Development and validation of a nomogram model for predicting the risk of MAFLD in the young population.

This study aimed to develop and validate a nomogram model that includes clinical and laboratory indicators to predict the risk of metabolic-associated fatty liver disease (MAFLD) in young Chinese individuals. This study retrospectively analyzed a cohort of young population who underwent health examination from November 2018 to December 2021 at The Affiliated Hospital of Southwest Medical University in Luzhou City, Sichuan Province, China. We extracted the clinical and laboratory data of 43,040 subjects and randomized participants into the training and validation groups (7:3). Univariate logistic regression analysis, the least absolute shrinkage and selection operator regression, and multivariate logistic regression models identified significant variables independently associated with MAFLD. The predictive accuracy of the model was analyzed in the training and validation sets using area under the receiver operating characteristic (AUROC), calibration curves, and decision curve analysis. In this study, we identified nine predictors from 31 variables, including age, gender, body mass index, waist-to-hip ratio, alanine aminotransferase, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, uric acid, and smoking. The AUROC for the subjects in the training and validation groups was 0.874 and 0.875, respectively. The calibration curves show excellent accuracy of the nomogram. This nomogram which was based on demographic characteristics, lifestyle habits, anthropometrics, and laboratory data can visually and individually predict the risk of developing MAFLD. This nomogram is a quick and effective screening tool for assessing the risk of MAFLD in younger populations and identifying individuals at high risk of MAFLD, thereby contributing to the improvement of MAFLD management.

Prognostic nomogram for colorectal cancer patients with multi-organ metastases: a Surveillance, Epidemiology, and End Results program database analysis.

BACKGROUND: A nomogram that integrates risk models and clinical characteristics can accurately predict the prognosis of individual patients. We aimed to identify the prognostic factors and establish nomograms for predicting overall survival (OS) and cause-specific survival (CSS) in patients with multi-organ metastatic colorectal cancer (CRC). METHODS: Demographic and clinical information on multi-organ metastases from 2010 to 2019 were extracted from the Surveillance, Epidemiology, and End Results (SEER) Program. Univariate and multivariate Cox analyses were used to identify independent prognostic factors that were used to develop nomograms to predict CSS and OS, and to assess the concordance index (C-index), area under the curve (AUC), and calibration curve. RESULTS: The patients were randomly assigned to the training and validation groups at a 7:3 ratio. A Cox proportional hazards model was conducted for CRC patients to identify independent prognostic factors, including age, sex, tumor size, metastases, degree of differentiation, stage T, stage N, primary and metastasis surgery. The competing risk models employed by Fine and Gray were used to identify the risk factors for CRC. Death from other causes was treated as a competing event, and Cox models were used to identify the factors for death to identify the independent factors of CSS. By incorporating the corresponding independent prognostic factors, we established prognostic nomograms for OS and CSS. Finally, we used the C-index, ROC curve, and calibration plots to assess the utility of the nomogram. CONCLUSIONS: Using the SEER database, we constructed a predictive model for CRC patients with multi-organ metastases. Nomograms provide clinicians with 1-, 3-, and 5-year OS and CSS predictions for CRC, allowing them to formulate appropriate treatment plans.

SLAMF6 is associated with the susceptibility and severity of rheumatoid arthritis in the Chinese population.

OBJECTIVES: A recently published genome-wide association study identified six novel loci associated with rheumatoid arthritis (RA) in Korean population. We aimed to investigate whether these newly reported RA-risk loci are associated with RA in the Chinese population and to further characterize the functional role of the susceptible gene. METHODS: The susceptible variants of RA were genotyped in 600 RA patients and 800 healthy controls, including rs148363003 of SLAMF6, rs117605225 of CXCL13, rs360136 of SWAP70, rs111597524 of NFKBIA, rs194757 of ZFP36L1 and rs1547233 of LINC00158. Synovial tissues were collected from the knee joint of 50 RA patients and 40 controls without osteoarthritis for the gene expression analysis. Inter-group comparisons were performed with the Chi-square test for genotyping data or with Student's t-test for gene expression analysis. RESULT: For rs148363003 of SLAMF6, RA patients were observed to have a significantly lower frequency of genotype CC (4.5% vs. 0.9%, p = 0.004) as compared with the controls. The frequency of allele C was remarkably higher in the patients than in the controls (11.5% vs. 8.0%, p = 0.002), with an odds ratio of 1.49 (95% CI = 1.16-1.92). There was no significant difference between the patients and the controls regarding genotype or allele frequency of the other 5 variants. The mRNA expression of SLAMF6 was 1.6 folds higher in the RA patients than in the controls. Moreover, SLAMF6 expression was 1.5 folds higher in patients with genotype CC than in the patients with genotype TT. CONCLUSIONS: SLAMF6 was associated with both the susceptibility and severity of RA in the Chinese population. Moreover, rs148363003 could be a functional variant regulating the tissue expression of SLAMF6 in RA patients. It is advisable to conduct further functional analysis for a comprehensive knowledge on the contribution of this variant to the development of RA.

ERCP combined with tumor markers in differential diagnosis of pancreatic cancer and pseudotumor-like pancreatitis.

PURPOSE: To investigate the significance of endoscopic retrograde cholangiopancreatography (ERCP) combined with tumor markers in the differential diagnosis of pancreatic cancer (PC) and pseudotumor-like pancreatitis (PLP). METHODS: A total of 186 patients with PC (pancreatic cancer group) and 89 patients with PLP (pseudotumor-like pancreatitis group) were selected as subjects, and another 268 healthy people during the same period were enrolled as control group. Serum carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) levels of subjects were compared among three groups, these subjects underwent ERCP, and its diagnostic value was analyzed. RESULTS: The levels of serum CEA and CA199 in both PLP and PC group were markedly higher than those in control group and PC group had considerably higher serum CEA and CA19-9 levels in comparison with PLP group (p<0.05). The results of area under curve (AUC) showed that ERCP had the highest diagnostic value, CA19-9 had the lowest diagnostic value, and the combined diagnosis had significantly increased accuracy and sensitivity and decreased specificity. CONCLUSION: The application of ERCP in combination with tumor markers in the differential diagnosis of PC and PLP can evidently improve the diagnostic sensitivity and accuracy, reduce the rate of missed diagnosis of PC, and elevate the survival rate . Therefore, ERCP combined with tumor markers has good application value in clinical practice.

Microencapsulation of recombinant adenovirus within poly-DL-lactide-poly(ethylene glycol) microspheres for enhanced gene transfection efficiency and inhibitory effects on hepatocellular carcinoma cells in vitro.

When gene therapy is performed for the treatment of malignant tumors, gene transfer efficiency and selectivity are highly important. Polymer vehicle microspheres are a novel type of therapy, which have been developed rapidly in recent years and are able to control drug release, prolong the biological half-life of drugs, decrease side effects and achieve targeted delivery. The present study was designed to construct a polymer microsphere-encapsulated recombinant adenovirus with human tissue inhibitors of the matrix metalloproteinase-1 (TIMP-1) gene, and to discuss its characterization for the purpose of liver cancer gene therapy. The microsphere was prepared from biodegradable poly-DL-lactide-poly(ethylene glycol) (PELA) encapsulating rAdTIMP-1, the recombinant adenovirus carrying TIMP-1, by a modified double-emulsion method. The particle morphology, diameter, virus encapsulation, loading rate and release kinetics of the rAd-microspheres were determined in vitro. Hepatocellular carcinoma (HCC) HepG2 cells were transfected with the rAd-microsphere and the efficiency of transfection was assessed by fluorescent microscopy. The production and expression of TIMP-1 was identified by gelatin zymography and western blot analysis, and the invasiveness was detected by a matrigel matrix invasion assay. The microsphere encapsulating rAdTIMP-1 was successfully constructed with a diameter of 1.965 µm, encapsulation efficiency of 60.0%, a viral load of 10.5 x 10(8)/mg, a virus release of ~60% within 120 h and a total release time of >240 h. The resultant rAd-microspheres were able to efficiently transfect HepG2 cells with the transfection efficiency enhanced by ~90%. As a result, the transfected HepG2 cells had significantly increased TIMP-1 enzyme activity and the expression of TIMP-1 was detected by western blot analysis. In addition, the proliferation and invasion ability of the HCC cells was markedly inhibited by the rAd-microspheres. The resultant rAd-microspheres, PELA-encapsulated recombinant TIMP-1 adenovirus, had enhanced transfection efficiency and were able to markedly inhibit the in vitro biological behavior of HepG2 cells. This provides an experimental basis for this polymer application and may pave the way for prospective in vivo clinical trials and further comprehensive therapy for liver cancer.

Immunogenicity and safety of the HPV-16/18 AS04-adjuvanted vaccine in healthy Chinese girls and women aged 9 to 45 years.

Immunogenicity and safety of the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine were evaluated in healthy Chinese females aged 9-45 years in 2 phase IIIB, randomized, controlled trials. Girls aged 9-17 years (ClinicalTrials.gov, NCT00996125) received vaccine (n = 374) or control (n = 376) and women aged 26-45 years (NCT01277042) received vaccine (n = 606) or control (n = 606) at months 0, 1, and 6. The primary objective was to show non-inferiority of anti-HPV-16 and -18 immune responses in initially seronegative subjects at month 7, compared with Chinese women aged 18-25 years enrolled in a separate phase II/III trial (NCT00779766). Secondary objectives were to describe the anti-HPV-16 and -18 immune response, reactogenicity and safety. At month 7, immune responses were non-inferior for girls (9-17 years) vs. young women (18-25 years): the upper limit of the 95% confidence interval (CI) for the geometric mean titer (GMT) ratio (women/girls) was below the limit of 2 for both anti-HPV-16 (0.37 [95% CI: 0.32, 0.43]) and anti-HPV-18 (0.42 [0.36, 0.49]). Immune responses at month 7 were also non-inferior for 26-45 year-old women vs. 18-25 year-old women: the upper limit of the 95% CI for the difference in seroconversion (18-25 minus 26-45) was below the limit of 5% for both anti-HPV-16 (0.00% [-1.53, 1.10]) and anti-HPV-18 (0.21% [-1.36, 1.68]). GMTs were 2- to 3-fold higher in girls (9-17 years) as compared with young women (18-25 years). The HPV-16/18 AS04-adjuvanted vaccine had an acceptable safety profile when administered to healthy Chinese females aged 9-45 years.

Prevalence and molecular characterisation of the sessile serrated adenoma in a subset of the Chinese population.

AIMS: The incidence and mortality rates from right-sided colorectal cancers (CRCs) have not decreased in recent years. It is very likely that a significant proportion of these cancers evolve from undetected sessile serrated adenomas (SSAs). The prevalence and molecular features of the SSAs in the Chinese population have seldom been investigated. METHODS: We retrospectively reviewed the colonoscopy database and pathology archives in our medical centre. Adenomatous polyposis coli (APC) and ß-catenin expressions were examined in 28 right hyperplastic polyps (RHPs) and 21 SSAs by immunohistochemical staining. The mutations of BRAF, KRAS, APC and ß-CATENIN were analysed by direct sequencing. The methylation status of APC promoter in these polyps was analysed by methylation-specific PCR and bisulfite sequencing. Samples of left hyperplastic polyps, traditional adenomas and CRC were used as controls. RESULTS: SSAs accounted for 4.9% of serrated polyps and 1.0% of all colorectal polyps. BRAF((V600E)) mutations were found in 14.3% of SSAs and 7.1% of RHPs. Nuclear accumulation of ß-catenin was seen in 28.6% of SSAs and 17.9% of RHPs. APC mutations were detected in 57.1% of SSAs and 67.9% of RHPs. APC methylation was detected in 14.3% of RHPs and 23.8% of SSAs. CONCLUSIONS: The prevalence of SSAs in a subset of the Chinese population is much lower than that in the Western population. BRAF((V600E)) mutation is not a frequent event in right colon serrated polyps in a subset of the Chinese population. APC mutation is possibly the main cause for the Wnt signalling activation in right colon serrated polyps.