Combining FITs and HRFQ with colonoscopy improve the cost-effectiveness of a 9-year mass colorectal cancer screening program.

BACKGROUND: Colorectal cancer (CRC) incidence has been increasing. Colonoscopy is still a gold standard method for its early diagnosis but using colonoscopy alone as a mass screening method is unrealistic. This study is to investigate whether combining fecal immunochemical test (FIT) and high-risk-factors questionnaire (HRFQ) with colonoscopy improve the cost-effectiveness of a mass CRC screening. PATIENTS AND METHODS: CRC screening protocol combining FITs and HRFQ in the first stage and colonoscopy in the second stage was used in 50 villages/towns in 2007-2015. Residents aged 40-74 years were eligible for this free screening. A total of 160 210 (76.12%) participants completed first-stage screening, and 28 679 (17.90%) participants were defined as positive, among which 21 715 (75.72%) participants completed colonoscopy and were included in the final analysis. Outcomes were followed up until 2020. RESULTS: The compliance was 76.12% and 75.72% in the first and second screening stage, respectively. A total of 252 CRC, 4033 adenoma, 1234 advanced neoplasm, and 5534 total neoplasm cases were detected in the screening. The positive predictive values of CRC, adenoma, advanced neoplasm, and total neoplasm were higher in FITs+ than those in the HRFQ+ population, respectively. A total of 64.60% and 43.42% total neoplasm cases were found in FITs+ and HRFQ+ (8.02% for both), respectively. The total colorectal neoplasm and CRC cases detected by combining HRFQ and FITs increased by 55.08% and 40.00%, respectively, and their increases were higher compared to HRFQ. The detection cost per any neoplasm by combining HRFQ and FITs was <$5331, while that by FITs and HRFQ alone was <$4570 and $5380, respectively. CONCLUSIONS: Combining FITs and HRFQ with colonoscopy improve the cost-effectiveness of a mass CRC screening program. This protocol can be recommended for most populations, especially those in the countries and areas with high population density and low physician/population ratio.

[Study of the methotrexate loaded extracellular vesicles in the treatment of experimental periodontitis in mice].

Objective: To investigate the therapeutic effect of methotrexate loaded vesicles on experimental periodontitis in mice. Methods: Extracellular vesicles (EVs) were isolated from human umbilical cord mesenchymal stem cells (hUC-MSC). Methotrexate loaded vesicles (MTX-EVs) were constructed, whose morphology and size were analyzed by using scanning electron microscopy and particle size analyzer. Western blotting was used to identify their surface specific proteins. C57BL/6J male mice of 4-5 weeks (provided by Experimental Animal Center of The Fourth Military Medical University) were selected, among which 8 were randomly selected by blind grasp method without treatment and fed normally as normal group, and others were induced to periodontitis models by local injection of lipopolysaccharide (LPS) into the periodontium. The LPS was injected once every day with a concentration of 2 g/L and a volume of 5 µl, lasting for two weeks. The mice with successfully induced periodontitis were randomly divided into 4 groups by blind grasping method, with 8 mice in each group. The LPS group was with no treatment, and the other three groups were treated with periodontal local injection of MTX, EVs or MTX-EVs, respectively. Two weeks later, enzyme-linked immunosorbent assay (ELISA) was used to detect the expressions of inflammatory cytokine interleukin (IL)-1ß, IL-6 and tumor necrosis factor-α (TNF-α) in gingival tissue. The amount of alveolar bone resorption of four groups was detected by using micro-CT scanning and HE staining. The expression proportion of the inflammatory factor in gingival tissue was analyzed by using flow cytometry. Results: The scanning electron microscopy results showed that EVs and MTX-EVs were circular or elliptical in shape. Dynamic light scattering (DLS) particle size analysis showed that the particle size of EVs was around 200 nm, while that of MTX-EVs was around 300 nm. The ELISA results showed IL-1ß levels in the normal group, LPS group, LPS+MTX group, LPS+EVs group and LPS+MTX-EVs group were (28.86±2.76), (51.50±2.04), (35.26±2.40), (45.49±2.04) and (35.77±3.49) ng/L. That is, the IL-1ß concentrations in the LPS+MTX group, LPS+EVs group and LPS+MTX-EVs group were significantly lower than that in the LPS group (P<0.05); the mass concentration of IL-1ß in the LPS +MTX-EVs group was significantly lower than that in the LPS+EVs group (P<0.05). The concentrations of IL-6 in the normal group, LPS group, LPS+MTX group, LPS+EVs group and LPS+MTX-EVs group were (125.44±4.12), (221.64±10.59), (178.16±16.90), (181.09±18.22) and (170.15±9.04) ng/L, among which the concentration of IL-6 in the last three groups were significantly lower than that in the LPS group (P<0.05). The mass concentration of IL-6 in the LPS+MTX-EVs group was significantly lower than those in the LPS+MTX group and LPS+EVs group (P<0.05). The concentrations of TNF-α in the normal group, LPS group, LPS+MTX group, LPS+EVs group and LPS+MTX-EVs group were (320.27±38.68), (479.62±40.94), (342.18±25.89), (415.88±12.01) and (325.75±30.83) ng/L, among which the concentrations of last three groups were significantly lower than the LPS group (P<0.05); the mass concentration of TNF-α in the LPS+MTX-EVs group was significantly lower than those in the LPS+EVs group and LPS+MTX group (P<0.05). The micro-CT results showed that the distance of cement-enamel junction-alveolar bone crest (CEJ-ABC) of the first molar and root (M1R1) in the normal group, LPS group, LPS+MTX group, LPS+EVs group and LPS+MTX-EVs group of mice were (0.11±0.03), (0.28±0.02), (0.23±0.03), (0.20±0.04), and (0.18±0.03) mm, respectively. Compared with the LPS group, the CEJ-ABC of the M1R1 in the LPS+MTX group, LPS+EVs group and LPS+MTX-EVs group were inhibited to varied degrees with statistically significant differences (P<0.05). Among them, LPS+MTX-EVs group had the best bone resorption inhibitioin effect compared to LPS+MTX group and LPS+EVs group, and the differences were statistically significant (P<0.05). The flow cytometry results indicated that the proportion of interferon-γ (IFN-γ) positive cells was (11.77±1.02)% in the LPS group, (6.87±0.65)% in the LPS+EVs group, and (4.15±0.92)% in the LPS+MTX-EVs group, respectively. The proportions of IFN-γ positive cells in the LPS+EVs group and LPS+MTX-EVs group were significantly lower than that in the LPS group (P<0.05), while the ratio of IFN-γ positive cells in the LPS+MTX-EVs group was found significantly lower than that in the LPS+EVs group (P<0.05). Conclusions: MTX-EVs can effectively alleviate the periodontal local inflammatory environment and reduce bone resorption of alveolar bone in periodontitis model mice.

[Effects of cognition-related lifestyles on early cognitive decline in community older adults in China].

Objective: To investigate the distribution characteristics of cognition-related lifestyles of elderly in communities and explore the integrated effects on early cognitive decline. Methods: The participants were from the Project of Prevention and Intervention of Neurodegenerative Disease for Elderly in China. A total of 2 537 older adults aged ≥60 years without dementia in the 2015 baseline survey and the 2017 follow-up survey were included. The information about their cognition-related lifestyles, including physical exercise, social interaction, leisure activity, sleep quality, smoking status, and alcohol consumption, were collected through questionnaire survey and the integrated scores were calculated. Multivariate logistic regression analysis was used to assess the association between integrated cognition-related lifestyle score and early cognitive decline. Results: In the 2 537 older adults surveyed, 28.7% had score of 5-6, while only 4.8% had high scores for all 6 healthy lifestyles. Significant differences in healthy lifestyle factor distributions were observed between men and women. Multivariate logistic regression model showed that the risks for early cognitive decline in the older adults who had lifestyle score of 4 and 5-6 were lower than that in those with lifestyle score of 0-3 (OR=0.683, 95%CI: 0.457-1.019; OR=0.623, 95%CI: 0.398-0.976; trend P=0.030). In the women, the risks for early cognitive decline was lower in groups with score of 4 and 5-6 than in group with score of 0-3 (OR=0.491, 95%CI: 0.297-0.812; OR=0.556, 95%CI: 0.332-0.929; trend P=0.024). Conclusion: Cognition-related healthy lifestyles are associated with significantly lower risk for early cognitive decline in the elderly, especially in women.

[Assessment of the diagnostic value and prognosis of different detection markers in endocervical adenocarcinoma].

Objective: To study the diagnostic value of different detection markers in histological categories of endocervical adenocarcinoma (ECA), and their assessment of patient prognosis. Methods: A retrospective study of 54 patients with ECA in the Cancer Hospital, Chinese Academy of Medical Sciences from 2005-2010 were performed. The cases of ECA were classified into two categories, namely human papillomavirus-associated adenocarcinoma (HPVA) and non-human papillomavirus-associated adenocarcinoma (NHPVA), based on the 2018 international endocervical adenocarcinoma criteria and classification (IECC). To detect HR-HPV DNA and HR-HPV E6/E7 mRNA in all patients, we used whole tissue section PCR (WTS-PCR) and HPV E6/E7 mRNA in situ hybridization (ISH) techniques, respectively. Additionally, we performed Laser microdissection PCR (LCM-PCR) on 15 randomly selected HR-HPV DNA-positive cases to confirm the accuracy of the above two assays in identifying ECA lesions. Receiver operating characteristic (ROC) curves were used to analyze the efficacy of markers to identify HPVA and NHPVA. Univariate and multifactorial Cox proportional risk model regression analyses were performed for factors influencing ECA patients' prognoses. Results: Of the 54 patients with ECA, 30 were HPVA and 24 were NHPVA. A total of 96.7% (29/30) of HPVA patients were positive for HR-HPV DNA and 63.3% (19/30) for HR-HPV E6/E7 mRNA, and 33.3% (8/24) of NHPVA patients were positive for HR-HPV DNA and HR-HPV E6/E7 mRNA was not detected (0/24), and the differences were statistically significant (P<0.001). LCM-PCR showed that five patients were positive for HR-HPV DNA in the area of glandular epithelial lesions and others were negative, which was in good agreement with the E6/E7 mRNA ISH assay (Kappa=0.842, P=0.001). Analysis of the ROC results showed that the AUC of HR-HPV DNA, HR-HPV E6/E7 mRNA, and p16 to identify HPVA and NHPVA were 0.817, 0.817, and 0.692, respectively, with sensitivities of 96.7%, 63.3%, and 80.0% and specificities of 66.7%, 100.0%, and 58.3%, respectively. HR-HPV DNA identified HPVA and NHPVA with higher AUC than p16 (P=0.044). The difference in survival rates between HR-HPV DNA (WTS-PCR assay) positive and negative patients was not statistically significant (P=0.156), while the difference in survival rates between HR-HPV E6/E7 mRNA positive and negative patients, and p16 positive and negative patients were statistically significant (both P<0.05). Multifactorial Cox regression analysis showed that International Federation of Obstetrics and Gynecology (FIGO) staging (HR=19.875, 95% CI: 1.526-258.833) and parametrial involvement (HR=14.032, 95% CI: 1.281-153.761) were independent factors influencing the prognosis of patients with ECA. Conclusions: HR-HPV E6/E7 mRNA is more reflective of HPV infection in ECA tissue. The efficacy of HR-HPV E6/E7 mRNA and HR-HPV DNA (WTS-PCR assay) in identifying HPVA and NHPVA is similar, with higher sensitivity of HR-HPV DNA and higher specificity of HR-HPV E6/E7 mRNA. HR-HPV DNA is more effective than p16 in identifying HPVA and NHPVA. HPV E6/E7 mRNA and p16 positive ECA patients have better survival rates than negative.

[Analysis of time for diagnosis of nontuberculous mycobacterial lung disease and its associated factors in a tuberculosis-designated hospital in Shanghai].

Objective: To investigate the pathogenic characteristics, bacteriological diagnosis time and its associated factors among patients with nontuberculous mycobacterial (NTM) lung disease in a large tuberculosis-designated hospital in Shanghai from 2020 to 2021, in order to improve diagnosis efficiency and formulate precision treatment. Methods: On the basis of the Tuberculosis Database in Shanghai Pulmonary Hospital, NTM patients diagnosed by the Department of Tuberculosis between January 2020 and December 2021 were screened. Demographic, clinical and bacterial information were retrospectively collected. Chi-square test, paired-sample nonparametric test and logistic regression model were used to analyze the factors associated with the diagnosis time of NTM lung disease. Results: A total of 294 patients with bacteriologically confirmed NTM lung disease were included in this study, 147 males and 147 females with a median age of 61(46, 69) years. Of them, 227 (77.2%) patients had comorbidity of bronchiectasis. Species identification results showed that Mycobacterium Avium-Intracellulare Complex was the main pathogen of NTM lung disease (56.1%), followed by Mycobacterium kansasii (19.0%) and Mycobacterium abscessus (15.3%). Species such as Mycobacterium xenopi and Mycobacterium malmoense were rarely identified, accounting for a total proportion of only 3.1%. Positive culture rates for sputum, bronchoalveolar lavage fluid and puncture fluid were 87.4%, 80.3% and 61.5%, respectively. Paired-sample analysis showed that the positive rate of sputum culture was significantly higher than that of smear microscopy (87.1% vs. 48.4%, P<0.01), while no statistical difference was observed between sputum and bronchoalveolar lavage fluid on positive culture rate (78.7% vs. 77.3%, P>0.05). Patients with cough or expectoration were observed with 4.04-fold (95%CI 1.80-9.05) or 2.95-fold (95%CI 1.34-6.52) higher probability of positive sputum culture, compared to those without. Regarding bronchoalveolar lavage fluid, female or patients with bronchiectasis had a 2.82-fold (95%CI 1.16-6.88) or 2.38-fold (95%CI 1.01-5.63) higher probability to achieve a positive culture. The median time to diagnosis of NTM lung disease was 32 (interquartile range: 26-42) days. The results of multivariable analysis showed that patients with symptom of expectoration (aOR=0.48, 95%CI 0.29-0.80) needed a shorter diagnosis time in comparison with patients without expectoration. With Mycobacterium Avium-Intracellulare Complex as a reference, lung disease caused by Mycobacterium abscessus needed shorter diagnosis time (aOR=0.43, 95%CI 0.21-0.88), whereas those caused by rare NTM species were observed to require a longer diagnosis time (aOR=8.31, 95%CI 1.01-68.6). Conclusion: The main pathogen causing NTM lung disease in Shanghai was Mycobacterium Avium-Intracellulare Complex. Sex, clinical symptoms and bronchiectasis had an impact on the positive rate of mycobacterial culture. The majority of patients in study hospital were timely diagnosed. Clinical symptoms and NTM species were associated with the bacteriological diagnosis time of NTM lung disease.

[Bioinformatics analysis of differentially expressed genes associated with chronic schistosomiasis japonica-induced hepatic fibrosis].

OBJECTIVE: To screen differentially expressed genes (DEGs) associated with chronic schistosomiasis japonica-induced hepatic fibrosis and analyze their functions. METHODS: The dataset of gene expression profiles of patients with chronic schistosomiasis japonica-induced hepatic fibrosis was downloaded from the Gene Expression Omnibus (GEO) database, and DEGs were screened using R package. The biological functions of DEGs were characterized using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. In addition, the protein-protein interaction (PPI) network of DEGs was created to screen the hub genes. RESULTS: A total of 62 DEGs were identified, including 12 down-regulated genes and 50 up-regulated genes. GO enrichment analysis showed that DEGs were mainly enriched in 116 biological processes, including fatty acid, sulfur compound, acyl-coenzyme A and thioester metabolism; 19 cellular components, including mitochondrial matrix, outer mitochondrial membrane and organelle outer membrane; and 7 molecular functions, including insulin-like growth factor binding and oxidoreductase activity. KEGG pathway enrichment analysis that the DEGs were significantly enriched in phosphatidylinositol-3-kinase/serine/threonine protein kinase (PI3K/Akt), mitogen-activated protein kinase (MAPK), calcium metabolism and cyclic adenosine monophosphate (cAMP) signaling. PPI network analysis identified six hub genes involved in the development of chronic schistosomiasis japonica-induced hepatic fibrosis, including ACACA, ACSL1, GPAM, THRSP, PLIN1 and DGAT2, and ACSL1, ACACA and PLIN1 were the top 3 hub genes. CONCLUSIONS: ACSL1, ACACA and PLIN1 may be the hub genes associated with the development of chronic schistosomiasis japonica-induced hepatic fibrosis, and abnormal lipid metabolism mediated by these DEGs may play an important role in the development of chronic schistosomiasis japonica-induced hepatic fibrosis.

[Clinical characteristics and prognosis analysis of 498 cases with drug-induced liver injury].

Objective: To determine the risk factors, clinical characteristics and treatment prognosis, so as to provide reference for clinicians to diagnose, treat and prevent drug-induced liver injury (DILI). Methods: Data of 712 confirmed DILI cases were collected from the Second Affiliated Hospital of Kunming Medical University between 2013 to 2019. Among them, 498 cases were included in the study. All patients medical history, clinical manifestations and classification, laboratory parameters, disease severity, and mortality rate were collected. Statistical analysis was performed using t-test, Mann-Whitney U test/Pearson χ2 test/Fisher's exact test or Spearman's rank test. Results: Among the suspicious drugs causing DILI, single medication accounted for 89.56%, mainly including traditional Chinese medicine (56.43%), anti-tumor and immunomodulatory agents (8.03%), anti-infective drugs (4.42%), antipyretic and analgesic drugs (4.22%) %), etc., while combination medication accounted for 10.44%. The clinical classification was dominated with hepatocyte injury (63.05%), and there was a statistically significant difference in clinical classification among age groups (P<0.001). Age, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL) and total bile acid (TBA) had statistically significant difference among different suspicious drugs in DILI caused by different drug (P<0.001, 0.003, 0.001, <0.001 and <0.001). Laboratory test results showed that there were statistically significant differences in ALT, AST, ALP, γ-glutamyltransferase (GGT), TBA, international normalized ratio (INR), and eosinophils (P<0.001, <0.001, <0.001, 0.018, 0.003 and 0.019, respectively). Chronic hepatitis was more common in the 54 cases who completed histopathological examination of the liver biopsy. Fibrosis degree was higher in the Western medicine group than Chinese herbal medicine group (P<0.05), and the difference was statistically significant (P<0.05). 96.99% of DILI patients were cured or improved, and 3.01% of patients were uncured. Ordinal logistic regression analysis showed that GGT and INR were independent predictors of poor prognosis. Conclusions: Suspicious drugs for DILI are herbal/dietary supplements, anti-tumor and immunomodulatory, anti-infective, and antipyretic and analgesic. The most common clinical classification is hepatocyte injury. Most patients with DILI have a good prognosis after drug withdrawal and GGT and INR are independent predictors of poor prognosis.

[Influence of age on advanced neoplasia detection in colorectal cancer screening in population at high risk].

Objective: To compare the detection rate of advanced neoplasia and the number of people needing endoscopy in colorectal cancer screening giving at different starting age in population at high risk. Methods: Based on the screening project of early diagnosis and treatment of colorectal cancer in Jiashan county, Zhejiang province, two rounds of colorectal cancer screening were conducted between January 2007 and December 2020. After excluding participants who were not at high risk or had incomplete information, 27 130 participants and 31 205 participants were finally enrolled in round one and in round two, respectively. The spline analysis based on the generalized additive model was used to describe the trend of detection rate of advanced neoplasia with age. The detection rate and number of people needing endoscopy for the groups with starting age at 50, 45 and 40 years were calculated, and the differences in the detection rate were tested by χ2 goodness of fit test. Results: A total of 21 077 (77.69%) participants in round one and 25 249 (80.91%) participants in round two received endoscopy, in whom 1 097 (detection rate=52.05‰) and 1 151 (detection rate=45.59‰) had advanced neoplasia (cancers and advanced adenomas), respectively. The detection rate increased significantly with age, and the detection rate in round one were significantly higher than that in round two (P<0.05). The overall detection rates of advanced neoplasia for the groups with starting age at 50, 45 and 40 years were 61.11‰, 56.14‰ and 52.05‰ in round one, and 49.10‰, 46.75‰ and 45.59‰ in round two, respectively. The rates were significantly higher for the group with starting age at 50 years than that with starting age at 40 years in both round one and round two (P<0.05). The numbers of people needing endoscopy of advanced neoplasia for the groups with starting age at 50, 45 and 40 years were 17, 18, and 20 in round one, and 21, 22 and 22 in round two. Conclusions: The detection rate of advanced neoplasia increased with age. Starting screening at lower age might contribute to decreased detection rate and increased number of people needing endoscopy. However, the difference was limited.

Pilot study of fractional microneedling radiofrequency for hidradenitis suppurativa assessed by clinical response and histology.

BACKGROUND: Hidradenitis suppurativa (HS) is a devastating chronic inflammatory skin disease with frequent recurrences. Various systemic treatments and procedures have been used but the efficacy of fractional microneedling radiofrequency (FMR) has not been reported. AIM: To evaluate the clinical and histological efficacy of FMR in the treatment of HS lesions. METHODS: An 8-week, prospective, split-body, unblinded study was conducted, which enrolled 10 adult patients with mild to moderate HS to receive 3 sessions of FMR treatment biweekly. HS severity was assessed using the number and type of lesions, HS Physician Global Assessment (HS-PGA) and the modified Sartorius score (mSS). Skin biopsies were performed on participants to assess change in inflammation before and after FMR. RESULTS: Severity of HS was significantly reduced on the FMR-treated side of the body, but not on the control side. Inflammatory HS lesions were significantly reduced after 4 weeks, while HS-PGA and mSS were significantly decreased after 6 weeks. Immunohistochemistry staining showed decreased expression of inflammatory markers including neutrophil elastases, interleukin (IL)-8 and IL-17, tumour necrosis factor-α, transforming growth factor-ß1 and matrix metalloproteinases. CONCLUSION: FMR may be a viable treatment option for mild to moderate HS.

[Association between lifestyle-related factors and colorectal adenoma].

Objective: To explore the association between lifestyle-related factors and colorectal adenoma. Methods: Based on the Screening Project of Early Diagnosis and Treatment of Colorectal Cancer in Jiashan county Zhejiang province, from August 2012 to March 2018, information gathered through records on questionnaire and colonoscopic diagnosis were collected from participants with positive results during the primary screening stage. According to the findings of colonoscopy, 11 232 controls without any colorectal diseases and 3 895 cases with colorectal adenoma were included in the study. Multivariate logistic regression models were used to analyze the association between lifestyle-related factors and colorectal adenoma. Results: After adjusting for possible confounding factors, results from multivariate logistic regression analysis showed that smoking, alcohol drinking and obesity were positively related to the risk of colorectal adenoma, with ORs (95%CIs) as 1.38 (1.24-1.54), 1.37 (1.24-1.51) and 1.38 (1.20-1.59) respectively. However, regular aspirin intake was negatively related with the risk of colorectal adenoma (OR=0.65, 95%CI: 0.53-0.80). After stratified by sex and age, data showed that the associations between smoking, alcohol drinking and colorectal adenoma were statistically significant in males, and the association between regular aspirin intake and colorectal adenoma was also statistically significant in older participants (aged 60 years and older). Conclusion: Smoking, alcohol drinking, regular aspirin intake and obesity were associated with colorectal adenoma.

[Prospective evaluation on the impact of colonoscopy regarding the incidence of colorectal cancer].

Objective: To evaluate the impact of colonoscopy on the incidence of colorectal cancer (CRC). Methods: This study was based on the Screening Project of Early Diagnosis and Treatment of CRC in Jiashan county, Zhejiang province. After excluding participants with incomplete information, these with individual history of CRC, those with CRC, enteritis or ulcer, noticed through colonoscopy exam at baseline, a total of 25 894 participants were finally included. Cox proportional hazards regression model was used to analyze the association between colonoscopy and the incidence of CRC. Results: This study was followed up for 160 113 person-years with a median of 5.67 years. During the follow-up period, 127 of them developed the CRC. The incidence rates of CRC in participants, were 202.35 per 100 000 person-years, 40.93 per 100 000 person-years and 63.62 per 100 000 person-years, respectively among the following three groups: who did not take the colonoscopy, without colorectal lesions or with benign colorectal lesions noticed by the colonoscopy and the differences were statistically significant (P<0.05). After adjusting for potential confounding factors, the HRs(95%CI) of CRC were 0.24 (0.16-0.36) and 0.29 (0.17-0.49), among those who did not have or had colorectal lesions in the participants who underwent the colonoscopy. Stratified by anatomic site, age and sex, results showed that the associations among the aforementioned groups were relatively stable. Conclusion: Colonoscopy could effectively contribute to the reduction of CRC incidence in the high-risk population.

[The value of serum abnormal prothrombin in clinical application of hepatocellular carcinoma].

Objective: To examine the value of serum protein induced by vitamin K absence or antagonist-Ⅱ (PIVKA-Ⅱ) detection in the early diagnosis and surveillance of hepatocellular carcinoma (HCC). Methods: The clinical data of 215 patients with HCC admitted to Department of Hepatobiliary-Pancreatic Surgery of China-Japan Union Hospital of Jilin University from October 2017 to May 2018 were analyzed retrospectively. There were 172 males and 43 females, aged of (59.0±9.3) years old (range 34 to 86 years old). In addition, there were 85 non HCC patients were enrolled in the control group, 42 males and 43 females, aged (54.2±11.3) years old (range 22 to 80 years old). The blood sample of 3 ml was drawn from the elbow vein at 6∶00 am on the next day of admission, and then was kept in low temperature away from light, and sent for PIVKA-Ⅱ detection on the same day. The positive value of AFP was ≥20 µg/L and PIVKA-Ⅱ was ≥32 AU/L. The data were analyzed statistically by χ(2) test, t test or rank sum test. The correlation between AFP, PIVKA-Ⅱ and tumor maximum diameter was analyzed by linear regression. Results: The sensitivity of PIVKA-Ⅱ detection only for the diagnosis of HCC in all stages was significantly higher than AFP or equivalent to AFP, the overall sensitivity of PIVKA-Ⅱ and AFP was 85.1% and 52.1%, respectively. But the specificity of PIVKA-Ⅱ was lower than that of AFP, they were 78.8% and 96.5%, respectively. In particularly, in the earlier stage of HCC (Ⅰa) , the sensitivity of PIVAK-Ⅱ to HCC was 64.5%, while the AFP was only 26.3%. Combined detection of PIVKA-Ⅱ and AFP significantly improved the diagnostic rate of HCC to 88.4%, and the specificity to 76.5%. Moreover, there was a positive correlation between PIVKA-Ⅱ level and the maximum tumor diameter (r(2)=0.587, P<0.05), but there was no correlation between the AFP level and the maximum tumor diameter (r(2)=0.296, P>0.05). The positive rate of PIVKA-Ⅱ in the diagnosis of HCC with vascular invasion was also significantly higher than that of AFP (P<0.01) . Conclusions: PIVKA-Ⅱ can be used as a serological marker for HCC screening and diagnosis. In particular, PIVKA-Ⅱ detection was significantly sensitive than AFP in the earlier stage of HCC. Combined detection of PIVKA-Ⅱ and AFP can effectively improve the diagnostic rate of HCC in all stages. The significant elevation of PIVKA-Ⅱ is also helpful to determine the tumor aggressiveness, vascular invasion and prognosis of HCC patients.

The role of miR-99b in mediating hepatocellular carcinoma invasion and migration.

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "The role of miR-99b in mediating hepatocellular carcinoma invasion and migration, by C.-J. Liu, J.-H. Yang, F.-Z. Huang, J.-H. Yang, C.-P. Liu, X.-H. Mao, W.-M. Yi, X.-B. Shen, C. Peng, M.-F. Chen, B. Jiang, J.-S. Wu, published in Eur Rev Med Pharmacol Sci 2018; 22 (8): 2273-2281-DOI: 10.26355/eurrev_201804_14815-PMID: 29762829" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/14815.

[Effect of schistosomiasis japonica on the development of gastric and colorectal cancer].

OBJECTIVE: To examine the effect of schistosomiasis on the development of gastric cancer and colorectal cancer. METHODS: The clinical data of patients with gastric cancer and colorectal cancer with and without schistosomiasis japonica that were admitted to the Yijishan Hospital Affiliated to Wannan Medical College from January 2014 to December 2018 were collected. All cases were divided into schistosomal gastric cancer group and non - schistosomal gastric cancer group, schistosomal colorectal cancer group and non-schistosomal colorectal cancer group. The risk factors of gastric cancer and colorectal cancer were identified using univariate analysis and multivariate logistic regression analysis, and the effects of schistosomiasis on the development and progression of gastric cancer and colorectal cancer were evaluated. In addition, the survival of 32 patients with schistosomal colorectal cancer and 68 cases with non-schistosomal colorectal were estimated using telephone follow-up, and compared. RESULTS: There were 113 patients with schistosomal gastric cancer and 3 741 cases with non-schistosomal gastric cancer enrolled in this study, and there were significant differences between them in terms of sex ratio, age and prevalence of Helico-bacter pylori infection (all P values < 0.05). Logistic regression analysis revealed that age, H. pylori infection, and schistosomiasis were independent risk factors for gastric cancer (all P values < 0.05). There were 184 patients with schistosomal colorectal cancer and 2 205 cases with non-schistosomal colorectal cancer recruited in this study, and there were significant differences between them in terms of age, sex ratio, rate of history of alcohol consumption and rate of positive fecal occult blood test (all P values < 0.05). The phenotypes of both schistosomal and non-schistosomal colorectal cancer were predominantly ulcerative; however, the proportion of patients with invasive and protruded colorectal cancer was significantly greater than that of patients with non-schistosomal colorectal cancer (P = 0.003). Logistic regression analysis revealed that age (P = 0.003), gender (P = 0.002), phenotype (P = 0.005) and schistosomiasis (P = 0.029) were independent risk factors for colorectal cancer. The 5-year survival rate was significantly higher in patients with schistosomal colorectal cancer (68.90%) than in those with non-schistosomal colorectal cancer (46.40%), and the dead patients with schistosomal colorectal cancer had a significantly greater mean age than those with non-schistosomal colorectal cancer [ (66.33 ± 3.08) years vs. (56.29 ± 1.94), P < 0.05]. CONCLUSIONS: Schistosomiasis may alter the pathogenesis of colorectal cancer, resulting in the differences in the epidemiology, clinical characteristics and 5-year survival rate between patients with schistosomal and non-schistosomal colorectal cancer. Periodical gastrointestinal endoscopy and other examinations are recommended to exclude the likelihood of gastrointestinal cancers in men with anemia of unknown causes and at ages of 60 years living in schistosomiasis-endemic areas.

[Application of autologous cartilage in rhinoplasty for patients with traumatic nasal contraction and nasal dysfunction].

Objective: To explore the application and effect of autologous cartilage in rhinoplasty for patients with traumatic hernia and nasal dysfunction. Methods: From January 2017 to April 2019,30 patients with nasal trauma admitted to Department of Otorhinolaryngology Head and Neck Surgery, Daping Hospital, Army Medical University were treated for 6 days to 14 years. All patients were accompanied by different degrees of nasal deformity and nasal ventilatory disorders. They were classified into three categories: light, medium and heavy. All of them were open at the same time. Rhinoplasty and nasal septum deviation correction. For mild to moderate nasal deformity and nasal ventilatory disorders, ear cartilage was used to modify the tip of the nose and strengthen the nasal septal cartilage support to modify the deformity of the nasal back. For severe nasal deformity and nasal ventilatory disorders, we engraved the costal cartilage into a "Y" shaped monolithic stent or flank costal cartilage to form a 2+1 or 4+1 stent, and the costal cartilage stent and the septal cartilage tail end were sutured. Reshape the nasal septum frame support and the nasal column to avoid collapse of the nose. Results: Three patients had a septal hematoma after operation and recovered normally after cleansing. All patients were followed up for 2 months to 2 years, and no complications such as nasal septum perforation and nasal bridge collapse occurred. The postoperative cure rate was 60.0% (18/30). All patients had a grade I nasal drop after surgery, and the effective rate was 100% (30/30). The patient's preoperative measurement deviation was (6.85±2.43) mm, the postoperative measurement deviation was (2.4±1.58) mm, the preoperative nasal appearance VAS score was (1.93±1.31), and the postoperative nasal appearance VAS score was (6.60±1.16), the difference in facial appearance deviation and VAS score before and after surgery was statistically significant (P<0.05). All patients had improved nasal ventilation after operation. The preoperative nasal ventilation VAS score was (1.97±1.07), the postoperative nasal ventilation VAS score was (6.53±1.04), and the difference between preoperative and postoperative nasal ventilation VAS scores was statistically significant (P<0.05). Conclusions: Autologous cartilage is effective in rhinoplasty in patients with traumatic nasal contraction and nasal dysfunction. One stage open rhinoplasty and nasal septum deviation surgery are performed to shorten the treatment time and improve the nasal appearance and nasal ventilation function. The patients got satisfaction.

The combination therapy of HIF1α inhibitor LW6 and cisplatin plays an effective role on anti-tumor function in A549 cells.

Hypoxia-inducible factor 1α (HIF1α) has been demonstrated to be involved in the resistance of various human cancer cells to chemotherapies. However, the correlation between HIF1α and the sensitivity of human non-small cell lung cancer (NSCLC) cells to cisplatin has not been illuminated. The aim of the present study was to investigate the effects of HIF1α on drug resistance in NSCLC cells. A549 cells were incubated in 21% or 0.5% O2 followed by the assessment of the level of HIF1α with qRT-PCR and western blot and ROS level by DCFH-DA assays. Effects of hypoxia or HIF1α inhibitor LW6 on the proliferation and apoptosis of A549 cells were evaluated via CCK-8 and flow cytometry assays. IC50 of A549 cells to cisplatin was determined by MTT assay. The mitochondrial membrane potential (MMP) was measured via JC-1 staining. Moreover, the expression of apoptosis related protein (Bcl-2, Bax) and drug resistance related proteins (MDR1, MRP1) were measured by western blotting. Exposure of A549 cells to 1% O2 significantly up-regulated HIF1α expression, maintained cell viability to cisplatin but decreased the ROS level, which promoted chemoresistance to cisplatin. LW6-treated A549 cells showed an increase in ROS level that blocked the hypoxia induced resistance to cisplatin and in addition, decreased expression of MDR1 and MRP1 in cisplatin-treated cells. This study revealed that hypoxia-improved cisplatin chemoresistance of NSCLC cells by regulated MDR1 and MRP1 expression via HIF1α/ROS pathway is reversed by LW6, suggesting that LW6 may act as effective sensitizer in chemotherapy for NSCLC.

Scale law of complex deformation transitions of nanotwins in stainless steel.

Understanding the deformation behavior of metallic materials containing nanotwins (NTs), which can enhance both strength and ductility, is useful for tailoring microstructures at the micro- and nano- scale to enhance mechanical properties. Here, we construct a clear deformation pattern of NTs in austenitic stainless steel by combining in situ tensile tests with a dislocation-based theoretical model and molecular dynamics simulations. Deformation NTs are observed in situ using a transmission electron microscope in different sample regions containing NTs with twin-lamella-spacing (λ) varying from a few nanometers to hundreds of nanometers. Two deformation transitions are found experimentally: from coactivated twinning/detwinning (λ < 5 nm) to secondary twinning (5 nm < λ < 129 nm), and then to the dislocation glide (λ > 129 nm). The simulation results are highly consistent with the observed strong λ-effect, and reveal the intrinsic transition mechanisms induced by partial dislocation slip.

Atrophic acne scar: a process from altered metabolism of elastic fibres and collagen fibres based on transforming growth factor-ß1 signalling.

BACKGROUND: Atrophic acne scar, a persistent sequela from acne, is undesirably troubling to many patients due to its cosmetic and psychosocial aspects. Although there have been some reports emphasizing the role of early inflammatory responses in atrophic acne scarring, evolving perspectives on the detailed pathogenic processes are promptly needed. OBJECTIVES: Examining the histological, immunological and molecular changes in early acne lesions susceptible to atrophic scarring can provide new insights to understand the pathophysiology of atrophic acne scar. METHODS: We experimentally validated several early fundamental hallmarks accounting for the transition of early acne lesions to atrophic scars by comparing molecular profiles of skin and acne lesions between patients who were prone to scar (APS) or not (ANS). RESULTS: In APS, compared with ANS, devastating degradation of elastic fibres and collagen fibres occurred in the dermis, followed by their incomplete recovery. Abnormally excessive inflammation mediated by innate immunity with T helper 17 and T helper 1 cells was observed. Epidermal proliferation was significantly diminished. Transforming growth factor (TGF)-ß1 was drastically elevated in APS, suggesting that aberrant TGF-ß1 signalling is an underlying modulator of all of these pathological processes. CONCLUSIONS: These results may provide a basis for understanding the pathogenesis of atrophic acne scarring. Reduction of excessive inflammation and TGF-ß1 signalling in early acne lesions is expected to facilitate the protection of normal extracellular matrix metabolism and ultimately the prevention of atrophic scar formation. What's already known about this topic? The dermis of atrophic acne scars shows alteration of extracellular matrix components such as collagen fibres. Inflammation in acne lesions is associated with the development of acne scars. What does this study add? Abnormalities in the metabolism of collagen fibres and elastic fibres were observed in the early developmental stages of acne lesions that were progressing into atrophic scars. Exacerbated inflammation and aberrant epidermal proliferation by increased transforming growth factor (TGF)-ß1 signalling may affect the abnormal extracellular matrix metabolism. What is the translational message? Abnormal changes in elastic fibres and collagen fibres are found in the early developmental process of acne in patients who are prone to atrophic scarring. An early treatment regimen strongly inhibiting inflammation and TGF-ß1 signalling to help the normal recovery of the extracellular matrix components is required to prevent atrophic scarring.

Prevalence and natural course of pseudotumours after small-head metal-on-metal total hip arthroplasty: a minimum 18-year follow-up study of a previous report.

AIMS: The present study investigated the five-year interval changes in pseudotumours and measured serum metal ions at long-term follow-up of a previous report of 28 mm diameter metal-on-metal (MoM) total hip arthroplasty (THA). PATIENTS AND METHODS: A total of 72 patients (mean age 46.6 years (37 to 55); 43 men, 29 women; 91 hips) who underwent cementless primary MoM THA with a 28 mm modular head were included. The mean follow-up duration was 20.3 years (18 to 24). All patients had CT scans at a mean 15.1 years (13 to 19) after the index operation and subsequent follow-up at a mean of 20.2 years (18 to 24). Pseudotumour volume, type of mass, and new-onset pseudotumours were evaluated using CT scanning. Clinical outcomes were assessed by Harris Hip Score (HHS) and the presence of groin pain. Serum metal ion (cobalt (Co) and chromium (Cr)) levels were measured at the latest follow-up. RESULTS: At final follow-up, pseudotumours were observed in 26/91 hips (28.6%). There was an increase in volume of the pseudotumour in four hips (15.4%), no change in volume in 21 hips (80.8%), and a decrease in volume in one hip (3.8%). There were no new-onset pseudotumours. There was no significant difference in HHS between patients with and without pseudotumours. At final follow-up, mean serum Co ion levels and median Co:Cr ratios were significantly greater in patients with pseudotumours, but the serum Cr ion levels were not significantly different. CONCLUSION: At a mean 20 years of follow-up, pseudotumours were observed in 26/91 hips (28.6%) with no new-onset pseudotumours during subsequent follow-up. Most pseudotumours in small-head MoM THA were static in volume and asymptomatic with normal serum metal ion levels. Cite this article: Bone Joint J 2019;101-B:317-324.