Synergistic effects of achieving perinatal interventions on bronchopulmonary dysplasia in preterm infants.

To investigate the effect of perinatal interventions on the risk of severe BPD (sBPD) and death in extremely preterm infants (EPIs) and their synergistic effects. This was a secondary analysis of the prospective cohort Chinese Neonatal Network (CHNN). Infants with a birth weight of 500 to 1250 g or 24-28 weeks completed gestational age were recruited. The impacts and the synergistic effects of six evidence-based perinatal interventions on the primary outcomes of sBPD and death were assessed by univariate and multivariable logistic regression modeling. Totally, 6568 EPIs were finally enrolled. Antenatal corticosteroid (adjusted OR, aOR, 0.74; 95%CI, 0.65-083), birth in centers with tertiary NICU (aOR, 0.64; 95%CI, 0.57-0.72), preventing intubation in the delivery room (aOR, 0.65; 95%CI, 0.58-0.73), early caffeine therapy (aOR, 0.59; 95%CI, 0.52-0.66), and early extubating (aOR, 0.42; 95%CI 0.37-0.47), were strongly associated with a lower risk of sBPD and death while early surfactant administration was associated with a lower risk of death (aOR, 0.84; 95%CI, 0.72, 0.98). Compared with achieving 0/1 perinatal interventions, achieving more than one intervention was associated with decreased rates (46.6% in 0/1 groups while 38.5%, 29.6%, 22.2%, 16.2%, and 11.7% in 2/3/4/5/6-intervention groups respectively) and reduced risks of sBPD/death with aORs of 0.76(0.60, 0.96), 0.55(0.43, 0.69), 0.38(0.30, 0.48), 0.28(0.22, 0.36), and 0.20(0.15, 0.27) in 2, 3, 4, 5, and 6 intervention groups respectively. Subgroup analyses showed consistent results. CONCLUSION: Six perinatal interventions can effectively reduce the risk of sBPD and death in a synergistic form. WHAT IS KNOWN: • Bronchopulmonary dysplasia (BPD) is a multifactorial chronic lung disease associated with prematurity. The effective management of BPD requires a comprehensive set of interventions. However, the extent to which these interventions can mitigate the risk of severe outcomes, such as severe BPD or mortality, or if they possess synergistic effects remains unknown. WHAT IS NEW: • The implementation of various perinatal interventions, such as prenatal steroids, birth in centers with tertiary NICU, early non-Invasive respiratory support, surfactant administration within 2 hours after birth, early caffeine initiation within 3 days, and early extubation within 7 days after birth has shown promising results in the prevention of severe bronchopulmonary dysplasia (BPD) or mortality in extremely preterm infants. Moreover, these interventions have demonstrated synergistic effects when implemented in combination.

Heme induces intestinal epithelial cell ferroptosis via mitochondrial dysfunction in transfusion-associated necrotizing enterocolitis.

Transfusion-associated necrotising enterocolitis (TANEC) is a life-threatening disease with a poor prognosis in preterm infants. This study explored whether and how heme induces ferroptosis in TANEC gut injury. A TANEC mouse model and a cell culture system for heme and Caco-2 cells were established. Ferroptosis was assessed by measuring iron and malondialdehyde (MDA) levels and mitochondrial morphology in intestinal tissues and Caco-2 cells. Mitochondrial dysfunction was evaluated by measuring mitochondrial reactive oxygen species (ROS) production and membrane potential using JC-1. The intestinal injury grade was higher in the anemia-transfusion group than in the control group (p < .0001). Higher intestinal iron concentration (p < .0001), elevated levels of lipid peroxidation MDA (p = .0021), and ferroptotic mitochondrial morphological changes were found in mice of the anemia-transfusion group; specific ferroptosis inhibitor could alleviate anemia-transfusion gut injury, suggesting that ferroptosis play a role in the TANEC gut injury. Next, we explored whether heme released by hemolysis of erythrocytes induces ferroptosis in intestinal epithelial cells in vitro. The viability of Caco-2 cells significantly decreased after heme treatment (p < .0001). Iron accumulation, MDA elevated levels, and mitochondrial dysfunction also existed in the co-culture system, which ferroptosis inhibitors could reduce. In summary, ferroptosis was discovered in TANEC, and heme could induce ferroptosis in intestinal epithelial cells via mitochondrial dysfunction. Heme-inducing ferroptosis may be a possible mechanism and therapeutic target for TANEC.

Surface acoustic wave manipulation of bioparticles.

The introduction of surface acoustic waves (SAWs) into lab-on-a-chip microfluidic systems has contributed to the development of a new cutting-edge technology-SAW-based micro/nano manipulation. Recently, the SAW technology has emerged as an important tool for manipulating micro/nano particles/cell populations by virtue of its simplicity, biocompatibility, non-invasiveness, scalability, and versatility. In custom-designed acoustic fields, this technology can be used to manipulate cells, bacteria, exosomes, and even worms precisely, and it has been used in applications such as biomedical and point-of-care diagnostic systems. In this review paper, we start by providing a comprehensive overview of the fundamental working principle and numerical simulation of SAW-based manipulation. Then, we introduce the recent advancements in the manipulation of organisms based on standing and traveling SAWs, including separation, concentration, and transport. At the end of the review, we discuss the current challenges to and future prospects of SAW-based manipulation. The conclusion is that the SAW technology will open up a new frontier in the microfluidics field and contribute significantly to the development of bioengineering research and applications.

Comparison of lung ultrasound scores with clinical models for predicting bronchopulmonary dysplasia.

Lung ultrasound scores (LUSs) have been demonstrated to accurately predict moderate-to-severe bronchopulmonary dysplasia (msBPD). This study attempted to explore the additional value of LUSs for predicting msBPD compared to clinical multivariate models in different gestational age (GA) groups. The study prospectively recruited preterm infants with GA < 32 weeks. Lung ultrasound was performed on days 3, 7, 14, and 21 after birth. A linear mixed-effects regression model was used to evaluate LUS evolution in infants born before and after 28 weeks. The receiver operating characteristic (ROC) procedure was used to analyze the reliability of LUS and clinical multivariable models for predicting msBPD. The optimal time to predict msBPD in all infants was 7 days with a cut-off point of 5 (area under the ROC (AUROC) curve: 0.78, 95% confidence interval (CI): 0.71-0.84). In infants with GA ≥ 28 weeks, LUSs provided a moderate diagnostic accuracy for all four time points (AUROC curve: 0.74-0.78), and the AUROC curve for the clinical multivariable model on day 14 was 0.91 (95% CI: 0.84-0.96), which was significantly higher than that of LUSs (AUROC curve: 0.77, 95% CI: 0.68-0.85, P < 0.05). In infants born at 23-27 weeks, LUSs showed a low diagnostic accuracy with higher cut-off points to predict msBPD, and the AUROC curve for GA to predict msBPD was 0.75 (95% CI: 0.59-0.85), providing diagnostic accuracy similar to that of LUSs.  Conclusion: The contribution of LUSs to predict msBPD in infants with different GAs remains controversial and requires further investigation. What is Known: • Lung ultrasound scores (LUSs) have been demonstrated to accurately predict moderate-to-severe bronchopulmonary dysplasia in infants with gestational age (GA)＜32 weeks. What is New: • The LUSs evolution differed between extremely preterm infants born before 28 weeks and preterm infants born at 28-32 weeks of gestation. • LUSs provided similar moderate predictive performance as GA-adjusted LUS and clinical multivariate models in infants born after 28 weeks, while LUSs seem to be less helpful in infants born before 28 weeks.

Concentration optimization of combinatorial drugs using Markov chain-based models.

BACKGROUND: Combinatorial drug therapy for complex diseases, such as HSV infection and cancers, has a more significant efficacy than single-drug treatment. However, one key challenge is how to effectively and efficiently determine the optimal concentrations of combinatorial drugs because the number of drug combinations increases exponentially with the types of drugs. RESULTS: In this study, a searching method based on Markov chain is presented to optimize the combinatorial drug concentrations. In this method, the searching process of the optimal drug concentrations is converted into a Markov chain process with state variables representing all possible combinations of discretized drug concentrations. The transition probability matrix is updated by comparing the drug responses of the adjacent states in the network of the Markov chain and the drug concentration optimization is turned to seek the state with maximum value in the stationary distribution vector. Its performance is compared with five stochastic optimization algorithms as benchmark methods by simulation and biological experiments. Both simulation results and experimental data demonstrate that the Markov chain-based approach is more reliable and efficient in seeking global optimum than the benchmark algorithms. Furthermore, the Markov chain-based approach allows parallel implementation of all drug testing experiments, and largely reduces the times in the biological experiments. CONCLUSION: This article provides a versatile method for combinatorial drug screening, which is of great significance for clinical drug combination therapy.

Prediction of generalization of ocular myasthenia gravis under immunosuppressive therapy in Northwest China.

BACKGROUND: It is well demonstrated that immunosuppressants can reduce, but not eliminate the risk of generalized development in ocular myasthenia gravis (OMG). In this study, we aimed to explore the predictive factors of generalized conversion of OMG patients who received immunosuppressive treatments. METHODS: OMG patients under immunosuppressive treatments in Tangdu Hospital from June 2008 to June 2012 were retrospectively reviewed. Baseline clinical characteristics were documented. Patients were followed up regularly by face-to-face interview and the main outcome measure was generalized conversion. The logistic regression analysis was performed to determine the predictive factors of generalization of OMG. RESULTS: Two hundred twenty-three eligible OMG patients completed the final follow-up visit and 38 (17.0%) progressed to generalized MG (GMG) at a median time to generalization of 0.9 year. Patients with adult onset and positive repetitive nerve stimulation (RNS) of facial or axillary nerve had higher conversion rate than those with juvenile onset and negative RNS (p = 0.001; p = 0.019; p = 0.015, respectively). Adult-onset patients converted earlier than juvenile-onset OMG patients (p = 0.014). Upon multivariate logistic regression analysis, age of onset (Odds ratio [OR] 1.023, 95% confidence interval [CI] 1.006-1.041, p = 0.007) and positive facial nerve RNS (OR 2.826, 95%CI 1.045-5.460, p = 0.038) were found to be positively associated with generalized development. Moreover, an obviously negative association was found for disease duration (OR 0.603, 95%CI 0.365-0.850, p = 0.019). CONCLUSIONS: Age of onset, disease duration and facial nerve RNS test can predict generalized conversion of OMG under immunosuppressive therapy. Adult-onset, shorter disease duration and facial nerve RNS-positive OMG patients have a higher risk of generalized development.

Potential effects of SARS-CoV-2 infection during pregnancy on fetuses and newborns are worthy of attention.

The outbreak of the 2019 novel coronavirus disease (SARS-CoV-2) has resulted in a major epidemic threat worldwide. However, the effects of neoviruses on infected pregnant women and especially on their fetuses and newborns are not well understood. Most up-to-date evidences about how SARS-CoV-2 affected patients especially in pregnancy were collected by conducting a comprehensive search of medical literature electronic databases. Immune-related data of pregnant women, fetuses and newborns were further analysis. According to the limited literature, SARS-CoV-2 utilizes angiotensin converting enzyme 2 as its receptor and causes severe hypoxemia. Insufficiency of angiotensin converting enzyme 2 in pregnant women and the effects of hypoxia on the placental oxygen supply will cause severe perinatal complications. In addition, SARS-CoV-2 infection may disrupt maternal-fetal immune tolerance and cause immunological damage to embryos. Because of these reasons, pregnancy complications such as fetal demise or premature birth, preeclampsia, intrauterine growth restriction, respiratory dyspnea, nervous system dysplasia and immune system defects are likely to occur in pregnant women with COVID-19 or their newborns. Pregnant women infected with SARS-CoV-2 should be treated as a special group and given special attention. Fetuses and newborns of SARS-CoV-2-infected pregnant women should be given more protection to reduce the occurrence of adverse events. In this review, we intend to provide an overview of the physiological and immunological changes that induce the pregnancy complications. This article will benefit the treatment and prognosis of fetuses and newborns of SARS-CoV-2-infected pregnant women.

Imaging and Force Recognition of Single Molecular Behaviors Using Atomic Force Microscopy.

The advent of atomic force microscopy (AFM) has provided a powerful tool for investigating the behaviors of single native biological molecules under physiological conditions. AFM can not only image the conformational changes of single biological molecules at work with sub-nanometer resolution, but also sense the specific interactions of individual molecular pair with piconewton force sensitivity. In the past decade, the performance of AFM has been greatly improved, which makes it widely used in biology to address diverse biomedical issues. Characterizing the behaviors of single molecules by AFM provides considerable novel insights into the underlying mechanisms guiding life activities, contributing much to cell and molecular biology. In this article, we review the recent developments of AFM studies in single-molecule assay. The related techniques involved in AFM single-molecule assay were firstly presented, and then the progress in several aspects (including molecular imaging, molecular mechanics, molecular recognition, and molecular activities on cell surface) was summarized. The challenges and future directions were also discussed.

Umbilical cord milking reduces need for red cell transfusions and improves neonatal adaptation in preterm infants: Meta-analysis.

AIM: To assess effects of umbilical cord milking (UCM) on early blood pressure stabilization, hemoglobin (Hb), as well as incidence of transfusion and complications in preterm infants. METHODS: This meta-analysis was conducted by searching the Pubmed, EMBASE and Cochrane Library (until July 2014) databases. Any clinical trials, including randomized control trials, comparing UCM to immediate cord clamping (ICC) were analyzed. RESULTS: Six studies were included in this meta-analysis. In total, 292 preterm infants were treated with UCM, while 295 received ICC. Compared to ICC, UCM increased initial Hb significantly by 1.84 g/dL (weighted mean difference; 95%CI: 0.91-2.76; P < 0.0001) and decreased the incidence of transfusion with a pooled risk ratio of 0.74 (95%CI: 0.61-0.90; P = 0.002). Incidence of necrotizing enterocolitis (NEC), intraventricular hemorrhage (IVH) and mortality were significantly lower with UCM compared with ICC. Apgar score and temperature were not significantly different between the two groups. CONCLUSIONS: By facilitating the early stabilization of blood pressure, UCM at preterm birth was found to be comparatively safe and associated with lower blood transfusion exposure and lower incidence of IVH, NEC and death.

Thoracoscopic excision of two bronchogenic cysts located in highest upper mediastinum: Report of two cases.

Bronchogenic cysts are rare congenital malformation that need surgical removal. To date, bronchogenic cysts located in highest upper mediastinum excised by thoracoscopy have not been reported, though complete thoracoscopic extirpation of a bronchogenic cyst has been reported before. We excised two highest upper bronchogenic cysts by thoracoscopy successfully without any postoperative complication, demonstrating thoracoscopy could be a first-line therapeutic option even for highest upper mediastinum brochogenic cysts.

Postoperative pain in treatment of spontaneous pneumothorax with limited two-port thoracoscopy.

OBJECTIVES: To investigate effects of the limited two-port video assisted thoracic surgery on treatment of spontaneous pneumothorax. METHODS: A retrospective analysis of 96 patients with spontaneous pneumothorax who underwent video assisted thoracic surgery was conducted in the present study, in which 23 cases underwent the limited two-port video assisted thoracic surgery while 73 cases treated with the standard three-port video assisted thoracic surgery or the standard two-port video assisted thoracic surgery. The mean operation time, mean intraoperative blood loss and average postoperative hospital stay, average postoperative chest tube duration and postoperative pain rating were analyzed. RESULTS: There was no statistical difference existed in the mean operation time, mean intraoperative blood loss, average postoperative hospital stay, average postoperative chest tube duration between the two groups (P>0.05). However, the postoperative pain in the limited two-port video assisted thoracic surgery group was significantly lower than that of the traditional video assisted thoracic surgery group. CONCLUSION: Compared with that of the standard three-port video assisted thoracic surgery or the standard two- port video assisted thoracic surgery, there is better cosmetic effect, and lower grade postoperative pain in the limited two-port video assisted thoracic surgery.

S100A6 could not promote the differentiation of Calu-6 lung cancer cell line.

Background: Our previous study demonstrated that S100 calcium binding protein A6 (S100A6) impairs tumorigenesis by Calu-6 lung cancer cells, as well as inhibit their growth. However, the role that S100A6 plays in tumor cell differentiation has not been previously explored. This study aimed to confirm the effect of S100A6 on the direction of differentiation in the human lung cancer cell linem Calu-6m based on our previous published research. Materials and methods: A S100A6-overexpressing lentiviral vector was successfully constructed in our previous study. Nude mouse tumorigenicity was then applied successfully, and 15 mice were divided into three groups (Calu-6, Calu-6/neo, Calu-6/S100A6). After 5 weeks, we detected lung cancer markers with immunohistochemistry in mice tumor tissues, including the adenocarcinoma markers, TTF-1 and NapsinA, the squamous cell carcinoma markers, P40, CK5/6 and P63, and the small cell lung cancer markers CD56, Syn, CgA, TTF-1, CK, and Ki-67. Differences among the three groups were statistically compared. Results: All the above-mentioned markers were positive in the tumor tissues of all three groups, and there were no significant differences. Conclusion: S100A6 cannot promote differentiation of the undifferentiated human lung cancer cell line, Calu-6, into adenocarcinoma, squamous, or small cell carcinoma cell lines.

RBC transfusion and necrotizing enterocolitis in very preterm infants: a multicenter observational study.

The causal relationship between Packed red blood cell (RBC) transfusion and necrotizing enterocolitis (NEC) remains uncertain. This study aims to provide an exploration of transfusion and NEC in very preterm infants. Using data from the Chinese Neonatal Network cohort study between 2019 and 2021, the analysis focused on very preterm infants (with a birth weight of < 1500 g or a gestational age of < 32 weeks) who developed NEC after receiving transfusions. The time interval between the prior transfusion and NEC was analyzed. An uneven distribution of the time interval implies an association of transfusion and NEC. Additionally, multivariable logistic analysis was conducted to detect the prognosis of defined transfusion-associated NEC(TANEC). Of the 16,494 infants received RBC transfusions, NEC was noted in 1281 (7.7%) cases, including 409 occurred after transfusion. Notably, 36.4% (149/409) of post-transfusion NEC occurred within 2 days after transfusion. The time interval distribution showed a non-normal pattern (Shapiro-Wilk test, W = 0.513, P < 0.001), indicating a possible link between transfusion and NEC. TANEC was defined as NEC occurred within 2 days after transfusion. Infants with TANEC had a higher incidence of death (adjusted OR 1.69; 95% CI 1.08 to 2.64), severe bronchopulmonary dysplasia (adjusted OR 2.03; 95% CI 1.41 to 2.91) and late-onset sepsis (adjusted OR 2.06; 95% CI 1.37 to 3.09) compared with infants without NEC after transfusion. Unevenly high number of NEC cases after RBC transfusions implies transfusion is associated with NEC. TANEC is associated with a poor prognosis. Further research is warranted to enhance our understanding of TANEC.

New insights into intestinal macrophages in necrotizing enterocolitis: the multi-functional role and promising therapeutic application.

Necrotizing enterocolitis (NEC) is an inflammatory intestinal disease that profoundly affects preterm infants. Currently, the pathogenesis of NEC remains controversial, resulting in limited treatment strategies. The preterm infants are thought to be susceptible to gut inflammatory disorders because of their immature immune system. In early life, intestinal macrophages (IMφs), crucial components of innate immunity, demonstrate functional plasticity and diversity in intestinal development, resistance to pathogens, maintenance of the intestinal barrier, and regulation of gut microbiota. When the stimulations of environmental, dietary, and bacterial factors interrupt the homeostatic processes of IMφs, they will lead to intestinal disease, such as NEC. This review focuses on the IMφs related pathogenesis in NEC, discusses the multi-functional roles and relevant molecular mechanisms of IMφs in preterm infants, and explores promising therapeutic application for NEC.

Dynamic Characterization of Single Cells Based on Temporal Cellular Mechanical Properties.

The mechanical properties of cells play important roles in regulating the physiological activities of cells and reflect the state of macro-organisms. Although many approaches are available for investigating the mechanical properties of cells, the fluidity of cytoplasm across cell boundaries makes characterizing the dynamics of mechanical properties of single cells exceedingly difficult. In this study, we present a single cell characterization method by modelling the dynamics of cellular mechanical properties measured with an atomic force microscope (AFM). The mechanical dynamics of a single cell system was described by a linear model with a mechanical stimulus as virtual input and mechanical property parameters as outputs. The dynamic mechanical properties of a single cell were characterized by the system matrix of the single cell system. The method was used to classify different types of cells, and the experimental results show that the proposed method outperformed conventional methods by achieving an average classification accuracy of over 90%. The developed method can be used to classify different cancer types according to the mechanical properties of tumour cells, which is of great significance for clinically assisted pathological diagnosis.

Accurate and Automatic Extraction of Cell Self-Rotation Speed in an ODEP Field Using an Area Change Algorithm.

Cells are complex biological units that can sense physicochemical stimuli from their surroundings and respond positively to them through characterization of the cell behavior. Thus, understanding the motions of cells is important for investigating their intrinsic properties and reflecting their various states. Computer-vision-based methods for elucidating cell behavior offer a novel approach to accurately extract cell motions. Here, we propose an algorithm based on area change to automatically extract the self-rotation of cells in an optically induced dielectrophoresis field. To obtain a clear and complete outline of the cell structure, dark corner removal and contrast stretching techniques are used in the pre-processing stage. The self-rotation speed is calculated by determining the frequency of the cell area changes in all of the captured images. The algorithm is suitable for calculating in-plane and out-of-plane rotations, while addressing the problem of identical images at different rotation angles when dealing with rotations of spherical and flat cells. In addition, the algorithm can be used to determine the motion trajectory of cells. The experimental results show that the algorithm can efficiently and accurately calculate cell rotation speeds of up to ~155 rpm. Potential applications of the proposed algorithm include cell morphology extraction, cell classification, and characterization of the cell mechanical properties. The algorithm can be very helpful for those who are interested in using computer vision and artificial-intelligence-based ideology in single-cell studies, drug treatment, and other bio-related fields.

Integrative analysis links ferroptosis to necrotizing enterocolitis and reveals the role of ACSL4 in immune disorders.

Multiple types of regulated cell death (RCD) have been demonstrated to cause gut barrier dysfunction in necrotizing enterocolitis (NEC); however, whether and how ferroptosis is involved in NEC remains unknown. Here, ferroptosis was identified to play a role in NEC using bioinformatics analyses and wet experiments. Inhibition of ferroptosis significantly alleviated NEC in newborn mice. ACSL4 expression levels were augmented and positively correlated with ferroptosis in NEC. Surprisingly, ACSL4 was critically correlated with multiple types of RCD, including autophagy, apoptosis and pyroptosis, as well as hypoxia and inflammation. Besides, ACSL4 was positively correlated with the abundance of multiple types of immune cells, including macrophage, activated dendritic cell, neutrophil and regulatory T cell. Conclusively, we first identified the involvement and role of ferroptosis in NEC and revealed the potential effects of ACSL4 on immune disorders, which could provide a rationale for future research on ferroptosis in NEC.

Acircadian rhythm-related gene signature for predicting survival and drug response in HNSC.

Head and neck squamous cell carcinoma (HNSC) represents one of the most common malignant carcinomas worldwide. Because the 5-year survival rate of patients with HNSC is poor, it is necessary to develop an effective signature for predicting the risk of HNSC. To identify a circadian rhythm (CR)-related predictive signature, we analyzed the RNA-seq data of patients with HNSC from The Cancer Genome Atlas and Gene Expression Omnibus cohorts. Nine CR-related genes (PER2, PER3, GHRL, CSF2, HDAC3, KLF10, PRKAA2, PTGDS, and RORB) were identified to develop a CR-related signature. The area under the curve values for 5-year overall survival were 0.681, 0.700, and 0.729 in the training set, validation set, and an external independent test set (GSE41613), respectively. The Kaplan‒Meier curve analysis showed that the high-risk group had a reduced relapse-free survival compared with the low-risk group in the training set, validation set, and test set (P < 0.05). Finally, we observed that the CR-related gene signature was associated with the tumor immune microenvironment, somatic nucleotide variation, and drug response in HNSC. In conclusion, we developed a circadian rhythm-related gene signature for predicting overall survival in HNSC.

A Nomogram Combining a Four-Gene Biomarker and Clinical Factors for Predicting Survival of Melanoma.

BACKGROUND: Currently there is no effective prognostic indicator for melanoma, the deadliest skin cancer. Thus, we aimed to develop and validate a nomogram predictive model for predicting survival of melanoma. METHODS: Four hundred forty-nine melanoma cases with RNA sequencing (RNA-seq) data from TCGA were randomly divided into the training set I (n = 224) and validation set I (n = 225), 210 melanoma cases with RNA-seq data from Lund cohort of Lund University (available in GSE65904) were used as an external test set. The prognostic gene biomarker was developed and validated based on the above three sets. The developed gene biomarker combined with clinical characteristics was used as variables to develop and validate a nomogram predictive model based on 379 patients with complete clinical data from TCGA (Among 470 cases, 91 cases with missing clinical data were excluded from the study), which were randomly divided into the training set II (n = 189) and validation set II (n = 190). Area under the curve (AUC), concordance index (C-index), calibration curve, and Kaplan-Meier estimate were used to assess predictive performance of the nomogram model. RESULTS: Four genes, i.e., CLEC7A, CLEC10A, HAPLN3, and HCP5 comprise an immune-related prognostic biomarker. The predictive performance of the biomarker was validated using tROC and log-rank test in the training set I (n = 224, 5-year AUC of 0.683), validation set I (n = 225, 5-year AUC of 0.644), and test set I (n = 210, 5-year AUC of 0.645). The biomarker was also significantly associated with improved survival in the training set (P < 0.01), validation set (P < 0.05), and test set (P < 0.001), respectively. In addition, a nomogram combing the four-gene biomarker and six clinical factors for predicting survival in melanoma was developed in the training set II (n = 189), and validated in the validation set II (n = 190), with a concordance index of 0.736 ± 0.041 and an AUC of 0.832 ± 0.071. CONCLUSION: We developed and validated a nomogram predictive model combining a four-gene biomarker and six clinical factors for melanoma patients, which could facilitate risk stratification and treatment planning.