Exploring the clinical significance of IL-38 correlation with PD-1, CTLA-4, and FOXP3 in colorectal cancer draining lymph nodes.

Introduction: Colorectal 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. Results: Our 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. Discussion: Our 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.

CD64 plays a key role in diabetic wound healing.

Introduction: Wound 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. Objectives: We aimed to investigate the involvement of CD64 in diabetic wound healing using a DM animal model with CD64 KO mice. Methods: First, 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. Results: CD64 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. Conclusion: CD64 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.

The role of IL-36 and 37 in hepatocellular carcinoma.

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.

Assessing the impact of diverse mask types on COPD patients: a randomised controlled trial study protocol.

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.

Influenza vaccination rates among healthcare workers: a systematic review and meta-analysis investigating influencing factors.

Introduction: Healthcare 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. Methods: Cross-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. Results: A 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. Conclusion: The global influenza vaccination rate among healthcare workers is low, and comprehensive measures are needed to promote influenza vaccination among this population. Systematic review registration: www.inplysy.com, identifier: 202350051.

The Pro-Tumor Biological Function of IL-36α Plays an Important Role in the Tumor Microenvironment of HCC.

Purpose: To investigate the role of IL-36 in the tumorigenesis of hepatocellular carcinoma (HCC). IL-36 composed of a natural antagonist (IL-36Ra) and three agonists (IL-36α, -ß, -γ) that stimulate inflammation by binding to a common receptor consisting of IL-36R and IL-1RAcP. HCC is a common malignancy associated with high morbidity and mortality, often diagnosed at later stages. Although the exact role of IL-36α in HCC remains controversial, it is hypothesized that it may play a significant role in the development and progression of this cancer. Materials and Methods: In the current study, we measured both circulating and intrahepatic levels of IL-36α from HCC patients and healthy controls, using ELISA. The association between IL-36 and the differentiation of HCC was determined. Furthermore, the role IL-36 in both HCC and non-HCC cell lines was evaluated in vitro. Results: Circulating and intra-hepatic IL-36α was inversely correlated with differentiation of HCC, suggesting that IL-36α contribute to protection during the development of HCC. Based on bioinformatics, miR-27b-3p is closely related to downstream IL-36α. Thus, we determined miR-27b-3p expression in HCC tissues, showing upregulated miR-27b-3p was inversely correlated with IL-36α in HCC, perhaps via CXCL1 in HCC cells. It was confirmed that IL-36α inhibited HCC proliferation, viability and migration in vitro, consistent with reduced the expression of cytokines IL-1ß, IL-18, implying that IL-36α inhibited the possible involvement of pyroptosis. Conclusion: Our data suggests that IL-36α may be a potential therapeutic target and a prediction biomarker for the management of HCC.

The impact of wearing facemask on COPD patients: A protocol of a systematic review and meta-analysis.

INTRODUCTION: Chronic 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. METHODS: We 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. DISCUSSION: In 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 REGISTRATION: PROSPERO registration number CRD42022326265.

The impact of COVID-19 lockdown on nursing higher education at Chengdu University.

BACKGROUND: To combat/control the COVID-19 pandemic, a complete lockdown was implemented in China for almost 6 months during 2020. PURPOSE: To 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. METHODS: The 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. RESULTS: There 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. CONCLUSION: Suspension 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.

The safety concerns regarding immune checkpoint inhibitors in liver cancer patients rising mainly from CHB.

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.

Alterations in Gray Matter Morphology and Functional Connectivity in Adult Patients with Newly Diagnosed Untreated Hypothyroidism.

Background: Untreated adult hypothyroidism may be associated with cognitive and emotional impairment, but the precise underlying neuropathological mechanism is unknown. We investigated the brain morphological and functional abnormalities associated with cognition and emotion in hypothyroidism. Methods: This is a cross-sectional observational study. Forty-four newly diagnosed adult hypothyroid patients and 54 well-matched healthy controls (HCs) were enrolled. All participants underwent three-dimensional T1-weighted imaging and resting-state functional magnetic resonance imaging (MRI). Morphological and seed-based functional connectivity (FC) analyses were performed to compare the intergroup differences. Neuropsychological tests, including the Montreal Cognitive Assessment (MoCA) Scale, 24-item Hamilton Depression Rating Scale (HAMD-24), and Hamilton Anxiety Rating Scale (HAMA) were administered. Thyroid function test and blood lipid levels were measured. Correlations were computed between neuropsychological and biochemical measures with neuroimaging indices. Sensitive morphological or functional neuroimaging indicators were identified using receiver operating characteristic (ROC) analysis. Results: Compared with HCs, hypothyroid patients demonstrated lower total and subdomain scores on the MoCA and higher HAMD-24 and HAMA scores. Morphological analysis revealed the hypothyroid patients had significantly reduced gray matter (GM) volumes in the right superior frontal gyrus, superior temporal gyrus, left dorsolateral superior frontal gyrus, middle frontal gyrus, and supplementary motor area as well as significantly increased GM volumes in the bilateral cerebellar Crus I and left precentral gyrus. Furthermore, seed-based FC analysis of hypothyroid patients showed increased FC between the right cerebellar Crus I and left precentral gyrus, triangular part of the inferior frontal gyrus, and angular gyrus of the inferior parietal lobe. The language scores of the MoCA were positively correlated with Jacobian values of the left supplementary motor area (r = 0.391, p = 0.046) and precentral gyrus (r = 0.401, p = 0.039). ROC analysis revealed FC value between cerebellar Crus I and angular gyrus could differentiate groups with relatively high accuracy (sensitivity: 75%, specificity: 77.8%, area under the curve: 0.794 [CI 0.701-0.888], p < 0.001). Conclusions: Untreated adult-onset hypothyroidism may be associated with impaired cognition and anxiety or depression. GM morphological alterations and FC of the cerebellum with subregions of the frontal and parietal lobes may represent key neuropathological mechanisms underlying the cognitive deterioration and mood dysregulation observed in hypothyroid adults. Clinical Trial Registration Number: chiCTR2000028966.

The outcomes of lockdown in the higher education sector during the COVID-19 pandemic.

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.

The 20 years transition of clinical characteristics and metabolic risk factors in primary liver cancer patients from China.

Background: The 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. Methods: It 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. Results: The 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<0.05). Conclusions: It was gradually increased that age, the proportion of females, non-viral hepatitis-related causes, AFP-negative, and abnormal glucose/lipids among PLC patients. Proper control of glucose/lipids or ALT may improve the prognosis of PLCs.

Potential predictive value of CT radiomics features for treatment response in patients with COVID-19.

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.

Effect of MBSR, DBT and CBT on the hypertension patients with depression/anxiety: Protocol of a systematic review and Bayesian network meta-analysis.

INTRODUCTION: Hypertension, 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 METHODS: Literature 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. RESULTS: Effect 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 REGISTRATION: Prospero registration number: CRD42021248566.

Combination of IL-34 and AFP improves the diagnostic value during the development of HBV related hepatocellular carcinoma.

IL-34 involves in host immunity regulated carcinogenesis. Alpha-fetoprotein (AFP) is related to the development of HCC. We explored if combination of IL-34 and APF could improve the diagnostic value in HBV related hepatocellular carcinoma (HBV-HCC). Serum was obtained from HBV patients or healthy control. Liver tissue was obtained from liver biopsy in CHB, HBV related cirrhosis patients or curative resection in HBV-HCC patients. Serum IL-34 and MCSF, or intrahepatic IL-34, MCSF and CD68+ tumor associate macrophages (TAMs) were determined using ELISA or immunohistochemistry. Serum IL-34 was 1.7, 1.3 or 2.3-fold higher in HBV-HCC than that of CHB, HBV related cirrhosis or healthy control, which was inhibited following trans-hepatic arterial chemoembolization (TACE) in HBV-HCC patients. Intra-hepatic IL-34 was higher in HBV-HCC than that of the other three groups. Intra-hepatic IL-34 was associated with high HBV-DNA, HBeAg-, poor differentiation and small tumor size of HBV-HCC patients. Intra-hepatic TAMs in HBV-HCC were increased 1.7 or 1.3-fold, compared to that from CHB or HBV-cirrhosis patients. Intra-hepatic TAMs were associated with high HBV-DNA, high tumor differentiation, small tumor size, abnormal AFP and more tumor number. AFP plus serum IL-34, showed the highest AUC (0.837) with sensitivity (0.632) and highest specificity (0.931), suggesting that AFP plus IL-34 enhances the reliability for prediction of the development of HBV-HCC among CHB patients. Circulating and intra-hepatic IL-34 was upregulated gradually in HBV disease progression from CHB, cirrhosis and HCC. IL-34 may be used as a diagnostic biomarker and potential therapeutic target for the management of HBV-HCC.

Physical exercise/sports ameliorate the internet addiction from college students during the pandemic of COVID-19 in China.

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.