[Chinese expert guidance on overall application of lenvatinib in hepatocellular carcinoma].

Lenvatinib mesylate is an oral receptor tyrosine kinase inhibitor against targets of vascular endothelial growth factor receptors 1-3, fibroblast growth factor receptors 1-4, platelet-derived growth factor receptor α, stem cell growth factor receptor, and rearranged during transfection, et al. Lenvatinib has been approved by the National Medical Products Administration of China on September 4, 2018, for the first-line treatment of patients with unresectable hepatocellular carcinoma who have not received systematic treatment before. Up to February 2023, Lenvatinib has been listed in China for more than 4 years, accumulating a series of post-marketing clinical research evidences. Based on the clinical practice before and after the launch of lenvatinib and referring to the clinical experience of other anti-angiogenesis inhibitors, domestic multidisciplinary experts and scholars adopt the Delphi method to formulate the Chinese Expert Guidance on Overall Application of Lenvatinib in Hepatocellular Carcinoma after repeated discussions and revisions, in order to provide reference for reasonable and effective clinical application of lenvatinib for clinicians.

Magnitude and temporal trend of acne vulgaris burden in 204 countries and territories from 1990 to 2019: an analysis from the Global Burden of Disease Study 2019.

BACKGROUND: Acne vulgaris is widespread across the world. Mapping the latest magnitudes and temporal trends of acne vulgaris provides the essential foundation for targeted public policies at the national, regional and global levels. OBJECTIVES: In compliance with the framework of the Global Burden of Disease Study 2019, this study aimed to summarize the incidence, prevalence, DALYs and the corresponding secular trends of acne vulgaris by sex and age group in 204 countries from 1990 to 2019. METHODS: The average annual percentage change was calculated to depict the temporal trends in age-standardized rates (ASRs) of acne vulgaris burden by region, sex and age. RESULTS: Globally, it was estimated that there were 117·4 million [95% uncertainty interval (UI) 103·0-133.7] incident cases of acne vulgaris, 231·2 million (95% UI 208·2-255·5) prevalent cases and 5·0 (95% UI 3·0-7·9) million DALYs, with an increase of approximately 48% compared with 1990. Moreover, the overall ASRs of acne vulgaris increased by approximately 0·55% annually over the past three decades. We observed large disparities in ASRs of acne vulgaris with changing trends in sex, location and age. The ASR of acne vulgaris among women was around 1·3 times that of men, but the sex difference was narrowed because of the pronounced increase among men. The ASRs of acne vulgaris were higher in high-income regions, but the increasing trend was more pronounced in other regions. CONCLUSIONS: The burden rate of acne vulgaris continues to increase in almost all countries. Understanding the specific characteristics of acne vulgaris burden is essential to formulate more effective and targeted interventions for controlling acne burden.

Germline ATM variants predispose to melanoma: a joint analysis across the GenoMEL and MelaNostrum consortia.

PURPOSE: Ataxia-Telangiectasia Mutated (ATM) has been implicated in the risk of several cancers, but establishing a causal relationship is often challenging. Although ATM single-nucleotide polymorphisms have been linked to melanoma, few functional alleles have been identified. Therefore, ATM impact on melanoma predisposition is unclear. METHODS: From 22 American, Australian, and European sites, we collected 2,104 familial, multiple primary (MPM), and sporadic melanoma cases who underwent ATM genotyping via panel, exome, or genome sequencing, and compared the allele frequency (AF) of selected ATM variants classified as loss-of-function (LOF) and variants of uncertain significance (VUS) between this cohort and the gnomAD non-Finnish European (NFE) data set. RESULTS: LOF variants were more represented in our study cohort than in gnomAD NFE, both in all (AF = 0.005 and 0.002, OR = 2.6, 95% CI = 1.56-4.11, p < 0.01), and familial + MPM cases (AF = 0.0054 and 0.002, OR = 2.97, p < 0.01). Similarly, VUS were enriched in all (AF = 0.046 and 0.033, OR = 1.41, 95% CI = 1.6-5.09, p < 0.01) and familial + MPM cases (AF = 0.053 and 0.033, OR = 1.63, p < 0.01). In a case-control comparison of two centers that provided 1,446 controls, LOF and VUS were enriched in familial + MPM cases (p = 0.027, p = 0.018). CONCLUSION: This study, describing the largest multicenter melanoma cohort investigated for ATM germline variants, supports the role of ATM as a melanoma predisposition gene, with LOF variants suggesting a moderate-risk.

[Effect of placenta previa attached to cesarean scar for adverse pregnant outcomes in patients with placenta accreta spectrum disorders].

Objective: To investigate the effect of placenta previa attached to cesarean scar for adverse pregnant outcomes in patients with or without placenta accreta spectrum disorders (PAS). Methods: The clinical information of patients with cesarean section history and placenta previa during the perioperative period at Peking University First Hospital from January 1st, 2015 to December 31st, 2020 were collected retrospectively. There were 53 cases without PAS and 172 cases with PAS, 153 cases with abnormally invasive placenta (containing placenta increta and placenta percreta) and 72 cases without PAS or with placenta accreta. The pregnant outcomes including rate of postpartum hemorrhage, transfusion, hysterectomy between the above groups were compared. Multivariate analysis was performed to study the factors significantly associated with PAS. Results: Pregnant women with PAS were at higher risk of adverse pregnant outcomes than those without PAS. Patients with PAS had higher incidences of hysterectomy [12.2% (21/172) vs 0(0/53); P=0.005], postpartum hemorrhage [60.5% (104/172) vs 5.7% (3/53); P<0.01] and blood transfusion [66.9% (115/172) vs 7.5% (4/53); P<0.01]. In the subgroup analysis stratified by the type of PAS, patients with abnormally invasive placenta were at higher risk of hysterectomy [13.7% (21/153) vs 0 (0/72); P<0.01], postpartum hemorrhage [66.7% (102/153) vs 6.9% (5/72); χ²=70.873, P<0.01] and blood transfusion [74.5% (114/153) vs 6.9% (5/72); χ²=90.869, P<0.01]. After multiple logistic regression, the type of creta had the positive relation with postpartum hemorrhage (OR=27.622, 95%CI:9.873~77.280; P<0.01) and blood transfusion (OR=36.912, 95%CI:13.239~102.922; P<0.01). There were no significant correlations between adverse pregnant outcomes and the type of placenta previa or the times of cesarean section (all P>0.01). Conclusions: Placenta previa attached to cesarean scar without PAS or with placenta accreta could not act as the factor of predicting adverse pregnant outcomes in clinic. Placenta previa attached to cesarean scar with placenta increta or placenta percreta could increase the risk of adverse pregnant outcomes.

[microRNA-16-5p targeted tetraspanin 15 gene to inhibit the proliferation, migration and invasion of osteosarcoma cell through phospoinositide 3-kinase/protein kinase B signaling pathway].

Objective: To study the effects of miR-16-5p on proliferation, migration and invasion of osteosarcoma cells and its mechanism. Methods: Quantitative polymerase chain reaction (qPCR) and Western blotting were used to detect the mRNA and protein expression of miR-16-5p and TSPAN15 in human normal osteoblasts hFOB 1.19 and osteosarcoma cells MG63, Saos2 and HOS. The miR-16-5p or si-TSPAN15 was transfected into MG63 cells to observe its role in cell proliferation, migration and invasion. Cell proliferation was measured with MTT assay, cell migration and invasion were examined by Transwell, and the protein expression of CyclinD1, matrix metalloproteinase 2 (MMP-2), MMP-9, tetraspanin 15 (TSPAN15), phospha-tidylinositol3-kinase(p-PI3K) and phospha-protein kinase B(p-AKT) were determined by using Western blotting. The starbase website prediction combined with dual luciferase gene reporter assay was performed to analyze the targeting relationship between miR-16-5p and TSPAN15. miR-16-5p and pcDNA-TSPAN1 were co-transfected to assess the effect of high expression of TSPAN15 on overexpression of miR-16-5p-induced proliferation, migration and invasion of MG63 cells. Data comparison between the two groups was performed by using t test. Results: Compared with hFOB 1.19 cells (1.00±0.12), the expression of miR-16-5p was significantly decreased in MG63, Saos2 and HOS cells (0.32±0.05, 0.40±0.04, 0.45±0.06, respectively)(F=156.204, P<0.05), and TSPAN15 mRNA and protein levels were greatly increased (F=71.718, 110.350, both P<0.05). Overexpression of miR-16-5p obviously reduced the expression of CyclinD1, MMP-2, MMP-9 protein, cell viability, cell migration and invasion (F=150.136,117.228, 154.971, 89.479, 98.373, 130.880, all P<0.05) in MG63 cells. Knockdown of TSPAN15 greatly reduced CyclinD1, MMP-2, MMP-9 protein levels, cell survival rate, cell migration, and invasion number (F=93.206, 107.030, 109.326, 115.625, 146.113, 139.300, all P<0.05). Overexpression of miR-16-5p markedly decreased the expression of p-PI3K and p-AKT protein in MG63 cells (F=156.755, 181.419, both P<0.05). miR-16-5p targeted to regulate the expression of TSPAN15. High expression of TSPAN15 partially reversed the inhibitory effect of miR-16-5p on TSPAN15, CyclinD1, MMP-2, MMP-9, p-PI3K, p-AKT protein expression, cell viability, cell migration number and invasion number in MG63 cells. Conclusion: miR-16-5p inhibits the proliferation, migration and invasion of osteosarcoma cells by targeting the TSPAN15 gene and regulating the PI3K/AKT signaling pathway.

[Molecular epidemiology of Listeria monocytogenes isolated from ready-to-eat food in 2017 in China].

Objective: To analyze the molecular characteristics of Listeria monocytogenes strains from ready-to eat food in China. Methods: A total of 239 Listeria monocytogenes strains isolated from ready-to-eat food in 2017, all strains underwent whole-genome sequencing (WGS) , and comparisons uncovered population structure derived from lineages, clonal complex, serogroups, antimicrobial susceptibility and virulence, which were inferred in silico from the WGS data. Core genome multilocus sequence typing was used to subtype isolates. Results: All strains were categorized into three different lineages, lineage Ⅱ was the predominant types in food, and IIa was the main serogroups. CC8, CC101 and CC87 were the first three prevalent CCs among 23 detected CCs, accounting for 49.4%. Only 4.6% (11 isolates) of tested strains harbored antibiotic resistance genes, which were mostly trimethoprim genes (7 isolates, 2.9%). All strains were positive for LIPI-1, and only a part of strains harbored LIPI-3 and LIPI-4, accounting for 13.8% (33 isolates) and 14.2% (34 isolates), respectively. ST619 carried both LIPI-3 and LIPI-4. 51.5% (123 isolates) of strains carried SSI-1, and all CC121 strains harbored SSI-2. Different lineages, serogroups and CCs can be separated obviously through cgMLST analysis, and 24 sublineages were highly concordant with CCs. Conclusion: Ⅱa was the main serogroups in ready-to-eat food isolates in China; CC8, CC101 and CC87 were the prevalent CCs, and CC87 isolates was hypervirulent isolates, cgMLST method can be adopted for prospective foodborne disease surveillance and outbreaks detection.

[Pulmonary mucosa-associated lymphoid tissue lymphoma concurrent with lung squamous cell carcinoma: a case report and literature review].

Objective: To explore the clinical manifestations, imaging features, pathological features, diagnosis and treatment of pulmonary mucosal-associated lymphoid tissue(MALT)lymphoma concurrent with lung squamous cell carcinoma, and to improve the understanding of this disease. Methods: Using "Pulmonary mucosa-associated lymphoid tissue, squamous cell carcinoma" as the search term, from January 1, 1983 to August 31, 2020, a total of 3 cases were retrieved in the PubMed database. In the Wanfang database, using "Lung mucosa-associated lymphoid tissue, lung squamous cell carcinoma" as the search term, from January 1, 1990 to August 31, 2020, a total of 1 related document was retrieved. In the CNKI database, "(lung) mucosa-associated lymphoid tissue lymphoma, (lung) squamous cell carcinoma" was used as the search term, and no relevant case reports were retrieved. Results: A 64-year-old man was admitted to the hospital because of chest tightness and shortness of breath for 10 days, cough and fever for one day. Enhanced CT of the chest showed a soft tissue mass shadow in the right lower hilar area, with obstruction of the adjacent bronchus, and local mild enhancement, suggesting of right lower lung cancer. In addition, the CT scan also showed consolidated shadows in the lower lobes of both lungs, scattered nodules, multiple lymphadenopathy in the mediastinum, and a small amount of pleural effusion on the right. Under bronchoscopy, a cauliflower-like neoplasm was seen at the opening of the lower right basal section, about 7 mm×8 mm, and biopsy showed that part of the mucosal structure was destroyed, with disappearance of the squamous epithelial layer, and the nuclei were large and deeply stained, and some were distributed in nests, with poor keratinization and a small amount of necrosis, and fibrous tissue reaction. Immunostaining revealed that the tumor was positive for p40, CK5/6 and EGFR and negative forTTF-1, NapsinA, PD-L1, p53, with about 30% Ki-67 positive cells. A puncture biopsy of the right lower lobe showed that the alveolar cavity was filled with nested lymphoid cells, consisting of small lymphocytes, central cell-like cells and monocyte-like cells, with occasionally large cells. Immunostaining revealed CD20+, CD79a+, scattered CD3+, Bcl2+, SMA vascular+, Bcl6-, CK-, CD10-, CyclinD1-, with about 3% Ki-67 positive cells. The histopathological examinations confirmed the diagnosis of mucosal-associated lymphoid tissue extranodal marginal zone lymphoma(MALT lymphoma),and lung squamous cell carcinoma. Conclusions: Pulmonary mucosa-associated lymphoid tissue lymphoma complicated with lung squamous cell carcinoma is rare and easy to be missed and misdiagnosed. Chest CT imaging shows single or multiple nodules, mass shadows or consolidation, often accompanied by air-bronchial signs in the lesion, bronchiectasis, ground glass density around the lesion, hilar and mediastinal lymphadenopathy. Occasionally, pleural effusion can be seen. Lung biopsy is the gold standard for diagnosis.

[Study on the value of serum des-γ-carboxy prothrombin in predicting hepatocellular carcinoma recurrence after liver transplantation].

Objective: To explore the clinical value of serum des-γ-carboxy prothrombin (DCP) in predicting hepatocellular carcinoma recurrence after liver transplantation. Methods: A total of 115 cases with hepatocellular carcinoma who underwent liver transplantation in Zhongshan Hospital Affiliated to Fudan University from October 2016 to December 2018 were retrospectively analyzed. Receiver operating characteristic curve analysis, Mann-Whitney U test, Kaplan-Meier method, Log-Rank test, χ2 test, univariate and multivariate Cox regression analysis and other statistical methods were used to explore the value of DCP in predicting tumor recurrence after liver transplantation and its correlation with clinicopathological characteristics. Results: The preoperative serum DCP level in recurrent population after liver transplantation was significantly higher than that in non-recurrent population (P < 0.001). The optimal cut-off value of preoperative DCP for predicting recurrence was 200mAU/ml with the use of receiver operating characteristic curve. The sensitivity, specificity, Youden's index and the receiver operating characteristic curve was 87.90%, 57.30%, 0.452, and 0.726, respectively. Survival analysis results grouped by this cut-off value showed that patients with preoperative DCP ≥200mAU/ml had a higher probability of recurrence (P < 0.001). Further, subgroup survival analysis showed that patients with preoperative DCP≥200 mAU/ ml had a higher probability of recurrence than other cases of alpha-fetoprotein negative subgroup, cumulative tumor diameter ≤ 9 cm subgroup and Milan criteria subgroup (P < 0.05). Cox regression analysis showed that preoperative DCP≥200 mAU/ ml (P = 0.017) and cumulative tumor diameter > 9 cm (P = 0.014) was an independent risk factor for recurrence after liver transplantation. χ (2) test results showed that preoperative serum DCP level was correlated with gender, serum gamma glutamyltransferase level, serum alpha fetoprotein level, cumulative tumor diameter, vascular invasion, tumor differentiation and liver cancer transplant criteria (P < 0.05). Conclusion: Preoperative serum DCP can be used as a supplement to the existing liver cancer transplant criteria to predict hepatocellular carcinoma recurrence after liver transplantation. In addition, the accurate screening of patients with low risk of HCC recurrence after liver transplantation can improve the prognosis and efficacy of liver transplant patients.

[Effects of continuous positive airway pressure on periodic limb movements during sleep in patients with obstructive sleep apnea].

Objective: To investigate the effects of continuous positive airway pressure (CPAP) on periodic limb movements during sleep (PLMS) in patients with obstructive sleep apnea (OSA). Methods: The polysomnography (PSG) data of 828 consecutive OSA outpatients from January 2015 to January 2017 who had undergone overnight CPAP titration were analyzed retrospectively. On the basis of changes in periodic limb movements index (PLMI) values (cut off level≥15/h) from baseline PSG (BPSG) to CPAP titration PSG, patients were assigned to one of the following four groups: persistent, CPAP-emergent, CPAP-disappeared, and non-PLMS. Results: Among 828 patients, 756 (91.3%) were male and 72 (8.7%) were female. The mean age was (45.7±10.7) years old, the mean body mass index (BMI) was (27.6±3.5) kg/m(2). The rate of patients was 3.9% in the persistent group, 10.3% in the CPAP-emergent group, 7.5% in the CPAP-disappearance group, and 78.4% in the non-PLMS group. Multivariate Logistic regression analysis revealed that female appeared to be associated with the persistent group (P=0.004); older age and higher apnea-hypopnea index (AHI) on BPSG appeared to be associated with the CPAP-emergent group (P=0.012, 0.030). On the other hand, older age was negatively associated with the non-PLMS group (P=0.006). Conclusion: Elderly patients with higher AHI at BPSG may present with CPAP-emergent PLMS.

[Advances in research on cell fate determinant Numb regulating liver cancer].

Liver cancer is one of the most common malignant tumors in China, ranking fifth in malignant tumors and the third in tumor-related deaths. As a membrane-related protein, the asymmetric distribution of cell fate determinant Numb plays a key role in cell differentiation. Research reports that Numb may be closely associated to the occurrence and development of tumors. Recently, scholars have gradually valued its important role in liver cancer. This article briefly reviews the structure of Numb molecule, relationship between Numb and tumorigenesis, the molecular mechanism of Numb-regulated tumors, and the role of Numb in the development of liver cancer.

[The effect of extending proximal landing zone in thoracic endovascular aortic repair on the prognosis of Stanford type B aortic dissection].

With the continuous development of endovascular surgery, thoracic endovascular aortic repair (TEVAR) has gradually replaced traditional open surgery and has become the preferred treatment strategy for Stanford type B aortic dissection. However, the disadvantage of the short proximal landing zone greatly limited the indication of TEVAR surgery and affected the prognosis. In recent years, many strategies such as hybrid surgery, in vitro fenestrated and branched aortic endo-graft, chimney technique, in-situ fenestration technique, etc., have been developed, which greatly broadens the TEVAR indication and improved the prognosis.

Debunking Occam's razor: Diagnosing multiple genetic diseases in families by whole-exome sequencing.

BACKGROUND: Recent clinical whole exome sequencing (WES) cohorts have identified unanticipated multiple genetic diagnoses in single patients. However, the frequency of multiple genetic diagnoses in families is largely unknown. AIMS: We set out to identify the rate of multiple genetic diagnoses in probands and their families referred for analysis in two national research programs in Canada. MATERIALS & METHODS: We retrospectively analyzed WES results for 802 undiagnosed probands referred over the past 5 years in either the FORGE or Care4Rare Canada WES initiatives. RESULTS: Of the 802 probands, 226 (28.2%) were diagnosed based on mutations in known disease genes. Eight (3.5%) had two or more genetic diagnoses explaining their clinical phenotype, a rate in keeping with the large published studies (average 4.3%; 1.4 - 7.2%). Seven of the 8 probands had family members with one or more of the molecularly diagnosed diseases. Consanguinity and multisystem disease appeared to increase the likelihood of multiple genetic diagnoses in a family. CONCLUSION: Our findings highlight the importance of comprehensive clinical phenotyping of family members to ultimately provide accurate genetic counseling.

[Relationship between frailty and depression in elderly patients].

Objective: To investigate the relationship between frailty and depression by analyzing the clinical data, frailty and depression in the elderly outpatients. Methods: This study included outpatients who visited the Geriatric Section of West China Hospital from July 1, 2016 to December 31, 2016.Clinical characteristics and complications in patients were evaluated comprehensively.The debilitating condition of patient was assessed by the international society for elderly nutrition simple weakness questionnaire (Fatigue, Resistance, Ambulation, Illnesses, Loss of Weight.FRAIL). The depression was assessed by the 30-Item Geriatric Depression. Results: Regression analysis showed that pre-frail (OR 3.286, 95%CI 1.59-3.98) and frail (OR 4.139, 95%CI 1.52-14.40) elder adults had a higher risk of depression than other elders. Conclusion: Pre-frail and frail elders are at high risk of depression.

Mitochondrial genome of the shorthead catfish (Pelteobagrus eupogon): structure, phylogeny, and intraspecific variation.

The complete 16,532-nucleotide sequence of the mitochondrial genome of the shorthead catfish (Pelteobagrus eupogon) was determined using the long and accurate polymerase chain reaction method, and compared with the mitochondrial genome sequences of 49 other catfish species belonging to the order Siluriformes. The locations of protein-coding genes and ribosomal ribonucleic acids (RNAs) were identified by comparison with known sequences of other catfishes, including P. fulvidraco and P. nitidus. The P. eupogon mitochondrial genome was composed of 13 protein-coding genes, two ribosomal RNAs, 22 transfer RNA genes, and a non-coding control region. The gene order was identical to that of other Siluriformes. Phylogenetic analyses based on mitochondrial 12S ribosomal RNA, 16S ribosomal RNA, and 13 protein-coding gene sequence data sets were carried out to further clarify the relative phylogenetic position of P. eupogon, and identify phylogenetic relationships among 24 families of Siluriformes. Phylogenetic analyses Randomized Axelerated Maximum Likelihood (RAxML) 8.0.X were congruent with a basal split of the order into Clupeiformes, Characiformes, Cypriniformes, and Siluriformes, and supported a closer relationship of P. eupogon with Amblycipitidae than Siluridae. We therefore concluded that this species appears to be closely related to the Amblycipitidae. In the phylogenetic tree, the Amblycipitidae appeared as the most basal extant lineage within the Siluriformes, while the Bagridae appeared as the sister group of Cranoglanididae and Pangasiidae. The mitochondrial genome sequence of P. eupogon has been deposited in GenBank (accession No. KJ001784).

Immune Function Alterations during 12 Weeks of Abstinence in Heroin Users.

The intent of the study was to evaluate immune system changes during 12 weeks of abstinence in heroin users. We recruited men (N = 65) aged 18-45 years and collected demographic and heroin use pattern data. Serum blood levels of total interleukin 2 (IL-2), interferon γ (IFN-γ), immunoglobulin (Ig) A, IgG, and IgM were assessed at five time points. The IL-2 level was increased on day 84 as compared to that in healthy controls. The IFN-γ level was higher in heroin users than in healthy controls between days 0 and 28, and was decreased on day 84. IgG and IgM levels in heroin users were higher than those in healthy controls in our 12-week study, and were in positive correlation with the way of using the drug, duration of heroin dependence, and daily heroin intake. Our data revealed that the immune system was not restored during the 12 weeks of heroin withdrawal.

Common genetic variants in the 9p21 region and their associations with multiple tumours.

BACKGROUND: The chromosome 9p21.3 region has been implicated in the pathogenesis of multiple cancers. METHODS: We systematically examined up to 203 tagging SNPs of 22 genes on 9p21.3 (19.9-32.8 Mb) in eight case-control studies: thyroid cancer, endometrial cancer (EC), renal cell carcinoma, colorectal cancer (CRC), colorectal adenoma (CA), oesophageal squamous cell carcinoma (ESCC), gastric cardia adenocarcinoma and osteosarcoma (OS). We used logistic regression to perform single SNP analyses for each study separately, adjusting for study-specific covariates. We combined SNP results across studies by fixed-effect meta-analyses and a newly developed subset-based statistical approach (ASSET). Gene-based P-values were obtained by the minP method using the Adaptive Rank Truncated Product program. We adjusted for multiple comparisons by Bonferroni correction. RESULTS: Rs3731239 in cyclin-dependent kinase inhibitors 2A (CDKN2A) was significantly associated with ESCC (P=7 × 10(-6)). The CDKN2A-ESCC association was further supported by gene-based analyses (Pgene=0.0001). In the meta-analyses by ASSET, four SNPs (rs3731239 in CDKN2A, rs615552 and rs573687 in CDKN2B and rs564398 in CDKN2BAS) showed significant associations with ESCC and EC (P<2.46 × 10(-4)). One SNP in MTAP (methylthioadenosine phosphorylase) (rs7023329) that was previously associated with melanoma and nevi in multiple genome-wide association studies was associated with CRC, CA and OS by ASSET (P=0.007). CONCLUSION: Our data indicate that genetic variants in CDKN2A, and possibly nearby genes, may be associated with ESCC and several other tumours, further highlighting the importance of 9p21.3 genetic variants in carcinogenesis.

A meta-analysis on dose-response relationship between night shift work and the risk of breast cancer.

This study aimed to conduct a systematic review to sum up evidence of the associations between different aspects of night shift work and female breast cancer using a dose-response meta-analysis approach. We systematicly searched all cohort and case-control studies published in English on MEDLINE, Embase, PSYCInfo, APC Journal Club and Global Health, from January 1971 to May 2013. We extracted effect measures (relative risk, RR; odd ratio, OR; or hazard ratio, HR) from individual studies to generate pooled results using meta-analysis approaches. A log-linear dose-response regression model was used to evaluate the relationship between various indicators of exposure to night shift work and breast cancer risk. Downs and Black scale was applied to assess the methodological quality of included studies. Ten studies were included in the meta-analysis. A pooled adjusted relative risk for the association between 'ever exposed to night shift work' and breast cancer was 1.19 [95% confidence interval (CI) 1.05-1.35]. Further meta-analyses on dose-response relationship showed that every 5-year increase of exposure to night shift work would correspondingly enhance the risk of breast cancer of the female by 3% (pooled RR = 1.03, 95% CI 1.01-1.05; Pheterogeneity < 0.001). Our meta-analysis also suggested that an increase in 500-night shifts would result in a 13% (RR = 1.13, 95% CI 1.07-1.21; Pheterogeneity = 0.06) increase in breast cancer risk. This systematic review updated the evidence that a positive dose-response relationship is likely to present for breast cancer with increasing years of employment and cumulative shifts involved in the work.

[Shandong hilly rural natural population cohort study: method and baseline characteristics of survey subjects].

Objective: To understand the study method and the baseline characteristics of the survey subjects of Shandong hilly rural natural population cohort study, and provide reference for the research of the prevalence and risk factors of common chronic and non-communicable diseases. Methods: Baseline survey, including questionnaire survey, physical examination, biochemical index examination and blood and saliva collection, was conducted in local residents aged 20-79 years in Kongcun and Xiaozhi townships of Pingyin county, Shandong province, from 2017 to 2019. Shandong hilly rural natural population cohort was established and main baseline characteristics of the study subjects were statistically analyzed. Results: A total of 10 296 study subjects aged 54.45 years were included in the study, in whom 40.6% were males. Among the study subjects, 88.3% had education level of junior high school or below, 62.1% were famers, and 90.7% were married. Smokers accounted for 45.6% of men and 0.9% of women, and drinkers accounted for 65.8% of men and 3.0% of women, respectively. The self-reported rates of hypertension, diabetes, coronary heart disease, stroke and tumors were 19.8%, 3.2%, 2.8%, 2.7% and 1.2%, respectively. Conclusion: The Shandong hilly rural cohort natural population study provided important evidence for assessing the risk for common chronic and non-communicable diseases and disease prevention and control in hilly rural areas.

Prolactin serum levels and breast cancer: relationships with risk factors and tumour characteristics among pre- and postmenopausal women in a population-based case-control study from Poland.

BACKGROUND: Previous prospective studies have found an association between prolactin (PRL) levels and increased risk of breast cancer. Using data from a population-based breast cancer case-control study conducted in two cities in Poland (2000-2003), we examined the association of PRL levels with breast cancer risk factors among controls and with tumour characteristics among the cases. METHODS: We analysed PRL serum levels among 773 controls without breast cancer matched on age and residence to 776 invasive breast cancer cases with available pretreatment serum. Tumours were centrally reviewed and prepared as tissue microarrays for immunohistochemical analysis. Breast cancer risk factors, assessed by interview, were related to serum PRL levels among controls using analysis of variance. Mean serum PRL levels by tumour characteristics are reported. These associations also were evaluated using polytomous logistic regression. RESULTS: Prolactin levels were associated with nulliparity in premenopausal (P=0.05) but not in postmenopausal women. Associations in postmenopausal women included an inverse association with increasing body mass index (P=0.0008) and direct association with use of recent/current hormone therapy (P=0.0006). In case-only analyses, higher PRL levels were more strongly associated with lobular compared with ductal carcinoma among postmenopausal women (P=0.02). Levels were not different by tumour size, grade, node involvement or oestrogen receptor, progesterone receptor, or human epidermal growth factor receptor 2 status. CONCLUSIONS: Our analysis demonstrates that PRL levels are higher among premenopausal nulliparous as compared with parous women. Among postmenopausal women, levels were higher among hormone users and lower among obese women. These results may have value in understanding the mechanisms underlying several breast cancer risk factor associations.