Publisher Correction: MiR-21 and miR-183 can simultaneously target SOCS6 and modulate growth and invasion of hepatocellular carcinoma (HCC) cells.

Correction to: Eur Rev Med Pharmacol Sci 2015; 19 (17): 3208-3217. PMID: 26400524-published online on September 14, 2015. After publication, a reader brought to our attention a mistake in Figure 4. The journal found that Figure 3 was mistakenly inserted twice in the galley proof, resulting in the publication of the same figure for Figures 3 and 4. The publisher is, therefore, substituting Figure 4 with the correct figure provided at the time of submission as follows: There are amendments to this paper. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/9429.

CAR-T cell therapy targeting surface expression of TYRP1 to treat cutaneous and rare melanoma subtypes.

A major limitation to developing chimeric antigen receptor (CAR)-T cell therapies for solid tumors is identifying surface proteins highly expressed in tumors but not in normal tissues. Here, we identify Tyrosinase Related Protein 1 (TYRP1) as a CAR-T cell therapy target to treat patients with cutaneous and rare melanoma subtypes unresponsive to immune checkpoint blockade. TYRP1 is primarily located intracellularly in the melanosomes, with a small fraction being trafficked to the cell surface via vesicular transport. We develop a highly sensitive CAR-T cell therapy that detects surface TYRP1 in tumor cells with high TYRP1 overexpression and presents antitumor activity in vitro and in vivo in murine and patient-derived cutaneous, acral and uveal melanoma models. Furthermore, no systemic or off-tumor severe toxicities are observed in an immunocompetent murine model. The efficacy and safety profile of the TYRP1 CAR-T cell therapy supports the ongoing preparation of a phase I clinical trial.

Effects of Breathing Patterns on Amide Proton Transfer MRI in the Kidney: A Preliminary Comparative Study in Healthy Volunteers and Patients With Tumors.

BACKGROUND: The amide proton transfer-weighted (APTw) imaging for kidney diseases is important. However, the breathing patterns on APTw imaging remains unexplored. PURPOSE: This study aimed to investigate the effects of intermittent breath-hold (IBH) and free breathing (FB) on renal 3D-APTw imaging. STUDY TYPE: Healthy volunteers were enrolled prospectively, and renal clear cell carcinoma (RCCC) patients were included retrospectively. POPULATION: 58 healthy volunteers and 10 RCCC patients. FIELD STRENGTH/SEQUENCE: 3-T, turbo spin echo, and fast field echo. ASSESSMENT: 3D-APTw imaging was scanned using the IBH and FB methods in volunteers and using the IBH method in RCCC patients. The image quality was evaluated by three observers according to the 5-point Likert scale. Optimal images rated at three points or higher were used to measure the APT values. STATISTICAL ANALYSIS: The measurement repeatability was assessed using the intraclass correlation coefficient (ICC) and the Bland-Altman plot. The APT values were analyzed using McNemar's test, one-way analysis of variance, and t test. RESULTS: 50 healthy volunteers and 8 RCCC patients were enrolled. Renal 3D-APTw imaging using the IBH method revealed a higher success rate (88% vs 78%). The ICCs were excellent in the IBH group (ICCs > 0.74) and were good in the FB group (ICCs < 0.74). No significant differences in the APT values among various zones using the IBH (P = 0.263) or FB method (P = 0.506). The mean APT value using the IBH method (2.091% ± 0.388%) was slightly lower than the FB method (2.176% ± 0.292%), but no significant difference (P = 0.233). The APT value of RCCC (4.832% ± 1.361%) was considerably higher than normal renal using the IBH method. CONCLUSIONS: The study demonstrated that the IBH method substantially increased the image quality of renal 3D-APTw imaging. Furthermore, APT values may vary between normal and tumor tissues. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

[Pathological features of early gastric cancer and its background mucosa after eradication of Helicobacter pylori and their implications for biopsy diagnosis].

Objective: To investigate the clinicopathological changes of early gastric cancer, especially its background mucosa, after the eradication of Helicobacter pylori (H. pylori), and to investigate the causes of underdiagnosis in preoperative biopsy pathology. Methods: Ninety cases of early gastric cancer after H. pylori eradication and 120 cases of endoscopic submucosal dissection (ESD) specimens without H. pylori eradication and their corresponding biopsy specimens were collected from Beijing Friendship Hospital Affiliated to Capital Medical University during 2016-2021. The clinicopathological data of the patients were analyzed, and the histopathological characteristics and immunophenotypic results compared. Results: Compared with the early gastric cancer without H. pylori eradication history, the histopathological type of early gastric cancer after H. pylori eradication was differentiated adenocarcinoma, with staggered distribution of cancerous and non-cancerous epithelium in the tumor area. The morphologic characteristics of gastric mucosa in the background of early gastric cancer after H. pylori eradication, were distinctive, including widening of the opening of enterosylated glandular ducts, serrated change of luminal margin, eosinophilic and microvesicular cytoplasm of enterosylated epithelium. Low-grade atypia existed in gastric cancer epithelial cells after sterilization, which might lead to underdiagnosis or missed diagnosis in biopsy pathology. Conclusions: Early gastric cancer and its background mucosa after H. pylori eradication have unique morphological characteristics, which can be used as a clue for pathological diagnosis, improve the accuracy of biopsy pathology and reduce the underdiagnosis.

Baicalin Induced Apoptosis of Human Cholangiocarcinoma Cell through Activating AMPK/mTORC1/p70S6K Signaling Pathway.

Baicalin (naturally bioactive flavone compound isolated from Scutellaria baicalensis) has been demonstrated to exert strong anticancer activity against various tumor cells. However, the possibility of using baicalin for the treatment of cholangiocarcinoma and its effectiveness remain unstudied. The effect of baicalin on QBC939 cholangiocarcinoma cell culture was studied by assessing cell viability (CCK-8 test) and expression of the key proteins (Western blotting). Baicalin induced apoptosis of QBC939 cells in culture in a dose- and time-dependent manner. The proapoptotic effect was attributed to inhibition of the mTORC1-p70S6K signaling pathway resulting from baicalin-induced AMPK activation. These findings provide a new approach for cholangiocarcinoma treatment and serve as a basis for developing baicalin-based combination cancer therapy strategies.

Diagnostic magnetic resonance imaging in synovial chondromatosis of the temporomandibular joint.

The aim of this paper was to investigate the clinical and magnetic resonance imaging (MRI) features of synovial chondromatosis (SC) of the temporomandibular joint (TMJ). Fourteen patients with SC of the TMJ were included in the study. Clinical and MRI features were analysed and divided into three types based on MRI classification: type I with loose bodies, type II with homogeneous masses, and type III with a mixture of loose bodies and homogeneous masses. All SCs occurred in the superior compartment of the TMJ. There were two patients (14%) categorised as type I, five (36%) as type II and seven (50%) as type III. Four patients (29%) had disc perforation, and nine had bone erosion; among those nine, seven (78%) had type III and two (22%) type II. Histological examination showed inflammation and calcification in the synovial membrane and, and cartilage of the hyaline type in all cases. MRI has advantages in the diagnosis of SC.

Successful use of tofacitinib in epidermolysis bullosa pruriginosa.

This case report describes 26-year-old woman who had multiple clusters of pale-pink lichenoid papules since childhood and the accompanying itching was intense. Skin biopsy revealed obvious fissures had formed under the epidermis. The patient was diagnosed with epidermolysis bullosa pruriginosa and was successfully treated with tofacitinib.

[Clinical effect evaluation of high risk human papilloma virus E6/E7 mRNA in triaging women with atypical squamous cells of undetermined significance].

Objective: To evaluate the performance of high risk human papilloma virus (HR-HPV) E6/E7 mRNA in triaging women with atypical squamous cells of undetermined signification (ASCUS). Methods: The ASCUS cohort determined by liquid-based cytology test in the cervical cancer screening queue in Luoshan County, Xinyang City, Henan Province 2017 were selected. The population underwent colposcopy biopsy and pathological tests, combined with HPV16 or 18 (HPV16/18), HR-HPV DNA and HPV E6/E7 mRNA test. By using the pathological result as the gold standard, the sensitivity, specificity, positive predictor (PPV), negative prediction (NPV), referral rate and 95% confident interval (CI) of HPV E6/E7 mRNA, HR-HPV DNA, HPV16/18 were calculated, respectively. Results: The average age of 312 ASCUS women was 52.6±7.3 years old. Among the 290 women diagnosed as normal by pathology, 64 (22.1%) were HPV E6/E7 mRNA positive, 86 (29.7%) were HR-HPV DNA positive, and 19 (6.6%) were HPV16/18 positive. All of the cervical intraepithelial neoplasia (CIN) cases determined by pathology were both HPV E6/E7 mRNA and HR-HPV DNA positive. The sensitivity, specificity, PPV, NPV and referral rate of HPV E6/E7 mRNA for predicting CIN2+ lesion in women with ASCUS were 100.0% (95%CI: 72.3, 100.0), 77.8% (95%CI: 72.8, 82.1), 13.0% (95%CI: 7.2, 22.3), 100.0% (95%CI: 98.4, 100.0) and 24.7%. Compared with HPV E6/E7 mRNA, the sensitivity of HR-HPV DNA was similar with HPV E6/E7 mRNA, but with a lower specificity [70.2% (95%CI: 64.8, 75.1), P<0.05], a higher referral rate (32.1%, P<0.05); while HPV 16/18 had a high specificity (93.4%, 95%CI: 90.0, 95.7) and a low sensitivity (30.0%, 95%CI: 10.8, 60.3). Based on the age stratification by age 45, the sensitivity of HPV E6/E7 mRNA in both age groups was 100.0%. The specificity of HPV E6/E7 mRNA in group of ≥45 years was a little higher than that in group of <45 years [79.0% (95%CI: 73.7, 83.5) versus 68.3% (95% CI: 53.0, 80.4)], but the difference was not statistically significant (P>0.05). Conclusions: The ASCUS woman triaging effect of HPV E6/E7 mRNA detection is better than those of HR-HPV and HPV16/18 under certain conditions. The application of HPV E6/E7 mRNA detection to triage ASCUS population can avoid unnecessary colposcopy referral and reduce the missed diagnosis of cervical lesions.

Molecular epidemiology of Pseudomonas aeruginosa isolated from lower respiratory tract of ICU patients / Epidemiologia molecular de Pseudomonas aeruginosa isolada em pacientes com infecções do trato respiratório inferior admitidos em UTI

Lower respiratory tract infections (LRTIs) caused by Pseudomonas aeruginosa are the most common infection among hospitalized patients, associated with increased levels of morbidity, mortality and attributable health care costs. Increased resistant Pseudomonas worldwide has been quite meaningful to patients, especially in intensive care unit (ICUs). Different species of Pseudomonas exhibit different genetic profile and varied drug resistance. The present study determines the molecular epidemiology through DNA fingerprinting method and drug resistance of P. aeruginosa isolated from patients with LTRIs admitted in ICU. A total of 79 P. aeruginosa isolated from patients with LRTIs admitted in ICU were characterized by Restriction Fragment Length Polymorphism (RFLP), Random Amplified Polymorphic DNA (RAPD) and Repetitive Extrapalindromic PCR (REP-PCR). Antibiotic resistance was determined by minimum inhibitory concentration (MIC) assay while MDR genes, viz, blaTEM, blaOXA, blaVIM, blaCTX-M-15 were detected by polymerase chain reaction (PCR). Of the 137 Pseudomonas sp isolated from ICU patients, 57.7% of the isolates were reported to be P. aeruginosa. The overall prevalence of P. aeruginosa among the all included patients was 34.5%. The RAPD analysis yielded 45 different patterns with 72 clusters with 57% to 100% similarity level. The RFLP analysis yielded 8 different patterns with 14 clusters with 76% to 100% similarity level. The REP PCR analysis yielded 37 different patterns with 65 clusters with 56% to 100% similarity level. There was no correlation among the different DNA patterns observed between the three different methods. Predominant of the isolates (46.8%) were resistant to amikacin. Of the 79 isolates, 60.8% were positive for blaTEM gene and 39.2% were positive for blaOXA gene. P. aeruginosa was predominantly isolated from patients with LRTIs admitted in ICU. The difference in the similarity level observed between the three DNA fingerprinting methods indicates that there is high inter-strain variability. The high genetic variability and resistance patterns indicates that we should continuously monitor the trend in the prevalence and antibiotic resistance of P. aeruginosa especially in patients with LRTIs admitted in ICU.

Infecções do trato respiratório inferior (ITRIs) são as infecções mais comuns entre pacientes internados em unidade de terapia intensiva (UTI). Pseudomonas aeruginosa é a causa mais comum de ITRIs e está associada ao aumento da mortalidade. Diferentes espécies de Pseudomonas exibem diferentes perfis genéticos e resistência variada as drogas. O presente estudo determina a epidemiologia molecular através do método de fingerprinting de DNA e resistência as drogas de P. aeruginosa isoladas de pacientes com LTRIs internados em UTI. Um total de 79 P. aeruginosa isoladas de pacientes com ITRIs internados em UTI foram caracterizados por Polimorfismo de Comprimento de Fragmentos de Restrição (RFLP), DNA Polimórfico Amplificado ao Acaso (RAPD) e PCR Extrapalindrômico Repetitivo (REP-PCR). A resistência aos antibióticos foram determinadas pelos ensaios de concentrações inibitória mínima (MIC), enquanto os genes MDR, blaTEM, blaOXA, blaVIM, blaCTX-M-15 foram detectados pela reação em cadeia da polimerase (PCR). Das 137 Pseudomonas sp isoladas de pacientes de UTI, 57,7% dos isolados foram relatados como P. aeruginosa. A prevalência geral de P. aeruginosa entre os pacientes incluídos foram de 34,5%. A análise RAPD renderam 45 padrões diferentes com 72 clusters com nível de similaridade de 57% a 100%. A análise RFLP renderam 8 padrões diferentes com 14 clusters com 76% a 100% de similaridade. A análise de PCR do REP produziram 37 padrões diferentes com 65 clusters com nível de similaridade de 56% a 100%. Não houveram correlações entre os diferentes padrões de DNA observados entre os três diferentes métodos. Predominantes dos isolados (46,8%) eram resistentes à amicacina. Dos 79 isolados, 60,8% foram positivos para o gene blaTEM e 39,2% foram positivos para o gene blaOXA. P. aeruginosa foi predominantemente isolado de pacientes com ITRIs internados em UTI. A diferença no nível de similaridade observado entre os três métodos de fingerprinting do DNA indica que há alta variabilidade inter-strain. A alta variabilidade genética e os padrões de resistência indicam que devemos monitorar continuamente a tendência na prevalência e resistência a antibióticos de P. aeruginosa, especialmente em pacientes com ITRIs internados em UTI.

Key Parameters of Tumor Epitope Immunogenicity Revealed Through a Consortium Approach Improve Neoantigen Prediction.

Many approaches to identify therapeutically relevant neoantigens couple tumor sequencing with bioinformatic algorithms and inferred rules of tumor epitope immunogenicity. However, there are no reference data to compare these approaches, and the parameters governing tumor epitope immunogenicity remain unclear. Here, we assembled a global consortium wherein each participant predicted immunogenic epitopes from shared tumor sequencing data. 608 epitopes were subsequently assessed for T cell binding in patient-matched samples. By integrating peptide features associated with presentation and recognition, we developed a model of tumor epitope immunogenicity that filtered out 98% of non-immunogenic peptides with a precision above 0.70. Pipelines prioritizing model features had superior performance, and pipeline alterations leveraging them improved prediction performance. These findings were validated in an independent cohort of 310 epitopes prioritized from tumor sequencing data and assessed for T cell binding. This data resource enables identification of parameters underlying effective anti-tumor immunity and is available to the research community.

[Study on the relationship between adenoid and tonsil hypertrophy and obesity in children].

Objective: To study the relationship between adenoid hypertrophy, tonsillar hypertrophy and overweight or even obesity in children. Methods: A total of 799 children aged 2 to 12 years with tonsillar and adenoid hypertrophy from January 2015 to December 2019 in the Department of Otolaryngology Head Neck Surgery, the Sixth Medical Center of Chinese PLA General Hospital were selected. The body mass index (BMI) was calculated according to the height and weight measured routinely at the time of admission. The difference of BMI between children and normal children of the same age, and the correlation between adenoid, tonsil hypertrophy and obesity were compared. Chi-square test was used to compare the surgical children's BMI of different genders with normal children of the same age, and Spearman rank correlation was used to analyze the correlation between BMI and adenoid and tonsil hypertrophy. Results: The Spearman correlation coefficient between tonsil hypertrophy and BMI was 0.078, P=0.077, the Spearman correlation coefficient between adenoid hypertrophy and BMI was -0.058(P=0.100). χ(2) test showed that the proportion of overweight and obesity in school-age children (7~12 years old) was significantly higher than that in preschool children (2~6 years old), and the difference was statistically significant (χ(2)(male)=22.386, P(male)<0.001, χ(2)(female)=4.478, P(female)<0.001). Conclusion: There is no obvious correlation between adenoid hypertrophy, tonsil hypertrophy and overweight or obesity in children, but the probability of children overweight or obesity increases with age, and the proportion of obesity in children aged 7-12 years is higher.

Identification of serum exosomal miR-148a as a novel prognostic biomarker for breast cancer.

OBJECTIVE: Breast cancer (BC) is one of the most common malignanciesD. Li, J. Wang, L.-J. Ma, H.-B. Yang, J.-F. Jing, M.-M. Jia, X.-J. Zhang, F. Guo, J.-N. Gao affecting females. Aberrant expression of microRNAs (miRNAs) has been associated with carcinogenesis of BC. The aim of our study was to investigate the correlation of serum exosomal miR-148a expression and the clinical outcome of patients with BC. PATIENTS AND METHODS: Quantitative Real Time-Reverse Transcription Polymerase Chain Reaction (qRT-PCR) was applied to evaluate the expression level of serum exosomal miR-148a in patients with BC, patients with benign breast tumors, and healthy controls. Then, the clinical value of serum exosomal miR-148a in BC was evaluated. RESULTS: Serum exosomal miR-148a levels were gradually downregulated from healthy controls patients with benign breast tumors to BC patients. Serum exosomal miR-148a could well distinguish BC patients from healthy volunteers. The expression level of serum exosomal miR-148a in BC patients was significantly upregulated following surgery, while dropped in the cases with disease relapse. A significant association was found between serum exosomal miR-148a levels and the tumor-node-metastasis (TNM) stage, differentiation, and lymph node metastasis in BC. In addition, BC patients with lower expression of serum exosomal miR-148a levels suffered worse overall survival and disease-free survival than those with higher expression of serum exosomal miR-148a levels. Furthermore, serum exosomal miR-148a was an independent risk factor for BC. CONCLUSIONS: Our data have demonstrated that serum exosomal miR-148a is significantly reduced in patients with BC and downregulation of serum exosomal miR-148a is closely associated with unfavorable clinical outcome of BC, indicating that serum exosomal miR-148a might serve as a promising diagnostic and prognostic biomarker for BC.

[Performance of high-risk HPV typing test in early diagnosis of cervical cancer].

Objective: To evaluate the performance of High-risk HPV typing detection in cervical cancer screening. Methods: A total of 3 231 women were recruited as the subjects of cervical cancer screening from Jiyuan city of Henan provinces from June to July 2017. All women underwent HPV DNA test. The women with cytological examination ≥ASCUS or cytological examination negative and HPV 16/18 positive underwent colposcopy biopsy and pathological examination. Pathological diagnosis was used as the gold standard. Sensitivity, specificity, positive predictive value (PPV), negative predictive value(NPV) as well as corresponding 95% confidence interval (CI) of HR-HPV and HPV 16/18 were calculated. Results: The mean age of 3 231 subjects selected in this study was 46.84±10.00 (21-64) years old. 524 subjects had the positive results of HR-HPV, including 91 of HPV16 and 15 of HPV18. Pathological test result CIN2+ was the gold standard. The sensitivity and specificity of HR-HPV for cervical precancer lesions screening were 93.75 (95%CI: 79.85-98.27) and 84.56% (95%CI: 83.26-85.77), respectively. To compared with HR-HPV, HPV16/18 had low sensitivity (65.63%, 95%CI: 48.31-79.59)and higher specificity (97.44%, 95%CI: 96.83-97.93). After age stratification by age 30 and 45, the sensitivity of HPV 16/18 was same with HR-HPV (100%, 95%CI: 34.24-100.00), the specificity of HPV 16/18 was higher than HR-HPV (98.71%, 95%CI: 96.27-99.56 vs 84.48%, 95%CI: 79.27-88.58) in<30 age group.The sensitivity of HR-HPVin 30-45 and ≥45 age group were higher than HPV16/18 (85.71%, 95%CI: 48.69-97.43 vs 71.43%, 95%CI: 35.89-91.78, 95.65%, 95%CI: 79.01-99.23 vs 60.87%, 95%CI: 40.79-77.84), but the specificity werelower than HPV16/18 (86.89%, 95%CI: 84.58-88.90 vs 98.51%, 95%CI: 97.51-99.11、83.49%, 95%CI: 81.81-85.04 vs 96.80%, 95%CI: 95.94-97.48). Conclusions: HR-HPV detection has relatively high sensitivity and specificity in cervical cancer screening. For >30 years old women, HR-HPV is more recommended in cervical cancer screening. Therefore, HR-HPV detection is an effective method for cervical cancer screening.

[Influencing factors of postoperative acute kidney injury in patients undergoing cardiac surgery].

Objective: To analyze the influencing factors of acute kidney injury (AKI) in patients after cardiac surgery using levosimendan or dobutamine, and explore the effect of positive inotropic drugs on AKI. Methods: The clinical data of 417 patients undergoing cardiac surgery from January to June 2018 in Beijing Anzhen Hospital and treated with levosimendan or dobutamine during perioperative period were retrospectively reviewed and collected. Patients were divided into AKI group and non-AKI group according to whether AKI occurred. Univariate logistic regression analysis was used to analyze the factors related to the occurrence of AKI. The statistically significant factors (P<0.05) were further included in the multivariate logistic regression analysis. Results: Totally, 417 patients were enrolled in the study, with a mean age of (58.2±10.4) years old and a male rate of 65.0% (n=271), and the AKI incidence rate was 25.2% (105/417). Univariate logistic regression analysis showed that male, chronic kidney disease, high serum creatinine level in preoperative period, aortic obstruction time ≥ 120 minutes and extracorporeal circulation time ≥ 120 minutes were risk factors for AKI (all P<0.05). Vasodilator and levosimendan treatment during perioperative period were protective factors (P<0.05). Multivariate logistic regression analysis showed that chronic kidney disease (OR=17.291, 95%CI: 4.335-68.960, P<0.001) and high serum creatinine level (OR=1.097, 95%CI: 1.074-1.121, P<0.001) in preoperative period were independent risk factors for AKI. Perioperative application of levosimendan (OR=0.533, 95%CI: 0.288-0.984, P=0.044) was an independent protective factor. Conclusions: Risk factors for AKI after cardiac surgery include chronic kidney disease and high serum creatinine level in preoperative period. The use of levosimendan during preoperative period has the potential effect to protect against AKI.

Utility of the lateral arm free flap in oral cavity reconstruction: a single-centre experience with Chinese patients.

The lateral arm flap (LAF) may offer an alternative option for oral cavity repair. Twenty-five Chinese patients with oral cavity defects were reconstructed with a LAF. The anatomical characteristics of the flap, the donor site complications, and the functional and aesthetic assessments of recipient site were reviewed. The overall flap survival was 96.0% (24/25patients). The average pedicle length was 7.07±1.09cm when it was cut off at the insert of the deltoid, with an average arterial diameter of 1.30±0.37mm and vein diameter of 2.06±0.48mm. The average flap length was 7.06±1.01cm, and the average flap breadth was 5.28±0.66cm, with the average flap size ranging from 18 to 42cm2. One to three reliable perforators supplied the flap, with the proximal, middle, and distal perforators being located at 9.9±1.1cm, 8.6±1.4cm, and 5.7±1.2cm from the lateral epicondyle, respectively. The donor defect was closed primarily and healed uneventfully. A longitudinal scar was the most common morbidity of the donor site. The function and shape of the reconstructed tissues were well restored. The LAF provides a reliable choice for reconstructing medium-sized oral cavity defects, with minimal donor-site morbidity and ideally functional and aesthetic rehabilitation of the recipient site.

[Evaluation the triage performance of p16/Ki-67 dual staining for HR-HPV positive women].

Objective: This study aimed to evaluate the clinical performance of p16/Ki-67 dual staining for triage high risk HPV (HR-HPV) infected women. Method: Target objects were women who infected HR-HPV and received colposcopy examination between April and December of 2016 at the Second Affiliated Hospital of Zhengzhou University. Gynecologists collected the cervical exfoliated cells from eligible women for p16/Ki-67 dual staining, LBC testing and HPV DNA testing. Histology diagnosis were used as gold standard. Sensitivities, specificities, positive predictive values (PPVs), negative predictive values (NPVs) of p16/Ki-67 dual staining, LBC testing and HPV16/18 testing for triage of HR-HPV positive population were calculated and compared. Results: A total of 295 HR-HPV infected women were selected, and the mean age was (44.29±11.48) years old. Positive rates of p16/Ki-67 dual staining, HPV16/18 testing and LBC testing were 70.17% (207), 56.95% (168) and 85.76% (253), respectively. When CIN2+as the endpoint, among the three triage methods, sensitivity of p16/Ki-67 dual staining was 90.00% (95%CI: 85.06%-93.43%), higher than the value of HPV 16/18 testing, but lower than the value of LBC testing. Specificity, PPV and NPV of p16/Ki-67 dual staining were the highest [71.58% (95%CI: 61.81%-79.67%), 86.96% (95%CI:81.69%-90.88%) and 77.27% (95%CI: 67.49%-84.78%)]. When detection for CIN3+, sensitivity of p16/Ki-67 dual staining was 92.90% (95%CI: 87.74%-95.99%), lower than the value of LBC testing, but higher than the value of HPV16/18 testing. Specificity of p16/Ki-67 dual staining was 55.00% (95%CI: 46.74%-63.00%), lower than the value of HPV16/18 testing, but higher than the value of LBC testing. PPV of p16/Ki-67 dual staining was 69.57% (95%CI: 62.99%-75.43%), lower than the value of HPV 16/18 testing, but higher than the value of LBC testing. NPV of p16/Ki-67 dual staining was 87.50% (95%CI: 78.99%-92.87%), higher than value of HPV 16/18 testing, but lower than the value of LBC testing. Conclusion: p16/Ki-67 dual staining has better clinical effects than HPV 16/18 testing and LBC testing for triage women with HR-HPV infection.

[Anti-myelin-associated glycoprotein antibody positive IgM monoclonal gammopathy related peripheral neuropathy: 11 cases and literature review].

Objective: To improve the understanding of rare anti-myelin-associated glycoprotein (MAG) positive IgM monoclonal gammopathy related peripheral neuropathy (IgM-PN) . Methods: Eleven cases of IgM paraproteinemia and anti-MAG antibody positive neuropathy diagnosed since 2014 in Peking Medical Union College Hospital were summarized. The medical records including clinical manifestation, lab results, treatment and prognosis were analyzed. Results: Among the 11 patients (8 male and 3 female) , the median onset age is 63 years old (range from 52 to 77 years old) . The peripheral neuropathy of 9 patients were characterized by distal onset of numbness, 6 patients suffered from muscle weakness. The nerve conduction velocity study indicated that all 11 patients had demyelinating peripheral nerve damage, which was sensory predominant and more severe in lower limbs, 6 of them had secondary axonal damage. Monoclonal IgM gammopathy was identified in all 11 patients, among which 6 were IgM κ, 2 IgG κ and IgM κ bi-clonal, 3 IgM λ. Three patients were diagnosed with Waldenström's macroglobulinaemia. The anti-MAG-IgM antibody was positive in all 11 cases. After diagnosis, 9 patients received combination chemotherapy including rituximab or rituximab treatment alone. The monoclonal IgM level declined significantly in 7 patients. The neuropathy was stable or improved. Conclusions: Anti-MAG antibody positive IgM-PN is a rare M protein related disease. In peripheral neuropathy with undetermined etiology, we suggest to screen M protein and anti-MAG antibody. Chemotherapy including rituximab or rituximab alone is recommended as first-line therapy.

[Study on the relationship between EPHX1 gene polymorphism and antioxidant capacity in patients with chronic obstructive pulmonary disease].

Objective: To explore the difference of mRNA, protein expression levels and the indexes of peripheral blood antioxidant capacity in peripheral blood lymphocytes of different EPHX1 genotypes in chronic obstructive pulmonary disease(COPD). Methods: A case-control study was conducted to collect peripheral blood samples of 220 stable chronic COPD patients with smoking history and 230 healthy smokers (control group) from October 2016 to February 2018 in the First Affiliated Hospital of Kunming Medical University, and the genetic testing was carried out according to the operation instructions of BigDye Terminator v1.1 DNA Sequencing Kit. Based on their EPHX1 exon 3 and exon 4 polymorphism status, the EPHX1 was classified into 4 groups, i. e., normal activity, slow activity, extremely slow activity and fast activity. Then COPD patients were allocated to either a slow activity group (slow and very slow activity) or a fast activity group (normal and fast activity) according to EPHX1 genotype and gene activity. The expression of EPHX1 mRNA and protein in peripheral blood lymphocytes were detected by qRT-PCR and Western blot, and indexes of serum antioxidant capacity was detected by corresponding kits. Results: (1)The 2(-ΔΔCt) of the control group was 1.000, and the 2(-ΔΔCt) of the COPD group was 1.052±0.023. There was no significant difference in the level of EPHX1 mRNA expression between the two groups (t=1.992 P=0.865). The level of EPHX1 mRNA expression in the slow activity group was not different significantly compared to that in the fast-active group (1.053±0.023 vs 1.048±0.021, t=1.133, P=0.260). (2)The level of EPHX1 protein expression by Western blot analysis showed that the EHPX1/GAPDH gray ratio was not different significantly between the COPD group and the control group (0.613±0.089 vs 0.602±0.075, t=0.805, P=0.422). The level of EPHX1 protein expression in the slow activity group was not significantly different compared to that in the fast activity group (0.606±0.088 vs 0.622±0.092, t=-0.786 P=0.434). (3)There were significant differences in indexes of antioxidant capacity between the control group and the COPD group (P<0.05). There were significant differences in indexes of antioxidant capacity between the slow activity group and the fast activity group of COPD patients (P<0.05). Conclusions: The different antioxidant capacity of COPD patients with different EPHX1 genotypes may be related to the polymorphism of EPHX1 gene affecting the activity of microsomal epoxidase, but not to the level of EPHX1 mRNA and protein expression.