MRI-based bone marrow radiomics for predicting cytogenetic abnormalities in multiple myeloma.

AIM: To develop a radiomics signature applied to magnetic resonance imaging (MRI)-images to predict cytogenetic abnormalities in multiple myeloma (MM). MATERIALS AND METHODS: Patients with newly diagnosed MM were enrolled retrospectively from March 2019 to September 2022. They were categorised into the high-risk cytogenetics (HRC) group and standard-risk cytogenetics (SRC) group. The patients were allocated randomly at a ratio of 7:3 into training and validation cohorts. Volumes of interest (VOI) was drawn manually on fat suppression T2-weighted imaging (FS-T2WI) and copied to the same location of the T1-weighted imaging (T1WI) sequence. Radiomics features were extracted from two sequences and selected by reproducibility and redundant analysis. The least absolute shrinkage selection operation (LASSO) algorithm was applied to build the radiomics signatures. The performance of the radiomics signatures to distinguish HRC with SRC was evaluated by ROC curves. The area under the curve (AUC), specificity, and sensitivity were also calculated. RESULTS: A total of 105 MM patients were enrolled in this study. The four and 11 most significant and relevant features were selected separately from T1WI and FS-T2WI sequences to build the radiomics signatures based on the training cohort. Compared to the T1WI sequence, the radiomics signature based on the FS-T2WI sequence achieved better performance with AUCs of 0.896 and 0.729 in the training and validation cohorts respectively. A sensitivity of 0.833, specificity of 0.667, and Youden index of 0.500 were achieved for the FS-T2WI radiomics signature in the validation cohort. CONCLUSIONS: The radiomics signature based on MRI provides a non-invasive and convenient tool to predict cytogenetic abnormalities in MM patients.

Hidden magnetism uncovered in a charge ordered bilayer kagome material ScV6Sn6.

Charge ordered kagome lattices have been demonstrated to be intriguing platforms for studying the intertwining of topology, correlation, and magnetism. The recently discovered charge ordered kagome material ScV6Sn6 does not feature a magnetic groundstate or excitations, thus it is often regarded as a conventional paramagnet. Here, using advanced muon-spin rotation spectroscopy, we uncover an unexpected hidden magnetism of the charge order. We observe an enhancement of the internal field width sensed by the muon ensemble, which takes place within the charge ordered state. More importantly, the muon spin relaxation rate below the charge ordering temperature is substantially enhanced by applying an external magnetic field. Taken together with the hidden magnetism found in AV3Sb5 (A = K, Rb, Cs) and FeGe kagome systems, our results suggest ubiqitous time-reversal symmetry-breaking in charge ordered kagome lattices.

Meta-analysis of the diagnostic value of serum procalcitonin for burn sepsis in adults.

OBJECTIVE: Serum procalcitonin (PCT) reflects the infection status of the organism and the severity of the infection. The purpose of this study was to systematically evaluate the diagnostic value of serum PCT for burn sepsis in adults and to provide a factual basis for future clinical diagnosis and decision-making. MATERIALS AND METHODS: On August 16, 2022, six databases were searched in this study and a total of 856 studies were found. The retrieved literature was comprehensively evaluated according to the inclusion and exclusion criteria, and the valid data were extracted and included for analysis. The number of true positives, false positives, true negatives and false negatives were used as indicators to evaluate the diagnostic value of serum PCT for burn sepsis in adults. RESULTS: In total, 15 studies met the inclusion criteria. Meta-analysis showed a combined sensitivity of 0.78 (95% CI: 0.69-0.84), a combined specificity of 0.85 (95% CI: 0.77-0.91), a combined positive likelihood ratio of 5.17 (95% CI: 3.25-8.25), a combined negative likelihood ratio of 0.26 (95% CI: 0.19-0.37), and a combined diagnostic ratio of 19.63 (95% CI: 10.17-37.90). The AUC was 0.88 (95% CI: 0.85-0.90). CONCLUSIONS: Serum PCT provides good early diagnostic benefits for burn sepsis in adults. More high-quality studies are required to clarify its specific early diagnostic value.

[Changes and clinical significance of erythrocyte lifespan in megaloblastic anemia].

Objective: To investigate the lifespan of erythrocytes in megaloblastic anemia (MA) patients. Methods: A prospective cohort study analysis. Clinical data from 42 MA patients who were newly diagnosed at the Department of Hematology, Lanzhou University Second Hospital from January 2021 to August 2021 were analyzed, as were control data from 24 healthy volunteers acquired during the same period. The carbon monoxide breath test was used to measure erythrocyte lifespan, and correlations between erythrocyte lifespan and laboratory test indexes before and after treatment were calculated. Statistical analysis included the t-test and Pearson correlation. Results: The mean erythrocyte lifespan in the 42 newly diagnosed MA patients was (49.05±41.60) d, which was significantly shorter than that in the healthy control group [(104.13±42.62) d; t=5.13,P=0.001]. In a vitamin B12-deficient subset of MA patients the mean erythrocyte lifespan was (30.09±15.14) d, and in a folic acid-deficient subgroup it was (72.00±51.44) d, and the difference between these two MA subsets was significant (t=3.73, P=0.001). The mean erythrocyte lifespan after MA treatment was (101.28±33.02) d, which differed significantly from that before MA treatment (t=4.72, P=0.001). In MA patients erythrocyte lifespan was positively correlated with hemoglobin concentration (r=0.373), and negatively correlated with total bilirubin level (r=-0.425), indirect bilirubin level (r=-0.431), and lactate dehydrogenase level (r=-0.504) (all P<0.05). Conclusions: Erythrocyte lifespan was shortened in MA patients, and there was a significant difference between a vitamin B12-deficient group and a folic acid-deficient group. After treatment the erythrocyte lifespan can return to normal. Erythrocyte lifespan is expected to become an informative index for the diagnosis and treatment of MA.

[Craniofacial anatomical Characteristics of patients with catathrenia].

Objective: To analyze whether the upper airway of patients with catathrenia has obstructive manifestations using nasal resistance, craniofacial, and upper airway imaging methods, which could benefit the exploration of the etiology and treatment options. Methods: From August 2012 to September 2019, a total of 57 patients with catathrenia in the Department of Orthodontics at Peking University Hospital of Stomatology were included in the study, including 22 males and 35 females, aged (31.1±10.9) years, with a body mass index of (21.7±2.7) kg/m2. All the patients were diagnosed by full-night polysomnography at the Sleep Division, Peking University People's Hospital, of which 10 patients were combined with obstructive sleep apnea hypopnea syndrome (OSAHS). The median groaning index of patients was 4.8 (1.8, 13.0) events/h. Nasal resistance and cone-beam CT were conducted on the patients, and measurements were performed on the craniofacial structures, upper airway, and surrounding soft tissues, compared with non-snoring normal occlusion individuals' references published by the same research team (144 college students recruited at Peking University and 100 non-snoring young adults with normal occlusion recruited at six universities in Beijing). Results: The total nasal resistance of patients with catathrenia was (0.26±0.08) Pa·cm-3·s-1. The patients had overall well-developed mandibular hard tissues. However, the patients were found with increased FH/BaN (steep anterior cranial base plane), increased MP/FH (forward rotation of the mandible); increased U1/NA and L1/MP (proclined upper and lower incisors). The sagittal diameter of the velopharynx [(19.2±4.5) mm] was significantly larger than the normal reference (t=8.44, P<0.001), while the sagittal diameter at the hypopharynx [(17.4±6.4) mm] was statistically smaller than the normal reference (t=-2.79, P=0.006). Catarhrenia patients combined with OSAHS presented longer soft palate, tongue, and lower hyoid bone than those with primary catathrenia. Conclusions: In patients with catathrenia, the overall craniofacial characteristics are well-developed skeletal structures, lower nasal resistance, proclined upper and lower incisors, wide upper sagittal development of the upper airway and narrow hypopharynx. Groaning sounds might be related to the narrowing of the hypopharynx during sleep.

Occurrence of Fusarium mycotoxins in freshly harvested highland barley (qingke) grains from Tibet, China.

Highland barley, also called "qingke" in Tibetan, is mainly cultivated in the Tibetan Plateau of China and has been used as a major staple food for Tibetans. Recently, Fusarium head blight (FHB) of qingke was frequently observed around the Brahmaputra River in Tibet. Considering the importance of qingke for Tibetans, the assessment of Fusarium mycotoxin contamination is essential for food safety. In this study, a total of 150 freshly harvested qingke grain samples were obtained from three regions around the Brahmaputra River in Tibet (China) in 2020. The samples were investigated for the occurrence of 20 Fusarium mycotoxins using high-performance liquid chromatography-tandem mass spectrometry (HPLC‒MS/MS). The most frequently occurring mycotoxin was enniatin B (ENB) (46%), followed by enniatin B1 (ENB1) (14.7%), zearalenone (ZEN) (6.0%), enniatin A1 (ENA1) (3.3%), enniatin A (ENA) (1.3%), beauvericin (BEA) (0.7%), and nivalenol (NIV) (0.7%). Due to the increase in altitude, the cumulative precipitation level and average temperature decreased from the downstream to the upstream of the Brahmaputra River; this directly correlated to the contamination level of ENB in qingke, which gradually decreased from downstream to upstream. In addition, the level of ENB in qingke obtained from qingke-rape rotation was significantly lower than that from qingke-wheat and qingke-qingke rotations (p < 0.05). These results disseminated the occurrence of Fusarium mycotoxins and provided further understanding of the effect of environmental factors and crop rotation on Fusarium mycotoxins.

Increased Expression of Efflux Pump norA Drives the Rapid Evolutionary Trajectory from Tolerance to Resistance against Ciprofloxacin in Staphylococcus aureus.

The intensively intermittent use of antibiotics promotes the rapid evolution of tolerance, which may lead to resistance acquisition in the following evolutionary trajectory. In addition to directly exporting antibiotics as an instant resistance strategy, efflux pumps are overexpressed in tolerant strains. To investigate how efflux pumps participate in resistance development from tolerance to resistance, we performed in vitro evolutional experiments against the antibiotic ciprofloxacin in norA efflux pump mutants of Staphylococcus aureus. These experiments demonstrated that overexpression of norA rapidly facilitated the development of ciprofloxacin resistance from tolerance to resistance through elevated spontaneous mutations. The generated resistance mutations were further fixed in the population by increasing survival ability. The observed Ser80Phe and Glu84Lys mutations in the topoisomerase IV ParC (GrlA in S. aureus) may be responsible for tolerant strains to develop resistance to ciprofloxacin since it has been reported that such mutations disrupt the water-metal ion bridge between quinolones and ParC. MepA and Sav1866 are related to the same antibiotic (ciprofloxacin) susceptibility as NorA, and they also contributed to resistance development against ciprofloxacin. MgrA positively regulated NorA expression and the development of ciprofloxacin resistance. Importantly, blocking the evolutionary pathway by coadministering ciprofloxacin with the efflux pump inhibitor reserpine effectively delayed the resistance acquisition in an in vitro experiment. This study illustrated the role of efflux pumps in the evolutionary trajectory from tolerance to resistance. The delayed resistance development caused by the efflux pump inhibitor illuminates a possible strategy for postponing the resistance acquisition from tolerance to resistance by disrupting efflux pumps.

Seroprevalence of antibodies to classical swine fever virus and porcine reproductive and respiratory syndrome virus in healthy pigs in Hunan Province, China.

Classical swine fever (CSF) and porcine reproductive and respiratory syndrome (PRRS) are responsible for major economic losses and represent a threat to the swine industry worldwide. Routine surveillance serology for CSF and PRRS viruses is critical to maintaining the health status of sow farms in Hunan Province, which is one of the top pig production provinces in China. The aim of our study was to investigate the serological statistics of CSF virus (CSFV) and PRRS virus (PRRSV) in Hunan Province. The cohort serum samples were collected from vaccinated and unvaccinated pigs. Our findings showed that the average rates of CSFV and PRRSV antibody seropositivity were 82.2% (95% CI: 80.1-84.3) and 84.8% (95% CI: 82.5-87.1), respectively, in the immunized group and that these rates were higher than those in the unvaccinated group (58.6% for CSFV and 47.8% for PRRSV). Additionally, the level of CSFV antibody in piglet serum declined gradually with age, whereas PRRSV-specific antibody level increased initially (1 to 2 weeks old) and then declined with age (2 to 4 weeks old). In summary, we investigated the difference in CSFV/PRRSV antibody levels among piglets at various weeks old (1 to 4 weeks) to further establish the duration of maternal immunity in piglets. In addition, routine monitoring of CSFV/PRRSV antibodies in immunized pigs was carried out to evaluate the efficacy of vaccination.

[Application of Raman-based technologies in the detection of urological tumors].

Urinary system tumors affect a huge number of individuals, and are frequently recurrent and progressing following surgery, necessitating lifelong surveillance. As a result, early and precise diagnosis of urinary system cancers is important for prevention and therapy. Histopathology is now the golden stan-dard for the diagnosis, but it is invasive, time-consuming, and inconvenient for initial diagnosis and re-gular follow-up assessment. Endoscopy can directly witness the tumor's structure, but intrusive detection is likely to cause harm to the patient's organs, and it is apt to create other hazards in frequently examined patients. Imaging is a valuable non-invasive and quick assessment tool; however, it can be difficult to define the type of lesions and has limited sensitivity for early tumor detection. The conventional approaches for detecting tumors have their own set of limitations. Thus, detection methods that combine non-invasive detection, label-free detection, high sensitivity and high specificity are urgently needed to aid clinical diagnosis. Optical diagnostics and imaging are increasingly being employed in healthcare settings in a variety of sectors. Raman scattering can assess changes in molecular signatures in cancer cells or tissues based on the interaction with vibrational modes of common molecular bonds. Due to the advantages of label-free, strong chemical selectivity, and high sensitivity, Raman scattering, especially coherent Raman scattering microscopy imaging with high spatial resolution, has been widely used in biomedical research. And quantity studies have shown that it has a good application in the detection and diagnosis of bladder can-cer, renal clear cell carcinoma, prostate cancer, and other cancers. In this paper, several nonlinear imaging techniques based on Raman scattering technology are briefly described, including Raman spectroscopy, coherent anti-Stokes Raman scattering, stimulated Raman scattering, and surface-enhanced Raman spectroscopy. And we will discuss the application of these techniques for detecting urologic malignancy. Future research directions are predicted using the advantages and limitations of the aforesaid methodologies in the research. For clinical practice, Raman scattering technology is intended to enable more accurate, rapid, and non-invasive in early diagnosis, intraoperative margins, and pathological grading basis for clinical practice.

[Clinical effects of in situ perforation of preserved split scar matrix in combination with scalp transplantation and vacuum sealing drainage in the treatment of hypertrophic scar in non-functional sites after burns].

Objective: To investigate the clinical effects of in situ perforation of preserved split scar matrix in combination with scalp transplantation and vacuum sealing drainage in the treatment of hypertrophic scar in non-functional sites after burns. Methods: A retrospective observational study was used. From June 2017 to June 2019, 33 patients (24 males and 9 females, aged 8-50 years) who met the inclusion criteria with hypertrophic scars in non-functional sites outside the face after burns were treated in General Hospital of TISCO (the Sixth Hospital of Shanxi Medical University). All patients underwent scalp transplantation after perforation of retained split scar matrix in situ (with scar thinning area of 90-500 cm2), and then the vacuum sealing drainage was performed. The hematoma and infection of wounds were observed on the 7th day after operation. At the same time, the survival rate of skin grafting was observed and calculated. The flatness and thickness of the scar in the operative area were observed in 12 months after operation, and the itching and pain of the patients were recorded. Vancouver Scar Scale was used to score the scar of patients before operation and at 3, 6 and 12 months after operation. The healing time and hair growth of donor site were observed. Data were statistically analyzed with repeated analysis of variance, paired sample t test and bonferroni correction. Results: On the 7th day after operation, local subcutaneous hematoma appeared in the wound of 2 patients, which healed after dressing change; no infection occurred. On the 7th day after operation, the survival rate of skin grafting of patients was 94.6%-99.0%(96.8±1.2)%. Scar flatness was well, the thickness of scar was not significantly higher than that of normal skin in 12 months after operation, and the symptoms of itching pain of patients disappeared or significantly relieved. Vancouver Scar Scale scores of patients before operation and at 3, 6, and 12 months after operation were 12.1±2.8, 8.5±1.5, 7.6±1.6, 6.7±1.3, respectively, and the scores of 3, 6, and 12 months after operation were all significantly lower than that before operation (with t values of 4.48, 4.06, and 3.97, respectively, P<0.01). All the donor sites of the head healed well in 4-7 days after operation. By 3-6 months after operation, all patients had good hair growth in the donor site and achieved no scar healing. Conclusions: The treatment of hypertrophic scar in non-functional sites outside the face after burns by in situ perforation of preserved split scar matrix in combination with scalp transplantation and vacuum sealing drainage can effectively improve the appearance of hypertrophic scar in non-functional areas after burn and reduce its degree of hyperplasia, with scar-free donor site healing.

Mixed-mode versus paper surveys for patient-reported outcomes after critical illness: A randomised controlled trial.

OBJECTIVE: The aim of the study was to determine the response rate to a mixed-mode survey using email compared with that to a paper survey in survivors of critical illness. DESIGN: This is a prospective randomised controlled trial. SETTING: The study was conducted at a single-centre quaternary intensive care unit (ICU) in Adelaide, Australia. PARTICIPANTS: Study participants were patients admitted to the ICU for ≥48 h and discharged from the hospital. INTERVENTIONS: The participants were randomised to receive a survey by paper (via mail) or via online (via email, or if a non-email user, via a letter with a website address). Patients who did not respond to the initial survey received a reminder paper survey after 14 days. The survey included quality of life (EuroQol-5D-5L), anxiety and depression (Hospital Anxiety and Depression Scale), and post-traumatic symptom (Impact of Event Scale-Revised) assessment. MAIN OUTCOME MEASURES: Survey response rate, extent of survey completion, clinical outcomes at different time points after discharge, and survey cost analysis were the main outcome measures. Outcomes were stratified based on follow-up time after ICU discharge (3, 6, and 12 months). RESULTS: A total of 239 patients were randomised. The response rate was similar between the groups (mixed-mode: 78% [92/118 patients] vs. paper: 80% [97/121 patients], p = 0.751) and did not differ between time points of follow-up. Incomplete surveys were more prevalent in the paper group (10% vs 18%). The median EuroQol-5D-5L index value was 0.83 [0.71-0.92]. Depressive symptoms were reported by 25% of patients (46/187), anxiety symptoms were reported by 27% (50/187), and probable post-traumatic stress disorder was reported by 14% (25/184). Patient outcomes did not differ between the groups or time points of follow-up. The cost per reply was AU$ 16.60 (mixed-mode) vs AU$ 19.78 (paper). CONCLUSION: The response rate of a mixed-mode survey is similar to that of a paper survey and may provide modest cost savings.

Hypoxia-mediated down-regulation of miRNAs’ biogenesis promotes tumor immune escape in bladder cancer

Background The study examines the function of hypoxia-mediated down-regulation of microRNAs (miRNAs) (mir-30c, mir-135a, and mir-27a) in the process of bladder cancer immune escape. Methods Quantitative Real-time PCR (qRT-PCR) was carried out to determine gene expression levels of Drosha and Dicer under hypoxia treatment, while western blotting and flow cytometry were used to determine protein expression. Seven reported miRNAs were identified via qRT-PCR assay. Flow cytometry detection of CD3/CD4/CD8-positive expression and statistics. Enzyme-linked immunosorbent assay (ELISA) detected cellular immune factors content. Cell apoptosis was checked via flow cytometry assay. Luciferase report assay and western blot assays were both used to verify the relationship between miRNAs and Casitas B-lineage lymphoma proto-oncogene b (Cbl-b). The animal model was established and Hematoxylin–eosin (HE) staining, TdT-mediated dUTP Nick-End Labeling (TUNEL) staining, and immunohistochemistry (IHC) assays were separately used to verify the conclusions. Results The CD3 + /CD4 + expression was increased in the hypoxia group, while CD3 + /CD8 + expression, the cellular immune factors content Interleukin-2 (IL-2) and Tumor Necrosis Factor-α (TNFα) along with the cell apoptosis were suppressed. The protein expression of Cbl-b was found to be up-regulated in the hypoxia group. After constructing the overexpression/ knockdown of Cbl-b in peripheral blood mononuclear cell (PBMC), Cbl-b has been found to promote tumor immune escape in bladder cancer. Furthermore, Cbl-b had been identified as the co-targets of mir-30c, mir-135a, and mir-27a and down-regulation of miRNA biogenesis promotes Cbl-b expression and deactivating T cells in vitro/in vivo. Conclusion Hypoxia-mediated down-regulation of miRNAs’ biogenesis promotes tumor immune escape in bladder cancer, which could bring much more advance to the medical research on tumors (AU)

[Curcumin induces human lens epithelial cell apoptosis and cell cycle arrest by inhibiting Wnt/ß-catenin signaling pathway].

OBJECTIVE: To investigate the effect of curcumin on cell cycle and apoptosis of human lens epithelial cells and the possible molecular mechanism. OBJECTIVE: Cultured human lens epithelial cell line HLEC-SRA01/04 was treated with 20, 40 and 60 µmol/L curcumin for 24 or 48 h. The cell proliferation inhibition rate was determined using MTT assay, and the changes in cell cycle, mitochondrial membrane potential and apoptosis rate were analyzed with flow cytometry. Western blotting was used to detect the expression levels of caspase-9, caspase-3, Bcl-2, Bax, cyclin B1, CDK1, ß-catenin, c-myc, and cyclin D1 in the cells. OBJECTIVE: Curcumin concentration- and time-dependently inhibited the proliferation of in HLEC-SRA01/04 cells as compared with the control cells (P < .05). Flow cytometric analysis showed that curcumin significantly increased apoptosis rate and cell percentage in G2/M phase and lowered mitochondrial membrane potential of HLEC-SRA01/04 cells in a concentrationdependent manner (P < 0.05). The results of Western blotting showed that curcumin also concentration-dependently increased the cellular expressions of caspase-3, caspase-9 and Bax and lowered the expressions of Bcl-2, cyclin B1, CDK1 and ß-catenin along with the downstream proteins cyclin D1 and c-myc in the Wnt/ß-catenin signaling pathway (P < 0.05). OBJECTIVE: Curcumin inhibits the proliferation of HLEC-SRA01/04 cells possibly by inhibiting the Wnt/ß-catenin signaling pathway and causing cell cycle arrest to induce cell apoptosis.

Circular RNA circCRIM1 suppresses lung adenocarcinoma cell migration, invasion, EMT, and glycolysis through regulating miR-125b-5p/BTG2 axis.

The article "Circular RNA circCRIM1 suppresses lung adenocarcinoma cell migration, invasion, EMT, and glycolysis through regulating miR-125b-5p/BTG2 axis, by S.-J. Zhang, J. Ma, J.-C. Wu, Z.-Z. Hao, Y.-A. Zhang, Y.-J. Zhang, published in Eur Rev Med Pharmacol Sci 2020; 24 (7): 3761-3774-DOI: 10.26355/eurrev_202004_20841-PMID: 32329853" has been withdrawn from the authors due to some technical reasons. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/20841.

CircRNA EPB41L2 inhibits tumorigenicity of lung adenocarcinoma through regulating CDH4 by miR-211-5p.

The article "CircRNA EPB41L2 inhibits tumorigenicity of lung adenocarcinoma through regulating CDH4 by miR-211-5p, by S.-J. Zhang, J. Ma, J.-C. Wu, Z.-Z. Hao, Y.-N. Zhang, Y.-J. Zhang, published in Eur Rev Med Pharmacol Sci 2020; 24 (7): 3749-3760-DOI: 10.26355/eurrev_202004_20839-PMID: 32329852" has been withdrawn from the authors due to inaccuracies and mistakes. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/20839.

Hypoxia-mediated down-regulation of miRNAs' biogenesis promotes tumor immune escape in bladder cancer.

BACKGROUND: The study examines the function of hypoxia-mediated down-regulation of microRNAs (miRNAs) (mir-30c, mir-135a, and mir-27a) in the process of bladder cancer immune escape. METHODS: Quantitative Real-time PCR (qRT-PCR) was carried out to determine gene expression levels of Drosha and Dicer under hypoxia treatment, while western blotting and flow cytometry were used to determine protein expression. Seven reported miRNAs were identified via qRT-PCR assay. Flow cytometry detection of CD3/CD4/CD8-positive expression and statistics. Enzyme-linked immunosorbent assay (ELISA) detected cellular immune factors content. Cell apoptosis was checked via flow cytometry assay. Luciferase report assay and western blot assays were both used to verify the relationship between miRNAs and Casitas B-lineage lymphoma proto-oncogene b (Cbl-b). The animal model was established and Hematoxylin-eosin (HE) staining, TdT-mediated dUTP Nick-End Labeling (TUNEL) staining, and immunohistochemistry (IHC) assays were separately used to verify the conclusions. RESULTS: The CD3 + /CD4 + expression was increased in the hypoxia group, while CD3 + /CD8 + expression, the cellular immune factors content Interleukin-2 (IL-2) and Tumor Necrosis Factor-α (TNFα) along with the cell apoptosis were suppressed. The protein expression of Cbl-b was found to be up-regulated in the hypoxia group. After constructing the overexpression/ knockdown of Cbl-b in peripheral blood mononuclear cell (PBMC), Cbl-b has been found to promote tumor immune escape in bladder cancer. Furthermore, Cbl-b had been identified as the co-targets of mir-30c, mir-135a, and mir-27a and down-regulation of miRNA biogenesis promotes Cbl-b expression and deactivating T cells in vitro/in vivo. CONCLUSION: Hypoxia-mediated down-regulation of miRNAs' biogenesis promotes tumor immune escape in bladder cancer, which could bring much more advance to the medical research on tumors.