Cancer metabolic reprogramming and precision medicine-current perspective.

Despite the advanced technologies and global attention on cancer treatment strategies, cancer continues to claim lives and adversely affects socio-economic development. Although combination therapies were anticipated to eradicate this disease, the resilient and restorative nature of cancers allows them to proliferate at the expense of host immune cells energetically. This proliferation is driven by metabolic profiles specific to the cancer type and the patient. An emerging field is exploring the metabolic reprogramming (MR) of cancers to predict effective treatments. This mini-review discusses the recent advancements in cancer MR that have contributed to predictive, preventive, and precision medicine. Current perspectives on the mechanisms of various cancer types and prospects for MR and personalized cancer medicine are essential for optimizing metabolic outputs necessary for personalized treatments.

Off­label and unapproved pediatric drug utilization: A meta­analysis.

Despite legislative enforcement on authorized drugs, off-label and unapproved pediatric drug use is prevalent. The present study aimed to assess the global prevalence of off-label and unlicensed prescriptions among hospitalized children via meta-analysis. A comprehensive examination of articles published between 1990 and 2023 from the PubMed, Scopus, Excerpta Medica Database, Web of Science and Google Scholar databases was conducted. Key word-based advanced searches were executed using the aforementioned databases. A total of 45 studies that reported the prescriptions of off-label and unlicensed drugs to pediatric patients were included. The global prevalence of off-label and unlicensed drug prescriptions to children in pediatrics or neonatal departments was 56%. Patient sample sizes varied from 40-13,426, with a range of 240-8,891 total prescriptions issued. Of the 45 studies examined, 22 studies originated from Europe, 13 from Asia, 3 from South America, 3 from Africa, and 2 each from North America and Australia. Africa had the highest prevalence rate at 66%, followed by Asia, South America, North America, Australia and Europe. The present meta-analysis demonstrated that the prevalence of off-label and unlicensed drug prescriptions given to pediatric patients was notably high and geographically diverse. Therefore, drug authorities should standardize pediatric prescription practices in future.

A mini-review-cancer energy reprogramming on drug resistance and immune response.

With the growing interest to harness cancer metabolism and energy reprogramming, this mini review aimed to explain the metabolic programming revealing the mechanisms regarding the treatment resistance. This mini review summarized the prominent cancer metabolic reprogramming on macromolecules. In addition, metabolic reprogramming explaining immune response and treatment resistance as well as energy reprogramming mechanisms are briefly discussed. Finally, some prospects in MR for reversing cancer drug resistance are highlighted.

Current advances in cancer energy metabolism under dietary restriction: a mini review.

The manipulation of the energy or source of food for cancer cells has attracted significant attention in oncology research. Metabolic reprogramming of the immune system allows for a deeper understanding of cancer cell mechanisms, thereby impeding their progression. A more targeted approach is the restriction of cancer cells through dietary restriction (CR), which deprives cancer cells of the preferred energy sources within the tumor microenvironment, thereby enhancing immune cell efficacy. Although there is a plethora of CR strategies that can be employed to impede cancer progression, there is currently no comprehensive review that delineates the specific dietary restrictions that target the diverse metabolic pathways of cancer cells. This mini-review introduces amino acids as anti-cancer agents and discusses the role of dietary interventions in cancer prevention and treatment. It highlights the potential of a ketogenic diet as a therapeutic approach for cancer, elucidating its distinct mechanisms of action in tumor progression. Additionally, the potential of plant-based diets as anti-cancer agents and the role of polyphenols and vitamins in anti-cancer therapy were also discussed, along with some prospective interventions for CR as anti-tumor progression.

Energy metabolism as the hub of advanced non-small cell lung cancer management: a comprehensive view in the framework of predictive, preventive, and personalized medicine.

Energy metabolism is a hub of governing all processes at cellular and organismal levels such as, on one hand, reparable vs. irreparable cell damage, cell fate (proliferation, survival, apoptosis, malignant transformation etc.), and, on the other hand, carcinogenesis, tumor development, progression and metastazing versus anti-cancer protection and cure. The orchestrator is the mitochondria who produce, store and invest energy, conduct intracellular and systemically relevant signals decisive for internal and environmental stress adaptation, and coordinate corresponding processes at cellular and organismal levels. Consequently, the quality of mitochondrial health and homeostasis is a reliable target for health risk assessment at the stage of reversible damage to the health followed by cost-effective personalized protection against health-to-disease transition as well as for targeted protection against the disease progression (secondary care of cancer patients against growing primary tumors and metastatic disease). The energy reprogramming of non-small cell lung cancer (NSCLC) attracts particular attention as clinically relevant and instrumental for the paradigm change from reactive medical services to predictive, preventive and personalized medicine (3PM). This article provides a detailed overview towards mechanisms and biological pathways involving metabolic reprogramming (MR) with respect to inhibiting the synthesis of biomolecules and blocking common NSCLC metabolic pathways as anti-NSCLC therapeutic strategies. For instance, mitophagy recycles macromolecules to yield mitochondrial substrates for energy homeostasis and nucleotide synthesis. Histone modification and DNA methylation can predict the onset of diseases, and plasma C7 analysis is an efficient medical service potentially resulting in an optimized healthcare economy in corresponding areas. The MEMP scoring provides the guidance for immunotherapy, prognostic assessment, and anti-cancer drug development. Metabolite sensing mechanisms of nutrients and their derivatives are potential MR-related therapy in NSCLC. Moreover, miR-495-3p reprogramming of sphingolipid rheostat by targeting Sphk1, 22/FOXM1 axis regulation, and A2 receptor antagonist are highly promising therapy strategies. TFEB as a biomarker in predicting immune checkpoint blockade and redox-related lncRNA prognostic signature (redox-LPS) are considered reliable predictive approaches. Finally, exemplified in this article metabolic phenotyping is instrumental for innovative population screening, health risk assessment, predictive multi-level diagnostics, targeted prevention, and treatment algorithms tailored to personalized patient profiles-all are essential pillars in the paradigm change from reactive medical services to 3PM approach in overall management of lung cancers. This article highlights the 3PM relevant innovation focused on energy metabolism as the hub to advance NSCLC management benefiting vulnerable subpopulations, affected patients, and healthcare at large. Supplementary Information: The online version contains supplementary material available at 10.1007/s13167-024-00357-5.

A bioinformatics approach to systematically analyze the molecular patterns of monkeypox virus-host cell interactions.

Monkeypox has been spreading worldwide since May 2022, when the World Health Organization (WHO) declared the outbreak a "public health emergency of international concern." The spread of monkeypox has posed a serious threat to the health of people around the world, but few studies have been conducted, and the molecular mechanism of monkeypox after infection remains unclear. We therefore implemented a transcriptome analysis to identify signaling pathways and biomarkers in monkeypox-infected cells to help understand monkeypox-host cell interactions. In this study, datasets GSE36854 and GSE11234 were obtained from GEO. Of these, 84 significantly different genes were identified in the dataset GSE36854, followed by KEGG, GO analysis protein-protein interaction (PPI) construction, and Hub gene extraction. We also analyzed the expression regulation of hub genes and screened for drugs targeting hub genes. The results showed that monkeypox-infected cells significantly activated the cellular immune response. The top 10 hub genes are IER3, IFIT2, IL11, ZC3H12A, EREG, IER2, NFKBIE, FST, IFIT1 and AREG. AP-26113 and itraconazole can be used to counteract the inhibitory effect of monkeypox on IFIT1 and IFIT2 and serve as candidate drugs for the treatment of monkeypox virus infection. IRF1 may also be a transcription factor of IFIT. Our results provide a new entry point for understanding how monkeypox virus interacts with its host.

Human myiasis in Sub-Saharan Africa: A systematic review.

BACKGROUND: Human myiasis is a parasitic dipteran fly infestation that infects humans and vertebrates worldwide. However, the disease is endemic in Sub-Saharan Africa and Latin America. In Sub-Saharan Africa, it is under-reported and therefore its prevalence is unknown. This systematic review aims to elucidate the prevalence of human myiasis, factors that influence the infection, and myiasis-causing fly species in SSA. The review also dwelled on the common myiasis types and treatment methods of human myiasis. METHODS: Here, we collect cases of human myiasis in Sub-Saharan Africa based on literature retrieved from PubMed, Google Scholar and Science Direct from 1959 to 2022. A total of 75 articles and 157 cases were included in the study. The recommendations of PRISMA 2020 were used for the realization of this systematic review. RESULTS: In total, 157 cases of human myiasis in SSA were reviewed. Eleven fly species (Cordylobia anthropophaga, Cordylobia rodhaini, Dermatobia hominis, Lucilia cuprina, Lucilia sericata, Oestrus ovis, Sarcophaga spp., Sarcophaga nodosa, Chrysomya megacephala, Chrysomya chloropyga and Clogmia albipuntum) were found to cause human myiasis in SSA. Cordylobia anthropophaga was the most prevalent myiasis-causing species of the reported cases (n = 104, 66.2%). More than half of the reported cases were from travelers returning from SSA (n = 122, 77.7%). Cutaneous myiasis was the most common clinical presentation of the disease (n = 86, 54.7%). Females were more infected (n = 78, 49.6%) than males, and there was a higher infestation in adults than young children. CONCLUSION: The findings of this study reveals that international travelers to Sub-Saharan Africa were mostly infested therefore, we recommend that both international travelers and natives of SSA be enlightened by public health officers about the disease and its risk factors at entry points in SSA and the community level respectively. Clinicians in Sub-Saharan Africa often misdiagnose the disease and most of them lack the expertise to properly identify larvae, so we recommend the extensive use of molecular identification methods instead.

High expression of KIFC1 is a poor prognostic biomarker and correlates with TP53 mutation in lung cancer.

The Kinesin Family Member C1 (KIFC1) is highly expressed in a variety of tumors. Since it is linked with tumorigenesis and progression, KIFC1 has emerged as a promising candidate for targeted chemotherapies. Thus, this study aims to find out the association between KIFC1 and lung cancer. The original data were assessed from The Cancer Genome Atlas and Gene Expression Omnibus databases. Compared to normal lung tissues, both mRNA and protein levels of KIFC1 were significantly increased in lung cancer tissues. The upregulation of KIFC1 was significantly correlated with sex, pathological stage, and TMN stage. Survival analysis revealed that increased KIFC1 expression was associated with poor overall survival, first-progression survival and post-progression survival in lung cancer. Based on the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis, we observed that KIFC1 upregulation was linked to enrichment of the cell cycle and TP53 signaling pathway. Additionally, the overexpression of KIFC1 was positively correlated with TP53 mutations in lung cancer. Based on real-world cohort results, western blotting and RT-qPCR showed high-KIFC1 expression in lung cancer, which may be related to the malignancy of lung cancer. Finally, experiments in vitro showed that KIFC1 inhibitor could significantly inhibit the proliferation and invasion of lung cancer cells. In conclusion, KIFC1 is a poor prognostic biomarker, and patients with high-KIFC1 levels may benefit from targeted therapy.

Cancer energy reprogramming and the immune responses.

Cancer as an uncontrolled growth of cells due to existing mutation in host cells that may proliferate, induce angiogenesis and sometimes metastasize due to the favorable tumor microenvironment (TME). Since it kills more than any disease, biomedical science does not relent in studying the exact pathogenesis. It was believed to be a problem that lies in the nucleus of the host cells; however, recent oncology findings are shifting attention to the mitochondria as an adjuvant to cancer pathogenesis. The changes in the gene are strongly related to cellular metabolism and metabolic reprogramming. It is now understood that reprogramming the TME will have a direct effect on the immune cells' metabolism. Although there are a number of studies on immune cells' response towards tumor energy reprogramming and cancer progression, there is still no existence with the updated collation of these immune cells' response to distinct energy reprogramming in cancer studies. To this end, this mini review shed some light on cancer energy reprogramming mechanisms and enzyme degradation pathways, the cancer pathogenicity activity series involved with reduced lactate production, the specific immune cell responses due to the energy reprogramming. This study highlighted some prospects and future experiments in harnessing the host immune response towards the altered energy metabolism due to cancer.

The connection between epigenetics and gut microbiota-current perspective.

Both the epigenetic changes and gut microbiota (GM) have attracted a growing interest in establishing effective diagnostics and potential therapeutic strategies for a number of diseases. These disorders include metabolic, central nervous system-related diseases, autoimmune, and gastrointestinal infections (GI). Despite the number of studies, there is no extensive review that connects the epigenetics modifications and GM as biomarkers that could confer effective diagnostics and confer treatment options. To this end, this review hopes to give detailed information on connecting the modifications in epigenetic and GM. An updated and detailed information on the connection between the epigenetics factors and GM that influence diseases are given. In addition, the review showed some associations between the epigenetics to the maternal GM and offspring health. Finally, the limitations of the concept and prospects into this new emerging discipline were also looked into. Although this review elucidated on the maternal diet and response to offspring health with respect to GM and epigenetic modifications, there still exist various limitations to this newly emerging discipline. In addition to integrating complementary multi-omics data, longitudinal sampling will aid with the identification of functional mechanisms that may serve as therapeutic targets. To this end, this review gave a detailed perspective into harnessing disease diagnostics, prevention and treatment options through epigenetics and GM.

Oligoribonuclease mediates high adaptability of P. aeruginosa through metabolic conversion.

BACKGROUND: Oligoribonuclease (orn) of P. aeruginosa is a highly conserved exonuclease, which can regulate the global gene expression levels of bacteria through regulation of both the nanoRNA and c-di-GMP. NanoRNA can regulate the expression of the bacterial global genome as a transcription initiator, and c-di-GMP is the most widely second messenger in bacterial cells. OBJECTIVE: This study seeks to elucidate on the regulation by orn on pathogenicity of P. aeruginosa. METHODS: P. aeruginosa with orn deletion was constructed by suicide plasmid homologous recombination method. The possible regulatory process of orn was analyzed by TMT quantitative labeling proteomics. Then experiments were conducted to verify the changes of Δorn on bacterial motility, virulence and biofilm formation. Bacterial pathogenicity was further detected in cell and animal skin trauma models. ELISA detection c-di-GMP concentration and colony aggregation and biofilm formation were observed by scanning electron microscope. RESULTS: orn deletion changed the global metabolism of P. aeruginosa and reduced intracellular energy metabolism. It leads to the disorder of the quorum sensing system, the reduction of bacterial motility and virulence factors pyocyanin and rhamnolipids. But, orn deletion enhanced pathogenicity in vitro and in vivo, a high level of c-di-GMP and biofilm development of P. aeruginosa. CONCLUSION: orn regulates the ability of P. aeruginosa to adapt to the external environment.

The influence of maternal diet on offspring's gut microbiota in early life.

BACKGROUND: The influence of maternal diet on offspring's health is an area of study that is linked to epigenetics. Maternal diet contributes to determining the health status of offspring and maternally linked mechanisms and is a global health challenge that requires attention. The impact of gut microbiota on host metabolism and offspring health is still not established. OBJECTIVE: In this review, we intend to discuss the evidence on the impact of maternal diet and the health of offspring gut microbiota. The paper focuses on the gut microbiome of animal models. It captures the maternal diet and its influence on the offspring's gut microbiota, behavior that is supported by cell experimental results. Both inflammation and immune status of offspring induced by maternal diet are discussed. Finally, this review used predicted biological pathways involved in maternal diet and offspring health, and the influence of maternal diet on gut microbiota and offspring behavior. Obesity, diabetes, asthma and allergies, and neurodegenerative disorders and prospects for maternal diet, and microbiota and offspring health were discussed. CONCLUSION: The review was able to gather that a high-fat diet during pregnancy created a long-lasting metabolic signature on the infant's innate immune system, altering inflammation in the offspring microbiota, which predisposed offspring to obesity and metabolic diseases in adulthood.

Respiratory syncytial virus infection disrupts pulmonary microbiota to induce microglia phenotype shift.

The lung-brain axis is an emerging biological pathway that is being investigated in relation to microbiome medicine. Increasing evidence suggests that pulmonary viral infections can lead to distinct pathological imprints in the brain, so there is a need to explore and understand this mechanism and find possible interventions. This study used respiratory syncytial virus (RSV) infection in mice as a model to establish the potential lung-brain axis phenomenon. We hypothesized that RSV infection could disrupt the lung microbiota, compromise immune barriers, and induce a significant shift in microglia phenotype. One week old mice were randomized into the control, Ampicillin, RSV, and RSV+Ampicillin treated groups (n = 6 each). Seven days after the respective treatments, the mice were anaesthetized. Immunofluorescence and real-time qRT-PCR was used to detect virus. Hematoxylin-eosin staining was used to detect histopathology. Malondialdehyde and superoxide dismutase were used to determine oxidative stress and antioxidant capacity. Real-time qRT-PCR and enzyme-linked immunosorbent assay (ELISA) were used to measure Th differentiation in the lung. Real-time qRT-PCR, ELISA, and confocal immunofluorescence were used to determine the microglia phenotype. 16S DNA technology was used to detect lung microflora. RSV infection induces elevated oxidative stress, reduced antioxidant, and significant dysbacteriosis in the lungs of mice. Pulmonary microbes were found to enhance Th1-type immunoreactivity induced by RSV infection and eventually induced M1-type dominant microglia in the brains of mice. This study was able to establish a correlation between the pulmonary microbiome and brain function. Therefore, we recommend a large sample size study with robust data analysis for the long-term effects of antibiotics and RSV infection on brain physiology.

Crosstalk between the lung microbiome and lung cancer.

The human microbiome is a complex ecosystem that mediates interaction between the human host and the environment. All of the human body is colonized by microorganisms. The lung as an organ used to be considered sterile. Recently, however, there has been a growing number of reports with evidence that the lungs are also in a state of carrying bacteria. The pulmonary microbiome is associated with many lung diseases and is increasingly reported in current studies. These include; chronic obstructive pulmonary disease (COPD), asthma, acute chronic respiratory infections, and cancers. These lung diseases are associated with reduced diversity and dysbiosis. It directly or indirectly affects the occurrence and development of lung cancer. Very few microbes directly cause cancer, while many are complicit in cancer growth, usually working through the host's immune system. This review focuses on the correlation between lung microbiota and lung cancer, and investigates the mechanism of action of lung microorganisms on lung cancer, which will provide new and reliable treatments and diagnosis of lung cancer in the future.

The gut microbiota pathway mechanisms of diabetes.

The contribution of dysbiotic gut microbiota configuration is essential when making reference to the metabolic disorders by increasing energy. It is important to understand that the gut microbiota induced metabolic disease mechanisms and inflammations. Thus it is imperative to have an insight into the state of all chronic subclinical inflammations influencing disease outcomes. However, from the emerging studies, there still exist inconsistencies in the findings of such studies. While making the best out of the reasons for inconsistencies of the findings, this review is designed to make a clear spell out as to the inconsistence of gut microbiota with respect to diabetes. It considered gut-virome alterations and diabetes and gut-bacteriome-gut-virome-alterations and diabetes as confounding factors. The review further explained some study design strategies that will spontaneously eliminate any potential confounding factors to lead to a more evidence based diabetic-gut microbiota medicine. Lipopolysaccharide (LPS) pro-inflammatory, metabolic endotoxemia and diet/gut microbiota insulin-resistance and low-grade systemic inflammation induced by gut microbiota can trigger pro-inflammatory cytokines in insulin-resistance, consequently, leading to the diabetic condition. While diet influences the gut microbiota, the consequences are mainly the constant high levels of pro-inflammatory cytokines in the circulatory system. Of recent, dietary natural products have been shown to be anti-diabetic. The effects of resveratrol on the gut showed an improved lipid profile, anti-inflammatory properties and ameliorated the endotoxemia, tight junction and glucose intolerance.

miR-34b/c-5p/CXCL10 Axis Induced by RSV Infection Mediates a Mechanism of Airway Hyperresponsive Diseases.

Background: RSV is closely correlated with post-infection airway hyperresponsive diseases (AHD), but the mechanism remains unclear. Objective: Due to the pivotal role of miRNAs in AHD, we analyzed the differentially expressed miRNAs (DEmiRs) in RSV-infected patients, asthma patients, and COPD patients from public datasets and explored the mechanisms of association between RSV and AHD. Methods: We obtained miRNA and mRNA databases of patients with RSV infection, as well as miRNA databases of asthma and COPD patients from the GEO database. Through integrated analysis, we screened DEmiRs and DEGs. Further analysis was carried out to obtain the hub genes through the analysis of biological pathways and enrichment pathways of DEGs targeted by DEmiRs and the construction of a protein-protein interaction (PPI) network. Results: The five differential molecules (miR-34b/c-5p, Cd14, Cxcl10, and Rhoh) were verified through in vivo experiments that had the same expression trend in the acute and chronic phases of RSV infection. Following infection of BEAS-2B cells with RSV, we confirmed that RSV infection down-regulated miR-34b/c-5p, and up-regulated the expression levels of CXCL10 and CD14. Furthermore, the results of the dual-luciferase reporter assay showed that CXCL10 was the target of hsa-miR-34c-5p. Conclusions: miR-34b/c-5p/CXCL10 axis mediates a mechanism of AHD.

The predicted mechanisms and evidence of probiotics on type 2 diabetes mellitus (T2DM).

Type 2 diabetes mellitus (T2DM) is a serious endocrine and metabolic disease that is highly prevalent and causes high mortality and morbidity rates worldwide. This review aims to focus on the potential of probiotics in the management of T2DM and its complications and to summarise the various mechanisms of action of probiotics with respect to T2DM. In this review, experimental studies conducted between 2016 and 2022 were explored. The possible mechanisms of action are based on their ability to modulate the gut microbiota, boost the production of short-chain fatty acids (SCFAs) and glucagon-like peptides, inhibit α-glucosidase, elevate sirtuin 1 (SIRT1) levels while reducing fetuin-A levels, and regulate the level of inflammatory cytokines. This review recommends carrying out further studies, especially human trials, to provide robust evidence-based knowledge on the use of probiotics for the treatment of T2DM.IMPACT STATEMENTT2DM is prevalent worldwide causing high rates of morbidity and mortality.Gut microbiota play a significant role in the pathogenesis of T2DM.Probiotics can be used as possible therapeutic tools for the management of T2DM.The possible mechanisms of action of probiotics include modulation of the gut microbiota, production of SCFAs and glucagon-like peptides, inhibition of α-glucosidase, raising SIRT1, reducing fetuin-A levels, and regulating the level of inflammatory cytokines.

Gimap5 promoted RSV degradation through interaction with M6PR.

Respiratory syncytial virus (RSV) is one of the main pathogens of viral pneumonia and bronchiolitis in infants and young children and life-threatening diseases among infants and young children. GTPases of the immune-associated protein family (GIMAP) are new family members of immune-associated GTPases. In recent years, much attention has been paid to the function of the GIMAP family in coping with infection and stress. Gimap5 is a member of the GIMAP family, which may be correlated with anti-infectious immunity. RT-qPCR, Western blot, and indirect immunofluorescence (IFA) were used to detect the expression of Gimap5, M6PR and IGF1R(the major RSV receptor). Transmission electron microscopy (TEM) was used to detect the degradation of RSV in Gimap5-overexpressed or -silent cell lines. Computer virtual screening was used to screen small molecule compounds targeting Gimap5 and the anti-RSV effects were explored through in vivo and in vitro experiments. GIMAP5 and M6PR were significantly downregulated after RSV infection. Gimap5 accelerated RSV degradation in lysosomes by interacting with M6PR, and further prevented RSV invasion by downregulating the expression of RSV surface receptor IGF1R. Three small molecule compounds targeting Gimap5 were confirmed to be the agonists of Gimap5. The three compounds effectively inhibited RSV infection and RSV-induced complications. Gimap5 promotes the degradation of RSV and its receptor through interacting with M6PR. Gimap5 agonists can effectively reduce RSV infection and RSV-induced complication in vivo and in vitro, which provides a new choice for the treatment of RSV.

Prevalence and associated influential factors of mental health problems among Chinese college students during different stages of COVID-19 pandemic: A systematic review.

This systematic review aims to take China as an example to determine the prevalence of mental health problems and associated influential factors of college students in different stages of the COVID-19 pandemic and provide a reference for effective intervention in the future. A systematic search was conducted on PubMed, Web of Science, Scopus, Science Direct, and Google scholar. A total of 30 articles were included. 1,477,923 Chinese college students were surveyed. In the early stage, the prevalence rates of depression, anxiety, stress, and PTSD ranged from 9.0% to 65.2%, 6.88%-41.1%, 8.53%-67.05%, and 2.7%-30.8%, respectively. Major risk factors were being a female, a medical student, isolation or quarantine, having family members or friends infected with COVID-19, and challenges of online learning. During the normalization stage, depression, anxiety, and insomnia prevalence rates ranged from 8.7% to 50.2%, 4.2%-34.6%, and 6.1%-35.0%, respectively. The main risk factors were self-quarantined after school reopening, regular taking temperature, and wearing face masks. The prevalence rates of mental health problems and associated influential factors unveiled in both stages showed that the students' mental health status was greatly affected. Therefore, a combination of efforts from the government, universities, and families or communities is highly needed to alleviate the mental health sufferings of students.