Superhydrophobic/ superoleophilic polystyrene-based porous material with superelasticity for highly efficient and continuous oil/water separation in harsh environments.

Three-dimensional separation materials with robust physical/chemical stability have great demand for effective and continuous separation of immiscible oil/water mixtures and water-in-oil emulsions, resulting from chemical leakages and discharge of industrial oily wastewaters. Herein, a superelastic polystyrene-based porous material with superhydrophobicity/superoleophilicity was designed and prepared by high internal phase emulsion polymerization to meet the aforementioned requirements. A flexible and hydrophobic aminopropyl terminated polydimethylsiloxane (NH2-PDMS-NH2) segment was introduced into the rigid styrene-divinylbenzene copolymer through 1, 4-conjugate addition reaction with trimethylolpropane triacrylate. The addition of NH2-PDMS-NH2 simultaneously improved the mechanical and hydrophobic properties of the porous material (the water contact angle from 141.2° to 152.2°). The material exhibited outstanding reversible compressibility (80% strain, even in liquid N2 environments) and superhydrophobic stability, even after being repeatedly compressed 100 times, water contact angle still remained above 150°. Meanwhile, the as-prepared material had outstanding hydrophobic stability in corrosive solutions (strong acidic, alkaline, high-salty, and even strong polar solvent), presence of mechanical interference, strong UV radiations, and high/low temperature environments. More importantly, the material could continuously and efficiently separate immiscible oil/water mixture and water-in-oil emulsions under the above conditions, showing huge potential for the large-scale remediation of complex oily wastewaters.

A Comparison of Quality of Life, Cosmesis and Cost-Utility of Open Surgery, Vacuum-Assisted Breast Biopsy and High Intensity Focused Ultrasound for Breast Fibroadenoma.

RATIONALE AND OBJECTIVES: To compare the quality of life (QOL), cosmesis and cost-utility of open surgery (OS), vacuum-assisted breast biopsy (VABB) and high intensity focused ultrasound (HIFU) for fibroadenoma (FA). MATERIALS AND METHODS: A total of 162 patients with 267 FAs were enrolled. Baseline characteristics and treatment information were recorded. Patients were followed up at 3-, 6- and 12-month post-treatment. QOL was evaluated by health survey. Breast cosmesis was evaluated by self-rating survey and Harvard Scale. A decision-analytic model was established and incremental cost was calculated for cost-utility analysis. RESULTS: For QOL evaluation, there was no difference of physical component summary (PCS) score in three groups (P > 0.05), while the mental component summary (MCS) score was significantly higher in HIFU group than the other two groups at 3- and 6-month post-treatment (P < 0.05). The proportion of patients satisfied with breast cosmesis was significantly higher in HIFU group (96.49%) than in VABB group (54.90%) and OS group (49.99%) (P < 0.05). By Harvard Scale, 27.78%, 78.42% and 100.00% of patients were rated as excellent and good in OS group, VABB group and HIFU group, respectively (P < 0.05). To acquire a quality-adjusted life year (QALY), cost of OS, VABB and HIFU was 1034.31 USD, 1776.96 USD and 1277.67 USD, respectively. When compared to OS, incremental cost analysis showed HIFU was cost-effective, while VABB was not. CONCLUSION: OS, VABB and HIFU were all effective and safe for FA, but among these three treatments, HIFU had the best QOL improvement, breast cosmesis and cost-effectiveness.

Nomogram incorporating Epstein-Barr virus DNA and a novel immune-nutritional marker for survival prediction in nasopharyngeal carcinoma.

BACKGROUND: Since Immune response, nutritional status and Epstein-Barr Virus (EBV) DNA status have been confirmed to be relevant to the prognosis of patients with nasopharyngeal carcinoma (NPC), we believe that the combination of these factors is of great value for improving the predictive ability. LA (lymphocytes × albumin), a novel indicator, had not been studied yet in NPC. We combined it with EBV DNA and used nomograms to increase the accuracy of prognosis. METHODS: A total of 688 NPC patients were retrospectively reviewed and further divided into training and validation cohort randomly. Kaplan-Meier analyses were used to to distinguish the different survival outcomes. Multivariate Cox analyses were used to identify the independent prognostic factors for progression-free survival (PFS) and overall survival (OS). Calibration curves, concordance indexes (C-indexes) and decision curve analyses (DCA) were used to evaluate the nomograms' predictive value. RESULTS: Patients with low LA and positive EBV DNA correlated with poorer 5-year PFS and OS (all P < 0.005). In multivariate Cox analyses, LA and EBV DNA were both confirmed to be independent prognostic factors for PFS and OS (all P < 0.05). Prognostic nomograms incorporating LA and EBV DNA achieved ideal C-indexes of 0.69 (95% CI: 0.65-0.73) and 0.77 (95% CI: 0.71-0.82) in the prediction of PFS and OS. Otherwise, the calibration curves and DCA curves also revealed that our nomograms had pleasant predictive power. CONCLUSIONS: LA is a novel and powerful biomarker for predicting clinical outcomes in NPC. Our nomograms based on LA and EBV DNA can predict individual prognosis more accurately and effectively.

Increased intrinsic membrane excitability is associated with hypertrophic olivary degeneration in spinocerebellar ataxia type 1.

One of the characteristic areas of brainstem degeneration across multiple spinocerebellar ataxias (SCAs) is the inferior olive (IO), a medullary nucleus that plays a key role in motor learning. In addition to its vulnerability in SCAs, the IO is also susceptible to a distinct pathology known as hypertrophic olivary degeneration (HOD). Clinically, HOD has been exclusively observed after lesions in the brainstem disrupt inhibitory afferents to the IO. Here, for the first time, we describe HOD in another context: spinocerebellar ataxia type 1 (SCA1). Using the genetically-precise SCA1 knock-in mouse model (SCA1-KI; both sexes used), we assessed SCA1-associated changes in IO neuron structure and function. Concurrent with degeneration, we found that SCA1-KI IO neurons are hypertrophic, exhibiting early dendrite lengthening and later somatic expansion. Unlike in previous descriptions of HOD, we observed no clear loss of IO inhibitory innervation; nevertheless, patch-clamp recordings from brainstem slices reveal that SCA1-KI IO neurons are hyperexcitable. Rather than synaptic disinhibition, we identify increases in intrinsic membrane excitability as the more likely mechanism underlying this novel SCA1 phenotype. Specifically, transcriptome analysis indicates that SCA1-KI IO hyperexcitability is associated with a reduced medullary expression of ion channels responsible for spike afterhyperpolarization (AHP) in IO neurons - a result that has a functional consequence, as SCA1-KI IO neuron spikes exhibit a diminished AHP. These results reveal membrane excitability as a potential link between disparate causes of IO degeneration, suggesting that HOD can result from any cause, intrinsic or extrinsic, that increases excitability of the IO neuron membrane.

An in vitro and in vivo study on extracorporeal transducer optimization for high-intensity focused ultrasound to improve the safety and efficacy of breast tumor ablation.

OBJECTIVE: To observe the characteristics of a new extracorporeal high intensity focused ultrasound transducer, titled Haifu system JCQ-B, and to compare its safety and efficacy for breast ablation with the standard Haifu system JC transducer. MATERIALS AND METHODS: Ox liver with pig skin and pork ribs were prepared in a semi-sphere shape, served as in vitro acoustic model. The udders of female goats were used as in vivo acoustic model. Both in vitro and in vivo models were ablated by either JCQ-B or JC transducer. The morphology of biological focal region (BFR), the coagulative necrosis volume, and the temperature increase were observed and compared. RESULTS: The BFR morphology of JCQ-B transducer was circular both in vitro and in vivo, with a length-width ratio close to one. Under the same sonication parameters (sonication power, time and depth in tissue), coagulation necrosis volume caused by JCQ-B transducer was larger than that caused by JC transducer both in vitro and in vivo. The increase in temperature in the near and far acoustic pathways with JCQ-B transducer was significantly lower than that of JC transducer in vitro. After receiving high sonication energy during in vivo experimentation, there were no complications observed after the ablation of JCQ-B transducer, while small skin damage was observed after the ablation of JC transducer. CONCLUSIONS: The JCQ-B transducer improved the safety and efficacy of treatment by optimizing BFR morphology and ablation efficiency, which could be applied in the treatment of breast tumor.

Optical Control of Protein Functions via Genetically Encoded Photocaged Aspartic Acids.

Site-specific protein decaging by light has become an effective approach for in situ manipulation of protein activities in a gain-of-function fashion. Although successful decaging of amino acid side chains of Lys, Tyr, Cys, and Glu has been demonstrated, this strategy has not been extended to aspartic acid (Asp), an essential amino acid residue with a range of protein functions and protein-protein interactions. We herein reported a genetically encoded photocaged Asp and applied it to the photocontrolled manipulation of a panel of proteins including firefly luciferase, kinases (e.g., BRAF), and GTPase (e.g., KRAS) as well as mimicking the in situ phosphorylation event on kinases. As a new member of the increasingly expanded amino acid-decaging toolbox, photocaged Asp may find broad applications for gain-of-function study of diverse proteins as well as biological processes in living cells.

Targeting Ion Channels and Purkinje Neuron Intrinsic Membrane Excitability as a Therapeutic Strategy for Cerebellar Ataxia.

In degenerative neurological disorders such as Parkinson's disease, a convergence of widely varying insults results in a loss of dopaminergic neurons and, thus, the motor symptoms of the disease. Dopamine replacement therapy with agents such as levodopa is a mainstay of therapy. Cerebellar ataxias, a heterogeneous group of currently untreatable conditions, have not been identified to have a shared physiology that is a target of therapy. In this review, we propose that perturbations in cerebellar Purkinje neuron intrinsic membrane excitability, a result of ion channel dysregulation, is a common pathophysiologic mechanism that drives motor impairment and vulnerability to degeneration in cerebellar ataxias of widely differing genetic etiologies. We further propose that treatments aimed at restoring Purkinje neuron intrinsic membrane excitability have the potential to be a shared therapy in cerebellar ataxia akin to levodopa for Parkinson's disease.

A comprehensive diagnostic scheme of morphological combined molecular methylation under bronchoscopy.

Methylated SHOX2 and RASSF1A genes are potential biomarkers for lung cancer diagnosis. Therefore, we explored the role of methylation detection combined with morphological bronchoscopic evaluation for lung cancer diagnosis. Bronchoscopy, methylation outcome, and pathological data were collected from 585 patients with lung cancer and 101 controls. The methylation status of the SHOX2 and RASSF1A genes were detected using real-time polymerase chain reaction quantification. Further, the sensitivity and area under the receiver operating characteristic curve of the three methods were analyzed. Among 686 patients, 57.1% had new lesions detected through bronchoscopy and 93.1% of these patients were diagnosed with malignant tumors. Besides, 42.9% of patients had no visible changes under bronchoscopy but there were still 74.8% of them diagnosed with malignant tumors. Bronchoscopy revealed that lung adenocarcinoma, lung squamous cell carcinoma, and small cell lung cancer mainly occurred in the upper and middle lobes. The sensitivity and specificity of methylation detection were 72.8% and 87.1% (vs. cytology 10.4% & 100%), respectively. Therefore, methylated SHOX2 and RASSF1A genes may be promising tumor markers in lung cancer diagnosis. Methylation detection can be an excellent supplementary tool for cytological diagnosis and, combined with bronchoscopy, could form a more effective diagnostic process.

Neuronal activity regulates Matrin 3 abundance and function in a calcium-dependent manner through calpain-mediated cleavage and calmodulin binding.

RNA-binding protein (RBP) dysfunction is a fundamental hallmark of amyotrophic lateral sclerosis (ALS) and related neuromuscular disorders. Abnormal neuronal excitability is also a conserved feature in ALS patients and disease models, yet little is known about how activity-dependent processes regulate RBP levels and functions. Mutations in the gene encoding the RBP Matrin 3 (MATR3) cause familial disease, and MATR3 pathology has also been observed in sporadic ALS, suggesting a key role for MATR3 in disease pathogenesis. Here, we show that glutamatergic activity drives MATR3 degradation through an NMDA receptor-, Ca2+-, and calpain-dependent mechanism. The most common pathogenic MATR3 mutation renders it resistant to calpain degradation, suggesting a link between activity-dependent MATR3 regulation and disease. We also demonstrate that Ca2+ regulates MATR3 through a nondegradative process involving the binding of Ca2+/calmodulin to MATR3 and inhibition of its RNA-binding ability. These findings indicate that neuronal activity impacts both the abundance and function of MATR3, underscoring the effect of activity on RBPs and providing a foundation for further study of Ca2+-coupled regulation of RBPs implicated in ALS and related neurological diseases.

Focused ultrasound ablation surgery for multiple breast fibroadenomas: pathological and follow-up results.

OBJECTIVE: To investigate the histopathological findings and follow-up outcome of focused ultrasound ablation surgery (FUAS) treatment of multiple fibroadenomas (FA). METHODS: A total of 20 patients with 101 multiple FAs were enrolled. After one session FUAS ablation, 21 lesions (≥15.0 mm) were surgically removed within one week for histopathological analysis, including 2, 3, 5-triphenyltetrazolium chloride (TTC) staining, H&E staining, nicotinamide adenine dinucleotide (NADH) -flavretin enzyme staining, Transmission electron microscope (TEM) and scanning electron microscope (SEM). The remaining 80 lesions were followed up at 3, 6 and 12 months after treatment. RESULTS: All ablation procedures were performed successfully. Pathologic findings showed that irreversible damage of FA was confirmed. TTC, H&E and NADH staining and TEM/SEM demonstrated tumor cell death and tumor structural destruction at the gross, cellular, and subcellular levels, respectively. The median shrinkage rate at 12 months post-FUAS was 66.4 (43.6, 89.5) %. CONCLUSION: Histopathological analysis for FAs after FUAS treatment proved that FUAS could effectively induce irreversible coagulative necrosis of FA, and the tumor volume would gradually shrink in follow-up. FUAS was safe and effective to treat multiple FAs with good cosmesis.Key pointsThis study was the first study of detailed histopathological analysis for FAs after FUAS treatment.FUAS can effectively induce irreversible coagulative necrosis of fibroadenoma cells.FUAS ablation of multiple fibroadenomas is safe and effective.

Ectopic scrotum and penoscrotal transposition: Case report and literature review.

Background: Ectopic scrotum (ES) is an extremely rare congenital scrotal malformation. Ectopic scrotum with VATER/VACTERL [vertebral defects (V), anal atresia or anorectal malformations (A), cardiac defects (C), tracheoesophageal fistula with or without esophageal atresia (TE), cardiac defects, renal malformations (R), and limb defects (L)] association is even rarer. There are no uniform guidelines for diagnosis and treatment. Clinical case: We described a 2-year-5-month-old boy who has ectopic scrotum and penoscrotal transposition and reviewed relevant literature in this report. We performed laparoscopy exploration, rotation flap scrotoplasty, and orchiopexy and achieved a great result during the postoperative follow-up. Conclusions: Combined with the previous literature, we made a summary to come up with a plan for the diagnosis and treatment of ectopic scrotum. Rotation flap scrotoplasty and orchiopexy are worthy of considering operative methods in treating ES. For penoscrotal transposition or VATER/VACTERL association, we can treat the diseases individually.

High precision tracking analysis of cell position and motion fields using 3D U-net network models.

Cells are the basic units of biological organization, and the quantitative analysis of cellular states is an important topic in medicine and is valuable in revealing the complex mechanisms of microscopic world organisms. In order to better understand cell cycle changes as well as drug actions, we need to track cell migration and division. In this paper, we propose a novel engineering model for tracking cells using cell position and motion fields (CPMF). The training sample does not need to be manually annotated, and we modify and edit it against the ground truth using auxiliary tools. The core idea of the project is to combine detection and correlation, and the cell sequence samples are trained by a U-Net network model composed of 3D CNNs, which can track the migration, division, and entry and exit of cells in the field of view with high accuracy in all directions. The average detection accuracy of the cell coordinates is 98.38% and the average tracking accuracy is 98.70%.

Systemic immune-inflammation index during treatment predicts prognosis and guides clinical treatment in patients with nasopharyngeal carcinoma.

PURPOSE: Systemic immune-inflammation index (SII) has been demonstrated to be closely associated with the poor prognosis of nasopharyngeal carcinoma (NPC). However, the role of SII during treatment of NPC has not been reported. This study aimed to determine the prognostic value of SII during treatment for NPC patients. METHODS: A total of 759 patients diagnosed with NPC were included in this retrospective study (393 in training cohort and 366 in validation cohort). The correlation between variables was analyzed by the chi-squared test, the Fisher's exact test or the likelihood test. Kaplan-Meier method and log-rank test were used to analyze progression-free survival (PFS) and overall survival (OS). The independent prognostic factors were determined by multivariate analysis of Cox proportional hazards regression model. The uncontrolled risk was analyzed by Logistic regression. Receiver operating characteristic (ROC) curves were used to assess prognostic value. RESULTS: The optimal cut-off point for the SII during treatment was 937.32. High SII during treatment group had higher uncontrolled risk than low SII during treatment group (p = 0.008). In multivariate Cox proportional hazard models analysis, SII during treatment was an independent prognostic factor for 5-year PFS (p < 0.001) and 5-year OS (p < 0.001). All results were found in the training cohort and confirmed in the validation cohort. CONCLUSIONS: The SII during treatment is a promising indicator of predicting the survival in NPC patients, especially the risk of uncontrolled occurrence. By monitoring the SII during treatment, it is possible to better evaluate the treatment effect and formulate personalized treatment.

A novel genome sequence of Jasminum sambac helps uncover the molecular mechanism underlying the accumulation of jasmonates.

Jasminum sambac is a well-known plant for its attractive and exceptional fragrance, the flowers of which are used to produce scented tea. Jasmonate (JA), an important plant hormone was first identified in Jasminum species. Jasmine plants contain abundant JA naturally, of which the molecular mechanisms of synthesis and accumulation are not clearly understood. Here, we report a telomere-to-telomere consensus assembly of a double-petal J. sambac genome along with two haplotype-resolved genomes. We found that gain-and-loss, positive selection, and allelic specific expression of aromatic volatile-related genes contributed to the stronger flower fragrance in double-petal J. sambac compared with single- and multi-petal jasmines. Through comprehensive comparative genomic, transcriptomic, and metabolomic analyses of double-petal J. sambac, we revealed the genetic basis of the production of aromatic volatiles and salicylic acid (SA), and the accumulation of JA under non-stress conditions. We identified several key genes associated with JA biosynthesis, and their non-stress related activities lead to extraordinarily high concentrations of JA in tissues. High JA synthesis coupled with low degradation in J. sambac results in accumulation of high JA under typical environmental conditions, similar to the accumulation mechanism of SA. This study offers important insights into the biology of J. sambac, and provides valuable genomic resources for further utilization of natural products.

A consensus on the management of allergy in kindergartens and primary schools / 中国学校卫生

Abstract@#Allergic diseases can occur in all systems of the body, covering the whole life cycle, from children to adults and to old age, can be lifelong onset and even fatal in severe cases. Children account for the largest proportion of the victims of allergic disease, Children s allergies start from scratch, ranging from mild to severe, from less to more, from single to multiple systems and systemic performance, so the prevention and treatment of allergic diseases in children is of great importance, which can not only prevent high risk allergic conditions from developing into allergic diseases, but also further block the process of allergy. At present, there is no consensus on the management system of allergic children in kindergartens and primary schools. The "Consensus on Allergy Management and Prevention in Kindergartens and Primary Schools", which includes the organizational structure, system construction and management of allergic children, provides evidence informed recommendations for the long term comprehensive management of allergic children in kindergartens and primary schools, and provides a basis for the establishment of the prevention system for allergic children.

Effect of neoadjuvant endocrine therapy on the acoustic environment in tissue of prostate cancer: a study of histopathological characteristics.

Background: Neoadjuvant endocrine therapy (NET) of prostate cancer (PCa) may alter the tissue acoustic environment (AET). The structure of tissue is an important factor affecting AET. The aim is to analyze changes in tissue structures after NET in PCa, focusing on calcifications, smooth muscle cells, and blood vessels. Methods: We collected 40 patients diagnosed with PCa by pathological examination between October 2020 and December 2022. Twenty patients who underwent radical prostatectomy (RP) after NET were designed as the test group. Twenty patients without NET were assigned to the control group. Calcifications, smooth muscle cells and blood vessels were observed by hematoxylin-eosin (HE) staining and Van Gieson (VG)-special staining respectively. Then the amount and acreage of calcified tissue, the number of smooth muscle cells and different types of blood vessels were quantitatively analyzed. Results: There was a subtle increase in the number (P=0.001) and the area (P<0.001) of calcification after NET. The total number of smooth muscle cells was significantly higher than that without NET (P<0.001). NET resulted in significantly fewer veins compared to those without NET (P<0.001). There was a little increase in the number of arteries after NET (P=0.001). The number of veins decreased was much greater than the number of arteries increased resulting in significantly fewer total vessels after NET (P<0.001). Conclusions: NET can lead to changes in calcifications, smooth muscle cells, and blood vessels within PCa tissues, which may cause alterations in AET.

Association between exposure to earthquake in early life and diabetes mellitus incidence in adulthood with the modification of lifestyles: Results from the Kailuan study.

Background: Exposure to disasters in early life may induce lifetime health risk, but investigation on earthquake exposure and DM in later life is still limited. The aim of the current study is to evaluate the association between exposure to the Tangshan Earthquake in early life and diabetes mellitus (DM) incidence in adulthood, and explore the modification of lifestyles on DM development. Methods: Participants who were free of DM at baseline from the Kailuan Study were included in this study. All participants were divided into fetal-exposed, infant-exposed, early childhood-exposed and nonexposed group. The effect of earthquake exposure on DM and modification of lifestyles were examined by multivariable-adjusted Cox proportional hazard model. Results: The exposed group had a higher risk of DM than nonexposed group, especially in infant-exposed and early childhood-exposed group, with hazard ratio (HR) of 1.62 [95% confidence intervals (CI), 1.21-2.17] and 1.46 (95% CI, 1.06-1.99), respectively. After stratifying by lifestyles, a significant modification was observed in alcohol consumption. Conclusion: Exposing to earthquake in early life could increase DM incidence in later life, and alcohol consumption might modify the effect of earthquake exposure on DM development. More attention should be paid on the preventions of DM among adults who exposed to earthquake in their early life.

Artificial intelligence in pancreatic cancer.

Pancreatic cancer is the deadliest disease, with a five-year overall survival rate of just 11%. The pancreatic cancer patients diagnosed with early screening have a median overall survival of nearly ten years, compared with 1.5 years for those not diagnosed with early screening. Therefore, early diagnosis and early treatment of pancreatic cancer are particularly critical. However, as a rare disease, the general screening cost of pancreatic cancer is high, the accuracy of existing tumor markers is not enough, and the efficacy of treatment methods is not exact. In terms of early diagnosis, artificial intelligence technology can quickly locate high-risk groups through medical images, pathological examination, biomarkers, and other aspects, then screening pancreatic cancer lesions early. At the same time, the artificial intelligence algorithm can also be used to predict the survival time, recurrence risk, metastasis, and therapy response which could affect the prognosis. In addition, artificial intelligence is widely used in pancreatic cancer health records, estimating medical imaging parameters, developing computer-aided diagnosis systems, etc. Advances in AI applications for pancreatic cancer will require a concerted effort among clinicians, basic scientists, statisticians, and engineers. Although it has some limitations, it will play an essential role in overcoming pancreatic cancer in the foreseeable future due to its mighty computing power.

Evaluating the learning curve of high intensity focus ultrasound for breast fibroadenoma by CUSUM analysis: a multi-center study.

OBJECTIVE: To explore the learning curve of high intensity focus ultrasound (HIFU) treatment for breast fibroadenoma. METHODS: A database of 110 patients with 255 breast fibroadenomas who underwent HIFU treatment at two different clinical centers (Center 1 and 2) were retrospectively analyzed. The learning curves of HIFU treatment for breast fibroadenoma were drawn by CUSUM analysis in two centers, respectively. According to the inflection point of the learning curves, the treatment was divided into two groups: initial phase and consolidation phase. HIFU treatment parameters were compared between two groups. The effectiveness and safety results were also evaluated. RESULTS: The inflection points of the learning curves were the 60th treatment in Center 1 and the 65th treatment in Center 2. The screening time, treatment time, sonication time and hyperechoic scale change time were significantly shorter in consolidation phase than those in initial phase of the two centers (p < 0.05). There were no differences in non-perfused volume (NPV) ratio and energy effect factor (EEF) between the two groups in Center 1, while in Center 2, these above-mentioned results in consolidation phase led to a greater improvement than those in initial phase. There was no difference of Visual Analogue Scale (VAS) scores and no adverse event observed in both centers. CONCLUSION: HIFU treatment for breast fibroadenoma was effective and safe. The learning curve of HIFU treatment for breast fibroadenoma can be completed after treating 60-65 tumors without increasing the safety risk.

T cell proliferation-related genes: Predicting prognosis, identifying the cold and hot tumors, and guiding treatment in clear cell renal cell carcinoma.

Background: Immunotherapy has become a new direction of current research because the effect of traditional radiotherapy and chemotherapy on clear cell renal cell carcinoma (ccRCC) is not satisfactory. T cell proliferation-related genes (TRGs) play a pivotal role in tumor progression by regulating the proliferation, activity, and function of immune cells. The purpose of our study is to construct and verify a prognostic model based on TRGs and to identify tumor subtypes that may guide treatment through comprehensive bioinformatics analyses. Methods: RNA sequencing data, clinical information, and somatic mutation data of ccRCC are obtained from The Cancer Genome Atlas (TCGA) database. We identified the prognosis-related TRGs which were differentially expressed between normal and tumor tissues. After dividing the patients into a train set and a test set according to proportion 1:1 randomly, the least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analysis were performed to construct a risk-stratified model. Its prediction performance was verified. Then, Gene Set Enrichment Analysis (GSEA), principal component analysis (PCA), tumor microenvironment (TME) analysis, and the half-maximal inhibitory concentration (IC50) prediction were performed between the different groups of patients. To further discuss the immunotherapy between hot and cold tumors, we divided all patients into two clusters based on TRGs through unsupervised learning. Analyzing the gene mutation and calculating the tumor mutation burden (TMB), we further explored the relationship between somatic mutations and grouping or clustering. Results: Risk-stratified model and nomogram predict the prognosis of ccRCC patients accurately. Functional enrichment analyses suggested that TRGs mainly focused on the biological pathways related to tumor progression and immune response. Different tumor microenvironment, drug resistance, and TMB can be distinguished clearly according to both risk stratification and tumor subtype clustering. Conclusion: In this study, a new stratification model of ccRCC based on TRGs was established, which can accurately predict the prognosis of patients. IC50 prediction may guide the application of anti-tumor drugs. The distinction between hot and cold tumors provides a reference for clinical immunotherapy.