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Background: In recent years, the research on symptom management in peritoneal dialysis (PD) patients has shifted from a single symptom to symptom clusters and network analysis. This study collected and evaluated unpleasant symptoms in PD patients and explored groups of symptoms that may affect PD patients with a view to higher symptom management., Methods: The symptoms of PD patients were measured using the modified Dialysis Symptom Index. The symptom network and node characteristics were assessed by network analysis, and symptom clusters were explored by factor analysis., Results: In this study of 602 PD patients (mean age 47.8 ± 16.8 years, 47.34% male), most had less than 2 years of dialysis experience. Five symptom clusters were obtained from factor analysis, which were body symptom cluster, gastrointestinal symptom cluster, mood symptom cluster, sexual disorder symptom cluster, and skin-sleep symptom cluster. Itching and decreased interest in sex may be sentinel symptoms, and being tired or lack of energy and feeling anxious are core symptoms in PD patients., Conclusions: This study emphasizes the importance of recognizing symptom clusters in PD patients for better symptom management. Five clusters were identified, with key symptoms including itching, decreased interest in sex, fatigue, and anxiety. Early intervention focused on these symptom clusters in PD patients holds promise for alleviating the burden of symptoms.

Background: CD46 has been revealed to be a key factor in malignant transformation and cancer treatment. However, the clinical significance of CD46 in cervical cancer remains unclear, and this study aimed to evaluate its role in cervical cancer diagnosis and prognosis evaluation., Methods: A total of 180 patients with an initial diagnosis of cervical cancer were enrolled at Taizhou Hospital of Zhejiang Province, China. The plasma levels of soluble CD46 (sCD46) and the expression of membrane-bound CD46 (mCD46) were detected by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry (IHC), respectively., Results: CD46 was found to be significantly upregulated in cervical cancer tissues vs. normal tissues, while no CD46 staining was detected in paired adjacent noncancerous tissues. CD46 staining was more pronounced in cancer cells than in stromal cells in situ (in tissues). Moreover, the plasma levels of sCD46 were able to some extent discriminate between cancer patients and healthy women (AUC=0.6847, 95% CI:0.6152-0.7541). Analysis of Kaplan-Meier survival curves revealed that patients with low CD46 expression had slightly longer overall survival (OS) than patients with high CD46 expression in the tumor microenvironment, but no significant difference. Univariate Cox regression analysis revealed that CD46 ( P =0.034) is an independent risk factor for OS in cervical cancer patients., Conclusion: The present study demonstrated that cervical cancer patients exhibit aberrant expression of CD46, which is closely associated with a poor prognosis, suggesting that CD46 plays a key role in promoting cervical carcinogenesis and that CD46 could serve as a promising potential target for precision therapy for cervical cancer., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yu, Yuan, Yan, Zhang and Xu.)

Objective: To investigate the changes in amplitude of low-frequency fluctuation (ALFF) and degree centrality (DC) values before and after acupuncture in young women with non-menstrual migraine without aura (MWoA) through rest blood-oxygen-level-dependent functional magnetic resonance imaging (BOLD fMRI)., Methods: Patients with non-menstrual MWoA (Group 1, n = 50) and healthy controls (Group 2, n = 50) were recruited. fMRI was performed in Group 1 at 2 time points: before acupuncture (time point 1, TP1); and after the end of all acupuncture sessions (time point 2, TP2), and performed in Group 2 as a one-time scan. Patients in Group 1 were assessed with the Migraine Disability Assessment Questionnaire (MIDAS) and the Short-Form McGill Pain Questionnaire (SF-MPQ) at TP1 and TP2 after fMRI was performed. The ALFF and DC values were compared within Group 1 at two time points and between Group 1 and Group2. The correlation between ALFF and DC values with the statistical differences and the clinical scales scores were analyzed., Results: Brain activities increased in the left fusiform gyrus and right angular gyrus, left middle occipital gyrus, and bilateral prefrontal cortex and decreased in left inferior parietal lobule in Group 1, which had different ALFF values compared with Group 2 at TP1. The bilateral fusiform gyrus, bilateral inferior temporal gyrus and right middle temporal gyrus increased and right angular gyrus, right superior marginal gyrus, right inferior parietal lobule, right middle occipital gyrus, right superior frontal gyrus, right middle frontal gyrus, right anterior central gyrus, and right supplementary motor area decreased in activity in Group 1 had different DC values compared with Group 2 at TP1. ALFF and DC values of right inferior temporal gyrus, right fusiform gyrus and right middle temporal gyrus were decreased in Group1 at TP1 compared with TP2. ALFF values in the left middle occipital area were positively correlated with the pain degree at TP1 in Group1 (correlation coefficient r, r = 0.827, r = 0.343; P < 0.01, P = 0.015). The DC values of the right inferior temporal area were positively correlated with the pain degree at TP1 in Group 1 (r = 0.371; P = 0.008)., Conclusion: Spontaneous brain activity and network changes in young women with non-menstrual MwoA were altered by acupuncture. The right temporal area may be an important target for acupuncture modulated brain function in young women with non-menstrual MwoA., (© 2024. The Author(s).)

Background: Osteoarthritis (OA) is the most prevalent form of degenerative whole-joint disease. Before the final option of knee replacement, arthroscopic surgery was the most widely used joint-preserving surgical treatment. Emerging regenerative therapies, such as those involving platelet-rich plasma, mesenchymal stem cells, and microfragmented adipose tissue (MFAT), have been pushed to the forefront of treatment to prevent the progression of OA. Currently, MFAT has been successfully applied to treat different types of orthopedic diseases., Aim: To assess the efficacy and safety of MFAT with arthroscopic surgery in patients with knee OA (KOA)., Methods: A randomized, multicenter study was conducted between June 2017 and November 2022 in 10 hospitals in Zhejiang, China. Overall, 302 patients diagnosed with KOA (Kellgren-Lawrence grades 2-3) were randomized to the MFAT group ( n = 151, were administered MFAT following arthroscopic surgery), or the control group ( n = 151, were administered hyaluronic acid following arthroscopic surgery). The study outcomes were changes in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, the visual analog scale (VAS) score, the Lequesne index score, the Whole-Organ Magnetic Resonance Imaging Score (WORMS), and safety over a 24-mo period from baseline., Results: The changes in the WOMAC score (including the three subscale scores), VAS pain score, and Lequesne index score at the 24-mo mark were significantly different in the MFAT and control groups, as well as when comparing values at the posttreatment visit and those at baseline ( P < 0.001). The MFAT group consistently demonstrated significant decreases in the WOMAC pain scores and VAS scores at all follow-ups compared to the control group ( P < 0.05). Furthermore, the WOMAC stiffness score, WOMAC function score, and Lequesne index score differed significantly between the groups at 12 and 24 mo ( P < 0.05). However, no significant between-group differences were observed in the WORMS at 24 mo ( P = 0.367). No serious adverse events occurred in both groups., Conclusion: The MFAT injection combined with arthroscopic surgery treatment group showed better mid-term clinical outcomes compared to the control group, suggesting its efficacy as a therapeutic approach for patients with KOA., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Human papillomavirus (HPV) 33 belongs to the Alphapapillomavirus 9 (α-9 HPV) species group, which also contains types 16, 31, 35, 52, 58 and 67. The purpose of this study was to investigate the genetic variations of HPV33 and to explore its carcinogenicity among women in Taizhou, Southeast China., Methods: Exfoliated cervical cells were collected for HPV genotyping. Only single HPV33 infection cases were selected, and their E6 and E7 genes were sequenced using the ABI 3730xl sequencer and then analysed using MEGA X., Results: From 2014 to 2020, a total of 185 single HPV33-positive specimens were successfully amplified. We obtained 15 distinct HPV33 E6/E7 variants, which were published in GenBank under accession numbers OQ672665-OQ672679. Phylogenetic analysis revealed that all HPV33 E6/E7 variants belonged to lineage A, of which 75.7% belonged to lineage A1. Compared with CIN1, the proportion of sublineage A1 in CIN2/3 was higher, but there was no significant difference (76.5% vs. 80.6%, P > 0.05). Altogether, 20 single nucleotide substitutions were identified, of which 6 were novel substitutions, including T196G (C30G), A447T, G458T (R117L), G531A, A704A, and C740T. In addition, no significant trends were observed between the nucleotide substitutions of HPV33 E6/E7 variants and the risk of cervical lesions., Conclusion: This study provides the most comprehensive data on genetic variations, phylogenetics and carcinogenicity of HPV33 E6/E7 variants in Southeast China to date. The data confirmed that cervical lesions among women in Taizhou are attributable to HPV33, which may be due to the high infection rate of sublineage A1 in the population., (© 2023. The Author(s).)

Purpose: Chronic inflammation has been proven to be an important factor in carcinogenesis. Cytokines are the central mediators in the inflammatory microenvironment, and their release may be influenced by soluble HLA-G (sHLA-G). The aim of this study was to monitor the dynamic process of these soluble factors in patients with cervical cancer at Taizhou Hospital of Zhejiang Province, trying to understand their relationship with diagnosis, treatment, and prognosis., Methods: We quantified plasma levels of sHLA-G and 12 cytokines using ELISA and flow cytometry, respectively, in the peripheral blood of patients with cervical cancer divided into three groups: preoperation, postoperation and clinical relapse. Healthy women were used as the control group. Data were analysed by non-parametric tests, receiver-operating characteristic (ROC) curves, and Kaplan-Meier plotter (log-rank test)., Results: In this study, our findings showed that preoperation plasma levels of sHLA-G and the cytokines IL-6, IL-10, and IFN-γ in cervical cancer patients had a good discriminatory effect between cervical cancer patients and healthy women. It should be noted that plasma levels of sHLA-G, IL-6, and IL-10 were significantly decreased within 30 days after radical hysterectomy (P < 0.05). A positive correlation was observed between IL-6 and IL-10, IL-8 and IL-17 levels preoperatively. In contrast, sHLA-G levels were negatively correlated with IL-10 but not with other cytokines. An increased survival rate in patients with cervical cancer was associated with IL-5 < 1.70 pg/mL, IL-17 < 2.30 pg/mL, and IFN-α < 2.26 pg/mL preoperatively. In addition, our findings showed that the levels of cytokines IL-6, IL-8, IL-12p70, IL-17, and IFN-γ may be related to 5-year relapse rates and/or the metastasis of cervical cancer., Conclusion: The current findings enhance our understanding of the dynamic process (preoperation, postoperation and clinical relapse) of sHLA-G and these cytokines in the plasma of patients with cervical cancer from diagnosis to prognosis. These biomarkers may play a potential therapeutic target role of such dynamic changes in the immunotherapy for cervical cancer., (© 2022. The Author(s).)

Background: Xq22.1-q22.3 deletion is a rare chromosome aberration. The purpose of this study was to identify the correlation between the phenotype and genotype of chromosome Xq22.1-q22.3 deletions., Methods: Chromosome aberrations were identified by copy number variation sequencing (CNV-seq) technology and karyotype analysis. Furthermore, we reviewed patients with Xq22.1-q22.3 deletions or a deletion partially overlapping this region to highlight the rare condition and analyse the genotype-phenotype correlations., Results: We described a female foetus who is the "proband" of a Chinese pedigree and carries a heterozygous 5.29 Mb deletion (GRCh37: chrX: 100,460,000-105,740,000) in chromosome Xq22.1-q22.3, which may affect 98 genes from DRP2 to NAP1L4P2. This deletion encompasses 7 known morbid genes: TIMM8A, BTK, GLA, HNRNPH2, GPRASP2, PLP1, and SERPINA7. In addition, the parents have a normal phenotype and are of normal intelligence. The paternal genotype is normal. The mother carries the same deletion in the X chromosome. These results indicate that the foetus inherited this CNV from her mother. Moreover, two more healthy female family members were identified to carry the same CNV deletion through pedigree analysis according to the next-generation sequencing (NGS) results. To our knowledge, this family is the first pedigree to have the largest reported deletion of Xq22.1-q22.3 but to have a normal phenotype with normal intelligence., Conclusions: Our findings further improve the understanding of the genotype-phenotype correlations of chromosome Xq22.1-q22.3 deletions.This report may provide novel information for prenatal diagnosis and genetic counselling for patients who carry similar chromosome abnormalities., (© 2023. The Author(s).)

Objective: Gastrointestinal dysfunction seriously affects the prognosis and quality of life of patients with multiple fractures. However, experimental evidence of this relationship is lacking. Here we describe a newly developed mouse model of postoperative gastrointestinal dysfunction after multiple fractures., Methods: Trauma severity was assessed using the injury severity score (ISS). Based on the ISS, a multiple fracture model was established in mice as follows: limb fractures with pelvic fractures and multiple rib fractures; limb fractures with multiple rib fractures; closed fracture of both forelegs with pelvic fracture and rib fractures; closed limb fractures; limb fracture with pelvic fracture; spinal fractures; hind leg fractures with pelvic fractures; pelvic fracture with multiple rib fractures; closed fracture of both fore legs with pelvic fracture; and closed fracture of both fore legs with multiple rib fractures. In each model group, gastrointestinal motility was assayed and the histopathology of the small intestine was examined. Western blot and immunohistochemical analyses of jejunal tissue were performed to detect c-kit protein expression, the level of which was compared with that of a control group. The results of ANOVA are expressed as mean ± standard deviation., Results: In mice with multiple fractures, food intake was greatly reduced, consistent with histopathological evidence of an injured intestinal epithelium. The jejunal tissue of mice in groups a, c, f, and h was characterized by extensively necrotic and exfoliated intestinal mucosal epithelium and inflammatory cell infiltration in the lamina propria. In the gastrointestinal function assay, gastrointestinal motility was significantly reduced in groups a, b, c, f, and g; these group also had a higher ISS (p < 0.01). The expression of c-kit protein in groups with gastrointestinal dysfunction was significantly up-regulated (p < 0.001) compared with the control group. The close correlation between c-kit expression and the ISS indicated an influence of trauma severity on gastrointestinal motility., Conclusion: Gastrointestinal dysfunction after multiple fractures was successfully reproduced in a mouse model. In these mice, c-kit expression correlated with gastrointestinal tissue dysfunction and might serve as a therapeutic target., (© 2023 The Authors. Orthopaedic Surgery published by Tianjin Hospital and John Wiley & Sons Australia, Ltd.)

Background: Physicians need an appropriate embryo transfer strategy to address the challenge of reducing multiple birth rates, while maintaining the couples' live birth rate during assisted reproductive technology., Methods: We included 10,060 frozen embryo transfer cycles from January 2015 to March 2020 in reproductive medical center of Ruijin hospital, Shanghai, China. Patients were grouped according to the number and grade of cleavage-stage embryo or blastocysts transferred. Live birth rate and multiple live birth rate were compared among groups of women of different ages. Multivariable logistic regression models were used to estimate the risk of multiple live birth using different combinations of transferred embryos., Results: The transfer of double good-quality embryos was an independent predictor for multiple birth in women aged <30 years and those aged 36-39 years [<30 years: aOR =1.54 (95% CI: 1.14-2.06, P < 0.01); 36-39 years: aOR =1.84 (95% CI: 1.0-3.4, P < 0.01)]. Further, for women aged <36 years, the transfer of good-quality + poor-quality blastocysts was an independent predictor for multiple birth rate [<30 years: aOR=2.46 (95% CI: 1.45-4.18, P < 0.01); 31-35 years: aOR =4.45 (95% CI: 1.97-10.06, P < 0.01)]., Conclusions: Single-good-quality blastocyst transfer is recommended for women of all ages. When good-quality cleavage embryos are available, the choice of single or double embryo transfer with good- or average-quality embryo should depend on the age of women. Double embryo transfer with the highest possible grade of embryos is recommended for women aged ≥40 years., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wu, Zhou, Xu, Chen, Xia, Zhao, Xu, Zhang and Niu.)

Background: Human leukocyte antigen G (HLA-G) is an immune checkpoint molecule with relevance in several cancers. The aim of this study was to evaluate the potential role of soluble HLA-G (sHLA-G), its genetic polymorphisms and its haplotype structure in the susceptibility and prognosis of primary cervical cancer in a Chinese Han population., Methods: We investigated sHLA-G plasma levels and 3' untranslated region (3'UTR) polymorphisms through ELISA and direct DNA sequencing, respectively, in cervical cancer patients (120 cases) and healthy control women (96 cases). The data were analyzed for associations using PowerMarker, Haploview, and GraphPad Prism., Results: In this study, 8 polymorphic sites, 16 haplotypes and 23 diplotypes in the HLA-G 3'UTR were identified in our study population. We observed that each pair of 8 polymorphic sites exhibited linkage disequilibrium. The heterozygote CT genotype at position +3422 (rs17875408) was more common in cervical cancer patients than in healthy women (OR=5.285, P <0.05). Haplotypes UTR-1, UTR-3, and UTR-7 accounted for more than 85% of both groups, but no significant difference was found. The frequency of the UTR-1/UTR-3 diplotype in patients was significantly higher than that in controls ( P <0.05). In addition, we further observed that HLA-G 3'UTR polymorphisms may influence the sHLA-G plasma level in patients' peripheral blood, especially 14 bp Ins/Del (rs371194629) and + 3142 C/G (rs1063320). A receiver operating characteristic (ROC) curve analysis showed that the sHLA-G level had good diagnostic performance in differentiating patients with cervical cancer from healthy women (AUC>0.7). Among patients, mean sHLA-G levels increased with increasing FIGO stages but were not related to the overall survival time., Conclusions: The results of the present study enhance our understanding of how HLA-G 3'UTR polymorphisms can influence the peripheral sHLA-G plasma level and play a key role in cervical carcinogenesis. This study further confirmed that sHLA-G may represent a novel plasma biomarker for the prognosis and potential therapeutic target of cervical cancer., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Gan, Di, Yan, Gao and Xu.)

Background: Human papillomavirus (HPV) 52 is one of the prevalent oncogenic HPV genotypes in East Asia. Chinese women have the highest susceptibility to the HPV52 type, but research data on HPV52 genetic variability and its carcinogenicity in China is lacking., Methods: The present study aimed to investigate the genetic variability of HPV52 currently circulating among Chinese women by PCR sequencing the entire E6 and E7 oncogenes. HPV52 sequence alignment, genetic heterogeneity analyses and maximum-likelihood phylogenetic tree construction were performed by BioEdit software and MEGA X software., Results: Between 2016 and 2018, the overall HPV infection rate was 21.3%, of which HPV52 was the most prevalent high-risk type (17.2%) in the Taizhou area, China. A total of 339 single HPV52-positive samples were included in this study. We obtained 27 distinct variation patterns of HPV52 with the accession GenBank numbers ON529577-ON529603. Phylogenetic analysis showed that 96.6% of HPV52 variants belonged to lineage B, which seemed to be uniquely defined by G350T, A379G (K93R) in the E6 gene and C751T, A801G in the E7 gene. Due to the dominance of lineage B in our study population, the results could not be used to assess the association of the HPV52 (sub)lineage with the risk of cervical lesions. In addition, no significant trends were observed between the nucleotide substitutions of HPV52 variants and the risk of cervical carcinogenesis., Conclusion: Our data showed that HPV52 variants were strongly biased towards lineage B. These results confirmed that cervical lesions in the Taizhou area are highly attributable to HPV52, which may be due to the high infection rate of lineage B in the population., (© 2022. The Author(s).)

Human leukocyte antigen G (HLA-G) is a potential checkpoint molecule that plays a key role in cervical carcinogenesis. The purpose of this study was to construct and validate a prognostic risk model to predict the overall survival (OS) of cervical cancer patients, providing a reference for individualized clinical treatment that may lead to better clinical outcomes. HLA-G-driven differentially expressed genes (DEGs) were obtained from two cervical carcinoma cell lines, namely, SiHa and HeLa, with stable overexpression of HLA-G by RNA sequencing (RNA-seq). The biological functions of these HLA-G-driven DEGs were analysed by GO enrichment and KEGG pathway using the "clusterProfiler" package. The protein-protein interactions (PPIs) were assessed using the STRING database. The prognostic relevance of each DEG was evaluated by univariate Cox regression using the TCGA-CESC dataset. After the TCGA-CESC cohort was randomly divided into training set and testing set, and a prognostic risk model was constructed by LASSO and stepwise multivariate Cox regression analysis in training set and validated in testing set or in different types of cervical cancer set. The predictive ability of the prognostic risk model or nomogram was evaluated by a series of bioinformatics methods. A total of 1108 candidate HLA-G-driven DEGs, including 391 upregulated and 717 downregulated genes, were obtained and were enriched mostly in the ErbB pathway, steroid biosynthesis, and MAPK pathway. Then, an HLA-G-driven DEG signature consisting of the eight most important prognostic genes CD46, LGALS9, PGM1, SPRY4, CACNB3, PLIN2, MSMO1 , and DAGLB was identified as a key predictor of cervical cancer. Multivariate Cox regression analysis showed that this signature is an independent risk factor for the overall survival of CESC patients. Kaplan-Meier survival analysis showed that the 5-year overall survival rate is 23.0% and 84.6% for the high-risk and low-risk patients, respectively ( P <0.001). The receiver operating characteristic (ROC) curve of this prognostic model with an area under the curve (AUC) was 0.896 for 5 years, which was better than that of other clinical traits. This prognostic risk model was also successfully validated in different subtypes of cervical cancer, including the keratinizing squamous cell carcinoma, non-keratinizing squamous cell carcinoma, squamous cell neoplasms, non-squamous cell neoplasms set. Single-sample gene set enrichment (ssGSEA) algorithm and Tumor Immune Dysfunction and Exclusion (TIDE) analysis confirmed that this signature influence tumour microenvironment and immune checkpoint blockade. A nomogram that integrated risk score, age, clinical stage, histological grade, and pathological type was then built to predict the overall survival of CESC patients and evaluated by calibration curves, AUC, concordance index (C-index) and decision curve analysis (DCA). To summarize, we developed and validated a novel prognostic risk model for cervical cancer based on HLA-G-driven DEGs, and the prognostic signature showed great ability in predicting the overall survival of patients with cervical cancer., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Xu, Wang, Xing and Wang.)

Background: The role of B cell subsets remained to be elucidated in a variety of immune diseases, though which was used as an effective biomarker for anti-inflammatory or antiviral response. This study aimed to evaluate the early changes of B cell subtypes distribution in elderly patients with community acquired pneumonia (CAP), as well as the association between B cell subtypes and prognosis., Methods: This prospective study included elderly patients with CAP, severe CAP (sCAP) and healthy elderly subjects between April 2016 and March 2018. Flow cytometry was used to detect CD3, CD20, HLA-DR, CD24, CD27, CD38, IgM, and IgD. CD20 + B cells were further divided into naïve B cells (Bn), IgM/D + memory B cells (IgM + Bm), switched B cells (SwB), and transitional B cells (Btr)., Results: A total of 22 healthy controls, 87 patients with CAP and 58 patients with sCAP were included in the study. Compared to CAP, sCAP was characterized by significantly lower absolute number of B cells, Bn and Btr, significantly lower Btr and Bn subset percentage, while percentage of IgM + Bm was significantly higher. Heat map showed Bn and Btr on day 3 and day 7 was negatively correlated with activated partial prothrombin time (APTT), international normalized ratio (INR), sequential organ failure assessment score (SOFA) and Acute Physiology and Chronic Health Evaluation II (APACHE II). After 28-day follow-up, Btr percentage in survival group was significantly higher. Receiver operator characteristic (ROC) curve analysis found that Btr count showed sensitivity of 48.6% and specificity of 87.0% for predicting the 28-day survival, with an area under the ROC curves of 0.689 (p = 0.019)., Conclusions: Severity and prognosis of CAP in elderly people is accompanied by changes in the B cell subsets. Btr subsets could play prognostic role for a short-term mortality of elderly CAP patients., (© 2022. The Author(s).)

Steroid-associated necrosis of the femoral head (SANFH) is one of the most common and refractory chronic diseases with increasing incidence. The typical pathological changes of SANFH include decreased osteogenic differentiation, enhanced intramedullary adipocytes deposition and impaired osseous circulation. In this study, we investigated the effects and potential mechanisms of Platelet-rich plasma (PRP) on SANFH. Sixty Sprague-Dawley rats were randomly divided into the control, PRP donor, model, and PRP groups. Compared to the model group, PRP treatment significantly increased the hemorheological indexes and serum levels of bone gla-protein (BGP) and vascular endothelial growth factor (VEGF), while decreased the levels of triglyceride (TG) and total cholesterol (TC). Meanwhile, Micro-CT and histopathological stain (Hematoxylin-eosin and Alcian blue-hematoxylin/orange G staining) were performed on the femoral head for morphological and histopathological evaluation, indicating that bone trabecular microstructure and bone mineral density (BMD) were significantly improved after PRP treatment. Immunohistochemical analysis revealed that PRP remarkably up-regulated the expression of osteogenic markers including β-catenin and alkaline phosphatase (ALP), angiogenic markers containing VEGF and platelet endothelial cell adhesion molecule-1 (CD31), while down-regulated adipogenic markers involving fatty acid-binding protein (FABP-4), and peroxisome proliferator-activated receptor gamma (PPAR-γ) in SANFH rat models. In summary, for the first time, PRP was demonstrated to prevent the development of SANFH through stimulating bone formation and vascularization as well as retarding adipogenesis.

Background: Human papillomavirus (HPV) type 16 accounts for a larger share of cervical cancer and has been a major health problem worldwide for decades. The progression of initial infection to cervical cancer has been linked to viral sequence properties; however, the role of HPV16 variants in the risk of cervical carcinogenesis, especially with longitudinal follow-up, is not fully understood in China., Methods: We aimed to investigate the genetic variability of HPV16 E6 and E7 oncogenes in isolates from cervical exfoliated cells. Between December 2012 and December 2014, a total of 310 single HPV16-positive samples were selected from women living in the Taizhou area, China. Sequences of all E6 and E7 oncogenes were analysed by PCR-sequencing assay. Detailed sequence comparison, genetic heterogeneity analyses and maximum-likelihood phylogenetic tree construction were performed with BioEdit Sequence Alignment Editor and MEGA X software. Data for cytology tests and histological diagnoses were obtained from our Taizhou Area Study with longitudinal follow-up for at least 5 years. The relationship between HPV16 variants and cervical carcinogenesis risk was analysed by the chi-square test or Fisher's exact test., Results: In this study, we obtained 64 distinct variation patterns with the accession GenBank numbers MT681266-MT681329. Phylogenetic analysis revealed that 98.3% of HPV16 variants belong to lineage A, in which the A4 (Asian) sublineage was dominant (64.8%), followed by A2 (12.1%), A1 (11.4%), and A3 (10.0%). The A4 (Asian) sublineage had a higher risk of CIN2+ than the A1-3 (European) sublineages (OR = 2.69, 95% CI = 1.04-6.97, P < 0.05). Furthermore, nucleotide variation in HPV16 E6 T178G is associated with the development of cervical cancer., Conclusion: These data could provide novel insights into the role of HPV16 variants in cervical carcinogenesis risk in China.

Human leukocyte antigen G (HLA-G) is known as a novel immune checkpoint molecule in cancer; thus, HLA-G and its receptors might be targets for immune checkpoint blockade in cancer immunotherapy. The aim of this study was to systematically identify the roles of checkpoint HLA-G molecules across various types of cancer. ONCOMINE, GEPIA, CCLE, TRRUST, HAP, PrognoScan, Kaplan-Meier Plotter, cBioPortal, LinkedOmics, STRING, GeneMANIA, DAVID, TIMER, and CIBERSORT were utilized. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed. In this study, we comprehensively analysed the heterogeneous expression of HLA-G molecules in various types of cancer and focused on genetic alterations, coexpression patterns, gene interaction networks, HLA-G interactors, and the relationships between HLA-G and pathological stage, prognosis, and tumor-infiltrating immune cells. We first identified that the mRNA expression levels of HLA-G were significantly upregulated in both most tumor tissues and tumor cell lines on the basis of in-depth analysis of RNAseq data. The expression levels of HLA-G were positively associated with those of the other immune checkpoints PD-1 and CTLA-4. Abnormal expression of HLA-G was significantly correlated with the pathological stage of some but not all tumor types. There was a significant difference between the high and low HLA-G expression groups in terms of overall survival (OS) or disease-free survival (DFS). The results showed that HLA-G highly expressed have positive associations with tumor-infiltrating immune cells in the microenvironment in most types of tumors ( P <0.05). Additionally, we identified the key transcription factor (TF) targets in the regulation of HLA-G expression, including HIVEP2, MYCN, CIITA, MYC, and IRF1. Multiple mutations (missense, truncating, etc.) and the methylation status of the HLA-G gene may explain the differential expression of HLA-G across different tumors. Functional enrichment analysis showed that HLA-G was primarily related to T cell activation, T cell regulation, and lymphocyte-mediated immunity. The data may provide novel insights for blockade of the HLA-G/ILT axis, which holds potential for the development of more effective antitumour treatments., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Xu, Gan, Xu, Li and Yan.)

Ethnopharmacological Relevance: Knee osteoarthritis (KOA) is the most common chronic joint disorder worldwide, which is also a principle consideration for disability. The Bushenhuoxue formula (BSHXF) is a traditional herbal formula which widely applied to the treatment of KOA. However, its pharmacological mechanisms of action have not been clarified., Aims of the Study: The study aimed to identify the potential targets and mechanisms of BSHXF in the treatment of KOA through pharmacology-based analyses and experimental validation., Materials and Methods: The TCMSP database was applied to obtain the chemical compounds and targets of BSHXF, while the protein targets in KOA were determined through GeneCards and OMIM databases. The herb-compound-target and protein-protein interaction (PPI) networks were constructed for topological analyses and hub-targets screening. GO and KEGG enrichment analyses were performed on these core nodes to identify the critical biological processes and signaling pathways. Then destabilization of medial meniscus (DMM)-induced C57BL/6J mice model was established to detect the level of apoptosis via TUNEL assessment, while the expressions of CASP3, CASP8 and CASP9 were determined by immunohistochemistry., Results: A total of 154 active compounds and 58 targets were predicted. DAVID, ClueGO and Metascape enrichment analyses all proved that BSHXF plays an essential role in regulating apoptosis. Moreover, 3 central nodes of BSHXF are recognized as the active factors involved in the main biological functions, suggesting a potential mechanism of BSHXF for KOA treatment. In vivo experiment revealed that BSHXF significantly inhibited apoptosis and down-regulated the expressions of CASP3, CASP8 and CASP9., Conclusion: Based on network pharmacology and experimental validation, our study indicated that BSHXF exerted anti-apoptosis effect through inhibiting the expressions of CASP3, CASP8 and CASP9, which could be considered as an effective method for KOA treatment., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Signaling pathway between human leukocyte antigen (HLA)-G and immune inhibitory receptors immunoglobulin-like transcript (ILT)-2/4 has been acknowledged as one of immune checkpoints, and as a potential target for cancer immunotherapy. Like other immune checkpoints, inter- and even intratumor heterogeneity of HLA-G could render a rather complexity for HLA-G-target immunotherapy. However, little information for intratumor heterogeneity of HLA-G is available. In this study, HLA-G expression in a serial section of colorectal cancer (CRC) lesions from three CRC patients (each sample with serial section of 50 slides, 10 randomized slides for each antibody), three different locations within a same sample (five CRC), and three case-matched blocks that each includes 36 esophageal cancer samples, were evaluated with immunohistochemistry using anti-HLA-G antibodies (mAbs 4H84, MEM-G/1 and MEM-G/2 probing for all denatured HLA-G isoforms, 5A6G7, and 2A12 probing for denatured HLA-G5 and HLA-G6 isoforms). Our results revealed that, in addition to the frequently observed inter-tumor heterogeneity, intratumor heterogeneous expression of HLA-G is common in different areas within a tumor in CRC and esophageal cancer samples included in this study. Moreover, percentage of HLA-G expression probed with different anti-HLA-G antibodies also varies dramatically within a tumor. Given HLA-G has been considered as an important immune checkpoint, intratumor heterogeneity of HLA-G expression, and different specificity of anti-HLA-G antibodies being used among studies, interpretation and clinical significance of HLA-G expression in cancers should be with caution., (Copyright © 2020 Zhang, Lin, Han, Zhang, Chen, Ye, Zhou, Xu, Gan and Yan.)

Background: Non-invasive prenatal testing (NIPT) has been established as a routine prenatal screening to assess the risk of common foetal aneuploidy disorder (trisomy 21, 18, and 13). NIPT has high sensitivity and high specificity, but false positive and false negative results still exist. False negative NIPT results involving Down syndrome are rare, but have a high clinical impact on families and society., Case Presentation: We described a case of a foetus that tested "negative" for trisomy 21 (Z-score was 0.664) by NIPT based on the semiconductor sequencing platform (SSP). The foetal fraction of cell-free DNA was 16.9%; this percentage was much larger than the threshold of 4% for obtaining accurate NIPT results. However, postnatally, the newborn was diagnosed with Down syndrome with the 46,XY,der(21;21)(q10;q10),+ 21 karyotype., Conclusions: We presented a case of false negative NIPT results, which may occur through biological mechanisms rather than poor quality, technical errors or negligence. It is imperative for clinical geneticists and their patients to understand that NIPT is still a screening test.

Human leukocyte antigen (HLA)-G, a non-classical HLA-class I molecule, has a low polymorphism frequency, restricted tissue distribution and immunoinhibitory property. HLA-G expression in tumor cells and cells chronically infected with virus may enable them to escape from host immune surveillance. It is well-known that the HLA-G molecule is a novel biomarker and potential therapeutic target that is relevant in various types of cancers, but its role in cervical cancer has not been fully explored. In this review, we aim to summarize and discuss the immunologic role of the HLA-G molecule in the context of HPV infections and the process of cervical cancer carcinogenesis. A better understanding of the potential impact of HLA-G on the clinical course of persistent HPV infections, cervical epithelial cell transformation, tumor growth, recurrence and metastasis is needed to identify a novel diagnostic/prognostic biomarker for cervical cancer, which is critical for cervical cancer risk screening. In addition, it is also necessary to identify HLA-G-driven immune mechanisms involved in the interactions between host and virus to explore novel immunotherapy strategies that target HLA-G/immunoglobulin-like transcript (ILT) immune checkpoints., (Copyright © 2020 Xu, Yan and Lin.)

It is well recognized that the association of human papillomavirus (HPV) and cervical carcinogenesis is based on the presence of HPV DNA sequence. The E6 and E7 oncoproteins encoded by high-risk HPV types play a key role in carcinogenesis. HPV58 type accounts for a larger share of cervical disease in China, whereas data on HPV58 genetic variability in China is limited. We aimed to evaluate the diversity of HPV58 genetic variants by sequencing the entire E6 and E7 genes. Phylogenetic trees were constructed by Maximum likelihood method by MEGA 5.05 software. In this study, the overall HPV infection rate was 22.6% (2891/12780) in Southeast China and the prevalence of HPV58 infection rate was 2.6% (335/12780). 26 nucleotides substitutions were observed in E6 and E7 genes with 10 novel substitutions and 17 non-synonymous substitutions. We obtained 25 distinct variation patterns which the accession GenBank numbers as MH348918-MH348942. All of HPV58 variants belong to lineage A, while no lineage B, C and D were detected in Taizhou area, Southeast China. The sublineage A1, A2, and A3 variants were found in 136 (68.3%), 39 (19.6%), and 24 (12.1%) of HPV58 isolates, respectively. The sublineage A3 variants with T20I/G63S substitutions at E7 oncoprotein carried a significantly higher risk for high-grade cervical intraepithelial neoplasia (CIN2 or worse, CIN2+) when compared with other HPV58 variants (odds ratio = 4.41, P < 0.05). Nevertheless, there was no association between HPV58 (sub) lineages and cervical lesions. These data provide the critical characteristics of HPV58 variants to assist further investigation of carcinogenic association and the development of next generation vaccines and diagnostic assays in China., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Human leukocyte antigen (HLA)-G is an immune checkpoint molecule, which expression in cervical cancer cells enables them to escape immunosurveillance. To date, limited information has been published on the association of HLA-G genetic background in malignant cells with levels of HLA-G expression and the clinical outcome of patients., Methods: We investigated the influence of the HLA-G 14 bp In/Del (rs66554220) and + 3142 C/G (rs1063320) polymorphisms in 130 cases of HPV16 infection, 130 cases of HPV18 infection and 185 age-matched, unrelated, HPV-negative, and cytologically normal Chinese Han women. Case-matched cervical biopsy tissues were evaluated by immunohistochemistry., Results: Our findings show that the frequency of alleles, 14 bp In (38.5% vs 29.2%, OR = 1.52, P  < 0.05) and + 3142 G (72.7% vs 57.0%, OR = 2.01, P  < 0.05), were significantly increased in the HPV18-infected group compared with the control group. The HLA-G polymorphisms (alleles 14 bp In and + 3142 G ) are also associated with the progression of HPV18-related cervical lesions. Moreover, HLA-G expression increased from CIN1 to CIN2/3 lesions and was highest in patients with adenocarcinoma; however, a significant association between these characteristics and the HLA-G polymorphisms was not observed., Conclusion: Our results support that the HLA-G 14 bp In and + 3142 G alleles are risk factors for HPV18 infections and influence the progression of HPV18-related cervical lesions. This suggests that HLA-G-driven immune mechanisms play an important role in cervical carcinogenesis., Competing Interests: We all agreed to submit our manuscript “Association of HLA-G 3′ UTR polymorphism and expression with the progression of cervical lesions in human papillomavirus 18 infections” to Infectious Agents and Cancer. This manuscript has not been submitted to elsewhere.The authors declare no conflict of interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Human papillomavirus (HPV) type 18 is predominantly associated with the development of cervical adenocarcinomas, whereas data on HPV18 genetic variability in China are limited. HPV18 genetic variants were formed phylogenetic tree, including lineages A, B, and C. We aimed to evaluate the diversity of HPV18 genetic variants by sequencing the entire E6, E7 and L1 genes. Between 2012 and 2015, a total of 138 (0.8%, 138/17669) women with single HPV18 infection were selected in this study. Finally, we observed 122 HPV18 isolates of the complete E6-E7-L1 sequences, and obtained 36 distinct variation patterns which the accession GenBank numbers as KY457805-KY457840. Except KY457805, KY457813, KY457819, KY457827, KY457829, the rest of HPV18 isolates (81.1%, 31/36) are novel variants. All of HPV18 variants belong to lineage A, while no lineage B, and C was found in our population of Taizhou region, Southeast China. Sublineage A1 was the most common variants (85.2%, 104/122), followed by sublineage A4, A3 and A5, while no sublineage A2 was obtained. Based on the tree topologies, there were three newly identified candidates' sublineages A6-A8. Out of 122 women, 67 (54.9%) had diagnosed by biopsy, including 49 women who diagnosed with cervicitis, 12 with cervical intraepithelial neoplasia (CIN)1, 4 with CIN2/3, and 2 with adenocarcinomas, respectively. Nevertheless, there was no association between HPV18 (sub) lineages and CIN1 or worse (CIN1+) lesions comparing with normal biopsies (P = .469). In conclusion, knowledge of the distribution of geographic/ethnical HPV18 genetic diversity provides critical information for developing diagnostic probes, epidemiologic correlate of cervical cancer risk and design of HPV vaccines for targeted populations., (Copyright © 2018. Published by Elsevier B.V.)

High-risk HPV (hrHPV) is related to cervical carcinogenesis, although clinical data comparing the natural history and carcinogenic potential of type-specific HPV remain limited. Furthermore, the nationwide prevalence rates of overall and type-specific HPV among women with cervical precancerous lesions and cancer have not been reported. Here, a meta-analysis was performed for type-specific HPV distribution among 30,165 HPV-positive women, including 12,094 invasive cervical cancers (ICCs), 10,026 cervical intraepithelial neoplasia grade 2/3 (CIN2/3), 3246 CIN1, and 4799 normal cervices from 45 PCR-based studies. We found that HPV16 was the most common hrHPV type involved in cervical disease. The HPV16 positivity rate varied little across normal (22.7%) and CIN1 individuals (23.6%) but increased through the CIN2 (37.6%) and CIN3 patients (51.9%) to 65.6% in ICC cases. HPV16, 18, 35, 39, 45, and 59 were more frequent in ICC than CIN3, with ICC:CIN3 ratios ranging from 2.3 for HPV18 to 1.1 for HPV35/45. HPV31, 33, 52, and 58 were more frequent in CIN3 compared with normal cervices but less common in ICC compared with CIN3 (ICC:CIN3 ratios ranging from 0.6 for HPV58 and 0.4 for HPV52). The ICC:normal ratios were particularly high for HPV18, 52 and 58 in West China (4.1, 3.9 and 2.9, respectively) and for HPV45 and 59 in North China (1.6 and 1.1, respectively). In summary, this study is the most comprehensive analysis of type-specific HPV distribution in cervical carcinogenesis and could be valuable for HPV-based cervical cancer screening strategies and vaccination policies in China., Competing Interests: CONFLICTS OF INTEREST The authors declare that they have no competing interests.

Objectives: High-risk human papillomaviruses (hrHPVs) are highly prevalent worldwide, and HPV genotypes differ between geographical regions; however, sexually transmitted HPV may lead to cervical carcinogenesis. The objective of this cross-sectional study was to estimate the prevalence characteristics of cervical HPV genotypes in Taizhou, Southeast China., Setting and Participants: A population-based sample of 37 967 eligible women (median age: 41.6; range: 15-90 years) visiting the Taizhou ENZE Medical Center in Taizhou (2012-2016) was analysed. HPV genotyping was performed on the collected specimens using a GP5+/bioGP6+-PCR/MPG assay by Luminex 200, which simultaneously identifies 27 different HPV genotypes and the β-globin gene (internal control)., Results: The overall HPV infection rate was 22.8% in the Taizhou-based population, and the prevalence of high-risk HPV, low-risk HPV and mixed high-risk and low-risk HPV infection was 14.2%, 5.7% and 3.0%, respectively. The most prevalent genotypes were HPV52 (19.7%), 16 (11.9%), 58 (11.5%), 39 (7.2%), 18 (6.6%) and 56 (5.6%). The rate of multiple-type HPV infection was 5.7% in the whole population, and the HPV52+58, HPV16+52 and HPV16+18 mixed genotypes were most common in women with multiple infections. The age-specific HPV prevalence showed a bimodal curve, with a first peak below the age of 21 years (41.6%), followed by a second peak in the age group of 56-60 years (28.5%). Moreover, the HPV infection rate differed significantly between the outpatient and physical examination groups (24.0% vs 19.5%, p < 0.0001). Further data comparisons showed that the distribution of HPV genotypes varied markedly between the two groups., Conclusions: Data from this study could be valuable for HPV-based cervical cancer screening efforts in certain areas, support the local vaccination programme in the Taizhou region and facilitate future diagnosis and treatment of HPV diseases., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Strong evidence implicates maternal phthalate exposure during pregnancy in contributing to adverse birth outcomes. Recent research suggests these effects might be mediated through the improper regulation of DNA methylation in offspring tissue. In this study, we examined associations between prenatal phthalate exposure and DNA methylation in human placenta. We recruited 181 mother-newborn pairs (80 fetal growth restriction newborns, 101 normal newborns) in Wenzhou, China and measured third trimester urinary phthalate metabolite concentrations and placental DNA methylation levels of IGF2 and AHRR. We found urinary concentrations of mono (2-ethyl-5- hydroxyhexyl) phthalate (MEHHP), and mono (2-ethyl-5-oxohexyl) phthalate (MEOHP) were significantly inversely associated with placental IGF2 DNA methylation. The associations were much more evident in fetal growth restriction (FGR) newborns than those in normal newborns. These findings suggest that changes in placental DNA methylation might be part of the underlying biological pathway between prenatal phthalate exposure and adverse fetal growth.

The various characteristics of DOM have great impact on the transformation process of contaminants in soil due to the generation of the feedback regulation in cycles of plant, Rhizosphere soil and environmental contaminants. Currently, more attention was paid on contaminants behaviors of adsorption, transformation, accumulation and detoxification than DOM derived from Rhizosphere soil. The chemical speciation of lead/cadmium and growth efficiency related variations were revealed in the growth process of Calendula officinalis seedlings, and the spectral characteristics of DOM in Rhizosphere loess were discussed with UV, FT-IR and 3D-EEMs spectra. The results showed: the dominant contents of lead/cadmium are in residual and exchangeable speciation, and the exchangeable contents increase greatly after the growth of Calendula officinalis seedlings. It causes negative effects on the height and emergency rate of Calendula officinalis seedlings with lead/cadmium, and the Calendula officinalis is able to positively improve loess characteristics. The root of Calendula officinalis appears to be longer, thinner and flexuous. The maximum absorption band of DOM in UV spectra locates in 200~240 nm, and the sharper and greater intensity of peaks can be detected under lead/cadmium stress. The absorption peaks in FT-IR spectra move from 3 444 and 1 637 to 3 440 and 1 645 cm-1, respectively, indicating the combination effects between metal ions and functional groups of—OH and CO. The dominant fluorescence peaks of DOM are found to be aroundλex/em=240/430, described as fulvic-acid like components, and metals in loess affect more on peaks intensity than locations. The characteristics of DOM in Rhizosphere loess of Calendula officinalis seedlings contain much micro-eco-environmental information, and the spectral approaches are efficient to reveal the relationship between DOM and chemical speciation of lead/cadmium.

Nemo-like kinase (NLK), as a mitogen activated protein kinase (MAPK)-like kinase, is involved in the development of several human cancers. In this study, we explored the expression of NLK in lung squamous cell carcinoma (SCC) and adenocarcinoma tissues, and investigated the associations among NLK, β-catenin, T-cell factor 4 (TCF4), and the clinicopathological factors of lung cancers. The expressions of NLK, β-catenin, TCF4 were examined in 109 cases of lung cancers using immunohistochemistry method. The expression of NLK was observed in the nuclei of lung cancer tissues, and was significantly higher in lung cancer tissues than that in corresponding normal lung tissues (t = 21.636, n = 109, P < 0.001). The high expression of NLK was found in 45 cases of lung SCCs (45/49, 91.84%), which was much more than that in adenocarcinomas (38/60, 63.33%) (P = 0.001). Furthermore, the high expression of NLK was negatively correlated with TCF4 expression and positively correlated with the membranous expression of β-catenin. In conclusion, the present study demonstrated that the expression of NLK was localized in nucleus and significantly increased in lung cancers. The expression of NLK was negatively correlated with TCF4 expression and positively correlated with β-catenin membranous expression in lung cancers.

As the central protein of the double strand breaks (DSB)-induced DNA repair pathway, NBS1 participates in detecting the DSBs and plays an essential role in maintaining genomic stability. Single nucleotide polymorphisms (SNPs) in NBS1 gene were commonly tested that associated with the susceptibility to multiple cancers, but the results remained controversial. Thus, we conducted two independent hospital-based case-control studies comprising 1,072 colorectal cancer patients and 1,263 controls to evaluate the association between four NBS1 SNPs and colorectal cancer risk. The result showed that rs2735383C/G polymorphism in the 3'-untranslated region (UTR) of NBS1 was significantly associated with risk of colorectal cancer using logistic regression (P<10(-4)). Furthermore, we observed that rs2735383CC genotype was associated with substantially increased risk of colorectal cancer (odds ratio=1.55, 95% confidence interval=1.27-1.94), compared with the rs2735383GC+GG genotypes. Further functional experiments demonstrated that the rs2735383C allele in the NBS1 disrupted the binding affinity of has-miR-509-5p to the NBS1 3'-UTR in colorectal cancer cells, affecting the NBS1 transcriptional activity and expression level. In conclusion, current evidence suggests that the rs2735383C/G polymorphism might contribute to the risk for colorectal cancer.

Objective: To investigate the associations between epidermal growth factor receptor (EGFR) gene mutations and serum tumor markers in advanced lung adenocarcinomas., Methods: We investigated the association between EGFR gene mutations and clinical features, including serum tumor marker levels, in 97 advanced lung adenocarcinomas patients who did not undergo the treatment of EGFR tyrosine kinase inhibitors. EGFR gene mutation was detected by real-time PCR at exons 18, 19, 20, and 21. Serum tumor marker concentrations were analyzed by chemiluminescence assay kit at the same time., Results: EGFR gene mutations were detected in 42 (43%) advanced lung adenocarcinoma patients. Gender (P=0.003), smoking status (P=0.001), and abnormal serum status of carcinoembryonic antigen (CEA, P=0.028) were significantly associated with EGFR gene mutation incidence. Multivariate analysis showed the abnormal CEA level in serum was independently associated with the incidence of EGFR gene mutation (P=0.046) with an odds ratio of 2.613 (95% CI: 1.018-6.710). However, receiver operating characteristic (ROC) curve analysis revealed CEA was not an ideal predictive marker for EGFR gene mutation status in advanced lung adenocarcinoma (the area under the ROC curve was 0.608, P=0.069)., Conclusions: EGFR gene mutation status is significantly associated with serum CEA status in advanced lung adenocarcinmoas. However, serum CEA is not an ideal predictor for EGFR mutation.

Previous study showed that aberrant HLA-G expression in cancer cells plays important roles in disease progression and it was associated with tumor metastasis and with poor survival in an animal model with ovarian cancer; however, the mechanisms remain to be explored. In this study, we found that HLA-G expression could dramatically decreased the NK cytotoxicity against the ovarian carcinoma cell line (HO-8910) engineered to express HLA-G (HO-8910-G), and matrix metalloproteinase-15 (MMP-15) expression was up-regulated in HO-8910-G cells. Consistent with this, a strong correlation between HLA-G and MMP-15 expression were observed in a cohort of ovarian cancer samples. Knockdown the HLA-G induced MMP-15 expression by small interfere RNA (siRNA) significantly decreased the HO-8910-G cell migration potential and tumor metastasis. Collectively, our study indicated that HLA-G involved in tumor invasiveness or metastasis may rely on the NK cytotoxicity inhibition and induction of MMP-15 expression in ovarian cancer., (Copyright © 2012 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.)

Aberrant HLA-G expression is associated with tumor invasiveness and poor clinical prognosis; however, there is a lack of preclinical animal model to address whether HLA-G plays a causal role in the unfavorable prognosis of malignancies. In the current study, ovarian carcinoma cell lines (HO-8910 and Ovcar-3) were transfected with HLA-G gene. HLA-G expression was analyzed with western blot and flow cytometry. Transwell experiment was performed to analyze the cell migration and invasion capability and/or multicellular spheroid formation was investigated with the 3D culture assay in vitro. The effects of HLA-G expression for tumor cell organ metastasis and for mouse survival was analyzed with the Balb/c nu/nu mouse model. Our data showed that HO-8910-G and Ovcar-3-G cells are of higher invasion potential compared with the parental HO-8910 and Ovcar-3 cells. Multicellular spheroid formation exists only in HO-8910-G cells in a 3D culture assay. In Balb/c nu/nu mouse model, widespread metastasis was observed in mice xenografted with HO-8910-G cells, but not in the group with parental cells. Mouse survival was dramatically decreased in HO-8910-G and Ovcar-3-G xenografted mice than that with HO-8910 and Ovcar-3 cells, respectively. In summary, our study provided the first evidence that HLA-G expression is associated with tumor metastasis and with poor survival in an animal model with ovarian cancer., (Copyright © 2011 UICC.)

Amniotic fluid cells (AFCs) are routinely obtained and expanded in vitro for prenatal diagnosis; nevertheless current knowledge about their properties is limited. The detailed mechanisms underlying normal pregnancies are yet to be discovered. The goal of this study was to identify the immunological aspects of AFCs including cytokine production and human leukocyte antigen (HLA) expression, and to discuss its implication for pregnancy. Eighty-six samples of AFCs were determined for HLA expression before and after culture. Cytokine production was measured with flow cytometry in AFC culture supernatants. Treatment of interferon (IFN)-gamma on induction of HLA-DR expression in cultured AFCs was also investigated. Data indicated that both fresh and cultured AFCs express HLA-I, HLA-G, but not HLA-DR, and the cultured AFCs predominately produce the cytokine interleukin (IL)-6. Importantly, we observed that IFN-gamma could induce HLA-DR expression on cultured AFCs in a dose-dependent manner. Taken together, our results indicated that AFCs are functionally active cells and are significant in pregnancy.