Integrated multi-omics analyses revealed the association between rheumatoid arthritis and colorectal cancer: MYO9A as a shared gene signature and an immune-related therapeutic target.

BACKGROUND: Our study aims to explore the relationship, shared gene signature, and the underlying mechanisms that connect rheumatoid arthritis (RA) to colorectal cancer (CRC). METHODS: Mendelian randomization (MR) analysis was conducted to assess the causality between RA and CRC. Summary statistic data-based Mendelian randomization (SMR) leveraging eQTL data was employed to identify the CRC-related causal genes. Integrated analyses of single-cell RNA sequencing and bulk RNA sequencing were employed to comprehensively investigate the shared gene signature and potential mechanisms underlying the pathogenesis of both RA and CRC. Predictive analysis of the shared hub gene in CRC immunotherapy response was performed. Pan-cancer analyses were conducted to explore the potential role of MYO9A in 33 types of human tumors. RESULTS: MR analysis suggested that RA might be associated with a slight increased risk of CRC (Odds Ratio = 1.04, 95% Confidence Interval = 1.01-1.07, P = 0.005). SMR analysis combining transcriptome analyses identified MYO9A as a causal gene in CRC and a shared gene signature in both RA and CRC. MYO9A may contribute to tumor suppression, while downregulation of MYO9A may impact CRC tumorigenesis by disrupting epithelial polarity and architecture, resulting in a worse prognosis in CRC. Additionally, MYO9A shows promise as a powerful predictive biomarker for cancer prognosis and immunotherapy response in CRC. Pan-cancer analyses demonstrated MYO9A may have a protective role in the occurrence and progression of various human cancers. CONCLUSION: RA might be associated with a slight increased risk of CRC. MYO9A is a shared gene signature and a potential immune-related therapeutic target for both CRC and RA. Targeting the MYO9A-mediated loss of polarity and epithelial architecture could be a novel therapeutic approach for CRC.

Gastroesophageal reflux disease with 6 neurodegenerative and psychiatric disorders: Genetic correlations, causality, and potential molecular mechanisms.

The comorbidities between gastroesophageal reflux disease (GERD) and various neurodegenerative and psychiatric disorders have been widely reported. However, the genetic correlations, causal relationships, and underlying mechanisms linking GERD to these disorders remain largely unknown. Here, we conducted a bidirectional Mendelian randomization (MR) analysis to determine the causality between GERD and 6 neurodegenerative and psychiatric disorders. Sensitivity analyses and multivariable MR were performed to test the robustness of our findings. Linkage disequilibrium score regression was used to assess the genetic correlation between these diseases as affected by heredity. Multiple bioinformatics tools combining two machine learning algorithms were applied to further investigate the potential mechanisms underlying these diseases. We found that genetically predicted GERD significantly increased the risk of Alzheimer's disease, major depressive disorder, and anxiety disorders. There might be a bidirectional relationship between GERD and insomnia. GERD has varying degrees of genetic correlations with AD, ALS, anxiety disorders, insomnia, and depressive disorder. Bioinformatics analyses revealed the hub shared genes and the common pathways between GERD and 6 neurodegenerative and psychiatric disorders. Our findings demonstrated the complex nature of the genetic architecture across these diseases and clarified their causality, highlighting that treatments for the cure or remission of GERD may serve as potential strategies for preventing and managing neurodegenerative and psychiatric disorders.

Association between Atopic Dermatitis and Colorectal Cancer: TET2 as a Shared Gene Signature and Prognostic Biomarker.

Background: Recent studies have linked atopic dermatitis (AD) to colorectal cancer (CRC) risk. Their causality and potential molecular mechanisms remain unclear. Methods: We performed Mendelian randomization (MR) analysis to evaluate the causality between AD and CRC. Summary statistic data-based Mendelian randomization (SMR) analysis was used to identify CRC-related causal genes. Transcriptome analyses and immunohistochemical methods were applied to investigate the shared gene signature and potential mechanisms that contribute to the pathogenesis of both AD and CRC. A predictive analysis was performed to examine the shared gene signature associated with immunotherapy response in CRC. Results: MR analysis indicated a causal association between AD and a decreased risk of CRC. SMR analysis uncovered TET2 as a CRC-related causal gene, showing an inverse relationship with the risk of CRC. Transcriptome analyses identified TET2 as a shared gene signature between AD and CRC. Decreased TET2 expression is associated with impaired demethylation and worse prognosis in CRC patients. We observed ten pathways related to the inflammatory response and immune regulation that may be shared mechanisms underlying both AD and CRC. These findings were validated through single-cell analysis. TET2 shows promise as a powerful predictive biomarker for cancer prognosis and immunotherapy response in CRC. Conclusion: There is a causal association between AD and a decreased risk of CRC. AD may influence the occurrence of CRC by modulating immune and inflammatory responses. TET2 could serve as a potential biomarker for prognosis and may be considered a novel therapeutic target for methylation and immune-related interventions.

Metabolic syndrome, its components, and gastrointestinal cancer risk: a meta-analysis of 31 prospective cohorts and Mendelian randomization study.

BACKGROUND AND AIM: Cohort studies have linked metabolic syndrome (MetS) to gastrointestinal (GI) cancer risk. We aimed to evaluate the associations between MetS, its components, and combinations of MetS components with eight GI cancers risk. METHODS: We conducted a systematic search of prospective cohort studies and performed a meta-analysis. Subgroup analyses regarding diagnostic criteria, sex, cancer sites, histological subtypes, ethnic groups, and studies adjusted for alcohol consumption were carried out. Mendelian randomization (MR) was employed to evaluate the causality between 17 MetS-related traits and eight GI cancers among Europeans and Asians separately. RESULTS: Meta-analyses of 31 prospective studies indicated that MetS was significantly associated with an increased risk of colorectal cancer (CRC) (RR [95% CI] = 1.13 [1.12-1.15]), esophageal cancer (EC) (RR [95% CI] = 1.17 [1.03-1.32]), gallbladder cancer (GBC) (RR [95% CI] = 1.37[1.10-1.71]), liver cancer (LC) (RR [95% CI] = 1.46 [1.29-1.64]), and pancreatic cancer (PaC) (RR [95% CI] = 1.25 [1.20-1.30]), but not gastric cancer (GC) (RR [95% CI] = 1.11 [0.96-1.28]). Regarding the associations between MetS components and GI cancers risk, the following associations showed statistical significance: obesity-CRC/LC/EC/, hypertriglyceridemia-LC/PaC, reduced high-density lipoprotein (HDL)-CRC/LC/GC/PaC, hyperglycemia-CRC/LC/PaC, and hypertension-CRC/LC/EC/PaC. Sex-specific associations were observed between individual MetS components on GI cancers risk. Among the top three common combinations in both sexes, obesity + HTN + hyperglycemia had the strongest association with CRC risk (RR [95% CI] = 1.54 [1.49-1.61] for males and 1.27 [1.21-1.33] for females). MR analyses revealed causality in 16 exposure-outcome pairs: waist-to-hip ratio/BMI/HbA1c-CRC; BMI/childhood obesity/waist circumference/T2DM/glucose-EC; BMI/waist circumference/cholesterol-LC; cholesterol/childhood obesity/waist circumference/HbA1c-PaC; and HbA1c-GBC. These results were robust against sensitivity analyses. CONCLUSIONS: Since MetS is reversible, lifestyle changes or medical interventions targeting MetS patients might be potential prevention strategies for GI cancers.

Nursing care of a child with severe interstitial pneumonia complicated by acute rejection after lung transplantation: a case report.

Background: Acute rejection after transplantation occurs as a result of complex immune responses following the detection of the major histocompatibility complex of the donors in recipients. As one of the risk factors of chronic rejection, acute rejection can directly lead to death. Therefore, early prevention and monitoring of transplant patients is critical. Pediatric acute rejection after lung transplantation is relatively rare compared to adults, and it remains a considerable challenge since information on rare primary disease complicated by acute rejection after lung transplantation in children is extremely limited, with only a single case series reported in the literature. Case Description: Here, we present a case of a 10-year-old female diagnosed with severe interstitial pneumonia, pulmonary heart disease and severe malnutrition. The patient underwent double-lung transplantation under general anesthesia. Through monitoring and management of immunosuppressants, prevention and control of infection, dynamic body fluid management, personalized nutritional support, psychological care and rehabilitation exercises, the patient achieved recovery and was safely discharged after 21 days. Conclusions: Characteristics of acute rejection after lung transplantation in children include rapid onset and progression of respiratory distress, significant difficulty in nursing and frustration in communication. Anti-infection, anti-rejection, and symptomatic measures in the acute phase are critical in controlling disease progression and improving prognosis.

Clinical Application of Antibody Immunity Against SARS-CoV-2: Comprehensive Review on Immunoassay and Immunotherapy.

The current COVID-19 global pandemic poses immense challenges to global health, largely due to the difficulty to detect infection in the early stages of the disease, as well as the current lack of effective antiviral therapy. Research and understanding of the human immune system can provide important theoretical and technical support for the clinical diagnosis and treatment of COVID-19, the clinical implementations of which include immunoassays and immunotherapy, which play a crucial role in the fight against the pandemic. This review consolidates the current scientific evidence for immunoassay, which includes multiple methods of detecting antigen and antibody against SARS-CoV-2. We compared the characteristics, advantages and disadvantages, and clinical applications of these three detection techniques. In addition to detecting viral infections, knowledge on the body's immunity against the virus is desirable; thus, the immunotherapy-based neutralizing antibody (nAb) detection methods were discussed. We also gave a brief introduction to the new immunoassay technology such as biosensing. This was followed by an in-depth and extensive review on a variety of immunotherapy methods. It includes convalescent plasma therapy, neutralizing antibody-based treatments targeting different regions of SARS-CoV-2, immunotherapy targeted on the host cell including inhibiting the host cell receptor and cytokine storm, as well as cocktail antibodies, cross-neutralizing antibodies, and immunotherapy based on cross-reactivity between viral epitopes and autoepitopes and autoantibody. Despite the development of various immunological testing methods and antibody therapies, the current global situation of COVID-19 is still tense. We need more efficient detection methods and more reliable antibody therapies. The up-to-date knowledge on therapeutic strategies will likely help clinicians worldwide to protect patients from life-threatening viral infections.

Public Health Measures and the Control of COVID-19 in China.

In December 2019, the COVID-19 pandemic quickly spread throughout China and beyond, posing enormous global challenges. With prompt, vigorous, and coordinated control measures, mainland China contained the spread of the epidemic within two months and halted the epidemic in three months. Aggressive containment strategy, hierarchical management, rational reallocation of resources, efficient contact tracing, and voluntary cooperation of Chinese citizens contributed to the rapid and efficient control of the epidemic, thus promoting the rapid recovery of the Chinese economy. This review summarizes China's prevention and control strategies and other public health measures, which may provide a reference for the epidemic control in other countries.

Humoral immune response of BBIBP COVID-19 vaccination before and after the booster immunization.

BACKGROUND: The inactivated Sinopharm/BBIBP COVID-19 vaccine has been widely used in the world and has joined the COVAX vaccine supply program for developing countries. It is also well adapted for usage in low- and middle-income nations due to their low storage requirements. OBJECTIVE: This study aims to report on the kinetics, durability, and neutralizing ability of the induced immunity of the BBIBP vaccine, and the intensified antibody response elicited by the booster. METHODS: A total of 353 healthy adult participants, aged 20-74 years, were recruited in this multicenter study. A standard dose of the BBIBP vaccine was administered (Month 0), followed by a second standard dose (Month 1), and a booster dose (after Month 7). Vaccine-induced virus-specific antibody levels (SARS-CoV-2-IgA/IgM/IgG), conventional virus neutralization test (cVNT), pseudovirus neutralization test (pVNT), and surrogate virus neutralization test (sVNT) were monitored over multiple time points. RESULTS: Neutralizing titers induced by the two doses of inactivated vaccine for COVID-19 peaked at Month 2 and declined to 33.89% at Month 6. Following the booster dose, elevated levels of antibodies were induced for IgA, IgG, and neutralizing antibodies, with neutralizing titer reaching 13.2 times that of before the booster. CONCLUSION: By monitoring the antibody titer levels postvaccination, this study has shown that serum antibody levels will decrease over time, but a notable spike in antibody levels postbooster highlights the anamnestic immune response. This signifies that the protection capability has increased following the injection of booster immunization.

Rapid Antigen Test Combine with Nucleic Acid Detection: A Better Strategy for COVID-19 Screening at Points of Entry.

The coronavirus disease 2019 (COVID-19) pandemic has imposed an enormous disease burden worldwide, and the Delta variant now has become dominant in 53 countries. Recently published studies have shown that during periods of high viral load, rapid antigen tests (RAT) yield similar results to reverse transcriptase-polymerase chain reaction (RT-PCR) tests, and when used in serial screening (e.g., every three days), it has a high sensitivity. In this perspective, we recommend RT-PCR combined with RAT at points of entry: (i) RAT can be added to the detection phase at ports of entry to detect asymptomatic infections as early as possible; (ii) RAT can be added to post-entry quarantine every three days or less to reduce the rate of missed detection in later quarantine; (iii) Adding regular RAT to regular PCR testing for key airport personnel to prevent cross-infection and conduct closed-off management. In the face of sporadic Delta variant outbreaks, the combination of the two could help rapid triage and management of suspected populations at an early stage and thus contain the outbreak more quickly and effectively. We also discuss the issue whether the current antigen detection reagents can cope with various SARS-CoV-2 variants.

Factors Affecting the Antibody Immunogenicity of Vaccines against SARS-CoV-2: A Focused Review.

Vaccines are a crucial part of the global anti-pandemic effort against COVID-19. The effects of vaccines, as well as their common influencing factors, are the most important issues that we should focus on at this time. To this end, we review statistics on immunogenicity after vaccination, using neutralizing antibodies as the main reference index. Age, infection history, and virus variants are compared, and vaccination program recommendations are made accordingly. Suggestions are made to address concerns raised by the vaccines' shortened development cycle, as well as the emergence of immunity escape of viral variants. Finally, a brief description and future prospects are provided based on the principle of the ADE effect and previous experience with similar viruses.

Diagnostic value of loop-mediated isothermal amplification assay for hand, foot, and mouth disease.

BACKGROUND: Nowadays, hand, foot, and mouth disease (HFMD) has a significant negative impact on children's health, especially in the Asia-Pacific region. Loop-mediated isothermal amplification assay (LAMP) is a highly efficient and convenient novel tool. However, its diagnostic accuracy for HFMD is still not clear. Therefore, we conducted a meta-analysis in order to evaluate the potential of LAMP assay for the diagnosis of HFMD, in which the reference standard was polymerase chain reaction (PCR). METHODS: A protocol was predetermined (CRD42020212882) in PROSPERO. We retrieved seven databases including PubMed for relevant studies published before October 2020. Articles were included if they compared the diagnostic efficiency of LAMP with PCR for HFMD through detecting clinical samples which was more than 15. Statistical analysis was performed by STATA 15.1 software. Risk of bias and applicability were assessed using Quality Assessment of Diagnostic Accuracy Studies. No funding was used for the study. RESULTS: A total of 18 retrospective studies including 2495 samples from China were finally included. Reference standards of them included RT-PCR and non-RT-PCR. The merged sensitivity and specificity with 95% confidence interval (95% CI) were 1.00 (0.97-1.00) and 0.97 (0.88-0.99), respectively. The pooled PLR, NLR, and DOR with 95% CI were 11.17 (5.91-21.11), 0.05 (0.03-0.09), and 538.12 (183.17-1580.83), respectively. The AUC of SROC was 1.00 (95% CI: 0.99-1.00). CONCLUSION: In conclusion, our research revealed high sensitivity and specificity of LAMP in diagnosing HFMD. However, more high-quality research is required to prove this conclusion.

Comparative efficacy and side-effect profile of ketamine and esketamine in the treatment of unipolar and bipolar depression: protocol for a systematic review and network meta-analysis.

INTRODUCTION: Despite a range of antidepressant drugs and therapies, approximately one-third of patients fail to achieve meaningful recovery, prompting the urgent need for more effective treatment for depression. Several open-label studies randomised controlled trials (RCTs) and meta-analyses have been conducted to confirm the therapeutic efficacy and side effects of ketamine and esketamine. Esketamine is (S)- enantiomer of ketamine; however, there is limited evidence comparing esketamine and ketamine in treating unipolar and bipolar depression have been published so far. METHODS AND ANALYSIS: We will include all double-blind RCTs comparing efficacy and side-effect profile of ketamine and esketamine in the treatment of unipolar and bipolar depression. Our primary outcomes will be study-defined response at endpoint assessment; dropouts due to adverse events and other adverse drug reactions. Published studies will be retrieved through relevant database searches. Reference selection and data extraction will be independently completed by two investigators, resolving inconsistencies by consensus or a discussion with the third investigator. For each outcome, we will undertake a network meta-analysis to synthesise all evidence. Local and global methods will be used to evaluate consistency. We will assess the quality of evidence contributing to network estimates with the Confidence in Network Meta-Analysis web application. ETHICS AND DISSEMINATION: This work does not require ethics approval as it will be based on published studies. This review will be published in peer-reviewed journals. PROSPERO REGISTRATION NUMBER: CRD42020201559.

Application of artificial intelligence in COVID-19 medical area: a systematic review.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has caused a large-scale global epidemic, impacting international politics and the economy. At present, there is no particularly effective medicine and treatment plan. Therefore, it is urgent and significant to find new technologies to diagnose early, isolate early, and treat early. Multimodal data drove artificial intelligence (AI) can potentially be the option. During the COVID-19 Pandemic, AI provided cutting-edge applications in disease, medicine, treatment, and target recognition. This paper reviewed the literature on the intersection of AI and medicine to analyze and compare different AI model applications in the COVID-19 Pandemic, evaluate their effectiveness, show their advantages and differences, and introduce the main models and their characteristics. METHODS: We searched PubMed, arXiv, medRxiv, and Google Scholar through February 2020 to identify studies on AI applications in the medical areas for the COVID-19 Pandemic. RESULTS: We summarize the main AI applications in six areas: (I) epidemiology, (II) diagnosis, (III) progression, (IV) treatment, (V) psychological health impact, and (VI) data security. The ongoing development in AI has significantly improved prediction, contact tracing, screening, diagnosis, treatment, medication, and vaccine development for the COVID-19 Pandemic and reducing human intervention in medical practice. DISCUSSION: This paper provides strong advice for using AI-based auxiliary tools for related applications of human diseases. We also discuss the clinicians' role in the further development of AI. They and AI researchers can integrate AI technology with current clinical processes and information systems into applications. In the future, AI personnel and medical workers will further cooperate closely.