Retraction Note: MiR-1294 acts as a tumor suppressor in clear cell renal cell carcinoma through targeting HOXA6.

The article "MiR-1294 acts as a tumor suppressor in clear cell renal cell carcinoma through targeting HOXA6", by W. Pan, L.-J. Pang, H.-L. Cai, Y. Wu, W. Zhang, J.-C. Fang, published in Eur Rev Med Pharmacol Sci 2019; 23 (9): 3719-3725-DOI: 10.26355/eurrev_201905_17797-PMID: 31114997 has been retracted by the Editor in Chief. Following some concerns raised on PubPeer regarding a possible manipulation in Figures 2 and 3, the Editor in Chief has started an investigation to assess the validity of the results as well as possible figure manipulation. The authors have been informed about the journal's investigation but remained unresponsive. The journal investigation revealed duplications in panels miR-1294 mimic - Caki01 and Caki01 of Figure 2D and in the Western blots of Figure 3 with previously published articles. Consequently, the Editor in Chief mistrusts the results presented and has decided to retract the article. This article has been retracted. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/17797.

SWI/SNF family mutations in advanced NSCLC: genetic characteristics and immune checkpoint inhibitors' therapeutic implication.

BACKGROUND: SWItch/Sucrose NonFermentable (SWI/SNF) mutations have garnered increasing attention because of their association with unfavorable prognosis. However, the genetic landscape of SWI/SNF family mutations in Chinese non-small-cell lung cancer (NSCLC) is poorly understood. In addition, the optimal treatment strategy has not yet been determined. PATIENTS AND METHODS: We collected sequencing data on 2027 lung tumor samples from multiple centers in China to comprehensively analyze the genomic characteristics of the SWI/SNF family within the Chinese NSCLC population. Meanwhile, 519 patients with NSCLC from Sun Yat-sen University Cancer Center were enrolled to investigate the potential implications of immunotherapy on patients with SWI/SNF mutations and to identify beneficial subpopulations. We also validated our findings in multiple publicly available cohorts. RESULTS: Approximately 15% of Chinese patients with lung cancer harbored mutations in the SWI/SNF chromatin remodeling complex, which were mutually exclusive to the EGFR mutations. Patients with SWI/SNFmut NSCLC who received first-line chemoimmunotherapy had better survival outcomes than those who received chemotherapy alone (median progression-free survival: 8.70 versus 6.93 months; P = 0.028). This finding was also confirmed by external validation using the POPLAR/OAK cohort. SWI/SNFmut NSCLC is frequently characterized by high tumor mutational burden and concurrent TP53 or STK11/KEAP mutations. Further analysis indicated that TP53 and STK11/KEAP1 mutations could be stratifying factors in facilitating personalized immunotherapy and guiding patient selection. CONCLUSIONS: This study provides a step forward in understanding the genetic and immunological characterization of SWI/SNF genetic alterations. Moreover, our study reveals substantial benefits of immunotherapy over chemotherapy for SWI/SNF-mutant patients, especially the SWI/SNFmut and TP53mut subgroups.

[Treatment status of tyrosine kinase inhibitor for newly-diagnosed chronic myeloid leukemia: a domestic multi-centre retrospective real-world study].

Objective: To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China. Methods: Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed. Results: 6 893 patients in CP (n=6 453, 93.6%) or AP (n=440, 6.4%) receiving initial imatinib (n=4 906, 71.2%), nilotinib (n=1 157, 16.8%), dasatinib (n=298, 4.3%) or flumatinib (n=532, 7.2%) -therapy. With the median follow-up of 43 (IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance (n=1 055, 15.3%), intolerance (n=248, 3.6%), pursuit of better efficacy (n=168, 2.4%), economic or other reasons (n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph(+) ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph(+) ACA, poorer TFS; Ph(+) ACA, poorer OS. Conclusion: At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

[To compare the efficacy and incidence of severe hematological adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia].

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.

[The facility design and operation effect of control vehicle emissions hazard in test section of automobile assembly workshop].

The hazard of vehicle emissions mainly come from the four wheel positioning, drum test and vehicle emissions test sections in automobile assembly workshop, which can lead to abnormal hemoglobin and hepatic insufficiency in workers. We researched on preventing toxic gases technologies for the vehicle emissions generated by these three sections, designed the ventilation facilities, and then detected and evaluated the operation effect, thereby improving the working environment, ensuring the occupational health of workers, and providing scientific basis for the control of vehicle emissions hazards.

[The influence of interaction between polygenic risk score and intestinal fungal microbiota on the risk of schizophrenia].

Objective: To investigate the effect of interaction between polygenic risk score (PRS) and intestinal fungal microbiota on the risk of Schizophrenia (SCH). Methods: A case-control study was carried out. Drug-naïve, first-episode SCH patients were selected from the Psychiatric Department of the First Affiliated Hospital of Zhengzhou University between October 2017 and October 2019. Meanwhile, healthy controls (HCs) were recruited from local communities through online advertisement or physical examination center. Intestinal fungal microbiota was characterized by the 18S rRNA sequencing platform. The association of fungal microbial dysbiosis (F_MD) index, α-diversity indices and PRS with SCH was detected by logistic regression analysis. Results: A total of 137 SCH patients (62 males and 75 females) and 76 HCs (31 males and 45 females) were included in the study. The age of SCH patients and HCs was (22.5±7.5) years and (22.8±2.3) years, respectively. The results of logistic regression analysis revealed that PRS (OR=1.111, 95%CI: 1.036-1.178, P=0.002) and the increase of F_MD index (OR=1.200, 95%CI: 1.124-1.281, P<0.001) were risk factors for developing SCH. The increase of fungal α-diversity Shannon (OR=0.813, 95%CI: 0.755-0.874, P<0.001) index, Simpson index (OR=0.218, 95%CI: 0.091-0.523, P<0.001) and abundance of key Aspergillus (OR=0.928, 95%CI: 0.864-0.996, P=0.040) decreased the risk of SCH. Aspergillus abundance was positively correlated with cognitive domains including working memory (r=0.280, P=0.001), verbal learning (r=0.253, P=0.003), reasoning and problem solving (r=0.191, P=0.028). Conclusion: The increase of PRS may increase the risk of SCH. The increase of fungal α-diversity indices and Aspergillus abundance may decrease the risk of SCH. The interaction between PRS and intestinal fungi (Shannon index, Simpson index and Aspergillus) is a related factor for the risk of SCH.

[Establishment of diagnostic model for schizophrenia based on neurotrophic factor and other biomarkers].

Objective: To construct a diagnostic model of schizophrenia (SCZ) based on biomarkers such as serum neurotrophic factor. Methods: Patients of schizophrenia (SCZ group) and healthy controls (HC group) who were admitted to the First Affiliated Hospital of Zhengzhou University from January 2017 to December 2019 were prospectively selected. In the SCZ group, the mental symptoms were assessed by the positive and negative symptom scale (PANSS), cognitive function was assessed by the MATRICS consensus cognitive battery (MCCB), brain-derived neurotrophic factor (BDNF), glial cell derived neurotrophic factor (GDNF), fasting glucose (FGB) and fasting insulin (FINS) levels were detected, and insulin resistance (HOMA-IR) was calculated. The same methods were used to evaluate cognitive function, measure BDNF, GDNF, FGB and FINS levels, and calculate HOMA-IR in HC group. The indexes with statistically significant differences between the two groups were selected to be included in the model. The diagnostic model was constructed by machine learning and verified by cross-validation method, the receiver operating curve (ROC) was plotted, and the area under the curve (AUC), sensitivity and specificity were calculated. Results: (1) A total of 142 patients (70 males and 72 females) with schizophrenia were finally included, and aged (25±4) years. Meanwhile, 140 healthy controls (72 males and 68 females) were also enrolled, and aged (26±4) years. In SCZ group, scores in all areas of cognitive function were lower than those in HC group (all P<0.001), the levels of serum BDNF and GDNF [(6.7±1.8) ng/ml and (405±93) pg/ml] were also lower than those in HC group [(12.3±3.2) ng/ml and (574±139) pg/ml] (both P<0.001), but the levels of FINS and HOMA-IR [(8.4±0.8) µU/ml and 1.7±0.3] were higher than those in HC group [(6.7±0.9) µU/ml and 1.4±0.3] (both P<0.001). (2) Correlation analysis showed that the level of serum BDNF had a negative correlation with negative symptom scores and total scores (r=-0.31, P<0.001; r=-0.17, P=0.040), but had a positive correlation with attention/alertness (CPT-IP) T scores, working memory (WSM-Ⅲ) T scores and visual learning (BVMT) T scores in SCZ group (r=0.39, 0.37 and 0.29, all P<0.001). The level of serum GDNF also had a positive correlation with CPT-IP T scores, WSM-Ⅲ T scores and BVMT T scores (r=0.32, P<0.001; r=0.23, P=0.007; r=0.40, P<0.001). The values of HOMA-IR had a positive correlation with social cognition (MSCEIT) T scores in SCZ group (r=0.18, P=0.033). (3) AUC of the early diagnosis model constructed by combining BDNF, GDNF and HOMA-IR was 0.890 (95%CI: 0.832-0.940), the accuracy was 0.89, the sensitivity and specificity was 0.94 and 0.82, respectively. Conclusion: The final diagnostic model based on biomarkers of serum neurotrophic factor has good diagnostic efficiency for SCZ, but large-scale independent sample verification is still needed.

[A multicenter study on the tolerance of intravenous low-dose cyclophosphamide in systemic lupus erythematosus].

OBJECTIVE: To compare the safety of low-dose cyclophosphamide and high-dose cyclophosphamide in the treatment of systemic lupus erythematosus (SLE). METHODS: A total of 1 022 patients with systemic lupus erythematosus from 24 hospitals in China between March 2017 to July 2018 were enrolled. Their clinical manifestations, laboratory tests, adverse events, reasons for stopping receiving intravenous cyclophosphamide and comorbidities were collected. Among them, 506 SLE patients received short-interval low-dose intravenous cyclophosphamide therapy (SILD IV-CYC, 400 mg every two weeks), and 256 patients underwent high-dose cyclophosphamide therapy (HD IV-CYC, 500 mg/m2 of body surface area every month), the side effects between the two groups were compared, the remaining 260 SLE patients were treated with IV-CYC irregularly. Moreover, a total of 377 patients in SILD IV-CYC group and 214 patients in HD IV-CYC group had medical records of the reasons for stopping recei-ving IV-CYC. The reasons for stopping receiving IV-CYC in these two groups were analyzed. RESULTS: In this study, only 40.27%(238/591)of the SLE patients stopped receiving intravenous cyclophosphamide for the causes of disease improvement, however, up to 33.67% (199/591) of the patients for the reason of drug-related side effects. There were 83 patients out of 214 (38.79%) with high-dose intravenous cyclophosphamide treatment who stopped receiving IV-CYC for the drug-related side effects, which was significantly higher than that in the low-dose cyclophosphamide group (30.77%, 116/337, P=0.048). Of theses 506 patients in SILD IV-CYC group, 88 (17.39%) patients experienced gastrointestinal reactions, 66 (13.04%) suffered from infections, 49 (9.68%) had myelosuppression and 68 (13.44%) had alopecia, respectively. Among the 256 patients in the HD IV-CYC group, 80 (31.25%) experienced gastrointestinal reactions, 57 (22.27%) suffered from infections, 51 (19.92%) had myelosuppression and 49 (19.14%) had alopecia. Moreover, 71 (25.18%) of 282 female patients with age between 16 to 45 years in SILD IV-CYC group had abnormal menstruation, while menstrual disorder occurred in 39.72% (56/141) patients of HD IV-CYC group. There was no difference of drug-induced hepatic injury, hemorrhagic cystitis and fatigue between the two groups. CONCLUSION: Low-dose cyclophosphamide showed a lower prevalence of adverse events than high-dose cyclophosphamide in systemic lupus erythematosus patients.

[Prognostic value of pulmonary hemodynamic parameters for predicting survival in acute coronary syndrome].

Objective: To explore the characteristics and prognostic value of pulmonary hemodynamics in patients with acute coronary syndrome (ACS). Methods: From a prospective multicenter registry study of pulmonary hypertension due to left heart disease, consecutive ACS patients who underwent coronary angiography in combination with left and right heart catheterization during hospitalization between January 2013 and November 2016 were involved. The primary endpoint was all-cause mortality. The prognostic variables identified by the Lasso analysis were included in the Global Registry of Acute Coronary Events (GRACE) score. Model performance was evaluated before and after the addition of hemodynamic parameters. Results: A total of 251 patients were enrolled, with age of (63.7±11.5) years. A total of 198 males (78.9%) and 53 females (21.1%) were recruited, and the median follow-up time was 34.7 months. Right heart catheterization-assessed mean pulmonary arterial pressure (mPAP), systolic pulmonary arterial pressure (sPAP) and diastolic pressure gradient (DPG) were found to be significant predictors for survival in ACS. Adjusted for age and sex, the adjusted HR (95%CI) of mPAP, sPAP and DPG were 1.068 (1.015-1.123), 1.033 (1.002-1.065) and 1.094 (1.008-1.187), respectively (P<0.05). Applied to the present cohort of 251 patients, the median of the GRACE score was 123 points, with a C-index of 0.703 (95%CI: 0.615-0.791) for predicting mortality. After the addition of mPAP or DPG to the GRACE score, the C-index increased to 0.715 (95%CI: 0.629-0.801) or 0.711 (95%CI: 0.625-0.797), respectively. When comparing two models before and after the addition of mPAP or DPG, the integrated discriminatory index (IDI) was 4.3% (95%CI: 0.2%-13.5%, P=0.030) and 3.0% (95%CI: 0.2%-11.1%, P=0.020), respectively. Conclusion: Pulmonary hemodynamics can be predictive for survival in ACS patients, providing incremental prognostic value to risk assessment in ACS.

[Association between body mass index and coronary heart disease in Qingdao: a prospective study].

Objective: To analyze the association between body mass index (BMI) and coronary heart disease. Methods: The data for the present study were from the prospective cohort study of China Kadoorie Biobank (CKB) in Qingdao, a total of 33 355 participants aged 30-79 years were included in the study. Cox regression analyses were performed to evaluate the association between BMI and coronary heart disease. Results: During the follow-up for an average 9.2 years, a total of 2 712 cases of ischemic heart disease (IHD) and 420 cases of major coronary events (MCE) were found. Multivariate Cox regression analysis showed that, compared with participants with normal BMI, the participants who were overweight had a 41% and 87% higher risk of IHD and MCE, the adjusted HR were 1.41 (95%CI: 1.27-1.56) and 1.87 (95%CI: 1.43-2.44), respectively. The participants who were obesity had 91% and 143% higher risk of IHD and MCE, the adjusted HR were 1.91 (95%CI: 1.72-2.13) and 2.43 (95%CI: 1.82-3.24), respectively. Conclusion: Overweight and obesity might increase the risk for IHD and MCE.

[Incidence and cause of abnormal cholesterol in children aged 2-18 years in a single center].

OBJECTIVE: To investigate the abnormality and distribution of plasma cholesterol levels in single-center hospitalized children. METHODS: The blood lipid levels of children aged 2-18 years who had blood lipid test results in Peking University First Hospital from June 2016 to June 2019 were etrospectively analyzed. Cholesterol oxidase method was used for total cholesterol, and high-density lipoprotein cholesterol and low-density lipoprotein cholesterol were detected by clearance method. The counting data were compared with chi-square test. RESULTS: The survey had involved 11 829 children (7 087 were boys and 4 742 were girls). 1 822 (15.4%) children were with elevated total cholesterol, 1 371 (11.6%) children with elevated low-density lipoprotein cholesterol, and 2 798 (23.7%) children with high-density lipoprotein cholesterol reduction. The total number of the children with abnormal cholesterol levels was 4 427 (37.4%). Among the 7 835 children who visited hospital due to the disease not commonly inducing dyslipidemia, 731 (9.3%) had elevated TC, 561 (7.2%) had elevated LDL-C, 1 886 (24.1%) had decreased HDL-C, and 2 576 (32.9%) had abnormal cholesterol levels. Among the children with different diseases, the difference in the incidence of abnormal cholesterol was statistically significant. The top three main groups of the children with increased total cholesterol and low-density lipoprotein cholesterol were "dyslipidemia", "urinary tract disease", and "nutritional disease"; The top three main groups of the children with reduced high-density lipoprotein cholesterol were "respiratory diseases", "dyslipidemia", "hematological diseases and malignant tumors". Among the 1 257 blood li-pid test results sent by other departments, 300 cases had abnormal cholesterol levels (23.8%). Among them, there were 70 children with hypercholesterolemia (5.6%), 44 children with increased low-density lipoprotein cholesterol (3.5%), and 224 children with reduced high-density lipoprotein cholesterol (17.8%). There were 365 (4.6%) children with low-density lipoprotein cholesterol ≥140 mg/dL (3.6 mmol/L) who needed to further exclude familiar hypercholesterolemia among the children who visited hospitals due to the disease not commonly inducing dyslipidemia. CONCLUSION: Children in hospitals have a high incidence of cholesterol abnormalities. Doctors need to pay more attention to the cholesterol diagnosis and management regardless of the discipline, which not only helps to control secondary hypercholesterolemia, but also provides the possibility of detecting familial hypercholesterolemia in time.

[Targeted killing of CD133+ lung cancer stem cells using paclitaxel-loaded PLGA-PEG nanoparticles with CD133 aptamers].

OBJECTIVE: To construct a polylactic acid-glycolic acid-polyethylene glycol (PLGA-PEG) nanocarrier (N-Pac-CD133) coupled with a CD133 nucleic acid aptamer carrying paclitaxel for eliminating lung cancer stem cells (CSCs). METHODS: Paclitaxel-loaded N-Pac-CD133 was prepared using the emulsion/solvent evaporation method and characterized. CD133+ lung CSCs were separated by magnetic bead separation and identified for their biological behaviors and gene expression profile. The efficiency of paclitaxel-loaded N-Pac-CD133 for targeted killing of lung cancer cells was assessed in vitro. SCID mice were inoculated with A549 cells and received injections of normal saline, empty nanocarrier linked with CD133 aptamer (N-CD133), paclitaxel, paclitaxel-loaded nanocarrier (N-Pac) or paclitaxel-loaded N-Pac-CD133 (n=8, 5 mg/kg paclitaxel) on days 10, 15 and 20, and the tumor weight and body weight of the mice were measured on day 40. RESULTS: Paclitaxel-loaded N-Pac-CD133 showed a particle size of about 100 nm with a high encapsulation efficiency (>80%) and drug loading rate (>8%), and was capable of sustained drug release within 48 h. The CD133+ cell population in lung cancer cells showed the characteristic features of lung CSCs, including faster growth rate (30 days, P=0.001) and high expressions of tumor stem cell markers OV6(P < 0.001), CD133 (P=0.001), OCT3/4 (P=0.002), EpCAM (P=0.04), NANOG (P=0.005) and CD44 (P=0.02). Compared with N-Pac and free paclitaxel, paclitaxel-loaded N-Pac-CD133 showed significantly enhanced targeting ability and cytotoxicity against lung CSCs in vitro (P < 0.001) and significantly reduced the formation of tumor spheres (P < 0.001). In the tumor-bearing mice, paclitaxel-loaded N-Pac-CD133 showed the strongest effects in reducing the tumor mass among all the treatments (P < 0.001). CONCLUSION: CD133 aptamer can promote targeted delivery of paclitaxel to allow targeted killing of CD133+ lung CSCs. N-Pac-CD133 loaded with paclitaxel may provide an effective treatment for lung cancer by targeting the lung cancer stem cells.

[Cognition and related factors on the use of HIV non-occupational post-exposure prevention among men who have sex with men].

Objective: To understand the cognition and related factors on the use of HIV non-occupational post-exposure prophylaxis (nPEP) among men who have sex with men (MSM). Methods: The snowballing method was applied to recruit research subjects who were ≥18 years old, had sex with men in the past three months, and were aware of nPEP in MSM groups in Beijing, Shenzhen, and Kunming from March 15 to April 14, 2019. Data on social demographics, behavioral characteristics, basic knowledge of nPEP, consultation, and using nPEP were collected through "i guardian Platform". The logistic regression model was used to analyze the related factors affecting the use of nPEP. Results: Among 1 809 investigated, 39.8% (720 persons) were aware of the basic knowledge of nPEP, 33.4% (605 persons) had consulted nPEP, and 15.0% (271 persons) had used nPEP. In addition, multivariate logistic regression analysis showed that factors as whether to have sex with men infected with HIV in the last three months (OR=2.58, 95%CI: 1.64-4.07), the frequency of HIV testing in the past year (OR=2.47, 95%CI: 1.28-5.11), nPEP knowledge awareness (OR=0.70, 95%CI: 0.49-0.99), whether to consult nPEP (OR=70.98, 95%CI: 40.51-136.83) were related to the use of nPEP. Conclusions: MSM still have poor cognition of nPEP. It is necessary to strengthen the publicity and education of nPEP in MSM and promote the use of nPEP after HIV exposure as soon as possible.

HPV16 infection promotes an M2 macrophage phenotype to promote the invasion and metastasis of esophageal squamous cell carcinoma

Objectives High-risk human papillomavirus (HR-HPV) is an important risk factor for esophageal cancer. Macrophages constitute a crucial immune medium for regulating HPV-related tumors; however, the specific regulatory mechanisms remain unknown. Therefore, the purpose of our current study was to investigate the mechanism by which HPV16E6 regulates macrophages to promote the invasion and metastasis of esophageal cancer. Methods HPV16E6 infection was detected by polymerase chain reaction. Immunohistochemistry was used to verify the distribution of tumor-associated macrophages (TAMs) and MMP-9 expression in esophageal squamous cell carcinoma tissues (ESCCs), and cancer adjacent normal tissues (CANs) from Kazakh patients. ESCC cells were transfected with a plasmid over-expressing HPV16E6 and non-contact cocultured with macrophages. Results The infection rate of HPV16E6 in Kazakh ESCCs was clearly higher than that in CANs (P < 0.05). The density of CD163-positive TAMs was significantly positively correlated with HPV16E6 infection in ESCCs (P < 0.05). After coculturing macrophages and EC9706 cells transfected with the HPV16E6 plasmid, the phenotype of macrophages transformed into M2 macrophages. The migration and invasion ability of ESCC cells were higher in the HPV16E6-transfected and coculture group than in the HPV16E6 empty vector-transfected and non-cocultured HPV16E6-transfected groups (all P < 0.05). The density of M2-like TAMs in ESCCs was positively correlated with the level of MMP-9 expression. MMP-9 expression in the HPV16E6-ESCC coculture macrophages group was substantially higher than that in controls (all P < 0.05). Conclusions HPV16 infection mediates tumor-associated macrophages to promote ESCC invasion and migration (AU)

[Effect of the correlation between gut microbiota and folic acid in first-episode schizophrenia].

Objective: To explore the effects of gut microbiota and the serum level of folicacid on psychiatric symptoms in first-episode, drug-free schizophrenic (SCZ) patients. Methods: A total of 100 first-episode, drug-free SCZ patients (SCZ group) from the First Affiliated Hospital of Zhengzhou University and 90 demographically matched healthy individuals (healthy control group) were enrolled. The serum level of folic acid was measured by the electrochemical luminescence method.Positive and Negative Syndrome Scale (PANSS) was used to assess the psychiatric symptoms and Matrics Consensus Cognitive Battery (MCCB) was used to evaluate cognitive function. Bacterial DNA was extracted from the fecal samples for high-through put sequencing of the 16S rRNA.The effects of gut microbiota and folic acid on the psychiatric symptoms and cognitive function in SCZ patients were explored. Results: A total of 41 males and 59 females, with an age of (22.6±8.2) years were included in the patient group, and 32 males and 58 females with an age of (23.0±3.0) years were included in the healthy control group. The fasting folic acid level inserum of the SCZ group was lower than that of healthy control group [6.92(4.98, 8.49) µg/L vs 8.93(7.13, 13.37) µg/L,P<0.001]. The relative abundance of genus Bifidobacterium[0.005(0.003, 0.013) vs 0.014(0.004, 0.031)] and genus Bacteroides[0.015(0.001, 0.091) vs 0.083(0.029, 0.193)]was lower in the SCZ group than that of the healthy control group (both P<0.001). In comparison with the healthy control group, scores of cognitive function in the seven domains were significantly lower in the SCZ group (all P<0.05). In the patient group, the serum level of folic acid was negatively related to the negative symptom score(r=-0.378, P<0.001), but had a positive correlation with the score of speed of processing (r=0.310, P=0.011).In the SCZ group, the relative abundance of the genus Bifidobacterium was positively correlated with the serum level of folic acid (r=0.374,P<0.001) and the score of speed of processing(r=0.330,P=0.003) respectively, but was negatively correlated with the general psychopathology score (r=-0.326, P=0.001). The results of multiple linear regression analysis showed that the interaction term between folic acid and genus Bifidobacteriumin in SCZ patients were correlated with the general psychopathology score, with a regression coefficient of -29.240 (F=8.655, P=0.007). There was no statistical correlation between the aforementioned interaction term and cognitive function (both P>0.05). Conclusion: In first-episode, drug-free SCZ patients, there were decreases in the serum folic acid level and the relative abundance of genus Bifidobacterium, which were related to the psychiatric symptoms, suggesting that these two substances can be used as potential objective indicators for evaluating psychiatric symptoms.

[Value of combined detection of ITGA4 and SFRP2 gene methylation in stool DNA in diagnosis and prognostic evaluation of colorectal tumors].

OBJECTIVE: To investigate the value of quantitative detection of ITGA4 and SFRP2 gene methylation in stool DNA for the early diagnosis and prognostic evaluation of colorectal tumors. OBJECTIVE: Real-time PCR was used for quantitative assessment of ITGA4 and SFRP2 gene methylation levels in stool samples of 85 patients with colorectal cancer, 65 patients with colorectal adenoma and 40 healthy subjects. OBJECTIVE: The 3 groups were comparable for age and gender composition. Methylated ITGA4 and SFRP2 promoters were detected in 48.2% and 62.4% of patients with colorectal cancer, respectively, with a combined positivity of 81.2%. ITGA4 and SFRP2 promoter methylation was detected in 23.1% and 43.1% of patients with colorectal adenoma, respectively, with a combined positivity of 69.2%. The positivity rates of ITGA4 and SFRP2 methylation were significantly higher in patients with colorectal cancer than in those with colorectal adenoma (P < 0.001; P= 0.001) and healthy subjects (P < 0.001; P < 0.001). In colorectal cancer group, ITGA4 and SFRP2 promoter methylation levels were correlated with postoperative tumor recurrence in colorectal cancer group, and the relapse-free survival rate was significantly lower in positive patients for ITGA4 and SFRP2 promoter methylation than in the negative patients (P=0.0002; P=0.007). Multivariate analysis with the COX proportional hazard regression model showed that methylation of ITGA4 and SFRP2 gene promoters (P=0.01) and the degree of tumor differentiation (P=0.03) were associated with the recurrence of colorectal cancer, and were independent risk factors for the recurrence of colorectal cancer. OBJECTIVE: Combined detection of ITGA4 and SFRP2 gene methylation levels in stool DNA can improve the early diagnosis rate of colorectal tumor. ITGA4 and SFRP2 promoter methylation and the degree of tumor differentiation are independent risk factors for colorectal cancer recurrence.

Retrospective Analysis on Traumatic Rupture of Intracranial Internal Carotid Artery in 11 Cases.

ABSTRACT: Objective To retrospectively analyze the characteristics of the traumatic rupture of intracranial internal carotid artery in order to provide reference for forensic expertise examination and identification. Methods A total of 11 autopsy cases of traumatic rupture of intracranial internal carotid artery were collected. The gender, age, cause of injury, blood loss on the scene, location of internal carotid artery rupture, hardening degree of the rupture of the wall, brain injury, blood ethanol content and cause of death were also recorded. Results All 11 cases died on the scene, of which 7 died from traffic accidents, 2 falls from height and 2 from bare handed injuries. None of the 11 victims suffered serious head and body surface injury. The internal carotid artery rupture in the 9 cases of traffic injury and fall from height injury occurred in the cavernous segment. In all these cases, there were transverse fractures of the middle cranial fossa with the carotid sulcus involved, and minor intracranial hemorrhage and brain contusion. In 2 cases of bare handed injuries, internal carotid artery rupture occurred in the ophthalmic artery segment, accompanied by fatal intracranial hemorrhage and diffuse axonal injury, but no skull fracture. All 11 cases showed full-thickness rupture of the vessel wall, and the long axis of the wounds was perpendicular to those of the artery. Conclusion The incidence of intracranial internal carotid artery rupture in high-energy trauma events such as traffic accidents and high falls deserves attention. Injuries of the cavernous segment or ophthalmic segment might be more common. The main injury mechanism of intracranial internal carotid artery rupture might be that the blood vessels were pulled and the bone fragments caused damage.

HPV16 infection promotes an M2 macrophage phenotype to promote the invasion and metastasis of esophageal squamous cell carcinoma.

OBJECTIVES: High-risk human papillomavirus (HR-HPV) is an important risk factor for esophageal cancer. Macrophages constitute a crucial immune medium for regulating HPV-related tumors; however, the specific regulatory mechanisms remain unknown. Therefore, the purpose of our current study was to investigate the mechanism by which HPV16E6 regulates macrophages to promote the invasion and metastasis of esophageal cancer. METHODS: HPV16E6 infection was detected by polymerase chain reaction. Immunohistochemistry was used to verify the distribution of tumor-associated macrophages (TAMs) and MMP-9 expression in esophageal squamous cell carcinoma tissues (ESCCs), and cancer adjacent normal tissues (CANs) from Kazakh patients. ESCC cells were transfected with a plasmid over-expressing HPV16E6 and non-contact cocultured with macrophages. RESULTS: The infection rate of HPV16E6 in Kazakh ESCCs was clearly higher than that in CANs (P < 0.05). The density of CD163-positive TAMs was significantly positively correlated with HPV16E6 infection in ESCCs (P < 0.05). After coculturing macrophages and EC9706 cells transfected with the HPV16E6 plasmid, the phenotype of macrophages transformed into M2 macrophages. The migration and invasion ability of ESCC cells were higher in the HPV16E6-transfected and coculture group than in the HPV16E6 empty vector-transfected and non-cocultured HPV16E6-transfected groups (all P < 0.05). The density of M2-like TAMs in ESCCs was positively correlated with the level of MMP-9 expression. MMP-9 expression in the HPV16E6-ESCC coculture macrophages group was substantially higher than that in controls (all P < 0.05). CONCLUSIONS: HPV16 infection mediates tumor-associated macrophages to promote ESCC invasion and migration.

Growth phase-dependent surface properties of Legionella pneumophila and their role in adhesion to stainless steel coated QCM-D sensors.

Legionella pneumophila cell surface hydrophobicity and charge are important determinants of their mobility and persistence in engineered water systems (EWS). These surface properties may differ depending on the growth phase of L. pneumophila resulting in variable adhesion and persistence within EWS. We describe the growth-dependent variations in L. pneumophila cell surface hydrophobicity and surface charge using the microbial adhesion to hydrocarbon assay and microelectrophoresis, respectively, and their role in cell adhesion to stainless steel using a quartz crystal microbalance with dissipation (QCM-D) monitoring instrument. We observed a steady increase in L. pneumophila hydrophobicity during their lifecycle in culture media. Cell surfaces of stationary phase L. pneumophila were significantly more hydrophobic than their lag and midexponential counterparts. No significant changes in L. pneumophila cell surface charge were noted. Morphology of L. pneumophila remained relatively constant throughout their lifecycle. In the QCM-D study, lag and exponential phase L. pneumophila weakly adhered to stainless steel surfaces resulting in viscoelastic layers. In contrast, stationary phase bacteria were tightly and irreversibly bound to the surfaces, forming rigid layers. Our results suggest that the stationary phase of L. pneumophila would highly favour their adhesion to plumbing surfaces and persistence in EWS.