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 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 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.

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.

The role of IL-35 and IL-37 in breast cancer - potential therapeutic targets for precision medicine.

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.

The Role of IL-37 and IL-38 in Colorectal Cancer.

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.

Models of cardiovascular surgery biobanking to facilitate translational research and precision medicine.

Biobanking in health care has evolved over the last few decades from simple biological sample repositories to complex and dynamic units with multi-organizational infrastructure networks and has become an essential tool for modern medical research. Cardiovascular tissue biobanking provides a unique opportunity to utilize cardiac and vascular samples for translational research into heart failure and other related pathologies. Current techniques for diagnosis, classification, and treatment monitoring of cardiac disease relies primarily on interpretation of clinical signs, imaging, and blood biomarkers. Further research at the disease source (i.e. myocardium and blood vessels) has been limited by a relative lack of access to quality human cardiac tissue and the inherent shortcomings of most animal models of heart disease. In this review, we describe a model for cardiovascular tissue biobanking and databasing, and its potential to facilitate basic and translational research. We share techniques to procure endocardial samples from patients with hypertrophic cardiomyopathy, heart failure with reduced ejection fraction, and heart failure with preserved ejection fraction, in addition to aortic disease samples. We discuss some of the issues with respect to data collection, privacy, biobank consent, and the governance of tissue biobanking. The development of tissue biobanks as described here has significant scope to improve and facilitate translational research in multi-omic fields such as genomics, transcriptomics, proteomics, and metabolomics. This research heralds an era of precision medicine, in which patients with cardiovascular pathology can be provided with optimized and personalized medical care for the treatment of their individual phenotype.

Cross-Sectional Study on Health Literacy and Internet Accessibility Among Patients With DM in Gansu, China.

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.

Clinical Implications of IL-32, IL-34 and IL-37 in Atherosclerosis: Speculative Role in Cardiovascular Manifestations of COVID-19.

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.

The Impact of COVID-19 on Primary Care General Practice Consultations in a Teaching Hospital in Shanghai, China.

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.

Oxidative stress in genetically triggered thoracic aortic aneurysm: role in pathogenesis and therapeutic opportunities.

Background: The primary objective of this review was to explore the contribution of oxidative stress to the pathogenesis of genetically-triggered thoracic aortic aneurysm (TAA). Genetically-triggered TAAs manifest substantial variability in onset, progression, and risk of aortic dissection, posing a significant clinical management challenge. There is a need for non-invasive biomarkers that predict the natural course of TAA and therapeutics that prevent aneurysm progression.Methods: An online systematic search was conducted within PubMed, MEDLINE, Scopus and ScienceDirect databases using keywords including: oxidative stress, ROS, nitrosative stress, genetically triggered thoracic aortic aneurysm, aortic dilatation, aortic dissection, Marfan syndrome, Bicuspid Aortic Valve, familial TAAD, Loeys Dietz syndrome, and Ehlers Danlos syndrome.Results: There is extensive evidence of oxidative stress and ROS imbalance in genetically triggered TAA. Sources of ROS imbalance are variable but include dysregulation of redox mediators leading to either insufficient ROS removal or increased ROS production. Therapeutic exploitation of redox mediators is being explored in other cardiovascular conditions, with potential application to TAA warranting further investigation.Conclusion: Oxidative stress occurs in genetically triggered TAA, but the precise contribution of ROS to pathogenesis remains incompletely understood. Further research is required to define causative pathological relationships in order to develop therapeutic options.

The Epidemiology of COVID-19 in the Gansu and Jinlin Provinces, China.

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.

The Role of Inflammation and Myeloperoxidase-Related Oxidative Stress in the Pathogenesis of Genetically Triggered Thoracic Aortic Aneurysms.

Genetically triggered thoracic aortic aneurysms (TAAs) are usually considered to exhibit minimal levels of inflammation. However, emerging data demonstrate that specific features of an inflammatory response can be observed in TAA, and that the extent of the inflammatory response can be correlated with the severity, in both mouse models and in human studies. Myeloperoxidase (MPO) is a key mediator of the inflammatory response, via production of specific oxidative species, e.g., the hypohalous acids. Specific tissue modifications, mediated by hypohalous acids, have been documented in multiple cardiovascular pathologies, including atherosclerosis associated with coronary artery disease, abdominal aortic, and cerebral aneurysms. Similarly, data are now emerging that show the capacity of MPO-derived oxidative species to regulate mechanisms important in TAA pathogenesis, including alterations in extracellular matrix homeostasis, activation of matrix metalloproteinases, induction of endothelial dysfunction and vascular smooth muscle cell phenotypic switching, and activation of ERK1/2 signaling. The weight of evidence supports a role for inflammation in exacerbating the severity of TAA progression, expanding our understanding of the pathogenesis of TAA, identifying potential biomarkers for early detection of TAA, monitoring severity and progression, and for defining potential novel therapeutic targets.

Bibliometric Analysis on COVID-19: A Comparison of Research Between English and Chinese Studies.

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.

Inverse correlation between Interleukin-34 and gastric cancer, a potential biomarker for prognosis.

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.

The RNA-binding fragile-X mental retardation protein and its role beyond the brain.

It is well-established that variations of a CGG repeat expansion in the gene FMR1, which encodes the fragile-X mental retardation protein (FMRP), cause the neurocognitive disorder, fragile-X syndrome (FXS). However, multiple observations suggest a general and complex regulatory role of FMRP in processes outside the brain: (1) FMRP is ubiquitously expressed in the body, suggesting it functions in multiple organ systems; (2) patients with FXS can exhibit a physical phenotype that is consistent with an underlying abnormality in connective tissue; (3) different CGG repeat expansion lengths in FMR1 result in different clinical outcomes due to different pathogenic mechanisms; (4) the function of FMRP as an RNA-binding protein suggests it has a general regulatory role. This review details the complex nature of FMRP and the different CGG repeat expansion lengths and the evidence supporting the essential role of the protein in a variety of biological and pathological processes.

IL-34, IL-36 and IL-38 in colorectal cancer-key immunoregulators of carcinogenesis.

Colorectal cancer (CRC) is still a big killer nowadays, but the precise underlying mechanism remains to be explored. It is believed that imbalance of host immunity in the local microenvironment plays a critical role in the tumorigenesis of CRC. IL-34 is inversely correlated with overall survival in CRC patients, perhaps via regulating terminal differentiation of a subset of macrophages (M2). It is believed that the recruitment/differentiation of M2 macrophages within the cancer simply represents an increase in number, but the function of these M2 macrophages may be compromised. IL-36s (IL-36α, ß and γ) are constitutively expressed in non-cancer colon tissue, but colonic IL-36α, IL-36ß and IL-36γ are substantially reduced in the CRC tissues (~ 80%). IL-36α is an independent factor affecting the survival of CRC patients. The level of IL-36α and/or IL-36γ in CRC tissue could potentially be used as biomarkers for predicting the prognosis of CRC at both the later or early stages of CRC. IL-38 is also an anti-inflammatory cytokine. Colonic IL-38 is ~ 95% lower in CRC compared to non-CRC colonic tissue, consistent with the positive correlation between differentiation of CRC, and colonic tumour expression of IL-38. IL-38 is a reliable/sensitive biomarker for distinguishing between CRC and non-cancer colonic tissue. There is a positive correlation between colonic IL-38 in CRC and prognosis and/or overall survival, particularly in advanced CRC, supporting IL-38 probably being a reliable and consistent independent factor in predicting the prognosis of CRC. The findings above may be useful in exploring therapeutic targeting for precision medicine.

The epidemiology of reverse transmission of COVID-19 in Gansu Province, China.

Background: The transmission of COVID-19 is about to come under control within China, however, an emerging challenge to the Chinese authorities is reverse transmission due to COVID-19 patients/carriers evacuating from overseas to China. Methods: We analysed the epidemiological characteristics of 311 Chinese citizens evacuated from Iran. All confirmed COVID-19 cases amongst the returnees were displayed by the spatial distribution pattern of the extent of COVID-19 infection. Results: Characteristics that differed significantly amongst these returnees compared to the original infected cohorts in Gansu were mean age, occupation and sex. Differences observed between infected patients and non-patients amongst returnees were age, sex, race, occupation, the use of facemasks, and residential situation in Iran. The clinical features that were significantly related to infection were chill, shortness of breath, chest pain and nausea. Spatial distribution pattern analysis indicated that infected returnees had resided within Iranian provinces that had experienced high levels of COVID-19. The spatial distribution of the original homes of these returnees before departure for Iran demonstrated that returnees will largely return to northwest China, to regions that have only experienced low levels of infection within China. Conclusion: Blocking the reverse transmission of COVID-19 is critical in preventing a secondary outbreak of COVID-19.

IL-36 s in the colorectal cancer: is interleukin 36 good or bad for the development of colorectal cancer?

BACKGROUND AND AIMS: Colorectal cancer (CRC) is a major killer. Host immunity is important in tumorigenesis. Direct comparison among IL-36α, IL-36ß 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-36ß and IL-36γ were determined, in comparison to non-cancer tissues. RESULTS: A significant association was observed between colonic IL-36α, IL-36ß or IL-36γ and the presence of cancer (with all P < 0.0001). Using ROC curve analysis, specificity and sensitivity of IL-36α, IL-36ß or IL-36γ were confirmed, with area under the curve (AUC) values of 0.68, 0.73 and 0.65, respectively. Significant differences in survival were observed between IL-36αhigh and IL-36αlow (P = 0.003) or IL-36γhigh and IL-36γlow (P = 0.03). Survival curves varied significantly when further stratification into sub-groups, on the basis of combined levels of expression of two isotypes of IL-36 was undertaken. A significant difference was observed when levels of IL-36α and IL-36ß were combined (P = 0.01), or a combination of IL-36α plus IL-36γ (P = 0.002). The sub-groups with a combination of IL-36αhigh plus IL-36ßhigh, or IL-36αhigh plus IL-36γlow exhibited the longest survival time among CRC patients. In contrast, the sub-groups of IL-36αlow plus IL-36ßhigh or IL-36αlow plus IL-36γhigh had the shortest overall survival. Using the log-rank test, IL-36αhigh expression significantly improved survival in patients with an invasion depth of T4 (P < 0.0001), lymph node metastasis (P = 0.04), TNM III-IV (P = 0.03) or with a right-sided colon tumour (P = 0.02). Similarly, IL-36γlow expression was significantly associated with improved survival in patients with no lymph node metastasis (P = 0.008), TNM I-II (P = 0.03) or with a left-sided colon tumour (P = 0.05). Multivariate analysis demonstrated that among IL-36α, IL-36ß and IL-36γ, only IL-36α (HR, 0.37; 95% CI, 0.16-0.87; P = 0.02) was an independent factor in survival, using Cox proportional hazards regression analysis. CONCLUSION: IL-36α or IL-36γ are reliable biomarkers in predicting the prognosis of CRC during the later or early stages of the disease, respectively. Combining IL-36α plus IL-36γ appears to more accurately predict the postoperative prognosis of CRC patients. Our data may be useful in the management of CRC.