[Predictive value of aMAP risk score for early recurrence of small hepatocellular carcinoma after microwave ablation].

Objective: To explore the value of the aMAP risk score (age, male, albumin-bilirubin, and platelets) to predict early recurrence within one year after microwave ablation in patients with small hepatocellular carcinoma. Methods: This was a retrospective study that enrolled 142 patients diagnosed with hepatocellular carcinoma who were treated with microwave ablation in the Department of Hepatology Unit of Nanfang Hospital, Southern Medical University from July 2016 to July 2021. The cohort enrolled 121 male and 21 female patients, including 110 patients that were <60 years old. All the patients were followed-up after microwave ablation to evaluate residual tumor and recurrence of tumor by computed tomography or magnetic resonance imaging. The observation indices mainly included general data and imaging data of patients. Using the X-tile tools, patients were divided into two groups: a high aMAP score group and a low aMAP score group. Multivariate Cox regression analysis was conducted for comparison of independent risk factors. Results: Multivariate Cox regression showed that high aMAP score, maximum tumor diameter >20 mm, and high AFP were the independent risk factors of early recurrence (all P<0.05). Kaplan-Meier survival curves showed that the median recurrence-free survival was 25.5 months in the low aMAP score group and 6.1 months in the high aMAP score group (P=0.001). Conclusions: The aMAP score could predict the early recurrence within 1 year of small hepatocellular carcinoma after microwave ablation. Patients with high aMAP score should undergo rigorous postoperative follow-up evaluations..

[Effects of enhancing the expression of aryl hydrocarbon receptor in post-traumatic mice macrophages on the inflammatory cytokine level and bactericidal ability].

Objective: To explore the expression pattern of aryl hydrocarbon receptor (AhR) in mice peritoneal macrophages (PMs) after major trauma and analyze the effects of enhanced AhR expression on the inflammatory cytokine level and bactericidal ability after trauma. Methods: The experimental study method was used. Forty 6-8-week-old male C57BL/6J mice (the same mouse age, sex, and strain below) were divided into control group, post trauma hour (PTH) 2 group, PTH 6 group, and PTH 12 group according to the random number table (the same grouping method below), with 10 mice in each group. Mice in the latter 3 groups were constructed as severe trauma model with fracture+blood loss, while mice in control group were left untreated. The primary PMs (the same cells below) were extracted from the mice in control group, PTH 2 group, PTH 6 group, and PTH 12 group when uninjured or at PTH 2, 6, and 12, respectively. Then the protein and mRNA expressions of AhR were detected by Western blotting and real-time fluorescence quantitative reverse transcription polymerase chain reaction, respectively, and the gene expressions of AhR signaling pathway related molecules were analyzed by transcriptome sequencing. Twenty mice were divided into control group and PTH 6 group, with 10 mice in each group, and the PMs were extracted. The level of ubiquitin of AhR was detected by immunoprecipitation. Twelve mice were divided into dimethyl sulfoxide (DMSO) alone group, PTH 6+DMSO group, MG-132 alone group, and PTH 6+MG-132 group, with 3 mice in each group. After the corresponding treatment, PMs were extracted, and the protein expression of AhR was detected by Western blotting. Twenty mice were constructed as PTH 6 model. Then, the PMs were extracted and divided into empty negative control adenovirus (Ad-NC) group and AhR overexpression adenovirus (Ad-AhR) group. The protein expression of AhR was detected by Western blotting at 36 h after some PMs were transfected with the corresponding adenovirus. The rest cells in Ad-NC group were divided into Ad-NC alone group and Ad-NC+endotoxin/lipopolysaccharide (LPS) group, and the rest cells in Ad-AhR group were divided into Ad-AhR alone group and Ad-AhR+LPS group. The expressions of interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) in the cell supernatant were detected by enzyme-linked immunosorbent assay at 12 h after the corresponding treatment (n=6). Twenty mice were obtained to extract PMs. The cells were divided into control+Ad-NC group, PTH 6+Ad-NC group, control+Ad-AhR group, and PTH 6+Ad-AhR group, and the intracellular bacterial load was detected by plate spread method after the corresponding treatment (n=6). Data were statistically analyzed with one-way analysis of variance, least significant difference test, analysis of variance for factorial design, and independent sample t test. Results: Compared with 1.16±0.28 of control group, the protein expressions of AhR in PMs in PTH 2 group (0.59±0.14), PTH 6 group (0.72±0.16), and PTH 12 group (0.71±0.17) were all significantly decreased (P<0.05). The overall comparison of the difference of AhR mRNA expression in PMs among control group, PTH 2 group, PTH 6 group, and PTH 12 group showed no statistical significance (P>0.05). The AhR signaling pathway related molecules included AhR, AhR inhibitor, cytochrome P450 family member 1b1, cytochrome P450 family member 11a1, heat shock protein 90, aryl hydrocarbon receptor-interaction protein, and heat shock protein 70 interaction protein. The heat shock protein 90 expression of PMs in PTH 2 group was higher than that in control group, while the expressions of other molecules did not change significantly after trauma. Compared with that in control group, the level of ubiquitin of AhR in PMs in PTH 6 group was increased. Compared with that in DMSO alone group, the protein expression of AhR in PMs in PTH 6+DMSO group was decreased, while that in PMs in MG-132 alone group had no significant change. Compared with that in PTH 6+DMSO group, the protein expression of AhR in PMs in PTH 6+MG-132 group was up-regulated. At transfection hour 36, compared with that in Ad-NC group, the protein expression of AhR in PMs in Ad-AhR group was increased. At treatment hour 12, compared with those in Ad-NC+LPS group, the expressions of IL-6 and TNF-α in PM supernatant of Ad-AhR+LPS group were significantly decreased (with t values of 4.80 and 3.82, respectively, P<0.05). The number of intracellular bacteria of 1×106 PMs in control+Ad-NC group, PTH 6+Ad-NC group, control+Ad-AhR group, and PTH 6+Ad-AhR group was (3.0±1.8), (41.8±10.2), (1.8±1.2), and (24.2±6.3) colony forming unit, respectively. Compared with that in PTH 6+Ad-NC group, the number of intracellular bacteria of PMs in PTH 6+Ad-AhR group was significantly decreased (t=3.61, P<0.05). Conclusions: Ubiquitin degradation of AhR in PMs of mice after major trauma results in decreased protein expression of AhR. Increasing the expression of AhR in post-traumatic macrophages can reduce the expressions of LPS-induced inflammatory cytokines IL-6 and TNF-α, and improve the bactericidal ability of macrophages after trauma.

Comparative Effectiveness of FOLFIRINOX Versus Gemcitabine and Nab-paclitaxel in Initially Unresectable Locally Advanced Pancreatic Cancer: A Population-based Study to Assess Subsequent Surgical Resection and Overall Survival.

AIMS: First-line FOLFIRINOX (FOLinic acid, Fluorouracil, IRINotecan, and OXaliplatin) and gemcitabine plus nab-paclitaxel (GnP) have been publicly funded for patients with unresectable locally advanced pancreatic cancer (uLAPC) in Ontario, Canada. We examined the overall survival and surgical resection rate after first-line FOLFIRINOX or GnP and determined the association between resection and overall survival in patients with uLAPC. MATERIALS AND METHODS: We conducted a retrospective population-based study including patients with uLAPC who received first-line treatment FOLFIRINOX or GnP from April 2015 to March 2019. The cohort was linked to administrative databases to ascertain demographic and clinical characteristics. Propensity score methods were used to balance differences between FOLFIRINOX and GnP. The Kaplan-Meier method was used to calculate overall survival. Cox regression was used to determine the association between receipt of treatment and overall survival, adjusting for time-dependent surgical resections. RESULTS: We identified 723 patients with uLAPC (mean age = 65.8, 43.5% female) who received FOLFIRINOX (55.2%) or GnP (44.8%). The median overall survival and 1-year overall survival probability were higher for FOLFIRINOX (13.7 months, 54.6%) than for GnP (8.7 months, 34.0%). Post-chemotherapy surgical resection occurred in 89 (12.3%) patients (FOLFIRINOX: 74 [18.5%] versus GnP: 15 [4.6%]), with no difference in survival since surgery between FOLFIRINOX and GnP (P = 0.29). After adjusting time-dependent post-treatment surgical resection, FOLFIRINOX (inverse probability treatment weighting hazard ratio 0.72, 95% confidence interval 0.61, 0.84) was independently associated with improved overall survival. CONCLUSIONS: In this real-world population-based study of patients with uLAPC, FOLFIRINOX was associated with improved survival and higher resection rates. FOLFIRINOX was associated with improved survival in patients with uLAPC after accounting for the effect of post-chemotherapy surgical resection, suggesting the benefit of FOLFIRINOX was not solely due to improving resectability.

[Multi-omics research contributes to early screening, diagnosis and treatment of liver cancer].

In 2016, the World Health Organization set an ambitious goal of reducing viral hepatitis-related deaths by 65% by 2030. The key to this goal is to reduce viral hepatitis-related HCC deaths. Liver cancer is the fourth most common malignant tumor and the second leading cause of cancer death in China. The onset of HCC is insidious, and most patients are already in the middle and late stage when diagnosed. Despite the great progress on management of HCC, the therapeutic effect and prognosis of HCC are still unsatisfactory. Therefore, multi-dimensional and comprehensive analysis of the mechanism of liver cancer, improving the early screening, diagnosis and treatment rate of liver cancer are the key points of reducing the harm of liver cancer in China. In recent years, multi-omics studies have been widely applied in the field of liver cancer, providing a basis for the pathogenesis of liver cancer, early detection and diagnosis, development of individual treatment strategies and prognosis assessment. This issue will focus on the application of genomics, proteomics, metabolomics and imaging omics in early screening, diagnosis and treatment of liver cancer.

[Research advances of metabolomics in early diagnosis of hepatocellular carcinoma].

Primary liver cancer is the second leading cause of death from malignant tumors in China, and hepatocellular carcinoma (HCC) is the main type. The disease stage at the time of HCC diagnosis largely determines the efficacy of subsequent treatment. Due to the HCC screening among high-risk population has not yet popularized, and the current diagnose method of early HCC is not satisfactory, the early HCC diagnosis rate is less than 30% in China. Metabolomics research emerging in recent years has promoted the research progress of HCC in many fields, such as elaborating the mechanism of occurrence and development, early prevention and diagnosis, exploring drug treatment targets. At the same time, a large number of serum metabolites with excellent sensitivity and specificity were discovered, which made up for the deficiency of traditional serological indicators and helped the early screening and early diagnosis of HCC. This review will summarize the studies on serum metabolomic markers of HCC in recent 5 years, explore the role of metabolomics in the early prediction and diagnosis of HCC and its application prospect.

Imaging Findings and Clinical Analysis of Primary Intracranial Pure Yolk Sac Tumors in Children and Adolescents: A Retrospective Study from China.

BACKGROUND AND PURPOSE: Primary intracranial pure yolk sac tumor is very rare. Our aim was to summarize the characteristics of primary intracranial pure yolk sac tumors from the clinical and imaging aspects in a retrospective study. MATERIALS AND METHODS: We studied 5 patients with primary intracranial pure yolk sac tumors in Guangzhou Women and Children's Medical Center from January 2015 to June 2021. A comprehensive literature search was performed on the electronic database of the China National Knowledge Infrastructure (1990 to June 2021). Clinical data based on age, sex, treatment, CT, and MR imaging findings were collected and analyzed. RESULTS: A total of 25 patients were included in the study, 21 boys and 4 girls. Twenty-one patients underwent plain MR imaging and an enhanced examination, 9 patients underwent DWI, and 12 patients underwent plain CT and/or an enhanced examination. The tumors were posterior fossa in 9 cases and supratentorial in 16 cases. All tumors showed marked enhancement after enhanced scanning by MR imaging or CT. The signal on DWI was similar to that of the cerebral cortex, and the ADC map was similar to or slightly higher than that of the cerebral cortex. Among the cases, 13 were followed up from 2 months to 5 years. There was no recurrence or metastasis in 9 patients with postoperative chemotherapy or chemoradiotherapy followed up for 1.5-5 years. Four patients died 2 months to 1.5 years after only an operation, or chemoradiotherapy but no operation. CONCLUSIONS: There are some relatively specific imaging findings of primary intracranial yolk sac tumors that could assist in their diagnosis. Surgery combined with radiation therapy and/or chemotherapy can achieve a better prognosis.

Real-world Safety of Bevacizumab with First-line Combination Chemotherapy in Patients with Metastatic Colorectal Cancer: Population-based Retrospective Cohort Studies in Three Canadian Provinces.

AIMS: To examine the real-world safety of adding bevacizumab to first-line irinotecan-based chemotherapy for patients with metastatic colorectal cancer (mCRC). MATERIALS AND METHODS: Patients diagnosed with CRC in three Canadian provinces (Ontario, Saskatchewan and British Columbia) who received publicly funded bevacizumab and/or irinotecan from 2000 to 2016 were identified from cancer registries. Propensity score 1:1 matching (PSM) and inverse probability of treatment weighting (IPTW) were performed to contemporaneous and historical controls, adjusting for baseline demographic and clinical characteristics. Safety end points evaluated during first-line treatment plus 30 days included mortality within 30 days and all-cause-, chemotherapy- and bevacizumab-related hospitalisations. Chemotherapy- and bevacizumab-related visits were defined as hospitalisations for specific conditions commonly associated with chemotherapy (e.g. infections) or bevacizumab (e.g. arteriovenous thromboembolism) using most responsible diagnosis codes. In PSM and IPTW-weighted cohorts, we assessed event frequencies using odds ratios from logistic regressions and event rate ratios using negative binomial regression models. The results from each province and comparison were pooled using random-effects meta-analysis. RESULTS: We identified 16 250 mCRC patients who received first-line irinotecan-based treatment. In PSM cohorts, bevacizumab was associated with fewer deaths within 30 days of treatment compared with contemporaneous (pooled odds ratio = 0.62; 95% confidence interval 0.50-0.75) and historical controls (pooled odds ratio = 0.73; 95% confidence interval 0.58-0.93). Hospitalisations were more frequent among patients treated with bevacizumab compared with historical controls but similar to contemporaneous controls. As patients receiving bevacizumab were exposed to a longer average treatment duration, across their full treatment duration, patients receiving bevacizumab had significantly lower rates of hospitalisations (contemporaneous pooled rate ratio = 0.56; 95% confidence interval 0.47-0.67; historical pooled rate ratio = 0.73; 95% confidence interval 0.56-0.95). Similar trends were observed for chemotherapy- and bevacizumab-related hospitalisations and in IPTW-weighted cohorts. DISCUSSION: We did not observe any increase in rates of hospitalisation or death within 30 days of treatment among mCRC patients treated with bevacizumab plus chemotherapy versus chemotherapy alone; these findings should be interpreted with caution due to the risk of residual confounding.

[Analysis of chronic obstructive pulmonary disease screening questionnaire and pulmonary function test among migrant workers exposed to dust].

Objective: To analyze the application of Chronic Obstructive Pulmonary Disease (COPD) Screening Questionnaire and pulmonary function test in dust-exposed migrant workers. Methods: In May 2019, 149 cases of dust exposed migrant workers were selected as the research subjects through the free clinic in the countryside. COPD Screening Questionnaire and lung function test were carried out to analyze the high-risk groups and the influencing factors of positive pulmonary function test results. Results: Among 149 cases of dust-exposed migrant workers, 107 (71.8%) were positive for questionnaire screening, 73 (49.0%) were positive for pulmonary function test, 75 (50.3%) were diagnosed with coal worker's pneumoconiosis, and 101 (67.8%) were diagnosed with lung function injury. The positive rate of pulmonary function of migrant workers with positive questionnaire screening results was significantly higher than that of those with negative results (P<0.05) . The results of multivariate analysis showed that compared with non-pneumoconiosis, the risk of positive pulmonary function test results was higher in dust-exposed migrant workers with stage Ⅲ pneumoconiosis (OR=16.462, 95%CI: 3.390-79.946; P<0.01) . Compared with non-smoking, the risks of positive pulmonary function test results of dust-exposed migrant workers with smoking index of 11-20 package years and >20 package years were higher (OR=19.814, 95%CI: 3.854-101.883; OR=9.733, 95%CI: 2.310-41.008; P<0.01) . Conclusion: The risk of COPD in dust-exposed migrant workers is high, so we should strengthen the early examination of the high pneumoconiosis stage and smoking population. The screening questionnaire can better screen out the high-risk groups of COPD, and it can be used as a basic screening tool.

[Hsa_circ_0006948 regulates the proliferation, migration and invasion in osteosarcoma by regulation of the expression of miR-490-3p target ATG7].

Objective: To investigate the effect of hsa_circ_0006948 (circ_0006948) on the proliferation, migration and invasion of osteosarcoma cells and the underlying mechanism. Methods: A total of 120 osteosarcoma tissues and 40 adjacent normal tissue samples were collected from patients admitted to the First People's Hospital of Shangqiu City from 2009 to 2015. Microarray analysis was performed to detect the differential expressions of circRNA in Saos-2 cell. The mRNA expressions of circ_0006948, microRNA (miR)-490-3p and autophagy-related protein 7 (ATG7) in osteosarcoma cells, NHOst cells, osteosarcoma tissues and adjacent tissues were detected by real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR). Cell clone formation assay was used to detect cell proliferation ability, Transwell assay was used to detect cell invasion ability, and cell scratch assay was used to detect cell migration ability. The interactions between circ_0006948 and miR-490-3p, miR-490-3p and ATG7 were detected by dual luciferase reporter gene assay. The correlation between miR-490-3p and ATG7 was analyzed by TargetScan database, and the expression levels of Bcl-2 and Bax proteins in cells were detected by western blot. Results: The mRNA expression levels of circ_0006948, miR-490-3p and ATG7 in SAOS-2 cells were significantly different from NHOst cells (P<0.01). The mRNA expression levels of circ_0006948, miR-490-3p and ATG7 in osteosarcoma tissues were significantly different from adjacent tissues (P<0.01). The numbers of cell clone, migration and mobility in circ_0006948-siRNA group were (32.78±1.76), (37.58±1.82) and (36.93±1.45)%, respectively, lower than (65.72±1.45), (78.63±1.93) and (65.32±1.74)% in the siRNA NC group (all P<0.01). The numbers of cell clone, migration and mobility in the miR-490-3p mimics group were (20.08±1.54), (30.24±1.78) and (21.15±1.68)%, respectively, lower than (60.36±1.83), (76.93±1.64) and (40.56±1.27)% in the mimics NC group (all P<0.01). The numbers of cell clone, migration and mobility in the miR-490-3p inhibitor+ siRNA NC group were (90.34±1.72), (120.89±2.34) and (70.83±1.93)%, respectively, higher than (61.27±1.73), (75.82±1.82) and (42.38±1.74)% in the inhibitor NC+ siRNA NC group (P<0.01). The numbers of cell clone, migration and mobility in the circ_0006948 siRNA+ miR-490-3p inhibitor group were (58.74±1.98), (73.46±1.04) and (40.35±1.72)%, respectively, lower than (90.34±1.72), (120.89±2.34) and (70.83±1.93)% in the miR-490-3p inhibitor+ siRNA NC group (P<0.01). The numbers of cell clone, migration and mobility in the ATG7 siRNA group were (20.56±1.87), (40.36±1.76) and (20.96±1.73)%, lower than (65.46±1.74), (90.87±2.32) and (40.87±2.03)% in the siRNA NC group (P<0.01). The absorbance of miR-490-3p mimics+ pcDNA-ATG7 group was 0.54±0.11, higher than (0.36±0.08) of miR-490-3p mimics group (P<0.05). The expression levels of Bax and Bcl-2 protein in Saos-2 cells of miR-490-3p mimics group were significantly different from mimics NC group (P<0.01). The protein expression levels of Bax and Bcl-2 in Saos-2 cells of miR-490-3p mimics + pcDNA-ATG7 group were significantly different from miR-490-3p mimics group (P<0.01). Conclusion: Circ_0006948 regulates ATG7 expression through miR-490-3p, therefore regulates the proliferation, migration and invasion of osteosarcoma cells.

[Association between obesity and risk for colorectal advanced adenoma].

Objectives: To understand the association between obesity and the risk for colorectal advanced adenoma. Methods: Community residents aged 45 to 74 who had participated in the Shanghai community-based colorectal cancer (CRC) screening project in 2008 were included in our study. Anthropometries information including body weight, height and risk factors for colorectal advanced adenoma were collected. Results on colonoscopic diagnosis and personal health records were used for supplementary outcome information retrieval. Multivariate Cox proportional hazard regression models were used to evaluate the hazard ratio (HR) and 95%CI of obesity on the risk for colorectal advanced adenoma. Results: 20 811 residents were followed up for 122 739.36 person-years, with a median follow-up time of 5.87 years. A total of 657 cases of advanced adenomas were identified. After adjusting for potential confounding risk factors such as age, sex, family history of CRC, level of education, marriage, cigarette smoking, alcohol drinking, foods intake including fat, fried or pickled, vegetables and fruits etc., the HR was 1.25 (95%CI: 1.04-1.51) for obese people when compared with the normal weight persons. Further stratified analysis by age, gender and family history of CRC, results showed that obese people had a much higher risk of colorectal advanced adenoma than those with normal weight (male: HR=1.57, 95%CI: 1.20-2.04; more than 60- year-old: HR=1.63, 95%CI: 1.23-2.16). Conclusion: Data from this large scale population-based study revealed that obesity might be an independent risk factor for colorectal advanced adenoma and the risk increases along with the increase of BMI in China.

Comprehensive analysis of lncRNA-mediated ceRNA network in papillary thyroid cancer.

OBJECTIVE: Papillary thyroid cancer (PTC) is one type of thyroid cancer. Although it has a good prognosis, the recurrence and metastasis rates remain high. MATERIALS AND METHODS: The microarray dataset GSE66783 was downloaded from the Gene Expression Omnibus (GEO). With the R package, the differentially expressed genes (DEGs) and lncRNAs between normal adjacent tissues and cancer tissues of PTC were identified. The miRNAs that were targeted by DElncRNAs and the mRNAs that were targeted by miRNAs were discovered through miRcode and through miRTarBase, TargetScan, and miRDB, respectively. Furthermore, the ceRNA network was constructed. GO and KEGG enrichment analyses were performed on the DEGs. The PPI network of the DEGs was obtained from the STRING database, and the top 5 hub genes that had a tight correlation with the disease were obtained by using Cytoscape. Finally, the study used the Kaplan-Meier method to analyze PTC patient survival time, and the Human Protein Atlas database was used to retrieve the expression of the hub genes in normal and PTC patient tissues. RESULTS: Five hub genes showed significant differences in expression in the PPI network, and 12 lncRNA-miRNA-mRNA pathways might participate in the potential pathophysiological process of PTC. CONCLUSIONS: The study indicated that these ceRNAs might contribute to future therapies for PTC.

[Exploring the clinical genetic characteristics and height for age growth curve of 210 patients with achondroplasia in China].

Objective: To summarize the clinical manifestation and genetic characteristics of Chinese patients with achondroplasia (ACH) which is caused by pathogenic variants fibroblast growth factor receptor 3 (FGFR3) gene and establish the reference value of height centiles and height for age growth curve of patients for a more practical, simple and useful growth evaluation tool in China. Methods: Through a nationwide cross-sectional survey in China from July 2019 to January 2020 designed by Department of Pediatric Endocrinology and Genetics, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, 210 subjects (110 boys, 100 girls), who harbored the pathogenic variant of FGFR3 gene and were diagnosed with achondroplasia, were recruited. The clinical and genetic data of enrolled subjects were collected and analyzed to explore the clinical genetic characteristics of Chinese ACH patients. Furthermore, according to the data of height (body length under 2 years old) of boy and girl subjects aged 0-12 years, centiles and height for age growth curve of achondroplasia were calculated and established by LMS method respectively. Results: The characteristic clinical manifestations of 210 Chinese patients (0-14 years old) were disproportionate short stature (206/210, 98.1%), macrocephaly and characteristic facial features (205/210, 97.6%), trident configuration of the hands (191/210, 90.9%), limbs deformity (156/210, 74.3%), together with normal intelligence. Up to 81.9% (172/210) of patients have different complications, and the kyphosis (121/210, 57.6%) and narrow thoracic (79/210, 37.6%) are common complications. Besides, up to 98.6% (207/210) of patients harbored hotspot variants of FGFR3 gene which cause G380R amino acid substitutions. It is notable that the growth pattern of boy and girl patients (0-12 years old) is obviously different from the normal children (t=9.849, 9.596, P<0.01) respectively. The height different between ACH patients and normal children gradually widened with age. The average height of the boy (49.2 cm) and girl patients(48.4 cm) of achondroplasia at birth was -1.22 s and -2 s, however, at the age of twelve, the average height of the boy(113.7 cm) and girl patients(112.4 cm) of achondroplasia was -5.23 s and -6.15 s compared to currently standard reference height for age growth curve of normal children in China, respectively. Conclusions: The results of our study demonstrated that in China disproportionate short stature, macrocephaly and characteristic facial features were typical manifestations of ACH patients, and that up to 98.6% of patients harbored hotspot variants of FGFR3 gene. In addition, the reference value of height centiles and height for age growth curve of ACH patients we establish will be a valuable tool for evaluating the growth pattern, monitoring factors affecting growth, estimating ultimate height, and assessing the curative effect of growth-promoting treatments in Chinese patients with achondroplasia.

[Cost-effectiveness of HIV self-testing strategy in men who have sex with men].

Objective: To analyze the cost-effectiveness and willingness-to-pay of HIV self-testing (HIVST) strategy and facility-based HIV rapid testing (HIV-RDT) strategy in men who have sex with men (MSM) in Zhuhai, and provide scientific evidence for making health policy. Methods: From the perspective of health service providers, the data of the costs and effectiveness of two HIV testing strategies in MSM in Zhuhai during January-September 2019 were collected, and a decision-tree model of cohort of 10 000 MSM was constructed by using software TreeAge Pro 2019 to measure the cost-effectiveness ratio (CER) and the incremental cost-effectiveness ratio (ICER). One-way and probability sensitivity analysis was performed for the uncertainty of the parameters in the model, and the cost-effectiveness and affordability curve was introduced to estimate the affordability of two strategies. Results: After the mobilization of MSM community-based organization through Internet and social media, 2 303 MSM had HIVST, in whom 33 were HIV positive (1.7%), and 816 MSM received HIV-RDT, in whom 35 were HIV positive (4.3%). The cost for per screening was 60.45 yuan and 240.43 yuan (RMB) respectively, and the cost for per positive screening was 4 218 yuan and 5 606 yuan (RMB) rerspectively. The results of the decision-tree model showed that the mean cost for a MSM using HIVST and using HIV-RDT was 44.67 yuan and 148.42 yuan (RMB) respectively, and the ICER was negative. HIVST strategy was a more cost-effective option when the willing-to-pay was below 6 528 yuan (RMB) for per positive screening, and HIV-RDT strategy was a more cost-effective option when the investment was higher than 6 528 yuan (RMB). Conclusion: HIVST strategy in Zhuhai is a public health project with economic value, and policy makers should strengthen the support to MSM community-based organization to promote the application of HIVST among MSM.

The long non-coding RNA DDX11-AS1 facilitates cell progression and oxaliplatin resistance via regulating miR-326/IRS1 axis in gastric cancer.

OBJECTIVE: The long non-coding RNA DDX11 antisense RNA 1 (DDX11-AS1) was found to be highly expressed in gastric cancer (GC). This study was to explore the role and molecular mechanism in oxaliplatin (OXA) resistance. PATIENTS AND METHODS: The levels of DDX11-AS1, microRNA-326 (miR-326) and insulin receptor substrate 1 (IRS1) were measured by quantitative Real-time polymerase chain reaction (qRT-PCR). Cell proliferation, migration, invasion and apoptosis were examined by methylthiazolyldiphenyl-tetrazolium bromide (MTT), transwell and flow cytometry assays, respectively. Levels of all protein were detected using Western blot. The correlation between miR-326 and DDX11-AS1/IRS1 was confirmed by Dual-Luciferase reporter and RNA immunoprecipitation (RIP) assays. The xenograft model was constructed to explore the effect of DDX11-AS1 in vivo. RESULTS: DDX11-AS1 was overexpressed in OXA-resistant GC tissues and cells, and DDX11-AS1 knockdown inhibited cell proliferation, migration, invasion and OXA resistance, and promoted apoptosis in OXA-resistant GC cells. Mechanically, DDX11-AS1 directly targeted miR-326 and miR-326 could bind to IRS1 in OXA-resistant GC cells. Functionally, silencing DDX11-AS1 repressed the progression and OXA resistance in OXA-resistant GC cells by down-modulating IRS1 expression via sponging miR-326 in vitro and in vivo. CONCLUSIONS: DDX11-AS1 accelerated the progression and OXA chemoresistance of GC cells in vitro and in vivo by sponging miR-326, thus increasing the expression of IRS1, suggesting DDX11-AS1 might be a promising prognostic biomarker and therapeutic target in GC.

Porphyromonas gingivalis Promotes Oral Squamous Cell Carcinoma Progression in an Immune Microenvironment.

Increasing evidence has revealed a significant association between microorganisms and oral squamous cell carcinoma (OSCC). Porphyromonas gingivalis, the keystone pathogen in chronic periodontitis, is considered an important potential etiologic agent of OSCC, but the underlying immune mechanisms through which P. gingivalis mediates tumor progression of the oral cancer remain poorly understood. Our cohort study showed that the localization of P. gingivalis in tumor tissues was related to poor survival of patients with OSCC. Moreover, P. gingivalis infection increased oral lesion multiplicity and size and promoted tumor progression in a 4-nitroquinoline-1 oxide (4NQO)-induced carcinogenesis mouse model by invading the oral lesions. In addition, CD11b+ myeloid cells and myeloid-derived suppressor cells (MDSCs) showed increased infiltration of oral lesions. Furthermore, in vitro observations showed that MDSCs accumulated when human-derived dysplastic oral keratinocytes (DOKs) were exposed to P. gingivalis, and CXCL2, CCL2, interleukin (IL)-6, and IL-8 may be potential candidate genes that facilitate the recruitment of MDSCs. Taken together, our findings suggest that P. gingivalis promotes tumor progression by generating a cancer-promoting microenvironment, indicating a close relationship among P. gingivalis, tumor progression of the oral cancer, and immune responses.

Multifunctional nanocomposites MGO/FU-MI inhibit the proliferation of tumor cells and enhance the effect of chemoradiotherapy in vivo and in vitro.

PURPOSE: The limitation of surgery, radiotherapy and chemotherapy in the treatment of cancer and the rise of the application of nanomaterials in the field of biomedicine have promoted the application of various nanomaterials in the combination of radiotherapy and chemotherapy in the treatment of cancer. To improve the efficiency of cancer treatment, the multifunctional nanocomposites MGO/FU-MI (MGO/FU-MI NCs) were used for combination chemotherapy and radiotherapy to verify its effectiveness in treating tumors. METHODS: The proliferation activity of MGO/FU-MI NCs on MC-38 and B16 cells was detected by CCK-8, and the level of apoptosis and reactive oxygen species were detected by flow cytometry. To verify its efficacy in the combination of chemoradiotherapy, different treatment regimens were developed for several groups of tumor-bearing mice. RESULTS: The MGO/FU-MI NCs can induce apoptosis, stimulate ROS production, and inhibit cell proliferation. In vivo experiments, when MGO/FU-MI NCs are used alone for chemotherapy, have a certain therapeutic effect on mouse tumors. When MGO/FU-MI NCs are combined with radiation, the tumor volume can be significantly reduced and the survival time of mice is significantly prolonged. CONCLUSION: The MGO/FU-MI NCs are very effective in the treatment of tumors when combined with radiotherapy and chemotherapy, and have the potential to be a combination of radiotherapy and chemotherapy.

Genetic variants in the folate metabolic pathway genes predict cutaneous melanoma-specific survival.

BACKGROUND: Folate metabolism plays an important role in DNA methylation and nucleic acid synthesis and thus may function as a regulatory factor in cancer development. Genome-wide association studies (GWASs) have identified some single-nucleotide polymorphisms (SNPs) associated with cutaneous melanoma-specific survival (CMSS), but no SNPs were found in genes involved in the folate metabolic pathway. OBJECTIVES: To examine associations between SNPs in folate metabolic pathway genes and CMSS. METHODS: We comprehensively evaluated 2645 (422 genotyped and 2223 imputed) common SNPs in folate metabolic pathway genes from a published GWAS of 858 patients from The University of Texas MD Anderson Cancer Center and performed the validation in another GWAS of 409 patients from the Nurses' Health Study and Health Professionals Follow-up Study, in which 95/858 (11·1%) and 48/409 (11·7%) patients died of cutaneous melanoma, respectively. RESULTS: We identified two independent SNPs (MTHFD1 rs1950902 G>A and ALPL rs10917006 C>T) to be associated with CMSS in both datasets, and their meta-analysis yielded an allelic hazards ratio of 1·75 (95% confidence interval 1·32-2·32, P = 9·96 × 10-5 ) and 2·05 (1·39-3·01, P = 2·84 × 10-4 ), respectively. The genotype-phenotype correlation analyses provided additional support for the biological plausibility of these two variants' roles in tumour progression, suggesting that variation in SNP-related mRNA expression levels is likely to be the mechanism underlying the observed associations with CMSS. CONCLUSIONS: Two possibly functional genetic variants, MTHFD1 rs1950902 and ALPL rs10917006, were likely to be independently or jointly associated with CMSS, which may add to personalized treatment in the future, once further validated. What is already known about this topic? Existing data show that survival rates vary among patients with melanoma with similar clinical characteristics; therefore, it is necessary to identify additional complementary biomarkers for melanoma-specific prognosis. A hypothesis-driven approach, by pooling the effects of single-nucleotide polymorphisms (SNPs) in a specific biological pathway as genetic risk scores, may provide a prognostic utility, and genetic variants of genes in folate metabolism have been reported to be associated with cancer risk. What does this study add? Two genetic variants in the folate metabolic pathway genes, MTHFD1 rs1950902 and ALPL rs10917006, are significantly associated with cutaneous melanoma-specific survival (CMSS). What is the translational message? The identification of genetic variants will make a risk-prediction model possible for CMSS. The SNPs in the folate metabolic pathway genes, once validated in larger studies, may be useful in the personalized management and treatment of patients with cutaneous melanoma.

[Study on changes of pulmonary function in patients with pneumoconiosis in three years].

Objective: To investigate the characteristics of pulmonary function changes and its possible influencing factors in patients with pneumoconiosis. Methods: In December 2019, pneumoconiosis patients hospitalized in four departments of occupational diseases in Hunan Occupational Disease Prevention and Control Hospital from December 2015 to December 2016 were selected as subjects. Lung function including forced vital capacity (FVC) , FVC%, forced expiratory volume in one second (FEV1) , FEV1%, forced expiratory volume in one second / forced vital capacity (FEV1/FVC) , diffusion capacity of the lung foe carbon monoxide% (DLCO%) 、maximal expiratory rlow 75% (MEF75%) , maximal expiratory rlow 50% (MEF50%) and maximal expiratory rlow 25% (MEF25%) were tested, and collect their age, occupation history, smoking history and Chronic Obstructive Pulmonary Disease Self Rating Questionnaire (CAT) score. They were followed up after 3 years to analyze the 3-year decline rates of lung function indicators and their relationship with stage of pneumoconiosis, age, smoking index, baseline values of lung function and CAT score. Results: 265 cases were studied effectively. After 3 years, the values of 9 lung function indicators of pneumoconiosis patients were significantly lower than those of 3 years ago (P<0.05) . The decline rates of FEV1%, FEV1/FVC, MEF75%, MEF50% and MEF25% were positively correlated with the stage of pneumoconiosis (r=0.250, 0.290, 0.219, 0.280, 0.141, P<0.05) . The decline rates of FEV1% and MEF75% were positively correlated with smoking index (r=0.148, 0.152, P<0.05) . The decline rates of DLCO% and MEF25% were positively correlated with the baseline value of initial pulmonary function (r=0.276, 0.153, P<0.05) , while the decline rates of FEV1%, FEV1/FVC and MEF50% were negatively correlated with the baseline values of initial pulmonary function (r=-0.215, -0.146, -0.214, P<0.05) . The decline rates of FVC%, FEV1%, MEF75% and MEF50% were positively correlated with the changes of CAT scores (r=0.147, 0.208, 0.210, 0.196, P<0.05) . Logistic regression analysis showed that old age and high initial value of DLCO% were the risk factor for the decline of DLCO% (OR=1.105、1.078, P<0.05) .High smoking index was the risk factors for the decline of MEF75% (OR=1.016, P<0.05) . High stage and the increase of CAT score were the risk factors for the decline of MEF50% (OR=1.548, 1.162, P<0.05) . High initial value of MEF25% was the risk factor for the decline of MEF25% (OR=1.010, P<0.05) . Conclusion: The pulmonary function index of pneumoconiosis patients declined significantly in 3 years. The stage of pneumoconiosis, age, smoking index and degree of pulmonary function damage were related to the decline rate of pulmonary function.