Coronavirus disease 2019 (COVID-19) poses a serious threat to human health and life. The effective prevention and treatment of COVID-19 complications have become crucial to saving patients’ lives. During the phase of mass spread of the epidemic, a large number of patients with pulmonary fibrosis and lung cancers were inevitably infected with the SARS-CoV-2 virus. Lung cancers have the highest tumor morbidity and mortality rates worldwide, and pulmonary fibrosis itself is one of the complications of COVID-19. Idiopathic lung fibrosis (IPF) and various lung cancers (primary and metastatic) become risk factors for complications of COVID-19 and significantly increase mortality in patients. Therefore, we applied bioinformatics and systems biology approaches to identify molecular biomarkers and common pathways in COVID-19, IPF, colorectal cancer (CRC) lung metastasis, SCLC and NSCLC. We identified 79 DEGs between COVID-19, IPF, CRC lung metastasis, SCLC and NSCLC. Meanwhile, based on the transcriptome features of DSigDB and common DEGs, we identified 10 drug candidates. In this study, 79 DEGs are the common core genes of the 5 diseases. The 10 drugs were found to have positive effects in treating COVID-19 and lung cancer, potentially reducing the risk of pulmonary fibrosis. SARS-CoV-2 infection can have serious pulmonary fibrosis consequences2. IPF is a chronic progressive lung disease, nintedanib and pirfenidone are FDA-approved for the treatment of IPF. After a COVID-19 infection, survivors are likely to develop bilateral interstitial pneumonia, which often leads to acute respiratory distress syndrome and pulmonary fibrosis. A number of risk factors are shared by both IPF and lung cancer, and patients with both conditions have a worse prognosis than patients with either. In relation to the severity of IPF, the lung cancer stage matters more than the interval between diagnosis and lung cancer3. Patients with cancer appear to be particularly vulnerable to COVID-19, as tumors can severely affect the immunological response to viral infection4. Delays in screening, diagnosis and treatment due to the COVID-19 pandemic could lead to excess cancer deaths and delay or even reverse projected mortality declines for some cancers5; i.e., cancer patients with COVID-19 have a significantly higher mortality rate than infected patients without cancer6. As a result, patients with underlying diseases such as pulmonary fibrosis and lung cancer are more likely to suffer serious complications or even death after SARS-CoV-2 infection.SARS-CoV-2 is a novel coronavirus. It has directly contributed to the worldwide COVID-19 pandemic7. Of all lung cancers, small cell lung cancer (SCLC), although less common, is a rapidly fatal disease for which there is little effective clinical treatment8. Most patients will die within one year. Non-small cell lung cancer (NSCLC) is the most common type of lung cancer and although the death rate is lower than that of SCLC, it kills more people than SCLC because of the disproportionate number of cases9. In addition to primary lung cancer, secondary lung cancer caused by metastases from other types of cancer also constitutes an important risk factor after SARS-CoV-2 infection.Patients with lung cancer, whose underlying lung function and endurance are poor, are more likely to experience more severe hypoxia and to progress more rapidly with COVID-19 infection, so treatment is urgently needed for lung cancer patients infected with COVID-1910. Surfactant protein D (SP-D) downregulates EGF signaling and inhibits lung cancer cell growth11. As an in vitro and in vivo test, SP-D was shown to suppress pulmonary metastases from CRC12.The lungs are the second most common site of metastasis from CRC after the liver. 11% of CRC patients present with isolated lung metastases and surgical removal of lung metastases is effective in some cases, but the prognosis is poorIn our study, five datasets were used to identify the biological relationships between COVID-19 and IPF, lung metastases from CRC, SCLC and NSCLC. First, differentially expressed genes were identified from the dataset, and then common differential genes were found for the five diseases. Using these common differential genes, further analyses, including enrichment analysis and pathway analysis, are performed to understand the biological processes involved in genome-based expression studies. PPI networks were made using common differential genes to collect the full range of hub genes. Common DEGs were also tracked according to GSE186460, GSE17978, GSE41258, GSE40275 and GSE33532 for transcriptional regulators. Finding the top 10 genes from hub genes is a key step in predicting potential drugs. Finally, an outlook on potential drugs for the hub gene is provided.https://www.ncbi.nlm.nih.gov/geo/)13 to find datasets with both onset lung tissue and normal lung tissue controls and to download the full data. The GEO accession ID for the COVID-19 dataset is GSE18646014, which consists of 4 COVID-19 samples and 11 normal lung tissue samples sequenced by a high-throughput sequencing system called Illumina HiSeq 2500 (Homo sapiens) provided by Dobosh B et al. The GEO accession ID for the IPF dataset is GSE1797815, which includes 38 IPF samples and 20 normal lung tissue samples sequenced by the high-throughput sequencing system called Duke Human Operon 36 k v4.0 spotted microarray provided by Emblom-Callahan MC et al.; the GEO accession ID for the CRC lung metastasis dataset is GSE4125816, which includes 20 lung metastasis samples from CRC and 7 normal lung tissue samples sequenced by the high-throughput sequencing system called [HG-U133A] Affymetrix Human Genome U133A Array provided by Sheffer M et al. The GEO accession ID for the SCLC datasets GSE4027517, comprising 15 SCLC samples and 43 normal lung tissue samples, was sequenced by the high-throughput sequencing system called Human Exon 1.0 ST Array  provided by Kastner et al. The GEO accession ID of the NSCLC dataset is GSE3353218, including 80 NSCLC samples and 20 normal lung tissue samples, provided by Meister M et al. called [HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array. See Table In order to obtain common genes between COVID-19, IPF, CRC lung metastasis, SCLC and NSCLC, we searched the GEO database from the NCBI —a comprehensive gene set enrichment web tool, GO enrichment and functional enrichment  studies were conducted22 to characterize biological mechanisms and signaling pathways for shared DEGs. At the time, we used four databases, including KEGG (Kyoto Encyclopedia of Genes and Genomes)23, WikiPathways, Reactome, and BioCarta, as sources of pathway classification to identify shared pathways between COVID-19, IPF, CRC lung metastasis, SCLC, and NSCLC. Typically, the KEGG pathway controls metabolic processes and makes genome analysis quite useful. The P-value < 0.05 was considered a standard indicator for quantifying the highest pathways listed.Analyzing gene set enrichment is an important analytical exercise for classifying common biological insights, such as biological processes and chromosomal locations associated with different interlinked diseaseshttps://string-db.org/) (Version 11.5)24 repository, we construct a protein PPI network from shared DEGs to describe functional and physical interactions between COVID-19, IPF, CRC lung metastasis, SCLC, and NSCLC. STRING envisions expanding PPI awareness through active interactive channels, including text mining, experimental databases, coexpression, culture, gene fusion, and coexistence under different taxonomic confidence levels . Moderate confidence was set at 0.5 to generate a common DEG PPI network. We then consumed our PPI network into Cytoscape (v.3.8.2) for visualization and further experimental PPI network studies. Cytoscape (v.3.8.2)-an open-source web visualization platform-serves as a flexible tool for combining multiple datasets to improve the performance of different interactions such as PPI, genetic interactions, and protein-DNA interactions25.Proteins conclude their journey into a cell with a similar protein affiliation formed by a Protein–Protein Interaction network, which indicates the protein mechanisms. In cell and systems biology, assessment and analysis of PPI networks and their functionalities are fundamental and key objectives for interpreting and gaining insight into cellular machinery operations. Using the STRING (http://apps.cytoscape.org/apps/Cytohubba)-a novel Cytoscape-plugin for ranking and extracting central or potential or target elements of biological networks based on various network characteristics. Cytohubba has 11 methods of investigating networks from different angles, with Maximal Clique Centrality (MCC) being the best of them26. Using the MCC method of Cytohubba, we identified the top 10 hub genes in the PPI network. Based on the proximity ranking characteristics of Cytohubba, we also categorized the shortest available pathways across hub genes.A PPI network consists of nodes, edges, and their connections, where hub genes are the most entangled nodes. Cytohubba  or the identification of drug molecules. Drug molecules were identified by Enrichr using the Drug Signatures database (DSigDB) based on COVID-19, IPF, CRC lung metastasis, SCLC, and NSCLC. The Enrichr web portal is one of the most popular online resources to explore the enrichment of gene sets across a genome-wide scale. DSigDB is the global archive for the reidentification of targeted drugs associated with DEGsOur study did not require ethical board approval because it did not contain human or animal trials. GEO belongs to public databases. The patients involved in the database have obtained ethical approval. Users can download relevant data for free for research and publish relevant articles. Our study is based on open source data, so there are no ethical issues and other conflicts of interest.To explore the interrelationships and significance of COVID-19, IPF, CRC lung metastasis, SCLC, and NSCLC, based on the human RNA-seq and microarray datasets from the NCBI, we identified dysregulated genes that stimulate COVID-19, IPF, CRC lung metastasis, SCLC, and NSCLC. The RNA-seq and microarray dataset experiments were performed in an R-language environment characterized by DESeq2 and limit packs with Benjamin-Hochberg's false discovery rate.COVID-19 has 7640 differential genes, of which 7211 are up-regulated and 429 are down-regulated; similarly, IPF has 2272 differential genes, of which 1420 are up-regulated and 852 are down-regulated; lung metastases from CRC have 2875 differential genes, of which 1387 are up-regulated and 1488 are down-regulated. SCLC has a total of 7164 differential genes, of which a total of 4088 are up-regulated and 3076 are down-regulated; NSCLC has a total of 4407 differential genes, of which a total of 2103 are up-regulated and 2304 are down-regulated.P-value < 0.05 and |logFC|≥ 1. After cross-referencing Jvenn , we identified 79 common DEGs from COVID-19, IPF, CRC lung metastasis, SCLC, and NSCLC datasets. This common set of genes was used to complete further experiments. The five diseases are linked because they share one or more genes. Figure All significant DEGs were extracted at 22. We have corrected the results for GO and Pathways using the improved method (Enrichr) to take the multiple comparison problem. GO, taking into account gene function and its composition provides a wide range of extensive computable knowledge resources for humans. Ontologies define theoretically defined bodies of information. An ontology and annotation serve to perform a detailed biological structural model, primarily for biological applications. The GO analysis was performed in terms of biological processes, cellular composition, and molecular function, and the GO database was selected as an annotation source. The top 10 terms for biological processes, molecular functions and cell composition categories are summarized in Table To determine the biological importance, pathway enrichment, and sharing of the DEGs highlighted in this study. GO and pathway enrichment analysis was carried out using Enrichr. Enrichr has a potentially improved method to compute enrichment, and the researchers demonstrated that this method might be better than the currently widely used Fisher exact testPathways analysis reveals how organisms respond to their inherent modifications. It is a model technique that demonstrates the interaction between diseases through fundamental molecular or biological processes. The most affected paths of the COVID-19, IPF, CRC lung metastasis, SCLC, and NSCLC joint DEGs were collected from four global databases, including KEGG, WikiPathways, Reactome and BioCarta. Table We used the online tool STRING to construct the protein network, the PPI network contains 79 nodes and 51 edges, see Fig. P-value , cyclosporine A, resveratrol alcohol, genistein, and enterolactone. These drugs may have potential activity in 5 diseases.43. 5-Fu-induced apoptosis in CRC is significantly reduced by dasatinib by inhibiting Src activation44. TRAF6 depletion induces decitabine resistance in triple-negative breast cancer by blocking decitabine-induced DNA methyltransferase DEGs radiation45. Cyclosporin A is a powerful immunosuppressive agent that acts on T-lymphocytes and blocks effective T-cell receptor signaling47. By blocking MEK/ERK/c-Fos pathways, immunosuppressants like cyclosporine A, which is used to treat non-small lung cancer, reduce TRPM6 expression48. Resveratrol alcohol has shown promising activity in preventing and treating cancer49. Resveratrol inhibits cancer progression by inducing p53-dependent cell death50. Pancreatic cancer cells can be inhibited in their growth and apoptosis can be induced by Genistein by inhibiting oncogenic miR-223 expression51. There is strong evidence that higher serum enterolactone concentrations and increased lignan intake improve patients' prognoses after menopause52.The anticancer agent dasatinib induces the apoptosis of cancer cells53. Children infected with Omicron have a lower risk of serious illness than children infected with Delta54.About 15 million people died in the first two years of the COVID-19 pandemic, according to new data from the World Health Organization (WHO). WHO estimates the global excess death toll in 2020 and 2021 at 14.9 million. Most of these deaths (84%) were concentrated in Southeast Asia, Europe and the Americas, and more than two-thirds (68%) occurred in just 10 countries57. In essence, COVID-19 can range from mild, self-limiting respiratory dis- ease to severe progressive pneumonia, multiorgan failure, and even death. SARS-CoV-2 infection, especially severe infection, is associated with an increased risk of longitudinal cognitive decline58. At the same time, SARS-CoV-2 has a high transmission rate, and there is a lack of adequate and effective treatments. Consequently, the increase in the number of respiratory distress cases has the potential to overwhelm global health care capacity59.The current global COVID-19 pandemic is caused by the rapid international spread of SARS-CoV-2 infection60. In critically ill COVID-19 patients, the host immune response is thought to play a key role in driving acute pneumonia with diffuse alveolar injury, inflammatory infiltration and microvascular thrombosis61. Expression of cell receptors (such as IFNGR1 and CXCR4) was reduced by a viral infection and is associated with suppression of associated signaling pathways and immune function62. A systematic evaluation in 2020 estimated that 28% of patients with severe COVID-19 had venous thromboembolism. Complications of COVID-19 thrombosis include arterial and venous events, and microvascular thrombosis may lead to diffuse alveolar damage, the main source of lung injury in COVID-19 patients64. Among COVID-19 patients, acute respiratory failure is the main reason for admission to the intensive care unit, and hypoxic respiratory failure is the most common life-threatening complication of COVID-1966.A recent study shows that tissue damage related to COVID-19 is mainly mediated by host innate immunity67. Recent studies have proven that COVID-19 is an independent risk factor for ischaemic stroke and acute myocardial infarction68. Additionally, older age is a significant independent predictor of mortality from SARS and Middle East respiratory syndrome (MERS). Similarly, increased age is associated with death among patients with COVID-1969. Many patients who die from COVID-19 are older and weaker with significantly compromised lung and/or immune function70.In addition, in patients with COVID-19, ACE2 may play a causative role in cardiovascular complications such as thrombosis, heart damage and heart failure. ACE2 may be the link between SARS-CoV-2 and the cardiac manifestations identified in global data on the COVID-19 pandemic71. While new treatments are being developed, there is growing interest in repurposing existing drugs for COVID-1973. Aside from the recently licensed LY-CoV1404 (bebtelovimab), there are no licensed monoclonal antibody therapies that adequately target all Omicron variants74. Itaconic acid supplementation and CLYBL inhibition are possible therapeutic options for the treatment of COVID-19 that aim to modulate host defense to combat SARS-CoV-2 infection75. Hydroxychloroquine has been widely promoted as a potential treatment for COVID-19 due to its anti-inflammatory effects and antiviral activity in vitro studies76. Azithromycin is a widely used drug that may reduce viral load when combined with hydroxychloroquine in patients with non-severe COVID-1977. Trials of the JAK inhibitors baricitinib and ruxolitinib have shown promise in controlling excessive inflammation in COVID-19 patients78. Bamlanivimab monotherapy was reported to reduce the incidence of SARS-CoV-2 infection. Tocilizumab is an effective treatment for COVID-19 in patients with evidence of hypoxia and inflammation79.Thus, to combat the COVID-19 pandemic, there is an urgent need to identify effective SARS-CoV-2 therapeutics that improve prognosis, particularly those with utility in the outpatient setting80. Vaccination will be a key strategy for limiting the spread of SARS-CoV-2, reducing mortality, and controlling the COVID-19 pandemic82. The Pfizer-BioNTech vaccine is 95% effective against laboratory-confirmed COVID-19, and the Oxford–AstraZeneca vaccine was found to be 70% effective against COVID-19 in seronegative participants83.Another strategy for combatting the global COVID-19 pandemic is to develop and produce COVID-19 vaccines84. However, failure to provide effective cancer treatment to many cancer patients during a pandemic increases cancer morbidity and mortality, which may be more serious than COVID-19 itself85. Patients with cancer are ostensibly more likely to develop and succumb to COVID-19 due to immunosuppression, increased comorbidity, and in the case of those with lung malignancies, potential pre-existing lung damage86.Several guidelines issued at the start of the COVID-19 pandemic recommended delaying systemic anticancer treatment until COVID-19 symptoms had completely subsided87. In essence, IPF is a chronic, progressive lung disease with a median survival time of 5.7 years88. Pulmonary fibrosis, similar to other types of fibrosis, is characterized by excessive accumulation of collagen and other matrix proteins, leading to distorting of pulmonary tissue structure and ultimately pulmonary failure89. Moreover, epithelial cell apoptosis and impaired autophagy are increasingly recognized as hallmarks of pulmonary fibrosis90. The causal role of endoplasmic reticulum stress in the pathogenesis of pulmonary fibrosis has been investigated91. The importance of CD4 + T cells producing interleukin-17A has been demonstrated in pulmonary fibrosis92.Results from a recent study suggest that severe COVID-19 can lead to bilateral interstitial pneumonia, which usually results in acute respiratory distress syndrome and pulmonary fibrosis in survivors93. Compared to these two FDA-approved therapeutics for IPF, nebulized triiodothyronine has shown comparable or better effects on pulmonary fibrosis or survival rates94.Previously, IPF has been treated with a variety of chemical agents and drugs. For example, nintedanib and pirfenidone are FDA-approved for the treatment of IPF because they slow disease progression and improve lung function, exercise tolerance, and progression-free survival95. The median overall survival (OS) and 5-year survival rates have historically been poor for patients with NSCLC96. The historical 5-year OS rate for locally advanced NSCLC patients treated with radical concurrent radiotherapy ranges from 25 to 30%97. As the leading cause of cancer-related deaths worldwide, adenocarcinoma of the lung accounts for approximately 50% of lung cancers, making it the most common subtype of NSCLC100. The highly aggressive NSCLC subtype squamous cell carcinoma of the lung accounts for one-third of all lung cancer cases102. The Keap1–Nrf2 pathway was associated with lung squamous cell carcinogenesis and chemoresistance104.According to one study, those with IPF had a significantly higher chance of developing lung cancer than those of the same sex and age. Research supports that lung cancer is the leading cause of cancer-related deaths worldwide, with NSCLC accounting for 85% of cases105. Maintenance therapy has become the standard of care for patients with advanced non-squamous NSCLC106. Of this total, approximately 50% of lung adenocarcinomas are molecularly subdivided, and their treatment depends on the presence of different molecular alterations, including EGFR mutations and ALK or ROS1 fusions, that confer sensitivity to selective kinase inhibitors107. For advanced EGFR-mutated lung adenocarcinoma, first-line therapy involves treatment with EGFR tyrosine kinase inhibitors108. There has been a study indicating that gene-based targeted therapy is the standard of care for patients with advanced NSCLC109. Atezolizumab monotherapy is effective in patients with PD-L1-selected advanced NSCLC110. In parallel, advances in immunotherapy have improved outcomes for a variety of cancers, including NSCLC111. For example, cancer immunotherapy with checkpoint inhibitors improves the survival rate of patients with NSCLC112. Based on the ability of immune checkpoint inhibitors to improve survival rates, these therapeutics have been approved for the treatment of a wide range of cancers, including NSCLC, melanoma, and uroepithelial cancer113. However, STK11 (LKB1) mutations are a major cause of primary resistance to immunotherapy in NSCLC114.Besides, there is growing interest in the potential benefits of antimetastatic treatment for cancers such as lung adenocarcinoma, as a large number of patients are initially diagnosed with localized disease115. All studies suggest that pneumonectomy/metastasectomy is safe and can be performed in the absence of significant morbidity116. For patients with non-metastatic lung cancer, a proportion of patients can be cured after initial surgical resection, radiotherapy and/or a combination of therapeutic approaches117.Surgical resection is currently the treatment option that provides the greatest long-term survival benefit for patients with early-stage NSCLC118. Triple-negative breast cancer is an aggressive form of invasive breast cancer defined by the lack of significant expression of the therapeutic target estrogen receptor, progesterone receptor and HER2119. circKIF4A is a prognostic biomarker and therapeutic target for triple-negative breast cancer120.Oxaliplatin is a first-line treatment for breast cancer and NSCLC121. Among lung cancer cases, 15–30% are SCLC and one-third are diagnosed at the limited stage122. SCLC is an aggressive high-grade neuroendocrine malignancy and one of the deadliest solid tumors123. Among cancer patients, those with SCLC have one of the worst survival rates, with an overall 5-year survival rate of approximately 5%125. SCLC is characterized by a rapid doubling time and high growth fraction, and approximately two-thirds of patients present with metastases at the time of diagnosis126. SCLC is thought to acquire metastatic ability early during tumor progression. A previous study found that NFIB was highly expressed in more than 50% of human SCLC metastases, suggesting that upregulation of this transcription factor may be a driver of SCLC metastasis127. CREBBP plays a key role as a tumor suppressor in SCLC128.Several other studies have reported that loss-of-function mutations in the RB1 gene are common in several refractory cancers, such as SCLC and triple-negative breast cancer129. The combination of a platinum drug and etoposide remains the mainstay treatment for SCLC130. However, cisplatin and etoposide improved progression-free survival (PFS) but failed to improve OS in patients with an extensive stage (ES)-SCLC131. The only FDA-approved drug for recurrent or progressive SCLC is topotecan, which has a response rate of 24% in patients with the platinum-sensitive disease and 2–6% in patients with platinum-refractory SCLC132. Although patients with SCLC usually respond initially to chemotherapy, the tumors almost always recur within 6–12 months, resulting in a 5-year survival rate of less than 7%133. Both DDR inhibition and immune checkpoint blockade are therapeutic strategies in preclinical and clinical development for patients with SCLC134. Patients with stage I to II SCLC have achieved long-term survival after radiotherapy with acceptable toxicity135. Suppression of DNA damage repair by poly [ADP-ribose] polymerase inhibitors have emerged as a potential therapeutic strategy for SCLC136. SCLC is sensitive to THZ1, a covalent CDK7 inhibitor with single-agent activity in T-cell acute lymphoblastic leukemia, MYCN- dependent neuroblastoma, and triple-negative breast cancer138. Pembrolizumab monotherapy is approved as a third-line or later therapy for metastatic SCLC139.SCLC is a rapidly fatal disease with few treatment options 142. Dietary and lifestyle factors may significantly affect the risk of recurrence and death from CRC143. For example, obesity is associated with reduced survival among patients with metastatic CRC, particularly those receiving antiangiogenic therapy144.CRC is the second leading killer behind lung cancer, but must not be underestimated. CRC is one of the most common malignancies of the digestive system and the second most common cancer in the United States; in this country, CRC causes more than 50,000 deaths each year145. Aspirin may be more effective in preventing sporadic CRC in which COX-2 is over-expressed. In CRC, delayed initiation of chemotherapy is associated with a reduction in overall survival146. In patients with stage III CRC, adjuvant chemotherapy may improve OS147. Activation of p38-MAPK signaling due to KRAS mutation in CRC enables secondary colonization of the lungs by established liver metastases148.COX-2 overexpression has been observed in a variety of malignancies, including lung and CRCs149. Human metastatic lung cancer has high levels of HO1 and Bach1; thus, HO1 inhibitors represent an effective therapeutic strategy to prevent lung cancer metastasis150.The specific EGFR inhibitor cetuximab has been used to treat metastatic CRC, metastatic NSCLC and head and neck cancer151. Compared to infection with the Delta variant, with Omicron carries a significantly lower risk of serious outcomes, with a greater reduction in the risk of more serious endpoints but the significant variation with age152. Since the beginning of the pandemic, more than 400 million cases of SARS-CoV-2 infection have been confirmed, including in people with chronic diseases such as cancer, diabetes and heart disease. These people are at high risk of serious illness and death associated with SARS-CoV-2 infection due to poor immune function as a result of pre-existing disease. The ultimate aim of this study was to improve the survival rate of patients with chronic diseases who are infected with SARS-CoV-2.Since the World Health Organization declared a global pandemic on 11 March 2020, SARS- CoV-2 has caused more than 6.2 million deaths worldwide153. The pandemic has severely crowded out medical resources, and deaths from other diseases, such as CRC, have risen sharply. There are two main targets of CRC metastasis, the liver and lungs, but liver metastases are the most common. The liver has the considerable regenerative capacity and can regrow after partial surgical resection, whereas the lungs have no regenerative capacity, and lung function is irreversibly impaired after lung lobe removal due to CRC metastasis. The respiratory system is overwhelmed when patients with CRC lung metastasis become infected with SARS- CoV-2.The COVID-19 pandemic poses an unprecedented challenge to global healthcare resources154. Some graphics-based epidemiological models to simulate disease production and transmission pathways can significantly improve disease transmission control155.Recent studies have shown that a network where nodes are people and edges represent their social connections can effectively mimic the spreading of the virusThere are many limitations to the treatment of cancer. One flaw of chemotherapy drugs is the inability to distinguish between malignant and normal cells; although chemotherapeutics kills cancer cells, they also non-selectively kill normal stem cells that must divide to maintain tissue homeostasis. In contrast, targeted drugs affect specific lesions, accumulating at the target site or releasing an active ingredient at the target site. However, mutation of the target renders the targeted drug ineffective, and drug resistance can occur with the long-term application. Immunotherapy aims to activate the host immune system, relying on its function to kill cancer cells and debulk tumors; this treatment approach is currently only effective in some cancers, and long-term treatment carries the risk of the cytokine storm.Chemotherapy, targeted therapy and immunotherapy essentially kill cancer cells but have no effect on SARS-CoV-2. Only symptomatic treatment for COVID-19 is available, and eliminating the infection is dependent on the host immune system. Chemotherapy, targeted therapy and immunotherapy suppress immune function in cancer patients to varying degrees. If these patients are infected with SARS-CoV-2 while on treatment, their immune function will decrease drastically or even collapse, leading to a variety of serious complications and eventually systemic organ failure and death.As mentioned above, although some specific drugs against SARS-COV-2 have been successfully developed, it is unclear whether they can have a positive effect in the treatment of lung cancer. People are more willing to discover and adopt existing drugs that are now well established to treat covid-19 and its complications. This article uses bioinformatics methods to screen out the 10 most meaningful drugs that act together on these five diseases. We found that these drugs have a positive effect in treating COVID-19 and lung cancer, potentially reducing the risk of pulmonary fibrosis caused by COVID-19. During the COVID-19 pandemic, in-depth research on these drugs may have certain reference significance for the prevention and treatment of complications in lung cancer patients infected with SARS-COV-2.In this study, we identified 79 DEGs between COVID-19, IPF, CRC lung metastasis, SCLC and NSCLC. In our opinion, these DEGs are the common core genes of the 5 diseases. Meanwhile, based on the transcriptome features of DSigDB and common DEGs, we identified 10 drug candidates. The treatment of COVID-19 and lung cancer with these drugs may show positive results, potentially reducing the risk of COVID-19-induced pulmonary fibrosis. This research provides new ideas that have not yet been experimentally validated, and additional scientific research is needed to validate our findings and hypotheses.


Coronary revascularization in patients with spontaneous coronary artery dissection (SCAD) is challenging. Indications and results of percutaneous coronary interventions (PCI) in SCAD patients are not well established.To assess indications and results of PCI in SCAD.The minimum basic data set of the Spanish National Health System (years 2016−2019) was used to identify 804 episodes of acute myocardial infarction (AMI) and SCAD, with a crude in-hospital mortality rate of 3%. Of these, 368 (46.8%) patients were revascularized with PCI during admission whereas 436 (54.2%) were managed conservatively.p = 0.004). However, after adjusting by propensity score (223 pairs) the in-hospital mortality rate was similar in the two groups . Readmissions at 30-days were higher in patients managed conservatively  and this difference was maintained after propensity score adjustment .Revascularization and in-hospital mortality rates both declined over the study period (p for trend both < 0.05). SCAD patients treated with PCI were older, more frequently male, and had higher frequency of diabetes, ST-segment elevation AMI and cardiogenic shock, compared to patients managed conservatively. The crude in-hospital mortality rate was higher in patients treated with PCI (4.9% vs. 1.4%; Revascularization is frequently used in unselected patients with AMI and SCAD but its use is declining. Patients with SCAD treated with PCI have a higher in-hospital mortality but this appears to be explained by their adverse baseline clinical characteristics. Spontaneous coronary artery dissection (SCAD) is a rare but increasingly recognized cause of acute myocardial infarction (AMI) –4. This This study sought to assess the baseline characteristics and clinical outcomes  of patients with SCAD undergoing coronary revascularization, using the registry of the minimum basic data set (MBDS) of the Spanish National Health System (NHS).This is a retrospective observational study of all patients discharged from Spanish NHS hospitals with a diagnosis of AMI, during the period from 01 January 2016 to 31 December 2019. The source of the data was the MBDS of the NHS, using the coding of the International Classification of Diseases 10th Edition Clinical Modification (ICD-10-CM) .with a PCI procedure (AMI-SCAD-PCI); and (2) patients with primary or secondary diagnoses of AMI (ICD-10 codes: I21.x) with primary or secondary diagnoses of SCAD (ICD-10 code: I25.42) –both diagnosis present at admission- without a PCI (AMI-SCAD-NPCI).The study population was divided into two groups: (1) patients with primary or secondary diagnosis of AMI (ICD-10 codes: I21.x) with primary or secondary diagnosis of SCAD (ICD-10 code: I25.42) –both diagnosis present at admission- Multiple hospitalizations resulting from transfers between hospitals were considered as a single care episode. Episodes corresponding to patients under 18 years of age, those registered as voluntary discharges or with an unknown discharge outcome, episodes with stays of 1 day or less and discharged at home, were excluded. Moreover, to increase the diagnostic accuracy of SCAD, episodes with primary or secondary diagnosis of perforation or accidental injury during medical procedure; primary or secondary diagnosis of native or grafted coronary artery arteriosclerosis or transplanted heart disease, or chronic ischemic heart disease; secondary diagnostic of arteriosclerosis; or previous history of AMI, coronary angioplasty or aortocoronary revascularization surgery, were also excluded. ICD-10-CM codes used to identify exclusions are shown in t-test or Mann-Whitney U test, according to their distribution for the unmatched comparison. Temporal trends were analyzed using a χ2 for trend.Categorical variables were expressed as number and percentage, while continuous variables were expressed as mean and standard deviation (SD) or median and interquartile range [25th−75th percentile] according to their distribution. Qualitative variables were analyzed using the chi-squared or the Fisher’s exact test and differences in continuous variables were compared using a 2-sided Student’s Centers for Medicare and Medicaid Services (CMS) for the AMI  > 1.00. Backward elimination regression was then performed with significance for inclusion being p < 0.05 and for elimination being ≥ 0.10. In-hospital mortality ratios were calculated from these specified models and the calibration was analyzed graphically after grouping patients in deciles with respect to the predicted probabilities, and tabulating the mean predicted vs. observed probabilities. Discrimination was assessed by the area under the receiver operating characteristic curves (AUROC). From the specified models, the ratios of in-hospital mortality (RSMR) were calculated , based on the methodology of the , ICD 10,lculated . Cox modp-Value of < 0.05 was considered to be statistically significant. The graphical representation of the matching process was made using Kernel density plots. Statistical analyses were performed with STATA 16 and SPSS v21.0.To minimize potential selection biases in the comparison of outcomes between the two groups, the impact on in-hospital mortality and 30-day readmissions by cardiovascular causes was further assessed by matching propensity scores , selecting among the episodes with AMI-SCAD-PCI those with a profile more similar to each episode of AMI-SCAD-NPCI, according to the variables statistically significant in the risk-adjustment models. The matching was made from the risk adjustment models , with a p = 0.019). The crude in-hospital mortality rate was higher in AMI-SCAD-PCI patients compared with those with AMI-SCAD-NPCI .A total of 804 episodes of AMI-SCAD were identified after exclusions , with a p < 0.001) and calibration (p < 0.001). Coronary revascularization did not have a statistically significant effect on in-hospital mortality when was tested in the logistic regression model .The multilevel logistic regression model for in-hospital mortality did not show an effect at hospital level (median OR: 1). The logistic regression model for in-hospital mortality showed a good discrimination . Mortality results are summarized in In addition, propensity score matching resulted in 223 pairs. p < 0.001). In addition, readmissions due to AMI were also more frequent among AMI-SCAD-NPCI patients . Cox regression model for 30-days readmissions by cardiovascular causes showed a fair discrimination  (p = 0.001). The adjusted hazard ratio for cardiovascular readmissions in AMI-SCAD-PCI patients was also lower than in AMI-SCAD-NPCI patients . Propensity score matching for 30-days cardiovascular readmissions resulted in 196 pairs (p = 0.001). Readmission results are summarized in The crude readmission rate was 1.6% in AMI-SCAD-PCI patients compared with 7.1% in AMI-SCAD-NPCI (2−0.743) . Female The main findings of this large nationwide study on SCAD are the following: (1) Coronary revascularization is still frequently performed in patients with AMI caused by SCAD; (2) Revascularization rates diminished overtime during the study period; (3) SCAD patients undergoing revascularization during hospital admission present with adverse clinical characteristics as compared with those managed conservatively; (4) In-hospital mortality is three-fold higher in patients requiring revascularization, as compared with those managed with medical therapy alone, but after adjusting for the adverse baseline characteristics of revascularized patients, the differences in mortality were no longer statistically significant; (5) Recurrent hospitalization for cardiovascular causes is higher in SCAD patients managed conservatively than in those requiring coronary revascularization and this difference persists after adjusting for potential confounders. Recurrent AMI at 30-days was also more frequently seen in patients treated conservatively.A careful assessment of the clinical presentation and angiographic findings is critical in the clinical decision-making process of coronary revascularization in SCAD. Consensus documents on this entity emphasize that clinical presentation mandates PCI in selected high-risk patients to improve myocardial perfusion and reduce myocardial damage –7. PatieRevascularization of patients with SCAD is challenging and associated with a relatively high rate of procedural-related complications –7. TheseThere are no randomized clinical trials comparing coronary revascularization vs. a conservative medical management in SCAD. Accordingly, the management of these patients is primarily based on observational studies and experts’ opinion –7. CurreObservational studies: Most observational studies assessing results of coronary revascularization in SCAD are small and confounded by selection bias and lack of long-term follow-up and, therefore, the results should be interpreted with major caution. In a classical retrospective study from the Mayo Clinic, Tweet et al. (p < 0.001), and at a median follow-up of 3.7 years . Interestingly, the need for repeated revascularization was higher in the PCI group. However, the results were not corrected for the higher-risk characteristics of patients requiring revascularization. Recently, Kotecha et al. ((a) t et al.  analyzedt et al. , from tha et al.  compareda et al. , 17 compa et al. .Finally, although in our study PCI was more frequently used in men, most previous studies have found a similar rate of coronary revascularization in women and men with SCAD –21. A reMeta-analyses: Meta-analyses are an attractive tool to evaluate all the available evidence, particularly when pooling of small observational studies is required because large studies are unavailable. In an early meta-analysis including 440 SCAD patients Shamloo et al. ((b) o et al.  found tho et al.  performeo et al.  includedAdministrative studies: To the best of our knowledge, the present study is the first analysis comparing the results of coronary revascularization in unselected SCAD patients using a large nationwide administrative dataset. Most previous studies on SCAD using administrative databases have not focused on revascularization results. A recent study using the Nationwide Readmissions Database (years 2010−2015) analyzed SCAD patients according to revascularization status, but only in women ≤ 60 years presenting with AMI , as compared with the conservative therapy group , had more frequently STEMI and cardiogenic shock. Admission to teaching hospitals was associated with conservative therapy. Propensity-score matched analyses (546 pairs) found no significant difference in in-hospital death, 30-day readmission, and recurrent AMI, between the strategies. However, the reason to perform revascularization in up to 2/3 of the SCAD patients in this study, was not clarified. In our study, we did not exclude patients by age or gender. Moreover, the Spanish NHS covers virtually all the population with a medical emergency (including AMI). In addition, most of our patients were treated conservatively, according to recent recommendations. Whether this difference in the revascularization rates is a result of a more recent analysis (years 2016−2019 in our series) or a more conservative approach to SCAD in Europe, as compared with the United States, remains unclear. Interestingly, we detected a declining use of revascularization during the study period. Although one might attribute the declining mortality seen in more recent years to a more frequent use of conservative medical management, this assumption remains speculative, and only should be considered as hypothesis generationg, because this relationship cannot be demonstrated from our data. Furthermore, we used a very strict and restrictive methodology to identify SCAD patients and also well-established criteria  to adjust for the differences between patients with and without revascularization. Our results, demonstrating that the worse prognosis of SCAD patients requiring revascularization is a consequence of their adverse clinical characteristics, are consistent with and complement previous findings from clinical registries on this condition ((c) with AMI . This re years 200−2015 anI n = 1,23, 68%, aondition –17. MoreSome study limitations should be acknowledged. An inherent limitation of any study on AMI based on administrative datasets is the lack of the required clinical and anatomic granularity that impedes a precise characterization of the patients’ profile. The incidence of SCAD is low but variable in the different previous studies in relation to the definition used and the type of study , 26–29. Coronary revascularization is still frequently used in unselected patients with SCAD presenting with AMI although its use is declining in recent years. These patients have adverse clinical characteristics as compared with patients managed medically which appear to explain their higher in-hospital mortality. However, readmissions for cardiac causes at 1 month are reduced in SCAD patients undergoing revascularization during the index hospitalization.Spontaneous coronary artery dissection patients requiring revascularization have adverse clinical characteristics that explain their higher hospital mortality. Revascularization should not be withhold in SCAD when clinically indicated.falf@hotmail.com.The datasets presented in this article come from a nationwide administrative public registry. Requests to access the datasets should be directed to FA, Ethical review and approval was not required for the study on human participants in accordance with the local legislation and institutional requirements. Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.All authors contributed to the design, analysis, drafting, and approved the final version.


Receiver operating characteristic (ROC) curve was conducted to assess the value in predicting effectiveness of oral rehydration saline treatment. The results showed that 33 cases were responders, and 47 were non-responders. Blood sodium  and pre-treatment 24-hour urinary sodium excretion  mmol/24 h, p < 0.001) were lower in responders than in non-responders. The baseline 24-hour urinary sodium excretion was positively correlated to the duration from tilting to the positive response appearance in head-up tilt test . The cut-off value of baseline 24-hour urinary sodium excretion of the therapeutic effectiveness of oral rehydration saline on vasovagal syncope cases was 83 mmol/24 h, yielding a sensitivity of 87% and a specificity of 73% with AUC of 0.842 (p < 0.001). In conclusion, 24-hour urinary sodium excretion could be a useful biomarker to predict the therapeutic response to oral rehydration saline in pediatric cases of vasovagal syncope.The study was designed to explore whether 24-hour urinary sodium excretion could predict the therapeutic effectiveness of oral rehydration saline in pediatric cases of vasovagal syncope. Eighty children suffering from vasovagal syncope with oral rehydration saline treatment in Department of Pediatrics, Peking University First Hospital, China, were recruited into the study. They were followed up for 3  months after treatment. Pre-treatment demographic, clinical, head-up tilt test-based hemodynamic and laboratory variables were compared between responders and non-responders. After univariate analysis, variables with  Vasovagal syncope is a prevalent disease entity of syncope in children, accounting for more than 60% of all pediatric fainting cases . Oral reAt present, it is believed that the pathogenesis of vasovagal syncope mainly includes low circulatory blood volume ,5, high Body mass index (BMI) is a classic and easy-to-obtain measure which is correlated with the body blood volume ,10. It hThis is a case-series study. The study included 84 vasovagal syncope patients who visited the pediatric department, Peking University First Hospital, China and received oral rehydration saline treatment from August 2012 to June 2021. Their median age was 10 years ,12,13. TBased on the Chinese guidelines , vasovagInclusion criteria were: (1) pediatric patients aged 5–16 years old hospitalized at Peking University First Hospital; (2) children diagnosed with vasovagal syncope; (3) with oral rehydration salt treatment; and (4) with demographic data, complete clinical data, electrocardiogram, head-up tilt test data and 24 h urine sodium data.Exclusion criteria were: (1) patients with unknown diagnosis or diagnosis of vasovagal syncope combined with postural tachycardia syndrome; (2) patients with cardiac syncope or pseudosyncope; (3) patients with vomiting, diarrhea, administration of antiemetic, laxatives and diuretics; (4) oral rehydration saline treatment time less than 1 month ; and (5)Head-up tilt test program and positive tests were consistent with the previous description ,14. The A standard urine collection process was offered to each patient, who was asked to collect all urine for 24 h except the first urine. For females, 24 h urine was obtained outside the menstrual period. The 24-hour urinary sodium excretion was tested in an automatic chemical analyzer using standard biochemical detection methods, as described previously ,16.All enrolled children were treated with oral rehydration saline. After three months of sustained treatment, patients were followed up by a professionally trained researcher at the outpatient department of Peking University First Hospital, China or over telephone. None of the patients experienced adverse reactions to saline treatment, such as hypertension. For each patient, a syncope symptom score was assessed both before and after the treatment and those with a score of ≥1 were included in the study as described previously . Treatmet-tests. If the data were not normally distributed, they were presented as median and interquartile range, and analyzed by the Mann–Whitney U test. The stepwise logistic regression was executed to test the associated variables with the therapeutic response to oral rehydration saline. To evaluate the correlation between two variables, we used the Spearman test. The predictive value was defined by Youden indices using receiver operating characteristic (ROC) curve. The predictive ability was measured using the area under the curve (AUC). p < 0.05 denoted statistical significance.Data were analyzed with SPSS 26.0 . The normality of distribution of continuous variables was measured by the Kolmogorov–Smirnov test. Normal distribution data were presented as mean and standard deviation, and analyzed by Student p > 0.05). However, blood sodium, pre-treatment 24-hour urinary sodium excretion and symptom scores after treatment were lower in responders than in non-responders (p < 0.05)  were lost from follow-up . The rem < 0.05) .p < 0.05).The two significant baseline variables obtained from the univariate analysis in the comparison between responders and non-responders (blood sodium and 24-h sodium excretion) were further analyzed by binary logistic regression. The result showed that the twenty-four-hour urine sodium excretion was found to be associated with therapeutic response to oral rehydration saline   .p < 0.001)  . The cutOur study revealed that baseline 24-hour urinary sodium excretion was notably lower in responders than in non-responders. The baseline 24-hour urinary sodium excretion less than 83 mmol/24 h could predict the response to oral rehydration saline treatment in pediatric cases of vasovagal syncope.Many medical centers use salt supplements as the first-line treatment of vasovagal syncope ,18, but The main components of oral rehydration saline are water and sodium salt. As we know, the amount of sodium in the body impacts the amount of extracellular fluid (including plasma) . SupplemIndeed, sensitivity and specificity of BMI  were similar  to thoseIn this study, we showed that the 24-hour urinary sodium excretion was positively correlated to head-up tilt test response time of children with vasovagal syncope. However, the data are scattered underscoring the big interindividual variability, and the r value is low (r = 0.289), which may also be affected by the relatively small sample size. We also showed that the responders had significantly lower baseline 24 h urine sodium excretion than the non-responders. In particular, patients with 24-hour urinary sodium excretion lower than 83 mmol/24 h before treatment responded well to oral rehydration saline, with a predictive sensitivity of 87% and a specificity of 73%, helping in offering an individualized treatment to the affected patients.There are, of course, some limitations in our study. Firstly, the short follow-up period, small sample size and potential selection bias intrinsic to study design may lead to biased results. Secondly, this study assessed each patient’s 24-hour urinary sodium excretion only once, and daily changes are also possible. In future trials, 24-hour urinary sodium excretion should be repeatedly assessed in post-treatment patients. Thirdly, our study only included those treated with oral rehydration saline alone, which, as a basic non-pharmacological treatment, may often be used by physicians in children with milder conditions, leaving our study with some selection bias that needs to be further confirmed in future prospective studies. In addition, in an effort to standardize fluid and salt intake, in this preliminary study, we tested only commercial oral rehydration solutions. However, the simple advice of generous drinking and eating salty is the most widespread management strategy for vasovagal syncope. This should be investigated in further studies. In conclusion, despite the present limitations, this study showed that 24-hour urinary sodium excretion is a valuable indicator for predicting the response to oral rehydration saline treatment in pediatric cases of vasovagal syncope potentially providing some basis for an individualized treatment of vasovagal syncope. Large sample-sized and sufficiently powered studies are warranted to confirm these results.


Whether the safety and efficacy of hepatic resection differ between patients whose hepatocellular carcinoma (HCC) is related to non-alcoholic fatty liver disease (NAFLD) or has other aetiologies is unknown. A systematic review was performed to explore potential differences between such conditions.PubMed, EMBASE, Web of Science, and Cochrane Library were systematically searched for relevant studies that reported hazard ratios (HRs) for overall and recurrence-free survival between patients with NAFLD-related HCC or HCC of other aetiologies.versus 64.0 per cent, P < 0.001). The two groups suffered similar rates of perioperative complications and mortality. Patients with NAFLD-related HCC had slightly higher overall survival  and recurrence-free survival  than those with HCC of other aetiologies. In the various subgroup analyses, the only significant finding was that Asian patients with NAFLD-related HCC had significantly better overall survival  and recurrence-free survival  than Asian patients with HCC of other aetiologies.The meta-analysis involved 17 retrospective studies involving 2470 patients (21.5 per cent) with NAFLD-related HCC and 9007 (78.5 per cent) with HCC of other aetiologies. Patients with NAFLD-related HCC were older and had higher body mass index (BMI), but were less likely to have cirrhosis -related hepatocellular carcinoma (HCC) have similar perioperative complications and mortality compared with those with HCC of other aetiologies. Patients with NAFLD-related HCC have potentially higher overall and recurrence-free survival than those with HCC of other aetiologies. The main causes of HCC are chronic alcohol abuse and chronic infection with hepatitis B virus (HBV) or hepatitis C virus (HCV). The incidence of viral hepatitis-related HCC has decreased in recent years with the emergence and popularization of anti-hepatitis vaccines and antiviral drugs6. Over the past decade, an increasingly prevalent risk factor for HCC in many countries is non-alcoholic fatty liver disease (NAFLD)8. NAFLD refers to a spectrum of liver damage ranging from simple steatosis to non-alcoholic steatohepatitis (NASH), then fibrosis and cirrhosis, and finally to hepatocarcinogenesis. Although the annual incidence of HCC is lower among NAFLD patients than among those infected with HBV or HCV, 25 per cent of the global population is estimated to have NAFLD—with even higher prevalence in high-income areas10—and the prevalence of NAFLD and NAFLD-related HCC is increasing in various countries11–14. These considerations highlight the importance of preventing and treating NAFLD-related HCC.Hepatic resection is the only curative treatment for patients with hepatocellular carcinoma (HCC)16. It is not clear whether these differences translate into a different prognosis after hepatic resection. Two meta-analyses have evaluated the safety and prognosis of hepatic resection for treating NAFLD-related HCC18, but they included relatively few original studies, and several relevant studies have been published since then19–22. Moreover, the meta-analyses were less rigorous in their inclusion criteria, such that some patients in the observation group did not meet diagnostic standards for NAFLD-related HCC23–28, and some patients received palliative treatment instead of resection29–33. Therefore, it was important to conduct an updated systematic review and meta-analysis of relevant clinical studies to compare prognosis after resection between patients with NAFLD-related HCC and patients with HCC of other aetiologies. This updated systematic review aims to provide a reference for selecting treatment for patients with NAFLD-related HCC.Increasing evidence indicates that the pathogenesis and clinical manifestations of NAFLD-related HCC differ from those of HCC with other aetiologies. In addition, diabetes mellitus and obesity promote the progression of NAFLD to HCC34 and PRISMA (Appendix S1). This was a systematic review pooling published data, so no ethical approval was required; since this study incorporated only previously published literature, approval from the local ethics committee to perform the research and informed consent from the patients in the included studies were not obtained.This systematic review and meta-analysis was performed according to the guidelines of MOOSE 35. Patients in the present review were diagnosed with MAFLD if they had hepatic steatosis as well as one of the following: overweight/obesity, defined as a body mass index (BMI) greater than or equal to 23 kg/m2; type 2 diabetes; or other evidence of metabolic disorder35–38. Although MAFLD is closely linked to these metabolic disorders39, its epidemiology is quite similar to that of NAFLD40, so we grouped together data for HCC patients with either NAFLD or MAFLD.In this review, patients with NAFLD-related HCC were grouped together with patients whose HCC was related to metabolic-associated fatty liver disease (MAFLD), which is the term recently proposed to replace NAFLD. MAFLD has been defined as chronic disease involving metabolic dysfunction that leads to accumulation of fat in the liver, such that fat mass accounts for greater than 5 per cent of total liver massThe inclusion criteria, structured according to participants, interventions, comparisons, and outcomes (PICO) were as follows: adult HCC patients without geographical or aetiological limitations; patients who underwent hepatic resection, including laparotomy or laparoscopic surgery; patients who could be assigned to either a group with HCC related to NAFLD or MAFLD, or a group with HCC of other aetiologies; studies reporting data on overall survival (OS) and/or recurrence-free survival (RFS) as outcomes; and studies with a cohort or case-control design. Randomized clinical trials were not included.Exclusion criteria were as follows: the study was a case report, review, or meta-analysis; patients received other therapies for HCC, such as radiofrequency ablation, sorafenib, lenvatinib, or other first-line therapies; or patients had other malignancies in addition to HCC. When multiple studies involved overlapping patient populations, only the largest study was included.PubMed, EMBASE, Scopus, and Cochrane Library databases were systematically searched. Since NAFLD was first proposed in 1980, the database search time was set as 1 January 1980 to 25 June 2022, and the language of publication was limited to English. Search terms were: HCC, hepatoma, liver neoplasm, NAFLD, MAFLD, NASH, surgery, and survival. For example, the search string for the PubMed database was ‘(hepatocellular carcinoma OR liver neoplasm) AND  AND (surgery OR resection OR hepatectomy) AND survival’.Two researchers (J.-Y.S. and Z.-J.D.) independently searched and screened the literature, then extracted relevant data from the included studies. Inconsistencies in the data were resolved through discussion with a third researcher (J.-H.Z.). The literature was screened based on titles, abstracts, and, when necessary, the full text. The following data were extracted from included studies: name of first author, publication year, country, inclusion interval, sample size, HCC aetiology and rate in the control group, average or median age of subjects, BMI, rate of cirrhosis, tumour stage, perioperative mortality, incidence of complications, OS, and RFS. For raw data that were not available, efforts were made to contact the corresponding author.41. Other aetiologies of HCC included: viral hepatitis, related to HBV or HCV infection; alcoholic cirrhosis; and cryptogenic cirrhosis.The primary outcome was the comparison of post-hepatectomy OS between patients with NAFLD- or MAFLD-related HCC (observation group) and patients with HCC with other aetiologies (control group). OS was defined as the time between the day of hepatectomy and the patient’s all-cause death or the end of follow-up. The secondary outcomes included RFS, perioperative mortality, and complication rates. RFS was defined as the time from the day of hepatectomy to the time of HCC recurrence or death, with the first HCC occurrence considered the primary event. Perioperative mortality was defined as death within 30 or 90 days after hepatectomy. Complications were defined as ‘major’ if they were graded as 3a or above according to the Clavien–Dindo classification systemAppendix S2)42. The scale includes eight multiple-choice questions that relate to patient selection, comparisons, and outcomes. Studies were assigned up to nine stars; those receiving at least seven stars were considered of good quality, while those receiving four to six stars were considered of fair quality. Inconsistencies were resolved through discussion with a third researcher (J.-H.Z.).Two researchers (J.-Y.S. and Z.-J.D.) independently evaluated the quality of the included studies using the Newcastle–Ottawa scale (NOS) for quality assessment  if they showed a skewed distribution. OS and RFS in both groups were assessed by combining log-transformed hazard ratios (HRs) and corresponding 95 per cent confidence intervals using an inverse variance, random-effects model. HRs and 95 per cent confidence intervals were extracted directly from the included literature; if these data were not reported, they were estimated indirectly using Parmar’s methodI² statistic and Cochran’s Q test44. The I2 gives a percentage representing the magnitude of heterogeneity between groups. A percentage of 25 per cent was taken to indicate low heterogeneity, a percentage of 50 per cent was taken to indicate moderate heterogeneity, and a percentage of 75 per cent was taken to indicate high heterogeneity. Publication bias was assessed using Egger’s and Begg’s regression analysis of funnel plots45. Subgroup analysis was performed based on geographical region where studies were performed, or based on HCC aetiology. Sensitivity analysis was performed in which individual studies were omitted and the meta-analysis was repeated. Median OS and RFS at 1, 3, and 5 years were estimated with bubble charts, where the size of each bubble represented the sample size of the given study3. Meta-analyses were performed using RevMan (version 5.4.0) and R . All statistical tests were two-sided, and differences associated with P < 0.050 were considered statistically significant.Statistical heterogeneity was assessed using Higgins’ 23–28 or who received palliative treatment29–33, because the studies did not report survival data46 or because of repeat publication47. In the end, 17 retrospective studies were included 48–60.A total of 2492 publications were retrieved from relevant databases based on the inclusion and exclusion criteria. Thirteen publications were excluded because they included patients without steatosisTable 1. The studies covered 28 years (1991–2019). Of the 17 studies, 10 applied standard definitions of NAFLD57–59, 4 applied standard definitions of MAFLD60, 2 applied standard definitions of steatosis56, and 1 applied a standard definition of NASH52. Patients in all studies except one underwent hepatectomy; those in the study applying a standard definition of NASH52 underwent liver transplantation, hepatectomy, and radiofrequency ablation, all of which are radical treatments. All studies had a retrospective cohort design and most (94.1 per cent) showed high quality except one with fair quality53 (Table S1).Basic characteristics of the literature included in this systematic review are shown in Table 1). The prevalence of NALFD-related HCC in Asian patients was significantly higher compared with that in European and US patients . Compared with patients with HCC of other aetiologies, those with NAFLD-related HCC had a higher BMI, they were older in 11 studies59, and they showed significantly lower cirrhosis rates in 11 studies57 of the 15 that reported cirrhosis rates53–60. When cirrhosis rates were calculated across all patients pooled from the studies, prevalence was significantly lower in the observation group than in the control group (P < 0.001). Patients with HCC irrespective of aetiology from Asia and those from the USA and Europe had a similar proportion of cirrhosis . Among patients with NAFLD-related HCC, patients from Asia had a significantly higher proportion of cirrhosis than those from the USA and Europe . However, among patients with HCC of other aetiologies, US and European patients had a significantly higher proportion of cirrhosis than those from Asia . Moreover, the proportion of cirrhosis among patients with NAFLD-related HCC was significantly lower than that among those with alcohol-, HBV-, or HCV-related HCC .The 17 studies included 11 477 patients, including 2470 (21.5 per cent) with NAFLD-related HCC and 9007 (78.5 per cent) with HCC of other aetiologies  and control group .Eight studies reported the incidence of perioperative complications, which was higher in the observation group than in the control group in four studies54, but similar between the observation and control groups in the remaining four studies57. When rates of perioperative mortality were calculated across all patients pooled from the studies, the rate was similar between the observation group  and control group .Seven studies reported perioperative mortality, which was higher in the observation group in three studies52–60 showed that patients with NAFLD-related HCC had marginally higher OS than those with HCC of other aetiologies , as well as higher median OS rates at 1 year (94.5 per cent versus 90.0 per cent), 3 years (75.3 per cent versus 70.2 per cent), and 5 years . This difference became significant among the subset of studies involving Asian patients , but not among the subset of studies involving patients from the US and Europe .Data pooled from the 16 studies that reported OSP = 0.134; Fig. S3) and those with HCC related to alcoholic or cryptogenic cirrhosis . In contrast, the OS of patients with HCC related specifically to NAFLD, based on studies applying standard definitions of NAFLD57–59, was significantly better than the OS of patients with HCC of other aetiologies .In subgroup analyses based on HCC aetiology, patients with NAFLD-related HCC showed similar OS to those with HCC related to HBV or HCV infection , as well as higher median RFS rates at 1 year (80.0 per cent versus 72.0 per cent), 3 years (52.1 per cent versus 45.3 per cent), and 5 years . This difference became significant among the subset of studies involving Asian patients , but not among the subset of studies involving patients from the US and Europe .Data pooled from the 16 studies that reported RFSP = 0.283; Fig. S6) and those with HCC related to alcoholic or cryptogenic cirrhosis . A similar result was found when considering the RFS of patients with HCC related specifically to NAFLD, based on studies applying standard definitions of NAFLD57–59 .In subgroup analyses based on HCC aetiology, patients with NAFLD-related HCC showed similar RFS to those with HCC related to HBV or HCV infection , Jung 202121 (MAFLD versus HBV), and Su 201553 (steatosis versus without) . Moreover, excluding each study one by one altered the meta-analysis of RFS in the case of Liu 202219 (MAFLD versus HBV), Pais 201751 (NAFLD versus HBV), Pais 201751 (NAFLD versus HCV), and Su 201553 (steatosis versus without) .None of the meta-analysis findings changed after the exclusion of patients who underwent liver transplantation or radiofrequency ablationP = 0.487; Fig. S9) or RFS .No significant publication bias was found in funnel plots for OS  and the inclusion criteria are more stringent. All patients in the analysis underwent hepatectomy, and all patients in the observation group fulfilled standard diagnostic criteria for NAFLD- or MAFLD-related HCC. Nevertheless, the meta-analyses showed substantial statistical heterogeneity, especially the meta-analysis of OS. This may reflect that patients were enrolled over a 28-year interval, different medical centres may define fatty liver in different ways, and the patient samples in individual studies differed substantially in the rates of cirrhosis. The influence of these factors on the meta-analyses could not be assessed because of the lack of patient-level data.The finding of similar OS and RFS between the two groups of patients contrasts with the significantly higher survival reported for patients with NAFLD- or MAFLD-related HCC in two previous meta-analyses involving 7226versus 9.0 per cent, P = 1.000) and mortality . These results likely reflect the substantial improvement in surgical techniques and perioperative management of hepatectomy. A systematic review of 14 808 patients who underwent hepatectomy for intermediate or advanced HCC found a low perioperative mortality of 2.7 per cent61.The patients with NAFLD- or MAFLD-related HCC in this review were older and more likely to have diabetes, obesity, hyperlipidaemia, or other metabolic disorders than the patients with HCC of other aetiologies. Nevertheless, the two groups showed similar rates of major perioperative complications . Cirrhosis is an independent risk factor for all-cause mortality in patients with NAFLD, NASH, or HCC. The finding that OS and RFS were significantly higher among patients with NAFLD- or MAFLD-related HCC than among those with HCC of other aetiologies in Asia but not in Europe and the USA may reflect regional differences in HCC aetiology and tumour characteristics63. For example, hepatectomy is often used in Asia to treat HCC patients for whom surgery is not recommended in the USA or Europe64–66. Finally, the results may also reflect the relatively small number of patients from Europe and the USA in the meta-analysis.One explanation for the finding, across all studies, that patients with NAFLD- or MAFLD-related HCC have slightly better OS or RFS than patients with HCC of other aetiologies is the fact that the first group of patients showed a significantly lower prevalence of cirrhosis . However, other studies found that lenvatinib treatment may lead to better OS, while immune checkpoint inhibitors may lead to worse OS when treating NAFLD-related HCC compared with HCC of other aetiologies68. In addition to hepatectomy, liver transplantation and radiofrequency ablation can be applied as radical therapies against HCC. One meta-analysis reported similar post-transplantation OS between patients with NASH-related HCC or HCC of other aetiologies69. Two cohort studies found similar post-ablation OS between patients with NAFLD-related HCC and patients with HCC of other aetiologies70.Many of the patients in five studies71.Half of the patients with NAFLD-related HCC had no cirrhosis. This rate was as high as 63.7 per cent in the US and European populations. However, the proportion of patients without cirrhosis among those with alcohol-, HBV-, or HCV-related HCC was only 35.4 per cent, 33.5 per cent, and 29.7 per cent respectively. Therefore, patients with NAFLD without cirrhosis still need regular surveillance for HCC. This finding based on patients with HCC after hepatectomy was consistent with a previous meta-analysis that included patients with NAFLD-related HCC who underwent curative and palliative treatment strategiesDespite the stricter inclusion criteria, the present meta-analysis involved a substantially larger sample than previous ones. In addition, the present meta-analysis included MAFLD-related HCC and took into account the prevalence of cirrhosis, incidence of major perioperative complications, and mortality. However, it was limited by the fact that the included studies had a retrospective cohort design, with no access to patient-level data. Most patients in the meta-analysis came from Asia, which may reduce the generalizability of the results to other regions. Finally, heterogeneity among included studies was large.This study systematically reviewed post-hepatectomy outcomes of patients with HCC of different aetiologies. The analysis suggests that patients with NAFLD- or MAFLD-related HCC show similar major perioperative complications, mortality, OS, and RFS compared with patients with HCC of other aetiologies. However, Asian patients may have better survival if their HCC is related to NAFLD or MAFLD. The surveillance for HCC in NAFLD patients without cirrhosis is equally important as surveillance for HCC in NAFLD patients with cirrhosis.zrac167_Supplementary_DataClick here for additional data file.