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ObjectiveExperimental animal models have been used for decades to study the development and progression of chronic obstructive pulmonary disease (COPD). However, there is a lack of methods for constructing animal models of COPD for optimal modelling. This systematic literature review (SLR) aimed to assess the various methods used to establish COPD animal models, highlight their advantages and limitations, and explore more optimized approaches for establishing such models.MethodsA systematic search was performed in four English databases (PubMed, Embase, Web of Science, and the Cochrane Library) and four Chinese databases (Chinese Biomedical Literature Database, China National Knowledge Infrastructure, China Science and Technology Journal Database, and Wanfang Database). Of the 8,015 retrieved full-text manuscripts, 453 were selected.ResultsSmoking (n = 140), smoking combined with lipopolysaccharide (LPS) (n = 275), smoking combined with protease drip (PPE) (n = 10), smoking combined with bacteria (n = 23), and smoking combined with particulate matter (PM2.5) (n = 5) were the most used methods for establishing animal models of COPD. Rats and mice were the most frequently selected experimental animals, with male animals accounting for 79.47% of the total. A total of 92.49 and 29.14% of the articles reviewed considered lung pathology of experimental animals only and lung pathology and lung function tests, respectively.ConclusionOur review suggests that the best way to establish an animal model of COPD is to combine smoking with LPS. Although findings from animal models of COPD cannot be directly extrapolated to human COPD, they could provide useful tools for further investigation into human COPD disease.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023407555, Identifier PROSPERO CRD42023407555.

Abstract Objective To evaluate mindfulness-based intervention for hypertension with depression and/or anxiety. Methods 10-week mindfulness-based intervention, including health education for hypertension, exclusively for the control group, was administered to the intervention group to assist sixty hypertension patients with depression/anxiety. Among them, the intervention group comprised 8 men and 22 women, with a mean age of 60.02 years and a mean duration of hypertension of 6.29 years. The control group consisted of 14 men and 16 women with a mean age of 57.68 years and a mean duration of hypertension of 6.32 years. The severity of depressive and/or anxiety symptoms was assessed using the 9-item Patient Health Questionnaire (PHQ-9) and the 7-item Generalized Anxiety Disorder scale (GAD-7), along with blood pressure (BP) measurements taken twice daily. The study utilized a self-made self-efficacy scale and awareness of physical and mental health to evaluate mental health and state. Results The depression PHQ-9 or GAD-7 scores reduced by 21.1% or 17.8% in the mindfulness-based intervention group, compared to the control (Z = -2.040, P = 0.041) post 10-week period, suggesting significant reduction in anxiety/stress. These results were consistent with a reduction in systolic BP of 12.24 mm Hg (t = 6.041, P = 0.000). The self-efficacy score of the mindfulness intervention group significantly improved compared to the control (t = 7.818, P

Gastrointestinal mucosal surface is frequently under challenge due to it’s the large surface area and most common entry of microbes. IL-37, an anti-inflammatory cytokine, regulates local and systemic host immunity. H. pylori infection leads to the inhibition of IL-37 in the gastric mucosa, contributing to heightened mucosal inflammation and destruction, thereby facilitating increased proliferation of H. pylori. Food allergy, due to immune dysregulation, also contribute to GI injury. On the other hand, elevated levels of IL-37 observed in gastric cancer patients align with reduced host immunity at the cellular and humoral levels, indicating that IL-37 may contribute to the development of gastric cancer via suppressing pro-inflammatory responses. While IL-37 provides protection in an IBD animal model, the detection of highly produced IL-37 in IBD patients suggests a stage-dependent role, being protective in acute inflammation but potentially exacerbates the development of IBD in chronic conditions. Moreover, elevated colonic IL-37 in CRC correlates with overall survival time and disease time, indicating a protective role for IL-37 in CRC. The differential regulation and expression of IL-37 between upper- and lower-GI organs may be attributed to variations in the microbial flora. This information suggests that IL-37 could be a potential therapeutic agent, depending on the stage and location.

AimsTo evaluate the effects of acupuncture and/or nicotine patches on smoking cessation.MethodsEighty-eight participants were randomly allocated into four groups: acupuncture combined with nicotine patch (ACNP), acupuncture combined with sham nicotine patch (ACSNP), sham acupuncture combined with nicotine patch (SACNP), and sham acupuncture combined with sham nicotine patch (SACSNP). The primary outcome was self-reported smoking abstinence verified with expiratory Carbon Monoxide (CO) after 8 weeks of treatment. The modified Fagerstrom Test for Nicotine Dependence (FTND) score, Minnesota Nicotine Withdrawal Scale (MNWS), and the Brief Questionnaire of Smoking Urge (QSU-Brief) score were used as secondary indicators. SPSS 26.0 and Prism 9 software were used for statistical analyses.ResultsSeventy-eight participants completed the study. There were no significant differences in patient characteristics at baseline across the four groups. At the end of treatment, there was a statistically significant difference (χ2 = 8.492, p = 0.037) in abstaining rates among the four groups. However, there were no significant differences in the reduction in the number of cigarettes smoked daily (p = 0.111), expiratory CO (p = 0.071), FTND score (p = 0.313), and MNWS score (p = 0.088) among the four groups. There was a statistically significant difference in QUS-Brief score changes among the four groups (p = 0.005). There was no statistically significant interaction between acupuncture and nicotine patch.ConclusionAcupuncture combined with nicotine replacement patch therapy was more effective for smoking cessation than acupuncture alone or nicotine replacement patch alone. No adverse reactions were found in the acupuncture treatment process.Clinical trial registrationhttp://www.chictr.org.cn/showproj.aspx?proj=61969, identifier ChiCTR2100042912.

IntroductionProstate Cancer (PCa) remains a significant concern in male cancer-related mortality. Tumour development is intricately regulated by the complex interactions between tumour cells and their microenvironment, making it essential to determine which is/are key factor(s) that influence the progression of PCa within the tumour microenvironment.Materials and methodsThe current study utilised histopathology and immunohistochemistry to determine the expression of IL-38 in PCa and analysed the correlation between the expression level of IL-38 within PCa and clinical pathological characteristics.ResultsThere was a significant increase in IL-38 expression in PCa tissues compared to adjacent non-PCa tissues (P < 0.0001). In addition, IL-38 expression was significantly higher in tumour cells with a high proliferation index compared to those with a low value-added index. ROC curve analysis demonstrated that IL-38 has high specificity and sensitivity for the diagnosis of PCa (AUC=0.76). Moreover, we Probed the cellular source of IL-38 in prostate cancer tissue by immunofluorescence double staining. Additionally, within PCa, the expression of IL-38 was inversely correlated with the expression levels of CD8 and PD-1. Survival analysis revealed a significantly lower overall survival rate for PCa patients with high IL-38 expression (P=0.0069), and when IL-38 was co-expressed with CD8, the survival rate of the IL-38high/CD8low group was decreased significantly. Multivariate analysis indicated that the expression level of IL-38 and TNM staging were independent predictors of survival in PCa patients.ConclusionThese findings suggest that IL-38 plays a crucial role in the development of PCa, and the exploration of the correlation between IL-38 and various immune factors in the tumour microenvironment further reveals its mechanism of action, making it a potential target for immunotherapy in PCa.

BackgroundThe progress in Colorectal cancer (CRC) screening and management has resulted in an unprecedented caseload for histopathological diagnosis. While artificial intelligence (AI) presents a potential solution, the predominant emphasis on slide-level aggregation performance without thorough verification of cancer in each location, impedes both explainability and transparency. Effectively addressing these challenges is crucial to ensuring the reliability and efficacy of AI in histology applications.MethodIn this study, we created an innovative AI algorithm using transfer learning from a polyp segmentation model in endoscopy. The algorithm precisely localized CRC targets within 0.25 mm² grids from whole slide imaging (WSI). We assessed the CRC detection capabilities at this fine granularity and examined the influence of AI on the diagnostic behavior of pathologists. The evaluation utilized an extensive dataset comprising 858 consecutive patient cases with 1418 WSIs obtained from an external center.ResultsOur results underscore a notable sensitivity of 90.25% and specificity of 96.60% at the grid level, accompanied by a commendable area under the curve (AUC) of 0.962. This translates to an impressive 99.39% sensitivity at the slide level, coupled with a negative likelihood ratio of

IntroductionColorectal cancer (CRC) presents a substantial challenge characterized by unacceptably high mortality and morbidity, primarily attributed to delayed diagnosis and reliance on palliative care. The immune response of the host plays a pivotal role in carcinogenesis, with IL-38 emerging as a potential protective factor in CRC. However, the precise involvement of IL-38 among various leucocytes, its interactions with PD-1/PD-L1, and its impact on metastasis require further elucidation.ResultsOur investigation revealed a significant correlation between IL-38 expression and metastasis, particularly concerning survival and interactions among diverse leucocytes within draining lymph nodes. In the mesentery lymph nodes, we observed an inverse correlation between IL-38 expression and stages of lymph node invasions (TNM), invasion depth, distance, and differentiation. This aligns with an overall survival advantage associated with higher IL-38 expression in CRC patients’ nodes compared to lower levels, as well as elevated IL-38 expression on CD4+ or CD8+ cells. Notably, a distinct subset of patients characterized by IL-38high/PD-1low expression exhibited superior survival outcomes compared to other combinations.DiscussionOur findings demonstrate that IL-38 expression in colorectal regional nodes from CRC patients is inversely correlated with PD-1/PD-L1 but positively correlated with infiltrating CD4+ or CD8+ lymphocytes. The combined assessment of IL-38 and PD-1 expression in colorectal regional nodes emerges as a promising biomarker for predicting the prognosis of CRC.

IntroductionWound healing poses a clinical challenge in diabetes mellitus (DM) due to compromised host immunity. CD64, an IgG-binding Fcgr1 receptor, acts as a pro-inflammatory mediator. While its presence has been identified in various inflammatory diseases, its specific role in wound healing, especially in DM, remains unclear.ObjectivesWe aimed to investigate the involvement of CD64 in diabetic wound healing using a DM animal model with CD64 KO mice.MethodsFirst, we compared CD64 expression in chronic skin ulcers from human DM and non-DM skin. Then, we monitored wound healing in a DM mouse model over 10 days, with or without CD64 KO, using macroscopic and microscopic observations, as well as immunohistochemistry.ResultsCD64 expression was significantly upregulated (1.25-fold) in chronic ulcerative skin from DM patients compared to non-DM individuals. Clinical observations were consistent with animal model findings, showing a significant delay in wound healing, particularly by day 7, in CD64 KO mice compared to WT mice. Additionally, infiltrating CD163+ M2 macrophages in the wounds of DM mice decreased significantly compared to non-DM mice over time. Delayed wound healing in DM CD64 KO mice correlated with the presence of inflammatory mediators.ConclusionCD64 seems to play a crucial role in wound healing, especially in DM conditions, where it is associated with CD163+ M2 macrophage infiltration. These data suggest that CD64 relies on host immunity during the wound healing process. Such data may provide useful information for both basic scientists and clinicians to deal with diabetic chronic wound healing.

Introduction Wearing masks has proven beneficial in preventing respiratory pathogen infections in individuals with chronic obstructive pulmonary disease (COPD). However, the impact of different mask types on physiological indicators and daily physical activity in COPD patients remains uncertain. This study aims to assess the immediate effects of various mask types on cardiopulmonary function indicators, subjective perceptions and the 6-minute walking distance (6MWD) in individuals with COPD.Methods and analysis This randomised controlled trial will enrol 129 stable COPD patients. Participants will be randomly divided into three groups: control, N95 mask and surgical mask groups. Each group will undergo both a 6-minute seated test and a 6-minute walk test (6MWT), without or with their respective masks. A 10-minute interval will be provided between the two phases. The primary indicators of the study include the 6MWD and blood oxygen saturation. Secondary outcomes encompass blood pressure, pulse rate, Borg score, Rate of Perceived Exertion (RPE) score and subjective perception score. Oxygen saturation, pulse rate and blood pressure will be recorded four times during the trial, while Borg and RPE scores will be compared before and after the 6MWT. Additionally, subjective perception scores will be collected after each mask-wearing stage.Ethics and dissemination This study has received approval from the Ethics Committee of the Affiliated Hospital of Gansu University of Chinese Medicine (approval number: 202335). We plan to disseminate research results through publication in a peer-reviewed journal or presentation at a conference.Trial registration number ChiCTR2300074554.

Hepatocellular carcinoma (HCC) has garnered considerable attention due to its morbidity and mortality. Although the precise mechanisms underlying HCC tumorigenesis remain to be elucidated, evidence suggests that host immunity plays a pivotal role in its development. IL-36 and IL-37 are important immunoregulatory cytokines classified as pro-inflammatory and anti-inflammatory respectively. In the context of HCC, the downregulation of intrahepatic IL-36 is inversely correlated with cirrhosis, but positively correlated with 5-year survival rates, suggesting that IL-36 offers protection during HCC development. However, IL-36 may lose its hepatoprotective effects as the disease progresses to HCC in the context of dysregulated immunity in cirrhotic patients. Substantially increased circulating IL-36 in HCC patients is likely a systemic response to HCC stimulation, but is insufficient to suppress progression towards HCC. Intrahepatic IL-37 is suppressed in HCC patients, consistent with the inverse correlation between intrahepatic IL-37 and the level of AFP in HCC patients, suggesting IL-37 exerts hepatoprotection. There is no significant difference in IL-37 among differentiations of HCC or with respect to clinical BCLC stages or cirrhosis status in HCC patients. However, IL-37 protection is demonstrated in an IL-37 transfected HCC animal model, showing significantly reduced tumour size. IL-36/37 may inhibit HCC by enhancing M1 tumour-associated macrophages while not affecting M2 macrophages. The interplay between IL-36 (pro-inflammatory) and IL-37 (anti-inflammatory) is emerging as a crucial factor in host protection against the development of HCC. Further research is needed to investigate the complex mechanisms involved and the therapeutic potential of targeting these cytokines in HCC management.

The rapid advancement of modern technology has significantly driven progress in various IT-related activities, resulting in a substantial increase in internet penetration rates, particularly among college students. The utilization of the internet has become one of the most essential tools in our modern society. However, internet addiction (IA) has emerged as a serious concern, particularly among college students, adversely affecting academic performance and having significant psychological and psychiatric implications. The aim of the current study was to determine the impact of physical exercise, gender and academic year on IA among college students. In the present study, we investigated internet usage, engagement in sports activities, and academic performance among college students from Western, Middle, and Eastern regions of Chinese universities. It’s noteworthy that most of the respondents were freshmen. Our findings indicate that freshmen students were more susceptible to experiencing IA. Approximately 75% of students engaged in leisure sports activities, revealing an inverse correlation between sports activity and IA. This correlation aligns with the level of sports involvement, emphasizing the potential benefits of physical activity in mitigating IA. However, our study did not uncover any correlation between geographic location and the occurrence of IA, nor did it find differences between medical and non-medical students. Furthermore, our study revealed no significant variations in IA among students from different ethnic backgrounds. The underlying mechanism of IA is being currently determined. Our data suggest that physical exercise, gender, and academic year have a significant impact on IA among college students.

Abstract Introduction This study aims to explore the predictive value of CT radiomics and clinical characteristics for treatment response in COVID‐19 patients. Methods Data were collected from clinical/auxiliary examinations and follow‐ups of COVID‐19 patients. Whole lung radiomics feature extraction was performed at baseline chest CT. Radiomics, clinical, and combined features (nomogram) were evaluated for predicting treatment response. Results Among 36 COVID‐19 patients, mild, common, severe, and critical disease symptoms were found in 1, 21, 13, and 1 of them, respectively. Twenty‐five (1 mild, 18 common, and 6 severe) patients showed a good response to treatment and 11 poor/fair responses. The clinical classification (p = 0.025) and serum creatinine (p = 0.010) on admission and small area emphasis (p = 0.036) from radiomics analysis significantly differed between the two groups. Predictive models were constructed based on the radiomics, clinical features, and nomogram showing an area under the curve of 0.651, 0.836, and 0.869, respectively. The nomogram achieved good calibration. Conclusion This new, non‐invasive, and low‐cost prediction model that combines the radiomics and clinical features is useful for identifying COVID‐19 patients who may not respond well to treatment.

IntroductionHealthcare workers risk of exposure to the influenza virus in their work, is a high-risk group for flu infections. Thus WHO recommends prioritizing flu vaccination for them–an approach adopted by >40 countries and/or regions worldwide.MethodsCross-sectional studies on influenza vaccination rates among healthcare workers were collected from PubMed, EMBASE, CNKI, and CBM databases from inception to February 26, 2023. Influenza vaccination rates and relevant data for multiple logistic regression analysis, such as odds ratios (OR) and 95% confidence intervals (CI), were extracted.ResultsA total of 92 studies comprising 125 vaccination data points from 26 countries were included in the analysis. The meta-analysis revealed that the overall vaccination rate among healthcare workers was 41.7%. Further analysis indicated that the vaccination rate was 46.9% or 35.6% in low income or high income countries. Vaccination rates in the Americas, the Middle East, Oceania, Europe, Asia, and Africa were 67.1, 51.3, 48.7, 42.5, 28.5, and 6.5%, respectively. Influencing factors were age, length of service, education, department, occupation, awareness of the risk of influenza, and/or vaccines.ConclusionThe global influenza vaccination rate among healthcare workers is low, and comprehensive measures are needed to promote influenza vaccination among this population.Systematic review registrationwww.inplysy.com, identifier: 202350051.

Abstract Introduction Tobacco hazard is one of the most serious public health problems, accounting for up to 6 million deaths worldwide p.a. We aim to determine the efficacy and safety of acupuncture and/or nicotine replacement therapy on smoking cessation. Methods We will recruit 96 participants who are willing to quit smoking by acupuncture and/or nicotine replacement therapy in Chengguan, Xigu and Heping Districts, Lanzhou city, for multicenter randomized, double-blind, double-dummy controlled clinical trial. Following obtained the informed consent forms, all eligible participants will be randomly divided into 4 groups: (1) acupuncture combined with nicotine patch, (2) acupuncture combined with sham nicotine patch, (3) sham acupuncture combined with nicotine patch, and (4) sham acupuncture combined with sham nicotine patch. These participants will be treated with different intervention modalities for 8 weeks and then will be followed-up for 8 weeks. The SPSS 26.0 software will be applied to analyze the clinical effects and adverse reactions of different intervention measures for smoking cessation. Discussion This trial is a prospective, pragmatic, randomized, multicenter trial study protocol. The outcomes will illustrate the efficacy and safety of acupuncture and/or nicotine patches for smoking cessation. Provide smokers with a superior smoking cessation program. Trial registration Chinese Clinical Trial Registry ChiCTR2100042912 . Registered on January 31, 2021.

Aim: To analyze the safety of immune checkpoint inhibitors in primary liver cancer patients and to identify the risk factors for immune-related adverse events (irAEs).Methods: The study enrolled 106 patients with primary liver cancer, including 81 with hepatocellular carcinoma and 25 with intrahepatic cholangiocarcinoma. We analyzed the differences between groups in irAE occurrence, including those with and without targeted drugs and those who received interventional therapy.Results: The incidence of irAEs was 39%, with thyroid function, liver function, and skin events being the most common. There was no correlation among irAE incidence and the liver cancer type, stage, or severity; grade of Child–Pugh score; and Barcelona Clinical Liver Cancer classification. However, being overweight was a significant risk factor for irAEs, correlating with high body mass index. The combination of targeted drugs and/or transcatheter arterial chemoembolization therapy did not increase the incidence of irAEs.Conclusion: Being overweight is a potential risk factor for irAEs in primary liver cancer patients. However, there is no correlation between irAE incidence and the liver cancer type, stage, or severity or a combination of targeted drugs or transarterial chemoembolization therapy.

BackgroundThe clinical characteristics of primary liver cancer (PLC) patients are changing, maybe due to hepatitis viral vaccination and lifestyle changes, etc. The linkage between these changes and outcomes among these PLCs has not yet been fully elucidated.MethodsIt was identified total of 1691 PLC cases diagnosed between 2000 ~ 2020. Cox proportional hazards models were utilized to determine the connections between the clinical presentations and their close risk factor(s) from PLC patients.ResultsThe average age of PLC patients increased gradually from 52.74 ± 0.5 years in 2000 ~ 2004 to 58.63 ± 0.44 years in 2017 ~ 2020, accompanied by an increased proportion of females from 11.11% to 22.46%, and non-viral hepatitis-related PLC was raised from 1.5% to 22.35%. 840 (49.67%) PLC patients with alpha-fetoprotein (AFP) < 20ng/mL (AFP-negative). The mortality was 285 (16.85%) or 532 (31.46%) PLC patients with alanine transaminase (ALT) between 40 ~ 60 IU/L or ALT > 60 IU/L. The PLC patients with pre-diabetes/diabetes or dyslipidemia also increased from 4.29% or 11.1% in 2000 ~ 2004 to 22.34% or 46.83% in 2017 ~ 2020. The survival period of the PLC patients with normoglycemia or normolipidemic was 2.18 or 3.14 folds longer than those patients with pre-diabetes/diabetes or hyperlipidemia (P

Abstract Background Immunoglobulin light chain (AL) amyloidosis commonly affects the kidney or heart, but may also involve the liver at a histopathological level. Early diagnosis of AL amyloidosis is important for proper management with desirable outcome. We reported here an unusual case of AL amyloidosis, presenting primarily with multiple serous cavity effusion, accompanied with rapidly progressive cholestasis. Case presentation A previously healthy 63-year-old man presented with dysuria, frequent urination, oliguria and oedema of lower extremities for one month, accompanied with jaundice and hypoproteinemia. CT demonstrated multiple serous cavity effusion, focal hypodense lesions in the liver, and focal low-density in the spleen. Laparoscopy with liver biopsy revealed liver and spleen fibrosis with congestion, no visceral rupture, following haemorrhagic ascites from abdominocentesis. This patient was transferred to our (tertiary) hospital. The diagnosis of amyloidosis was confirmed with histopathology/immunohistochemistry. Haematopoietic stem cell transplantation was not applicable, however chemotherapy was advised, due to the patient’s Mayo score 3. The patient declined chemotherapy and was self-discharged back to his hometown hospital with palliative care, however only lasted a further one-month. Discussion The lesson we have learnt from this case that any patients with multiple serous cavity effusion and isolated hepatic involvement, primary amyloidosis should be considered. Multiple serous cavity effusion may serve as an indicator for poor prognosis of hepatic AL amyloidosis.

IntroductionChronic obstructive pulmonary disease (COPD) is a common, irreversible but preventable disease characterized by persistent respiratory symptoms. The mortality rate of COPD is predicted to reach 5.4 million by the year 2060. Despite its heavy burden on healthcare expenditure worldwide, only 15% of cases are medically identified. The potential benefits of facemask-wearing for COPD patients remain a topic of debate.MethodsWe will conduct a systematic review of all randomized trials and non-randomized controlled trials to evaluate the impact of facemasks on COPD patients. Our review will be based on literature obtained through a comprehensive search strategy across multiple electronic databases, including the Cochrane Library, Embase, PubMed, Web of Science, the Chinese Biomedical Database (SinoMed), and China National Knowledge Infrastructure (CNKI), with no restrictions on language or date of publication. Two independent researchers will extract and assess all relevant data using pre-designed data extraction forms. The included studies will be assessed using the Cochrane RoB2 tool and the suggested risk of bias criteria proposed by the Effective Practice and Organization of Care reviews group of the Cochrane collaboration. The quality of evidence will be assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. We will use Review Manager 5.4 software for statistical analysis.DiscussionIn the context of COVID-19, it is important for COPD patients to wear facemasks. This study aims to conduct a comprehensive and systematic assessment of the impact of facemasks on the physiology and activity of COPD patients.Trial registrationPROSPERO registration number CRD42022326265.

BackgroundTo combat/control the COVID-19 pandemic, a complete lockdown was implemented in China for almost 6 months during 2020.PurposeTo determine the impact of a long-term lockdown on the academic performance of first-year nursing students via mandatory online learning, and to determine the benefits of online teaching.MethodsThe recruitment and academic performance of 1st-year nursing students were assessed between 2019 [prior to COVID-19, n = 195, (146 women)] and 2020 [during COVID-19, n = 180 (142 women)]. The independent sample t test or Mann-Whitney test was applied for a comparison between these two groups.ResultsThere was no significant difference in student recruitment between 2019 and 2020. The overall performance of the first-year students improved in the Biochemistry, Immunopathology, Traditional Chinese Medicine Nursing and Combined Nursing courses via mandatory online teaching in 2020 compared with traditional teaching in 2019.ConclusionSuspension of in-class learning but continuing education virtually online has occurred without negatively impacting academic performance, thus academic goals are more than achievable in a complete lockdown situation. This study offers firm evidence to forge a path for developments in teaching methods to better incorporate virtual learning and technology in order to adapt to fast-changing environments. However, the psychological/psychiatric and physical impact of the COVID-19 lockdown and the lack of face-to-face interaction on these students remains to be explored.

To control COVID-19 pandemic, complete lockdown was initiated in 2020. We investigated the impact of lockdown on tertiary-level academic performance, by comparing educational outcomes amongst first-year students during second semester of their medical course prior to and during lockdown. Evidence: The demographics, including educational outcomes of the two groups were not significantly different during semester one (prior to the lockdown). The academic performance amongst women was better than men prior to lockdown. However, the scores were improved significantly for both sexes during lockdown in 2020, following the complete online teaching, compared to that in 2019, showing no significant difference between men and women in 2020, for English and Chinese History. There were significant different scores between men and women in lab-based Histology Practice in 2019 (in-person tuition) and 2020 (online digital tuition), although only a significant improvement in women was observed between 2019 and 2020. Implication: the forced change to online delivery of the second semester of the first-year medical program in 2020 due to the COVID-19 pandemic did not result in any decline in assessment outcomes in any of the subjects undertaken. We believe extensive online digital media should continue to be available to students in future.

IntroductionHypertension, one of the most common chronic diseases worldwide, usually requires lifetime managing blood pressure (BP) with medications. Due to quite large number of hypertension patients co-exist with depression and/or anxiety, and non-cooperated with medical instruction, consequently management of BP is impaired with serious complications, resulting in compromised quality of life. Consequently quality of life of such patients is impaired with serious complications. Therefore, management of depression and/or anxiety is equally important as the treatment of hypertension. Depression and/or anxiety are independent risk factors of hypertension, which is supported by the finding that there is close correlation between hypertension are depression/or anxiety. Psychotherapy (non-drug treatment) maybe useful for hypertensive patients with depression and/or anxiety to improve their negative emotions. We aim to quantify the effective of psychological therapies in the management of hypertension patients with depression or anxiety, by comparing and ranking a network meta-analysis (NMA).Materials and methodsLiterature search for randomized controlled trials (RCTs) will be performed in five electronic databases from inception to December 2021, including PubMed, the Cochrane library, Embase, Web of Science, and China Biology Medicine disc (CBM). The search terms mainly include "hypertension", "mindfulness-based stress reduction" (MBSR), "cognitive behavioral therapy" (CBT) and "dialectical behavior therapy" (DBT). Cochrane Collaboration quality assessment tool will be used for the risk of bias assessment. A Bayesian network meta-analysis will be performed, using WinBUGS 1.4.3, and Stata 14 will be applied to draw the network diagram, while RevMan 5.3.5 will be used to produce funnel plot for assessing the risk of publication bias. Recommended rating, development and grade methodology will also be utilized to assess the quality of evidence.ResultsEffect of MBSR, CBT and DBT will be evaluated by traditional meta-analysis directly and Bayesian network meta-analysis indirectly. Our study will provide the evidence on the efficacy and safety of psychological treatments in the hypertension patients with anxiety. There is no research ethical requirement because this is a systematic review of published literature. The results of this study will be published in a peer-reviewed journal.Trial registrationProspero registration number: CRD42021248566.

Breast cancer is still a major concern due to its relatively poor prognosis in women, although there are many approaches being developed for the management of breast cancer. Extensive studies demonstrate that the development of breast cancer is determined by pro versus anti tumorigenesis factors, which are closely related to host immunity. IL-35 and IL-37, anti-inflammatory cytokines, play an important role in the maintenance of immune homeostasis. The current review focuses on the correlation between clinical presentations and the expression of IL-35 and IL-37, as well as the potential underlying mechanism during the development of breast cancer in vitro and in vivo. IL-35 is inversely correlated the differentiation and prognosis in breast cancer patients; whereas IL-37 shows dual roles during the development of breast cancer, and may be breast cancer stage dependent. Such information might be useful for both basic scientists and medical practitioners in the management of breast cancer patients.

BackgroundSince the emergence of COVID-19, mandatory facemask wearing has been implemented around the world to prevent viral transmission, however, the impact of wearing facemasks on patients with COPD was unclear.MethodsThe current study undertakes a systematic review and meta-analysis of a comprehensive literature retrieval from six databases, based on the pre-determined eligibility criteria, irrespective of language. The risk of bias was assessed using an established instrument. We primarily focused on analyzing ETCO2, SpO2, and heart and respiratory rates, and also considered the impacts on physiological and exercise performance. A descriptive summary of the data and possible meta-analysis was performed. Forest plots were generated to pool estimates based on each of the study outcomes.ResultsOf the 3,751 publications considered, six publications were selected for a systematic review and two publications were included for meta-analysis, however, the quality of these six studies was relatively low overall. In the case of inactivity, the facemask wearing COPD cohort had higher respiratory rates than that of the non-facemask wearing cohort (MD = 1.00 and 95% CI 0.47–1.53, P < 0.05). There was no significant difference in ETCO2 (MD = 0.10 and 95% CI −1.57–1.78, P > 0.05) and heart rate (MD = 0.40 and 95% CI −3.59–4.39, P > 0.05) nor SpO2 (MD = −0.40 and 95% CI −0.84–0.04, P > 0.05) between the COPD patients with and without facemasks. Furthermore, it was observed that the only significant differences between the COPD patients with and without facemasks undertaking different activities were FEV1 (%) (MD = 3.84 and 95% CI 0.14–7.54, P < 0.05), FEV1/FVC (%) (MD = 3.25 and 95% CI 0.71–5.79, P < 0.05), and blood lactate (MD = −0.90 and 95% CI −1.73 to −0.07, P < 0.05).ConclusionWearing facemasks decreased the exercise performance of patients with COPD, however, it had minimal impact on physiological indexes. Further investigations will be performed on the high-quality data from randomized control studies.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=326265, identifier: CRD42022326265.

Hepatocellular carcinoma (HCC) remains a major challenge to clinicians due to its unacceptably high mortality and morbidity. The etiology of HCC is multi-faceted, including viral infection, alcoholism and non-alcoholic fatty liver disease. Dysregulated host immunity contributes to tumorigenesis among these susceptible individuals with pre-existing condition(s). IL-32 and IL-34 are key cytokines driving the development of chronic inflammatory conditions such as rheumatoid arthritis, systemic lupus erythematosus, as well as chronic liver diseases. IL-32 and IL-34 play an important role augmenting the development of HCC, due to their direct influence over host inflammation, however, new roles for these cytokines in HCC are emerging. Here we comprehensively review the latest research for IL-32 and IL-34 in HCC, identifying a subset of potential therapeutic targets for use in precision medicine.

IL-38, an anti-inflammatory cytokine, is a key regulator of homeostasis in host immunity. Intestinal immunity plays a critical role in defence against pathogenic invasion, as it is the largest surface organ and the most common entry point for micro-organisms. Dysregulated IL-38 activity is observed in several autoimmune diseases including systemic lupus erythematosus and atherosclerosis. The protective role of IL-38 is well illustrated in experimental colitis models, showing significantly worse colitis in IL-38 deficient mice, compared to wildtype mice. Moreover, exogenous IL-38 has been shown to ameliorate experimental colitis. Surprisingly, upregulated IL-38 is detected in inflamed tissue from inflammatory bowel disease patients, consistent with increased circulating cytokine levels, demonstrating the complex nature of host immunity in vivo. However, colonic IL-38 is significantly reduced in malignant tissues from patients with colorectal cancer (CRC), compared to adjacent non-cancerous tissue. Additionally, IL-38 expression in CRC correlates with 5-year survival, tumour size and differentiation, suggesting IL-38 plays a protective role during the development of CRC. IL-38 is also an independent biomarker for the prognosis of CRC, offering useful information in the management of CRC. Taken together, these data demonstrate the role of IL-38 in the maintenance of normal intestinal mucosal homeostasis, but that dysregulation of IL-38 contributes to initiation of chronic inflammatory bowel disease (resulting from persistent local inflammation), and that IL-38 provides protection during the development of colorectal cancer. Such data provide useful information for the development of novel therapeutic targets in the management of intestinal diseases for more precise medicine.

BackgroundExercise is associated with a less atherogenic lipid profile; however, there is limited research on the effect of exercise on atherosclerotic plaque composition and markers of plaque stability.MethodsA total of 110 apolipoprotein (apo)E−/− mice were placed on a chow diet and randomly assigned to control or exercise for a period of 10 weeks, commencing either at 12 weeks of age (the early-stage atherosclerosis, EA group) or at 40 weeks of age (the late-stage atherosclerosis, LA group). At the end of the exercise period, blood was assayed for lipids. Histologic analysis of the aortic sinus was undertaken to assess plaque size and composition that includes macrophage content, monocyte chemoattractant protein (MCP)-1, matrix metalloproteinase-2 (MMP-2), and tissue inhibitors of metalloproteinase 1 and 2 (TIMP-1 and 2).ResultsA total of 103 mice (38 EA, 65 LA) completed the protocol. In the EA group, exercise reduced plasma total cholesterol (TC) (−16%), free cholesterol (−13%), triglyceride (TG) (−35%), and phospholipid (−27%) levels, when compared to sedentary control mice (p < 0.01). In the EA group, exercise also significantly reduced plaque stenosis (−25%, p < 0.01), and there were higher levels of elastin (3-fold increase, p < 0.0001) and collagen (11-fold increase, p < 0.0001) in plaques, compared to control mice. There was an increase in plaque MMP-2 content in the exercise group (13% increase, p < 0.05) but no significant difference in macrophage or MCP-1 content. In the LA group, exercise reduced plaque stenosis (−18%, p < 0.05), but there was no significant difference in plaque composition. There was no difference in macrophage, MCP-1, or MMP-2 content in the LA groups. TIMP-1 was lower with exercise in both the EA and LA groups (−59%, p < 0.01 and −51%, p < 0.01 respectively); however, there was no difference in TIMP-2 levels.ConclusionA 10-week exercise period reduces atherosclerotic plaque stenosis when commenced at both early- and late-stage atherosclerosis. Intervening earlier with exercise had a greater beneficial effect on lipids and plaque composition than when starting exercise at a later disease stage.

Abstract Background Gastric cancer (GC) is a malignancy with high morbidity/mortality, partly due to a lack of reliable biomarkers for early diagnosis. It is important to develop reliable biomarker(s) with specificity, sensitivity and convenience for early diagnosis. The role of tumour-associated macrophages (TAMs) and survival of GC patients are controversial. Macrophage colony stimulating factor (MCSF) regulates monocytes/macrophages. Elevated MCSF is correlated with invasion, metastasis and poor survival of tumour patients. IL-34, a ligand of the M-CSF receptor, acts as a “twin” to M-CSF, demonstrating overlapping and complimentary actions. IL-34 involvement in tumours is controversial, possibly due to the levels of M-CSF receptors. While the IL-34/M-CSF/M-CSFR axis is very important for regulating macrophage differentiation, the specific interplay between these cytokines, macrophages and tumour development is unclear. Methods A multi-factorial evaluation could provide more objective utility, particularly for either prediction and/or prognosis of gastric cancer. Precision medicine requires molecular diagnosis to determine the specifically mutant function of tumours, and is becoming popular in the treatment of malignancy. Therefore, elucidating specific molecular signalling pathways in specific cancers facilitates the success of a precision medicine approach. Gastric cancer tissue arrays were generated from stomach samples with TNM stage, invasion depth and the demography of these patients (n = 185). Using immunohistochemistry/histopathology, M-CSF, IL-34 and macrophages were determined. Results We found that IL-34 may serve as a predictive biomarker, but not as an independent, prognostic factor in GC; M-CSF inversely correlated with survival of GC in TNM III–IV subtypes. Increased CD68+ TAMs were a good prognostic factor in some cases and could be used as an independent prognostic factor in male T3 stage GC. Conclusion Our data support the potency of IL-34, M-CSF, TAMs and the combination of IL-34/TAMs as novel biological markers for GC, and may provide new insight for both diagnosis and cellular therapy of GC.

To determine the epidemiology of coronavirus disease (COVID-19) in a remote region of China, far from Wuhan, we analyzed the epidemiology of COVID-19 in Gansu Province. From January 23 through February 3, 2020, a total of 35 (64.8%) of 54 reported cases were imported from COVID-19–epidemic areas. Characteristics that differed significantly during the first and second waves of illness in Gansu Province were mean patient age, occupation, having visited epidemic areas, and mode of transportation. Time from infection to illness onset for family clusters was shorter in Gansu Province than in Wuhan, consistent with shortened durations from onset to first medical visit or hospitalization. Spatial distribution pattern analysis indicated hot spots and spatial outliers in Gansu Province. As a result of adequate interventions, transmission of the COVID-19 virus in Gansu Province is decreasing.

Abstract Background Alpha‐fetoprotein (AFP), routinely used for diagnosis of hepatocellular carcinoma (HCC), is limited with relatively low sensitivity and high false positivity in HBV‐related HCC (HBV‐HCC). Thus, an alternative approach was explored to improve specificity/sensitivity for diagnosis of HBV‐HCC, using the combination of AFP, inflammatory score, and liver function. Methods Chronic hepatitis B (CHB) (n = 510) and HBV‐HCC (n = 473) patients were identified retrospectively for this study. The diagnostic value of single vs combined biomarkers for HBV‐HCC was analyzed, using ROC curve. Results It was observed that elderliness, male sex, cirrhosis, HBeAg+ or no‐antiviral therapy, and elevation of ALT, AST, neutrophil‐lymphocyte ratio (NLR), and AFP were associated with developing HBV‐HCC. However, the cut‐off ALT defined by Chinese standard, but not by AASLD, was a risk factor. Interestingly, AFP of HBeAg‐ HBV‐HCC patients without cirrhosis was significantly higher than that of the HBeAg+ patients. AUC values for AFP, ALT, AST, or NLR were 0.84 (95% CI: 0.815‐0.862), 0.533 (95% CI: 0.501‐0.565), 0.696 (95% CI: 0.666‐0.725), or 0.684 (95% CI: 0.654‐0.713) with optimal cut‐off at 7.21 ng/mL, 43 IU/mL, 38 IU/mL, or 2.61, respectively. Combination of AFP with ALT, AST, and NLR improved the diagnostic performance for HBV‐HCC, compared to any of the single biomarkers or any other combinations among these patients (except no‐cirrhosis). Conclusions Elderliness, male sex, elevated ALT, AST, NLR, AFP, cirrhosis, HBeAg+, and no‐antiviral treatment were independent risk factors for HBV‐HCC. AASLD standard of ALT cut‐off value may not be suitable for the Chinese population. Regular monitoring of HCC among HBeAg‐ patients with abnormal AFP may improve the management of HBV‐HCC. The diagnostic performance of AFP combined with ALT, AST, and NLR for HBV‐HCC was superior to single biomarker or any other combinations among these patients, and its diagnostic equation can be used as useful tool for differentiation of HBV‐HCC from CHB.

Abstract Background and aims Colorectal cancer (CRC) is a major killer. Host immunity is important in tumorigenesis. Direct comparison among IL-36α, IL-36β and IL-36γ in the prognosis of CRC is unclear. Methods CRC tissue arrays were generated from colorectostomy samples with TNM stage, invasion depth and the demography of these patients (n = 185). Using immunohistochemistry/histopathology, IL-36α, IL-36β and IL-36γ were determined, in comparison to non-cancer tissues. Results A significant association was observed between colonic IL-36α, IL-36β or IL-36γ and the presence of cancer (with all P

Colorectal cancer (CRC) is a major killer. Dysregulation of IL-37 and IL-38, both anti-inflammatory cytokines, is observed in auto-immune diseases. The precise regulatory mechanisms of IL-37/IL-38 during the development of CRC remains unclear, but chronic intestinal inflammation is involved in the carcinogenesis of CRC. Constitutive production of colonic IL-37 and IL-38 is substantially reduced in CRC, consistent with an inverse correlation with CRC differentiation. Reduced colonic IL-37 and IL-38 is relating to CRC invasion and distant metastasis, suggesting a protective role for IL-38 within the tumor micro-environment. IL-38 is reduced in right-sided CRC compared to left-sided CRC, which is in line with multiple risk factors for right-sided CRC, including the embryonic development of the colon, and genetic differences in CRC between these two sides. Finally, colonic IL-37 and tumor associated neutrophils (TAN) seem to be independent biomarkers of prognostic value, whereas colonic IL-38 seems to be a reliable and independent biomarker in predicting the 5-year survival post-surgery in CRC. However, there is room for improvement in available studies, including the extension of these studies to different regions/countries incorporating different races, evaluation of the role of multi-drug resistance, and different subsets of CRC. It would be useful to determine the kinetics of circulating IL-38 and its relationship with drug resistance/targeted therapy. The measurement of colonic IL-38 at the molecular and cellular level is required to explore the contribution of IL-38 pathways during the development of CRC. These approaches could provide insight for the development of personalized medicine.

Objective: To determine the relationship between the health literacy of patients with diabetes mellitus (DM) and the accessibility of internet surfing for information concerning DM.Methods: A multistage stratified sampling method was utilized to conduct a questionnaire survey on DM health literacy and internet accessibility among 1,563 patients with DM in Gansu Province in 2020. Logistic regression was performed to analyze the factors that influence health literacy and internet accessibility; while the chi-square test was used to compare the differences in needs.Results: Among 1,563 valid questionnaires collected with an effective rate of 95.7%, there were 65.4, 66.3, or 51.1% of patients with DM were found to have good health knowledge, attitudes, or practice levels, respectively. Occupation, income, disease course of DM, and accessibility to the internet were the main factors influencing health literacy. Age, residency, occupation, education, income, and family history of DM were the factors influencing accessibility to internet surfing for DM. The expectations from patients with DM for the capacity to obtain DM information from traditional sources or through internet sources was 1,465 (93.7%) or 1,145 (73.3%), respectively. Patients with DM had a 2-fold higher desire to obtain DM health information from internet media if the patients had access to the internet than those without (P < 0.05).Conclusions: The socioeconomic status and access to the internet were the main contributing factors for health literacy, as socioeconomic status is closely related to access to the internet.

Atherosclerosis, which is a primary cause of cardiovascular disease (CVD) deaths around the world, is a chronic inflammatory disease that is characterised by the accumulation of lipid plaques in the arterial wall, triggering inflammation that is regulated by cytokines/chemokines that mediate innate and adaptive immunity. This review focuses on IL-32, -34 and -37 in the stable vs. unstable plaques from atherosclerotic patients. Dysregulation of the novel cytokines IL-32, -34 and -37 has been discovered in atherosclerotic plaques. IL-32 and -34 are pro-atherogenic and associated with an unstable plaque phenotype; whereas IL-37 is anti-atherogenic and maintains plaque stability. It is speculated that these cytokines may contribute to the explanation for the increased occurrence of atherosclerotic plaque rupture seen in patients with COVID-19 infection. Understanding the roles of these cytokines in atherogenesis may provide future therapeutic perspectives, both in the management of unstable plaque and acute coronary syndrome, and may contribute to our understanding of the COVID-19 cytokine storm.

Background: The COVID-19 (2019 novel coronavirus disease) pandemic is deeply concerning because of its massive mortality and morbidity, creating adverse perceptions among patients likely to impact on their overall medical care. Thus, we evaluated the impact of the COVID-19 pandemic on the pattern of primary care consultations within a Shanghai health district.Methods: A retrospective observational cohort study was performed, with data analyzed concerning the pattern of patient visits to general practitioners within the Tongren Hospital network (the sole provider of general practice to the population of 700,000). Data from all general practice consultations for adults were collected for the first 6 months of 2020, which included a 60-day lockdown period (January 24–March 24, 2020) and compared to corresponding data from the first 6 months of 2019. We evaluated changes to the numbers and patterns of primary care consultations, including subgroup analysis based on age, sex, and primary diagnosis.Results: A substantial reduction in patient visits, associated with increased median age, was observed during the first wave of the pandemic in the first 6 months of 2020, compared to the same interval during 2019. Additionally, reduced reappointments and waiting times, but increased costs per visit were observed. When analyzed by primary disease diagnosis, patient visits were reduced for all the major systems. The most striking visit reductions were in cardiovascular, respiratory, endocrine, and gastrointestinal diseases. However, psychological disorders were increased following lockdown, but there was also a dramatic fall in consultations for depression. Reduced monthly patient numbers correlated with both rate of reappointment and average waiting time during the first 6 months of both 2019 and 2020, but an inverse correlation was observed between cost per visit and monthly patient numbers. Specifically during the lockdown period, there was ~50% reduced patient visits.Conclusions: The lockdown has had a serious impact on patients' physical and psychological health. Our analysis provides objective health-related data that may inform the current controversy concerning the balance between the detrimental effects of the use of lockdown vs. the use of a more targeted approach to eliminate viral transmission. These data may improve decision-making in medical practice, policy, and education.

The COVID-19 outbreak has become a pandemic. The outbreak was able to be controlled in China by mid-April through the implementation of critical measures; however, significant reverse transmission has resulted in hot spots perturbing prevention and control. To date, there have only been a total of 92 indigenous COVID-19 cases confirmed in the Gansu Province, which is considered to be a consequence of the strict screening approach applied during the outbreak. The emergency response level to COVID-19 were able to be decreased from high to low, despite some relatively minor reverse transmission cases from other countries in March 2020. The stringent preparative measures undertaken by the Gansu authorities, involving high-level, streamlined cooperation between the transportation, quarantine, and medical resource departments, have underpinned this success. There has been an emergence of clusters of freshly infected COVID-19 patients in the Jilin Province in northeast China. The single largest cluster has been in Shulan of the Jilin Province, involving 43 confirmed infections. A strict lockdown was implemented immediately. The source of the current outbreak of COVID-19 is suggested to be travelers returning from Russia. The current strategy from the Chinese authorities is aimed at preventing reverse transmission via international importation to avert a rebound of COVID-19 in China. These data highlight the need for an exceptionally high level of vigilance and for a pre-emptive response that is informative for the development of policy to prevent a second and further waves of infections in general.

Background: As an emerging infectious disease, COVID-19 has garnered great research interest. We aimed to explore the differences between English language and Chinese language Medical/Scientific journals publications, particularly aiming to explore the efficacy/contents of the literature published in English and Chinese in relation to the outcomes of management and characterization of COVID-19 during the early stage of COVID-19 pandemic.Methods: Publications on COVID-19 research were retrieved from both English and Chinese databases. Bibliometric analyses were performed using VOSviewer 1.6.14, and CiteSpace V software. Network maps were generated to evaluate the collaborations between different authors, countries/provinces, and institutions.Results: A total of 143 English and 721 Chinese original research articles and reviews on COVID-19 were included in our study. Most of the authors and institutions of the papers were from China before March 1st, 2020, however, the distribution of authors and institutions were mainly in developed countries or more wealthy areas of China. The range of the keywords in English publications was more extensive than those in Chinese. Traditional Chinese Medicine was seen more frequently in Chinese papers than in English. Of the 143 articles published in English, 54 articles were published by Chinese authors only and 21 articles were published jointly by Chinese and other overseas authors.Conclusions: The publications in English have enabled medical practitioners and scientists to share/exchange information, while on the other hand, the publications in the Chinese language have provided complementary educational approaches for the local medical practitioners to understand the essential and key information to manage COVID-19 in the relatively remote regions of China, for the general population with a general level of education.

Background and AimsNecroptosis is a newly identified type of cell death with programmed pathways. The current study was performed to investigate necroptosis by measuring its key regulators; receptor interacting protein kinase 3 (RIPK3) and mixed lineage kinase domain-like (MLKL) in patients with Hepatitis B virus (HBV) related acute-on-chronic liver failure (ACLF).MethodsHBV-related ACLF (HBV-ACLF) patients (n = 90), non-ACLF patients without cirrhosis (N = 70), patients with cirrhosis (N = 40), and healthy controls (HCs; n = 70) were enrolled in the study. All patients were subject to serum RIPK3 measurement. Hepatic RIPK3 and MLKL were also determined in the livers of 18 patients and five donors, using immunohistochemistry.ResultsSerum RIPK3 was significantly elevated in HBV-ACLF patients compared to that of non-ACLF patients and the HCs. Serum RIPK3 in ACLF patients at recruitment was significantly higher in non-survivors than those in survivors at the 90-day follow-up. The predictive accuracy of serum RIPK3 at the 90-day outcome was relatively good with an area under the receiver operating curve (AUROC) of 0.72 (p < 0.001), similar to that of the model of end-staged liver disease (MELD) score (0.76, p < 0.001). The combined use of RIPK3 and MELD score further increased the AUROC to 0.80. The hepatic RIPK3 and MLKL measured by immunohistochemistry, significantly increased in the patients with HBV-ACLF than in the patients without ACLF and the HCs.ConclusionCirculating RIPK3 was significantly increased in patients with HBV-ACLF and was associated with a clinical outcome. The improved combined objective scores could offer additional prognostic value in ACLF patients, for physicians with more accurate expectations.

Summary: Preclinical studies have shown benefit of apolipoprotein A-I (apoA-I)/high-density lipoprotein (HDL) raising in atherosclerosis; however, this has not yet translated into a successful clinical therapy. Our studies demonstrate that apoA-I raising is more effective at reducing early-stage atherosclerosis than late-stage disease, indicating that the timing of HDL raising is a critical factor in its atheroprotective effects. To date, HDL-raising clinical trials have only been performed in aged patients with advanced atherosclerotic disease. Our findings therefore provide insight, related to important temporal aspects of HDL raising, as to why the clinical trials have thus far been largely neutral. Key Words: atherosclerosis, cholesterol, high-density lipoproteins

Abstract Background Chronic hepatitis B (CHB) remains a global health dilemma with high morbidity and mortality. Human males absent on the first (hMOF) (a histone acetyltransferase) is responsible for DNA damage repair, tumorigenesis and cell cycle regulation. Persistence of HBV DNA contributes to cirrhosis and hepatocellular carcinoma (HCC) in CHB patients. Histone acetyltransferase enhances HBV replication, however the precise underlying mechanism of hMOF in HBV replication in CHB patients remains to be explored. This study aims to investigate the correlation between hepatic hMOF and HBV DNA replication in CHB patients, and may provide new insights towards the treatment of CHB patients. Methods hMOF in liver biopsy (CHB, n = 33 HBeAg+; n = 20 HBeAg−, and three healthy controls) was determined, using immunohistochemistry, qPCR and Western blot. The correlation between hMOF and HBsAg, as well as, HBeAg were determined. Results A positive correlation between hMOF and HBV DNA in overall CHB patients was observed. A distinct positive correlation between hMOF and HBsAg and/or HBeAg in HBeAg+ CHB patients was also detected, however not observed between hMOF and HBsAg in HBeAg− CHB patients. No correlation was observed between hMOF and hepatic inflammation severity and fibrotic stage in CHB patients. Conclusions Hepatic hMOF might contribute to host HBV clearance in CHB patients and possible pathogenesis.

Abstract In recent years, considerable progress has been made in the molecular mechanisms of epigenetics in disease development and progression, the reversible characteristics of epigenetic modification provide new insights for the treatment of such diseases. The pathogenesis of diabetic retinopathy (DR) has not yet been fully understood, treatment of refractory and recurrent diabetic macular edema remains a big change in clinical practice. This review emphasizes that reversibility of epigenetic modification could provide a new strategy for the prevention and treatment of diseases.

Autophagy serves as a stress response and may contribute to the pathogenesis of avascular necrosis of the femoral head induced by steroids. Statins promote angiogenesis and ameliorate endothelial functions through apoptosis inhibition and necrosis of endothelial progenitor cells, however the process used by statins to modulate autophagy in avascular necrosis of the femoral head remains unclear. This manuscript determines whether pravastatin protects against dexamethasone-induced avascular necrosis of the femoral head by activating endothelial progenitor cell autophagy. Pravastatin was observed to enhance the autophagy activity in endothelial progenitor cells, specifically by upregulating LC3-II/Beclin-1 (autophagy related proteins), and autophagosome formation in vivo and in vitro. An autophagy inhibitor, 3-MA, reduced pravastatin protection in endothelial progenitor cells exposed to dexamethasone by attenuating pravastatin-induced autophagy. Adenosine monophosphate-activated protein kinase (AMPK) is a key autophagy regulator by sensing cellular energy changes, and indirectly suppressing activation of the mammalian target of rapamycin (mTOR). We found that phosphorylation of AMPK was upregulated however phosphorylation of mTOR was downregulated in pravastatin-treated endothelial progenitor cells, which was attenuated by AMPK inhibitor compound C. Furthermore, liver kinase B1 (a phosphorylase of AMPK) knockdown eliminated pravastatin regulated autophagy protein LC3-II in endothelial progenitor cells in vitro. We therefore demonstrated pravastatin rescued endothelial progenitor cells from dexamethasone-induced autophagy dysfunction through the AMPK-mTOR signaling pathway in a liver kinase B1-dependent manner. Our results provide useful information for the development of novel therapeutics for management of glucocorticoids-induced avascular necrosis of the femoral head.

The cells of the intestinal epithelium provide a selectively permeable barrier between the external environment and internal tissues. The integrity of this barrier is maintained by tight junctions, specialised cell-cell contacts that permit the absorption of water and nutrients while excluding microbes, toxins and dietary antigens. Impairment of intestinal barrier function contributes to multiple gastrointestinal disorders, including food hypersensitivity, inflammatory bowel disease (IBD) and colitis-associated cancer (CAC). Glycoprotein A33 (GPA33) is an intestinal epithelium-specific cell surface marker and member of the CTX group of transmembrane proteins. Roles in cell-cell adhesion have been demonstrated for multiple CTX family members, suggesting a similar function for GPA33 within the gastrointestinal tract. To test a potential requirement for GPA33 in intestinal barrier function, we generated Gpa33−/− mice and subjected them to experimental regimens designed to produce food hypersensitivity, colitis and CAC. Gpa33−/− mice exhibited impaired intestinal barrier function. This was shown by elevated steady-state immunosurveillance in the colonic mucosa and leakiness to oral TRITC-labelled dextran after short-term exposure to dextran sodium sulphate (DSS) to injure the intestinal epithelium. Gpa33−/− mice also exhibited rapid onset and reduced resolution of DSS-induced colitis, and a striking increase in the number of colitis-associated tumours produced by treatment with the colon-specific mutagen azoxymethane (AOM) followed by two cycles of DSS. In contrast, Gpa33−/− mice treated with AOM alone showed no increase in sporadic tumour formation, indicating that their increased tumour susceptibility is dependent on inflammatory stimuli. Finally, Gpa33−/− mice displayed hypersensitivity to food allergens, a common co-morbidity in humans with IBD. We propose that Gpa33−/− mice provide a valuable model to study the mechanisms linking intestinal permeability and multiple inflammatory pathologies. Moreover, this model could facilitate preclinical studies aimed at identifying drugs that restore barrier function.

Inflammatory bowel disease (IBD) is a group of disorders that are characterized by chronic, uncontrolled inflammation in the intestinal mucosa. Although the aetiopathogenesis is poorly understood, it is widely believed that IBD stems from a dysregulated immune response towards otherwise harmless commensal bacteria. Chemokines induce and enhance inflammation through their involvement in cellular trafficking. Reducing or limiting the influx of these proinflammatory cells has previously been demonstrated to attenuate inflammation. CXCR3, a chemokine receptor in the CXC family that binds to CXCL9, CXCL10 and CXCL11, is strongly overexpressed in the intestinal mucosa of IBD patients. We hypothesised that CXCR3 KO mice would have impaired cellular trafficking, thereby reducing the inflammatory insult by proinflammatory cell and attenuating the course of colitis. To investigate the role of CXCR3 in the progression of colitis, the development of dextran sulfate sodium (DSS)-induced colitis was investigated in CXCR3-/- mice over 9 days. This study demonstrated attenuated DSS-induced colitis in CXCR3-/- mice at both the macroscopic and microscopic level. Reduced colitis correlated with lower recruitment of neutrophils (p = 0.0018), as well as decreased production of IL-6 (p

Tumstatin is an anti-angiogenic collagen IV α3 fragment, levels of which are reduced in the airways of asthmatics. Its reduction may be due to the degradation by extracellular matrix (ECM) proteases. Cathepsins play a role in ECM remodelling, with cathepsin D, H and K (CTSD, CTSH and CTSK) being associated with lung diseases. CTSD modulates the NC1 domains of collagen molecules including tumstatin, while CTSH and CTSK are involved in ECM degradation. The role of these cathepsins in the regulation of tumstatin in the lung has not previously been examined. We demonstrated that CTSB, D, F, H, K, L and S mRNA was expressed in the airways. Quantification of immunohistochemistry showed that there is no difference in the global expression of CTSD, CTSH and CTSK between asthmatics and non-asthmatics. CTSD and CTSK, but not CTSH had the capacity to degrade tumstatin. No difference was observed in the activity of CTSD and H in bronchoalveolar lavage fluid of asthmatic and non-asthmatics, while CTSK was undetectable. This indicates that while CTSD possesses the potential to directly regulate tumstatin, and thus angiogenesis through this mechanism however, it is not likely to be involved in the dysregulation of tumstatin found in asthmatic airways.