retrospective study aimed to assess the frequency of functional cure among children undergoing antiviral treatment for active chronic hepatitis B (CHB). METHODS: A total of 372 children aged 1-16 years, with active CHB were enrolled and underwent either nucleos(t)ide analog monotherapy or combination therapy with interferon-α (IFN-α) for 24-36 months. All children attended follow-up visits every 3 months. Functional cure was defined as evidence of hepatitis B virus (HBV) DNA loss, circulating hepatitis B e antigen (HBeAg) loss/seroconversion, and hepatitis B surface antigen (HBsAg) loss. RESULTS: After 36 months of antiviral treatment and/or follow-up visits, children with CHB aged 1- < 7 years exhibited higher rates of HBV DNA clearance, HBeAg seroconversion, and HBsAg loss than CHB children ≥ 7-16 years of age (93.75% versus [vs.] 86.21% [p < 0.0001]; 79.30% vs. 51.72% [p < 0.0001]; and 50.78% vs. 12.93% [p < 0.0001], respectively). Longitudinal investigation revealed more rapid dynamic reduction in HBV DNA, HBeAg, and HBsAg levels in children aged 1-7 years than in those aged ≥ 7-16 years with CHB. According to further age-stratified analysis, HBsAg loss rates were successively decreased in children with CHB who were 1- < 3, 3- < 7, 7- < 12, and 12-16 years of age (62.61% vs. 41.13% vs. 25.45% vs. 1.64%, respectively; p < 0.0001) at 36 months. In addition, baseline HBsAg level < 1,500 IU/mL was found to favor disease cure among these pediatric patients. No serious adverse events were observed throughout the study period. CONCLUSION: Results of the present study demonstrated that children aged 1- < 7 years, with active CHB can achieve a high functional cure rate by undergoing antiviral therapy compared to those aged ≥ 7 years, who undergo antiviral therapy. These data support the use of antiviral treatment at an early age in children with CHB. However, future prospectively randomized controlled trials are necessary to validate the findings of this study.

Human apical-out nasal organoids reveal an essential role of matrix metalloproteinases in airway epithelial differentiation.

Extracellular matrix (ECM) assembly/disassembly is a critical regulator for airway epithelial development and remodeling. Airway organoid is widely used in respiratory research, yet there is limited study to indicate the roles and mechanisms of ECM organization in epithelial growth and differentiation by using in vitro organoid system. Moreover, most of current Matrigel-based airway organoids are in basal-out orientation where accessing the apical surface is challenging. We present a human apical-out airway organoid using a biochemically defined hybrid hydrogel system. During human nasal epithelial progenitor cells (hNEPCs) differentiation, the gel gradually degrade, leading to the organoid apical surfaces facing outward. The expression and activity of ECM-degrading enzymes, matrix metalloproteinases (MMP7, MMP9, MMP10 and MMP13) increases during organoid differentiation, where inhibition of MMPs significantly suppresses the normal ciliation, resulting in increased goblet cell proportion. Moreover, a decrease of MMPs is found in goblet cell hyperplastic epithelium in inflammatory mucosa. This system reveals essential roles of epithelial-derived MMPs on epithelial cell fate determination, and provides an applicable platform enabling further study for ECM in regulating airway development in health and diseases.

When and how does the practice environment most benefit the job outcomes of newly graduated nurses?

BACKGROUND: Providing a favourable practice environment has been regarded as an essential to improve the job outcomes of newly graduated nurses (NGNs). However, little is known about how and when NGNs can best utilize their practice environment to produce optimal job outcomes. AIM: The aim of this study, which is based on the Conservation of Resources Theory and the Social Cognitive Model of Career Self-Management, is to investigate whether NGNs who have a higher level of personal growth initiative are more likely to benefit from their practice environment and achieve better job outcomes by increasing their occupational self-efficacy. DESIGN: A cross-sectional study. METHODS: From 1 September 2022, to 30 September 2022, 279 NGNs from five Chinese state-owned hospitals were recruited for this study. The participants completed measures of practice environment, personal growth initiative, occupational self-efficacy, job stress, job satisfaction, turnover intention and quality of care. A descriptive analysis and a moderated mediation model were computed. Reporting adhered to the STROBE statement. RESULTS: The influence of the practice environment on job outcomes was significantly mediated by occupational self-efficacy, with personal growth initiative acting as a moderator of this mediation effect. CONCLUSIONS: NGNs who exhibited a higher degree of personal growth initiative were more likely to derive benefits from their practice environment and attain positive job outcomes by enhancing their occupational self-efficacy. To boost NGNs' occupational self-efficacy and achieve optimal job outcomes, hospital administrators may not only provide a supportive practice environment for them but also conduct interventions that promote their personal growth initiative. NO PATIENT OR PUBLIC CONTRIBUTION: This study was designed to examine the psychosocial factors associated with NGNs' job outcomes. The study was not conducted using suggestions from the patient groups or the public. IMPACTS: Our findings indicate that favourable practise contexts may not always benefit the nursing job outcome if NGNs do not exhibit a high level of personal growth initiative and produce increased occupational self-efficacy. Therefore, hospital administrators should consider implementing an intervention to improve the personal growth initiative of NGNs so that they can take full advantage of the practice environment and gain resources at work to create optimal job outcomes.

HIV chronicity as a predictor of hippocampal memory deficits in daily cannabis users living with HIV.

Background: Antiretroviral medications have increased the lifespan of persons living with HIV (PLWH) thereby unmasking memory decline that may be attributed to chronological age, HIV symptomatology, HIV disease chronicity, and/or substance use (especially cannabis use which is common among PLWH). To date, few studies have attempted to disentangle these effects. In a sample of daily cannabis-using PLWH, we investigated whether hippocampal memory function, assessed via an object-location associative learning task, was associated with age, HIV chronicity and symptom severity, or substance use. Methods: 48 PLWH (12.9 ± 9.6 years since HIV diagnosis), who were 44 years old on average (range: 24-64 years; 58 % male) and reported daily cannabis use (recent use confirmed by urinalysis) completed the study. We assessed each participant's demographics, substance use, medical history, current HIV symptoms, and hippocampal memory function via a well-validated object-location associative learning task. Results: Multiple regression analyses found that living more years since HIV+ diagnosis predicted significantly worse associative learning total score (r=-0.40) and learning rate (r=-0.34) whereas chronological age, cannabis-use characteristics, and recent HIV symptom severity were not significantly related to hippocampal memory function. Conclusions: In daily cannabis-using PLWH, HIV chronicity was related to worse hippocampal memory function independent from cannabis use, age, and HIV symptomatology. Object-location associative learning performance could serve as an 'early-warning' metric of cognitive decline among PLWH. Future research should examine longitudinal changes in associative learning proficiency and evaluate interventions to prevent hippocampal memory decline among PLWH. ClinicalTrials.gov: NCT01536899.

The use of episodic future thinking in people with overweight or obesity: A scoping review.

A growing number of studies have applied Episodic Future Thinking (EFT) to cognitive interventions in specific population. However, The variability in study populations may lead to inconsistent results and present challenges in the optimal intervention approach and scope of adaptation. This scoping review aimed to identify and describe specific methods, considerations, and results collected and reported in randomized controlled trials of EFT applied to diet and weight management in people with overweight or obesity. A systematic scoping review was conducted by published guidelines for this review. We conducted a structured search of English-language articles in Web of Science, PubMed, Embase, CINAHL, ProQuest, and Cochrane, with the literature focusing on studies published up to December 28, 2022. After screening and full-text review, 16 studies were included. The studies included people of all ages with overweight or obesity, including women, children, and home-based EFT interventions. The vast majority of intervention studies screened participants for psychological characteristics, and the effects of EFT applied in people with overweight or obesity were somewhat significant, although there was some variation in the literature. Although the individual heterogeneity of studies makes the synthesis of results somewhat variable, it still demonstrates the breadth and accessibility of EFT interventions in people with overweight or obesity. The application of EFT to individualized interventions in people with overweight or obesity is a further complement and optimization of weight management through behavioral cognitive therapy.

Type 17 mucosal-associated invariant T cells contribute to neutrophilic inflammation in patients with nasal polyps.

BACKGROUND: Immune regulation in chronic rhinosinusitis with nasal polyps (CRSwNP) with a neutrophilic endotype remains unclear. Mucosal-associated invariant T (MAIT) cells are tissue-resident innate T lymphocytes that respond quickly to pathogens and promote chronic mucosal inflammation. OBJECTIVE: We aimed to investigate the roles of MAIT cells in neutrophilic CRSwNP. METHODS: Nasal tissues were obtained from 113 patients with CRSwNP and 29 control subjects. Peripheral and tissue MAIT cells and their subsets were analyzed by flow cytometry. Polyp-derived MAIT cells were analyzed by RNA sequencing to study their effects on neutrophils. RESULTS: Endotypes of CRSwNP were classified as paucigranulocytic (n = 21), eosinophilic (n = 29), neutrophilic (n = 39), and mixed granulocytic (n = 24). Frequencies of MAIT cells were significantly higher in neutrophilic (3.62%) and mixed granulocytic (3.60%) polyps than in control mucosa (1.78%). MAIT cell percentages positively correlated with local neutrophil counts. MAIT cells were more enriched in tissues than in matched PBMCs. The frequencies of MAIT1 subset or IFN-γ+ MAIT cells were comparable among control tissues and CRSwNP subtypes. The proportions of MAIT17 subset or IL-17A+ MAIT cells were significantly increased in neutrophilic or mixed granulocytic polyps compared with controls. RNA sequencing revealed type 17 and pro-neutrophil profiles in neutrophilic polyp-derived MAIT cells. In patients with neutrophilic CRSwNP, the proportions of MAIT and MAIT17 cells were positively correlated with local proinflammatory cytokines and symptom severity. In vitro experiments demonstrated that neutrophilic polyp-derived MAIT cells promoted neutrophil migration, survival, and activation. CONCLUSIONS: MAIT cells from neutrophilic CRSwNP demonstrate type 17 functional properties and promote neutrophil infiltration in nasal mucosa.

Melatonin attenuates lipopolysaccharide-induced immune dysfunction in dendritic cells.

Melatonin, a ubiquitous hormone, is principally secreted from pineal gland in mammals and possesses strong antioxidant and anti-inflammatory properties. However, its specific roles in the immune functions of dendritic cells (DCs) during acute lung injury (ALI) remain unknown. In this study, we found that melatonin restored the body weight, decreased the lung weight/body weight ratio, alleviated the histopathological lung injury, and decreased the levels of cytokines (tumor necrosis factor-α (TNF-α), interleukin (IL)-12p70, IL-17, and IL-10) in bronchoalveolar lavage fluid of the lipopolysaccharide (LPS)-induced ALI murine model. Moreover, melatonin inhibited the major histocompatibility complex II (MHCII) expression of lung CD11b+ DCs after LPS challenge in vivo. In vitro, melatonin reversed the shape index, promoted the endocytosis, and inhibited phenotypic expression of MHCII, CD40, CD80, and CD86 in LPS-activated DCs. Furthermore, melatonin decreased the expression of an activated marker, CD69, and the secretion of pro-inflammatory cytokines (TNF-α, IL-12p70, and IL-17) after LPS challenge. It hampered the LPS-activated DCs migration by downregulating the C-C chemokine receptor 7 (CCR7) expression, and then weakened the ability of LPS-induced DCs to stimulate allogeneic CD4+ T cell proliferation. Melatonin shaped the immune function of DCs in a nuclear factor erythroid-2-related factor 2 (Nrf-2)/heme oxygenase-1 (HO-1) axis-dependent manner. These findings indicate that melatonin protects DCs from ALI-induced immunological stress and may be used to develop novel DC-targeting strategies for ALI therapy.

Hotspots and development frontiers of postoperative complications of AD: Bibliometric analysis - a review.

The research on the postoperative complications of aortic dissection (AD) has received great attention from scholars all over the world, and the number of research articles in this field has consistently increased year after year. However, no bibliometric reports have been published yet to analyze the scientific output and the current situation in this field. The Bibliometrix R-package, VOSviewer, and CiteSpace software were used to conduct a bibliometric analysis of the hotspots and development frontiers of AD. A total of 1242 articles were retrieved. The USA, China, and Japan had the highest number of publications. The five keywords with the highest frequency were "analysis," "incidence," "acute type," "graft," and "risk factor." The results also indicated that the research in related fields had shifted from surgical treatment and utilizing experience to the evidence-based exploration of risk factors and the construction of prediction models to help better manage postoperative complications of AD. This is the first bibliometric analysis of global publications on the postoperative complications of AD. The current research hotspots focus on three areas: common postoperative complications of AD, exploration of the related risk factors, and management of complications. Future research could focus on identifying risk factors through meta-analysis and using a multicenter database for AD as well as building relevant models to predict the development of complications to better facilitate the clinical management of AD patients.

How to help aortic dissection survivors with recovery?: A health promotion program based on the comprehensive theory of health behavior change and literature review.

For aortic dissection survivors, health promotion can help them recover from the disease, which requires systematic program support. The aim of this study was to construct a health promotion program for aortic dissection survivors. Literature search, group discussion, and expert consultation were used. The Integrated Theory of Health Behavior Change was the theoretical basis of the program. Multiple medical-related databases were searched. Based on a literature search and group discussion, 3 primary items, 8 secondary items, and 34 tertiary items were formed. After 2 rounds of expert consultation (number of experts = 25), 3 primary items, 16 secondary items, and 54 tertiary items were retained. The authority coefficients of the 2 rounds of experts were 0.890 and 0.905, respectively. The Kendall W coefficient of the 2 rounds were 0.210 to 0.370 (P < .05) and 0.221 to 0.378 (P < .05), respectively. The mean importance value and coefficient of variation of each item were >3.5 and <0.25, respectively. The health promotion program constructed in this study was reasonable and scientific, which could provide a reference for clinical work.

Sedentary Behavioral Studies of Young and Middle-Aged Adults with Hypertension in the Framework of Behavioral Epidemiology: A Scoping Review.

(1) Background: As times change, the detection rate of hypertension is increasing in the young and middle-aged population due to prevalent sedentary behaviors. The purpose of this study was to conduct a scoping review to identify and summarize the research on sedentary behavior in this population by separating it into five stages: the relationship between sedentary behavior and health; measurement modalities; influencing factors; interventions; and translational research in young and middle-aged adults with hypertension. (2) Methods: Using a scoping review research approach, the PubMed, Web of Science Core Collection, and MEDLINE databases were used to search for the literature on this subject from the date of the database's creation to 14 June 2022, and the behavioral epidemiology framework was used to classify the retrieved articles. (3) Results: A total of eight articles were included. Among them, there were six articles on the relationship between behavior and health, which includes blood pressure, insulin resistance, and the cardiovascular system; one article on the study of measurement methods, which was used for clinical decision making through decision trees; one article on influencing factors, which was divided into intrinsic and extrinsic factors; and no articles on intervention program development or the translation of intervention programs to further practice in this population. (4) Conclusions: Sedentary behavioral studies of young and middle-aged adults with hypertension are scarce and are generally carried out in the early stages of the condition. In the future, in-depth studies can be conducted on the dose-response relationship between sedentary behavior and health in this population; the development of easier and targeted measurement tools; the exploration of more influencing factors; and the effectiveness and translation of intervention programs.

Relations among perceived stress, fatigue, and sleepiness, and their effects on the ambulatory arterial stiffness index in medical staff: A cross-sectional study.

Objective: To explore the relations among perceived stress, fatigue, sleepiness, and the pathway of their effects on the ambulatory arterial stiffness index (AASI) among medical staff. Methods: This cross-sectional study was conducted at a tertiary hospital in Wuhan, China. Perceived stress, fatigue, and sleepiness were measured using the perceived stress scale (PSS), Fatigue assessment scale (FAS), and Epworth Sleepiness Scale (ESS), respectively. AASI was obtained from 24-h ambulatory blood pressure monitoring. Path analysis was used to clarify the relations among the PSS, FAS, and ESS scores, and their relations to AASI values. Results: A total of 153 participants were included herein. The PSS and FAS correlated with the ESS (r = 0.424, p < 0.001), and the PSS correlated with the FAS (r = 0.614, p < 0.001). In addition, the ESS correlated with the AASI (r = 0.225, p = 0.005). According to the path analysis results, the PSS and FAS had no direct effect on the AASI, but did have an indirect effect on this index (ß = 0.059, 95% confidence interval [CI] = 0.017-0.128, p = 0.005; ß = 0.059, 95%CI = 0.016-0.135, p = 0.006, respectively) by influencing the ESS (ß = 0.263, ß = 0.262, p = 0.004). Conclusion: Sleepiness was a mediator of the effects of perceived stress and fatigue on AASI.

Melatonin Suppresses LPS-Induced Oxidative Stress in Dendritic Cells for Inflammatory Regulation via the Nrf2/HO-1 Axis.

Melatonin, an indoleamine synthesized in the pineal gland of mammals, is a natural bioactive compound with powerful antioxidant and anti-inflammatory properties. Here, we evaluated whether melatonin has the capacity to moderate the oxidative stress of dendritic cells (DCs) for inflammatory control in an acute lung injury (ALI) model. Our findings showed that melatonin remarkably inhibited total nitric oxide synthase (T-NOS) activity, nitric oxide (NO) production, intracellular reactive oxygen species (ROS) levels, and lipid peroxidation (MDA detection) levels in both an LPS-induced murine ALI model and LPS-induced DCs. Meanwhile, the reduced glutathione (GSH) level and the GSH/GSSG ratio were recovered. In addition, antioxidant enzymes, such as glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD), were increased in these processes. Moreover, melatonin also inhibited the LPS-induced secretions of IL-1ß, IL-6, and TGF-ß in vivo and in vitro. Finally, we found that the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) axis was required in the inhibition of LPS-induced oxidative stress in DCs by melatonin. Altogether, these data indicate that melatonin strongly suppresses the LPS-induced oxidative stress in DCs, which is a promising DC-targeted strategy via inflammatory control for ALI treatment.

The Effect of Perceived Stress, Family Companionship, and Mental Health on the Subjective Happiness of Chinese Healthcare Workers: A Mixed Research Method.

Aim: This study aimed to understand the impact of perceived stress on the subjective happiness of Chinese healthcare workers (HCWs) and to further explore the chain-mediating role of family companionship and mental health. Background: In the face of tense doctor-patient relationships; a heavy workload; long working hours; seemingly endless shifts; potential professional title promotions; work performance assessments; and the difficult balance between family, work, and other aspects of life, HCWs are often under great pressure, which can endanger mental health and reduce subjective happiness. However, the role of healthcare workers' active participation in family companionship in mental health and subjective happiness is not clear. Method: We used a mixed research design to collect data in two locations (Hospital A and Hospital B) in Wuhan, China. A self-distributed questionnaire was assigned to HCWs through the Research Electronic Data Capture survey. A total of 368 valid surveys were obtained. Results: Hospital A's perceived stress level and mental health problems were more severe, while Hospital B had a higher subjective happiness score and more time to spend with their families. Subjective happiness was affected by children, education, occupation, health status, commuting time, and the scores of perceived stress and depression. The scores of perceived stress and mental health were significantly negatively associated with subjective happiness and family companionship, and there was a significant positive correlation between subjective happiness and family companionship. The results also showed that family companionship and mental health acted as serial mediators between perceived stress and subjective happiness. However, family companionship did not play a mediating role between perceived stress and subjective happiness. Most HCWs had work-family conflicts, and a high amount of work pressure and feelings of powerlessness and not having sufficient time were common when they accompanied their families. Conclusions: HCWs had a high level of perceived stress and psychological distress, and their subjective happiness score was lower than that of the general population. Many HCWs experienced negative emotions when taking care of their families. Only a small number of people had enough time to spend time with their families and perform more prominently in busier hospitals. More importantly, perceived stress can indirectly have an impact on subjective happiness through a chain-mediating effect of family companionship and mental health, and family companionship may not always promote subjective happiness unless mental health is maintained. Therefore, in the future, we can consider carrying out interventions based on family companionship and mental health among HCWs to promote the healthy and harmonious development of individuals, families, and hospitals.

The melanin inhibitory effect of plants and phytochemicals: A systematic review.

BACKGROUND: Melanin plays an important role in protecting human skin, while excessive synthesis of melanin can cause abnormal pigmentation and induce skin diseases. Long-term use of commercial whitening agents in managing skin melanin such as kojic acid and arbutin can lead to some negative effects such as dermatitis and liver cancer. Although past studies have researched the melanin inhibitory effect of plant extracts, the effective dose and mechanisms are not well summarized and discussed. This study aims to explore the melanin inhibitory property of phytochemicals and tries to answer the following research questions: (1) Which plant extracts and phytochemicals could inhibit melanin biosynthesis in the skin? what is the mechanism of action? (2) Have human trials been conducted to confirm their melanin inhibitory effect? (3) If not, which phytochemicals are recommended for further human trials? This article would provide information for future research to develop natural and safe skin whitening products. METHODS: A preferred reporting items for systematic reviews and meta-analyses (PRISMA) systematic review method and OHAT risk-of-bias tool were applied to screen literature from 2000 to 2021 and 50 research articles met the selection criteria. RESULTS: Flavonoids, phenolic acids, stilbenes and terpenes are main classes of phytochemicals responsible for the melanin inhibitory effects. The in vitro/in vivo melanin inhibitory effects of these plant extracts/phytochemicals are achieved via three main mechanisms: (1) the ethyl acetate extract of Oryza sativa Indica cv., and phytochemicals such as galangin and origanoside could manage melanin biosynthesis through competitive inhibition, non-competitive inhibition or mixed-type inhibition of tyrosinase; (2) phytochemicals such as ginsenoside F1, ginsenoside Rb1 and 4­hydroxy-3-methoxycinnamaldehyde could inhibit melanogenesis through down-regulating microphthalmia-related transcription factor (MITF) gene expression via different signalling pathways; (3) the ethanolic extracts of Dimorphandra gardneriana, Dimorphandra gardneriana, Lippia microphylla and Schinus terebinthifolius have a good ultraviolet absorption ability and high sun protective factor (SPF) values, thereby inhibiting UV induced melanogenesis in the skin. CONCLUSION: Although many plant extracts and phytochemicals have been found to inhibit melanin production, most of the results were only proved in cellular and/or animal models. Only the ethyl acetate extract of Oryza sativa Indica cv. panicle, and ginsenoside F1 were proved effective in human trials. Animal studies proved the effectiveness of galangin, origanoside, ginsenoside Rb1 and 4­hydroxy-3-methoxycinnamaldehyde with effective dose below 3 mM, and therefore recommended for future human trial. In addition, cellular studies have demonstrated the effectiveness of oxyresveratrol, mulberroside A, kurarinol, kuraridinol, plumbagin, (6aR,11aR)-3,8-dihydroxy-9­methoxy pterocarpan, ginsenoside Rh4, cardamonin, nobiletin, curcumin, ß-mangostin and emodin in inhibiting melanin synthesis at low concentrations of 20 µM and proved the low SPF values of Dimorphandra gardneriana, Dimorphandra gardneriana, Lippia microphylla and Schinus terebinthifolius extracts, and therefore recommended for further animal and human trials.

Preoperative serum hepatitis B virus DNA was a risk factor for hepatocellular carcinoma recurrence after liver transplantation.

BACKGROUND: Tumour characteristics and orthotopic liver transplantation (OLT) criteria are risks for recurrence of hepatocellular carcinoma (HCC). In Asia, most HCC is caused by chronic hepatitis B infection. Whether hepatitis B virus DNA (HBV DNA) is a risk factor for HCC recurrence after OLT is not clear. PATIENTS AND METHODS: In this retrospective study, we classified patients into groups of detectable and undetectable HBV DNA, non-HCC recurrence, and recurrence and performed analyses on differed characteristics between groups and risk factors for HCC recurrence after OLT. RESULTS: Among patients who underwent OLT for HCC, 117 were secondary to CHB infection. CHB was not a risk, but advanced tumour characteristics were risk factor for HCC recurrence. In patients with CHB-HCC, 24 (20.5%) of 117 patients had HCC recurrence. Compared to patients with HBV DNA undetectable (n = 75), patients with detectable HBV DNA (n = 42) had higher AFP concentration (p < .001), higher proportion of macrovascular invasion (p = .014), greater tumour diameter (p < .001), poorer TNM stage (p = .017), and higher proportion of extended OLT criteria (p = .011) and HCC recurrence (p = .036). Preoperative HBV DNA >2000 IU/mL was an independent risk factor for HCC recurrence (OR = 8.35, 95% CI 1.40, 50.00, p = .020). HBV DNA detectable was not a risk for HCC-related death. CONCLUSION: Individuals with preoperative undetectable HBV DNA had advanced tumour characteristics and a higher proportion of HCC recurrence. Antiviral treatment for HCC should be performed, and HBV DNA undetectable should be obtained before OLT. But for an urgent OLT, preoperative detectable HBV DNA may not affect long-term survival.KEY MESSAGESPatients with HBV DNA detectable had advanced tumour characteristics, a higher proportion of extended OLT criteria, and HCC-recurrence.HBV DNA >2000 IU/mL was a risk factor for HCC recurrence.HBV DNA detectable was not a risk for HCC related death; extended OLT criteria affected long-term survival.

The Combination of AFP and "Up-To-Seven" Criteria May Be a Better Strategy for Liver Transplantation in Chinese Cirrhotic HCC Patients.

Background: Orthotopic liver transplantation (OLT) is a life-saving option for patients with hepatocellular carcinoma (HCC), but the expanded OLT criteria remain controversial. Objective: The study aimed to explore whether expanded OLT criteria can be applied to Chinese cirrhotic patients with HCC. Methods: This retrospective study analyzed risk factors for HCC recurrence and death and compared patients' tumor characteristics and outcomes in groups of Milan, "Up-to-seven," and Hangzhou criteria, and groups between met and unmet the combinative criteria of "Up-to-seven" and AFP of < 1000 ng/mL. Results: Among 153 patients who underwent OLT for HCC from January 2015 to February 2019 in 4 years of follow-up, 20 (13.1%) patients had HCC recurrence, and 11 (7.2%) had HCC-related death. Multivariate Cox regression analysis showed that preoperative alpha-fetoprotein (AFP) of > 1000 ng/mL (hazard ratio [HR]: 10.05, 95% confidence interval [CI]: 2.45-41.13, P = 0.001) was an independent risk factor for HCC recurrence and HCC-related death (HR: 6.63, 95%CI: 1.31-33.52, P = 0.022). Patients who did not meet Milan criteria but satisfied the "Up-to-seven" criteria had no differences in overall survival (OS) (P = 0.69) and disease-free survival (DFS) (P = 0.35) than patients who met the Milan criteria. The combination of "Up-to-seven" criteria and AFP of < 1000 ng/mL differed significantly (HR: 18.9; 95% CI: 4.0-89.2; P < 0.001). Patients with HCC who met the "Up-to-seven" criteria and AFP of < 1000 ng/mL (n = 121) had excellent survival with 4-year OS of 91.6% (P < 0.001) and DFS of 90.8% (P < 0.001), which is significantly better compared to the other group (n = 32) (OS of 67.5% and DFS of 46.5%) and patients who met the Milan criteria (n = 108, OS of 89.8%, DFS of 89.6%), allowing 28.9% (13/45) of patients who did not meet the Milan criteria to benefit from OLT. Conclusion: Chinese cirrhotic patients with HCC who met the combinative criteria of "Up-to-seven" and AFP of < 1000 ng/mL had better survival than those who met the Milan criteria, and these combinative criteria benefited more patients and may become a better option for OLT.

Synthesis of Eco-Friendly Silver Nanoparticles Using Glycyrrhizin and Evaluation of Their Antibacterial Ability.

In the present study, the biosynthesis of silver nanoparticles (AgNPs) and their antibacterial activity against gram-positive and gram-negative bacteria were investigated. Glycyrrhizin (GL) was used as a reducing agent and stabilizer to rapidly prepare the AgNPs. The distinctive absorption peak at 419 nm confirmed the formation of GL-reduced AgNPs. The TEM and particle size analysis shows that the prepared GL-reduced AgNPs were mostly circular with good dispersion and a relatively uniform particle size of 35 nm on average. Fourier transform infrared spectroscopy analysis was performed to identify the possible biomolecules in the capping and active stabilization of the GL-reduced AgNPs. The antibacterial activity of the GL-reduced AgNPs was analyzed with the Oxford cup diffusion method and filter paper diffusion method. The experimental results show that these properties endowed the GL-reduced AgNPs with high antibacterial activity against Escherichia coli and Staphylococcus aureus and lay a foundation for the use of colloidal silver in antibacterial applications. The GL-reduced AgNPs also had stronger antibacterial activity than sodium citrate-reduced AgNPs, which indicates the advantages of GL-reduced AgNPs compared with sodium citrate-reduced AgNPs in inducing bacteriostasis. The cytotoxicity of GL-reduced AgNPs on human kidney epithelial 293A (HEK293) cells was evaluated via the MTT assay. The results show that GL-reduced AgNPs had lower toxicity to HEK293 cells than sodium citrate-AgNPs, which indicates that the as-prepared GL-reduced AgNPs are environmentally friendly.