Search

Unmanned aerial vehicles (UAVs) and light detection and ranging (LiDAR) can be used to analyze the geomorphic features in complex plateau mountains. Accordingly, a UAV–LiDAR system was adopted in this study to acquire images and lidar point-cloud dataset in the annular structure of Lufeng, Yunnan. A three-dimensional (3D) model was constructed based on structure from motion and multi-view stereo (SfM–MVS) in combination with a high-resolution digital elevation model (DEM). Geomorphic identification, measurement, and analysis were conducted using integrated visual interpretation, DEM visualization, and geographic information system (GIS) topographic feature extraction. The results indicated that the 3D geomorphological visualization and mapping were based on DEM, which was employed to identify the dividing lines and ridges that were delineated of the pit rim structure. The high-resolution DEM retained more geomorphic detail information, and the topography and the variation between ridges were analyzed in depth. The catchment and ponding areas were analyzed using accurate morphological parameters through a multi-angle 3D visualization. The slope, aspect, and topographic wetness index (TWI) parameters were analyzed through mathematical statistics to qualitatively and accurately analyze the differences between different ridges. This study highlighted the significance of the UAV–LiDAR high-resolution topographic measurements and the SfM–MVS 3D scene modelling in accurately identifying geomorphological features and conducting refined analysis. An effective framework was established to acquire high-precision topographic datasets and to analyze geomorphological features in complex mountain areas, which was beneficial in deepening the research on numerical simulation analysis of geomorphological features and reveal the process evolution mechanism. [ABSTRACT FROM AUTHOR]

To solve the problems of voltage violation and fast voltage fluctuation caused by photovoltaic (PV) grid connections in distribution networks, a two‐stage coordinated voltage control strategy for PV inverters with multimode coordinated operation in distribution networks (DNs) is proposed. It is based on the characteristics of PV inverters that can be regulated rapidly and continuously. First, the voltage control process is divided into two control stages according to the voltage change rate, and the corresponding voltage control models are established. Then, the operating modes of PV inverters are classified into three modes: economic prevention, economic control, and efficient control. Different operating modes are used to adapt to the two‐stage voltage control. Finally, a voltage fast control solution algorithm is proposed, which considers adaptive time delays and combines local measurement, prediction, and communication information to update control commands. The effectiveness and feasibility of the proposed voltage control strategy were demonstrated through simulation tests on a real 10‐kV line with a high PV penetration rate in the Anhui province of China. The results show that the proposed strategy can prevent voltage violation and sudden changes and can smooth out voltage fluctuation. [ABSTRACT FROM AUTHOR]

This study aimed to translate the Perspectives on Caring for Older Patients scale into Chinese, both the full and the shortened versions, and test its psychometric properties among Chinese nursing students. In this methodological research, the scale were translated and administered to 307 nursing students recruited from two universities in mainland China. The psychometric testing mainly included internal consistency reliability using Cronbachʼs alphas, 2‐week test–retest reliability using the intraclass correlation coefficient, convergent validity with Koganʼs Attitude toward Older People scale, and factorial validity using exploratory factor analysis. Cronbachʼs alphas for the full and the shortened version scales were 0.77 and 0.75, respectively. The intraclass correlation coefficient values of both versions exceeded 0.70 and their scores were moderately correlated with the Koganʼs Attitude toward Older People scaleʼs scores. While exploratory factor analyses revealed a six‐factor structure for the full version with factor loadings of five items below 0.3, the shortened version identified two factors with all factor loadings above 0.3. This study concluded that the psychometric properties of the full version scale were adequate and similar to those of the shortened version except for factorial validity. [ABSTRACT FROM AUTHOR]

As inherited genetic alterations are important etiological factors causing endometrial cancer (EC), our study aimed to outline the ethnic‐related prevalence and the associated clinical and biological characteristics of germline mutations in cancer predisposition genes in Chinese EC patients. One hundred ninety‐eight Chinese EC patients were screened for germline mutations in a panel of cancer susceptibility genes using next‐generation sequencing combined with multiplex ligation‐dependent probe amplification. First, we found that among patients under 50 years of age, 26% (18/69) carried germline genetic mutations, all involving mismatch repair (MMR) genes except for one mutation affecting BRCA1. Second, when we focused on Lynch syndrome (LS) with additional selected patients, 45 were identified to carry pathogenic mutations in MMR genes, with a higher frequency found in MSH2 and MSH6. We found that age at onset, personal and familial history together with immunohistochemical assay results were the most useful criteria for the diagnosis of LS although limitations in routine practice and the sensitivity and specificity of each parameter should be taken into account. One pathogenic mutation in the PALB2 gene was detected in a patient with no breast cancer in her family. Interestingly, we identified a family carrying pathogenic variant in both PMS2 and BRCA1 genes with distinct clinical phenotypes. Multigene panel testing should be recommended to patients based on their clinical information and tumor phenotype. Our study also showed the genetic complexity in EC, which requires further investigations. What's new? Endometrial cancer incidence is increasing in China, presumably owing in part to greater exposure to environmental risk factors such as obesity and hormone therapy. The degree to which hereditary factors influence endometrial cancer burden in Asian populations remains uncertain. Here, screening for germline mutations shows that more than one‐fourth of young Asian endometrial cancer patients carry variants in cancer predisposition genes, primarily mismatch repair (MMR) genes. Most variants affected MMR genes associated with Lynch syndrome. Multigene panel testing further led to the identification of rare mutations in patients with no apparent family history, highlighting a clinical need for mutational screening. [ABSTRACT FROM AUTHOR]

Triptolide (TPL) is an active extract from a Chinese herb, which has been used for centuries in China. TPL exhibits numerous bioactivities and pharmacological effects, including antitumor, anti-inflammatory and immunosuppressive activities. However, previous studies have further revealed a multi-target toxicity of TPL, including reproductive toxicity, hepatotoxicity and renal cytotoxicity. To validate the clinical benefit and reduce the risk of TPL application, studies have investigated the combination of TPL with other reagents to allow lower doses and decrease toxicity. The present study reported that TPL and the insulin-like growth factor-1 receptor (IGF1R) inhibitor AG1024synergistically inhibited cell proliferation and induced apoptosis in triple-negative breast cancer cells. Overexpression of B-cell lymphoma 2 partially reversed the TPL and AG1024-induced increase in apoptosis. A similar synergistic effect was observed with a combination of AG1024 and cisplatin, a DNA damage inducer, in MDA-MB-231 cells. These results suggested that inhibition of IGF1R may sensitize triple-negative breast cancer cells to DNA damage inducers. Using publicly available data from The Cancer Genome Atlas, an amplification and gain of copy number of IGF1R was observed in 38% of triple-negative breast tumors (n=82), 26% of estrogen receptor (ER)-negative tumors (n=174) and 10% of ER-positive tumors (n=594). Similarly, a higher alteration frequency of IGF1R was identified in basal-like breast tumors compared with luminal A/B-like breast tumors. Overexpressed proteins associated with these alterations were revealed to be significantly enriched in multiple oncogenic signaling pathways, key transcription factor networks and DNA repair pathways. In summary, the present study suggested that inhibition of IGFR signaling and induction of DNA damage may exhibit synergistic effects for the treatment of triple-negative and ER-negative breast cancer. [ABSTRACT FROM AUTHOR]

Spirotetramat were now widely used for control insecticides resistant aphids since 2011 in China. In order to elucidate the possible resistance mechanism, a laboratory selected resistant strain (SR) of cotton aphid was established with a 578.93-fold and 14.91-fold resistance ratio to spirotetramat for adult aphids and nymph, respectively, as compared with the susceptible strain (SS). In this study, a comparative proteomic analysis between SR and SS strains were conducted aims to better understand the resistant cotton aphids' spirotetramat tolerance mechanism. Approximately 493 protein spots were detected in the two-dimension polyacrylamide gel electrophoresis (2-DE). The intensities of 35 protein spots significantly changed, showing differences more than 2-fold in the SR strain compared with that in the SS strain. Of these spots, 20 protein spots were more abundant in the SR strain and 15 protein spots were more abundant in the SS strain. Twenty six differently expressed proteins were identified and categorized into several functional groups including carbohydrate and energy metabolism, antioxidant system, protein folding, amino acid metabolism, secondary metabolism and cytoskeleton protein, etc. Among these proteins, the acetyl-coA carboxylase (ACC), heat shock protein 70, ubiquitin-conjugating enzyme, fatty acid synthase, UDP-glucose 6-dehydrogenase, etc. are speculated confer the spirotetramat resistance in cotton aphids. [ABSTRACT FROM AUTHOR]

Purpose: Genetic variants of ovarian cancer (OV) show ethnic differences, but data from the Chinese population are still insufficient. Here, we elucidate the inheritance landscape in Chinese patients with OV and examine the functional implications of a Chinese-enriched RAD51D variant., Methods: Between 2015 and 2018, 373 consecutive patients with OV were prospectively enrolled. Variants of BRCA1/2 , other homologous recombination repair (HRR) genes, and DNA mismatch repair (MMR) genes were analyzed using next-generation sequencing. An enriched RAD51D variant was identified, and its functional effects were examined using Cell Counting Kit-8, colony formation, transwell migration, and drug sensitivity assays., Results: Overall, 31.1% (116/373) of patients had at least one pathogenic or likely pathogenic germline variant. BRCA1 and BRCA2 accounted for 16.09% and 5.36%, respectively, with one patient having both variants. In addition, 32 (8.58%) patients carried other HRR gene variants, whereas three (0.8%) patients had MMR gene variants. The RAD51D variant ranked third (8/373, 2.1%), and its rate was much higher than that in other populations. Remarkably, all eight patients harbored the RAD51D K91fs variant (c.270_271dup, p.Lys91Ilefs*13) and demonstrated satisfactory platinum response and favorable prognosis. This variant confers enhanced sensitivity to poly (ADP-ribose) polymerase inhibitors in OV cells. However, the effects on platinum sensitivity were inconsistent across different cell lines. Against the background of the TP53 variant, RAD51D K91fs variant showed increased sensitivity to cisplatin., Conclusion: Our study revealed the inheritance landscape of OV and identified an enriched RAD51D variant in Chinese patients with OV. This can serve as an important reference for OV management and a potential therapeutic target.

Background: Diffuse large B-cell lymphoma (DLBCL), an aggressive and heterogenic malignant entity, is still a challenging clinical problem, since around one-third of patients are not cured with primary treatment. Next-generation sequencing (NGS) technologies have revealed common genetic mutations in DLBCL. We devised an NGS multi-gene panel to discover genetic features of Chinese nodal DLBCL patients and provide reference information for panel-based NGS detection in clinical laboratories., Methods: A panel of 116 DLBCL genes was designed based on the literature and related databases. We analyzed 96 Chinese nodal DLBCL biopsy specimens through targeted sequencing., Results: The most frequently mutated genes were KMT2D (30%), PIM1 (26%), SOCS1 (24%), MYD88 (21%), BTG1 (20%), HIST1H1E (18%), CD79B (18%), SPEN (17%), and KMT2C (16%). SPEN (17%) and DDX3X (6%) mutations were highly prevalent in our study than in Western studies. Thirty-three patients (34%) were assigned as genetic classification by the LymphGen algorithm, including 12 cases MCD, five BN2, seven EZB, seven ST2, and two EZB/ST2 complex. MYD88 L265P mutation, TP53 and BCL2 pathogenic mutations were unfavorable prognostic biomarkers in DLBCL., Conclusions: This study presents the mutation landscape in Chinese nodal DLBCL, highlights the genetic heterogeneity of DLBCL and shows the role of panel-based NGS to prediction of prognosis and potential molecular targeted therapy in DLBCL. More precise genetic classification needs further investigations., (© 2024. The Author(s).)

We developed a deep learning framework to accurately predict the lymph node status of patients with cervical cancer based on hematoxylin and eosin-stained pathological sections of the primary tumor. In total, 1524 hematoxylin and eosin-stained whole slide images (WSIs) of primary cervical tumors from 564 patients were used in this retrospective, proof-of-concept study. Primary tumor sections (1161 WSIs) were obtained from 405 patients who underwent radical cervical cancer surgery at the Fudan University Shanghai Cancer Center (FUSCC) between 2008 and 2014; 165 and 240 patients were negative and positive for lymph node metastasis, respectively (including 166 with positive pelvic lymph nodes alone and 74 with positive pelvic and para-aortic lymph nodes). We constructed and trained a multi-instance deep convolutional neural network based on a multiscale attention mechanism, in which an internal independent test set (100 patients, 228 WSIs) from the FUSCC cohort and an external independent test set (159 patients, 363 WSIs) from the Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma cohort of the Cancer Genome Atlas program database were used to evaluate the predictive performance of the network. In predicting the occurrence of lymph node metastasis, our network achieved areas under the receiver operating characteristic curve of 0.87 in the cross-validation set, 0.84 in the internal independent test set of the FUSCC cohort, and 0.75 in the external test set of the Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma cohort of the Cancer Genome Atlas program. For patients with positive pelvic lymph node metastases, we retrained the network to predict whether they also had para-aortic lymph node metastases. Our network achieved areas under the receiver operating characteristic curve of 0.91 in the cross-validation set and 0.88 in the test set of the FUSCC cohort. Deep learning analysis based on pathological images of primary foci is very likely to provide new ideas for preoperatively assessing cervical cancer lymph node status; its true value must be validated with cervical biopsy specimens and large multicenter datasets., (Copyright © 2023 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.)

Clear cell carcinoma (CCC) of the abdominal wall is a rare and agressive disease. We aim to elucidate the clinical and prognostic characteristics of this disease. Medical records of ten patients diagnosed with CCC of the abdominal wall at Fudan University Shanghai Cancer Center were reviewed. We illustrate the clinical characteristics, treatment modality, and development of local recurrence or distant metastasis, as well as the survival outcome. The median (range) age of patients was 47 (39-61) years old. All patients had a history of cesarean section and abdominal wall endometriosis. All patients had primary surgery before referred to our center. Seven patients had only tumor resection, while two patients had lymph node metastasis at primary diagnosis. Four patients underwent supplementary surgery, and all postoperative pathology were negative. Genetic analyses had also been performed. The median (range) follow-up time was 20 (12-59) months. Local recurrence and lymph node metastasis were the most common recurrence types. The median (95% confidence interval) PFS was 11 (8.08-13.92) months. In summary, primary surgery should consider wide tumor resection and lymph node dissection. Adjuvant chemotherapy and radiotherapy should be recommended for potential benefits. More cases are still needed to elucidate the clinical management of this disease., (© 2022. The Author(s).)

Background: Mitochondrial DNA (mtDNA) pathogenic variants have been identified to be associated with maternally inherited essential hypertension (MIEH). However, the distinctive clinical features and molecular pathogenesis of MIEH are not fully understood., Methods: In this study, we collected a Chinese MIEH family with extraordinary higher penetrance of essential hypertension (88.89%) and early ages of onset (31-40 years old), and performed clinical and genetic characterization for this family. The complete mitochondrial genome of the proband was sequenced and analyzed., Results: The maternally related members in this family were presented with severe increased blood pressure, left ventricular remodeling, and metabolic abnormalities. Through sequencing the entire mtDNA of the proband and performing systematic analysis of the mtDNA variants with a phylogenic approach, we identified a potentially pathogenic tRNA variant (m.15992A>G in the MT-TP gene) that may account for the MIEH in this family. One nonsynonymous variant (m.15077G>A in the MT-CYB gene) was identified to play a synergistic role with m.15992A>G to cause a high penetrance of MIEH., Conclusions: Our results, together with previous findings, have indicated that tRNA pathogenic variants in the mtDNA could act important roles in the pathogenesis of MIEH through reducing mitochondrial translation and disturbing mitochondrial function., (© American Journal of Hypertension, Ltd 2021. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Previous genotyping-based assays have identified non-coding variants of several interleukins (ILs) being associated with genetic susceptibility to leprosy. However, understanding of the involvement of coding variants within all IL family genes in leprosy was still limited. To obtain the full mutation spectrum of all ILs in leprosy, we performed a targeted deep sequencing of coding regions of 58 ILs genes in 798 leprosy patients (age 56.2 ± 14.4; female 31.5%) and 990 healthy controls (age 38.1 ± 14.0; female 44.3%) from Yunnan, Southwest China. mRNA expression alterations of ILs in leprosy skin lesions or in response to M. leprae treatment were estimated by using publicly available expression datasets. Two coding variants in IL27 (rs17855750, p.S59A, p = 4.02 × 10 -8 , odds ratio [OR] = 1.748) and IL1RN (rs45507693, p.A106T, p = 1.45 × 10 -5 , OR = 3.629) were significantly associated with leprosy risk. mRNA levels of IL27 and IL1RN were upregulated in whole blood cells after M. leprae stimulation. These data showed that IL27 and IL1RN are leprosy risk genes. Further functional study is required for characterizing the exact role of ILs in leprosy., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Since 2010, the Chinese have become one of the most aged populations in the world, leading to a severe burden of neurodegenerative disorders. Alzheimer's disease (AD) is the most prevalent neurodegenerative disease and has a high genetic heritability. In the past two decades, numerous genetic analyses, from linkage analyses and candidate gene studies to genome-wide association studies (GWASs) and next-generation sequencing studies, have identified dozens of AD susceptibility or causal genes. These studies have provided a comprehensive genetic view and contributed to the understanding of the pathological and molecular mechanisms of the disease. However, most of the recognized AD genetic risk factors have been reported in studies based on European populations or populations of European ancestry, and data about the genetics of AD from other populations has been very limited. As China has the largest AD population in the world and because of the remarkable genetic differences between the East and the West, deciphering the genetic basis and molecular mechanism in Chinese patients with AD may add key points to the full characterization of AD. In this review, we present an overview of the current state of AD genetic research in China, with an emphasis on genome-level studies. We also describe the challenges and opportunities for future advances, especially for in-depth collaborations, brain bank construction, and primate animal modeling. There is an urgent need to promote public awareness and increase our collaborations and data sharing.

Alzheimer's disease (AD) is the most common form of dementia. The deposition of β-amyloid (Aβ) plaques in the brain was considered one of the main neuropathological hallmarks of AD. As the loss of synapses always occurs during AD progression, AD has been gradually regarded as a "synaptopathy." The activity-regulated cytoskeleton-associated protein (Arc) was recently identified as a key factor for AD due to its active roles in synaptic plasticity, learning, memory, and Aβ generation. However, there is little evidence to support the association of the Arc gene with AD. In this study, a two-stage case-control study of 1471 Han Chinese was conducted to investigate the genetic association between the Arc gene and AD. Variant rs10097505 in the 3'UTR region was significantly associated with AD. The whole exons of the Arc gene were also screened in 99 AD patients with a high heritability (familial and/or onset age <55 years old). One missense variant (c.20G>A, p.T7I) was identified in two AD patients but was absent in the controls from the general populations. Both rs10097505 and c.20G>A were predicted to be potentially pathogenic. Further luciferase assay, data mining, and integrative analyses revealed that the AD-risk genotype AA of rs10097505 was associated with an increased Arc mRNA expression and an elevated Aβ level. Our results indicated that the Arc gene would confer susceptibility to AD in Han Chinese, probably through changing the protein structure or affecting the Arc expression in brain tissues, which would finally contribute to the pathogenesis and development of AD.

Background: The pathogen Mycobacterium leprae of leprosy is heavily dependent on the host energy metabolites and nutritional products for survival. Previously we and others have identified associations of several mitochondrion-related genes and mitochondrial DNA (mtDNA) copy number alterations with leprosy and/or its subtype. We hypothesized that genetic variants of mtDNA replication-related genes would affect leprosy., Objective: We aimed to identify genetic associations between the mtDNA replication-related genes TFAM, POLG and leprosy., Methods: Genetic association study was performed in 2898 individuals from two independent sample sets in Yunnan Province, China. We first screened 7 tag SNPs of TFAM and POLG in 527 leprosy cases and 583 controls (Sample I). Expression quantitative trait loci (eQTL) analysis and differential mRNA expression were analyzed to discern potential effect of risk variants. The entire exon region of TFAM and POLG were further analyzed in 798 leprosy cases and 990 controls (Sample II; 4327 East Asians from the ExAC dataset was included as a reference control) by using targeted gene sequencing for fine mapping potentially causal variants., Results: Two tag SNPs of TFAM (rs1049432, P=0.007) and POLG (rs3176238, P=0.006) were associated with multibacillary leprosy (MB) in Sample I and the significance survived correction for multiple comparisons. SNPs rs1937 of TFAM (which was linked with rs1049432) and rs61756401 of POLG were associated with leprosy, whereas no potentially causative coding variants were identified in Sample II. The eQTL analysis showed that rs1049432 was a significant cis eQTL for TFAM in nerve tissue (P=1.20×10 -12 ), and rs3176238 was a significant cis eQTL for POLG in nerve (P=3.90×10 -13 ) and skin tissues (P=2.50×10 -11 ). Consistently, mRNA level of POLG was differentially expressed in leprotic skin lesions., Conclusions: Genetic variants of TFAM and POLG were associated with leprosy in Han Chinese, presumably by affecting gene expression., (Copyright © 2017 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.)

Essential hypertension (EH) is a common complex disorder with high heritability. Maternal inherited pattern was observed in some families with EH, which was known as maternally inherited essential hypertension (MIEH). Mitochondrial DNA (mtDNA) mutations were identified to account for some MIEH in previous studies. In the present study, we characterized clinical manifestations and the complete mitochondrial genome of a Chinese family with MIEH. Through analyzing the whole mtDNA genome of the proband, we identified a mutation m.5512A > G in the MT-TW gene that changed a highly conserved nucleotide and could potentially affect the function of tRNA Trp . Furthermore, significantly exercise intolerance, left ventricular remodeling and increased arterial stiffness were observed in carriers with mutation m.5512A > G, which further supported the potentially pathogenic effect of m.5512A > G in MIEH., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The aim of this study was to examine the reliability and validity of the Chinese version of the Daily Living Self-Efficacy Scale (DLSES) in stroke patients. In total, 172 participants were recruited from a local hospital in China. The internal consistent reliability and convergent validity of the total scale and activities of daily living (ADL) and psychosocial functioning subscales were examined and factor analysis was carried out. Cronbach's αs for the Chinese version of the DLSES, ADL subscale, and psychosocial subscale were 0.96, 0.90, and 0.95, respectively. In the factor analysis, two factors (ADL and psychosocial functioning) were extracted, explaining 84.4% of the total variance in self-efficacy (χ/d.f.=2.19, root mean square error of approximation=0.08, normed fit index=0.95, comparative fit index=0.98, incremental fit index=0.98). Convergent validity was confirmed by positive relationships between the Chinese version of the DLSES and the Modified Fall Efficacy Scale (r=0.87). The ADL subscale was associated positively with the Barthel Index (r=0.74) and the psychosocial functioning subscale was associated negatively with the Functional Activities Questionnaire (r=-0.73) and Center for Epidemiologic Studies Depression Scale (r=-0.44). The Chinese version of the DLSES was shown to be a reliable and valid measure of self-efficacy in stroke patients.

Drug addiction is one of the most serious social problems in the world today and addicts are always at a high risk of acquiring HIV infection. Mitochondrial impairment has been reported in both drug addicts and in HIV patients undergoing treatment. In this study, we aimed to investigate whether mitochondrial DNA (mtDNA) haplogroup could affect the risk of drug addiction and HIV-1 infection in Chinese. We analyzed mtDNA sequence variations of 577 Chinese intravenous drug addicts (289 with HIV-1 infection and 288 without) and compared with 2 control populations (n = 362 and n = 850). We quantified the viral load in HIV-1-infected patients with and without haplogroup A status and investigated the potential effect of haplogroup A defining variants m.4824A > G and m.8794C > T on the cellular reactive oxygen species (ROS) levels by using an allotopic expression assay. mtDNA haplogroup A had a protective effect against drug addiction but appeared to confer an increased risk of HIV infection in addicts. HIV-1-infected addicts with haplogroup A had a trend for a higher viral load, although the mean viral load was similar between carriers of haplogroup A and those with other haplogroup. Hela cells overexpressing allele m.8794 T showed significantly decreased ROS levels as compared to cells with the allele m.8794C (P = 0.03). Our results suggested that mtDNA haplogroup A might protect against drug addiction but increase the risk of HIV-1 infection. The contradictory role of haplogroup A might be caused by an alteration in mitochondrial function due to a particular mtDNA ancestral variant.

The immune response is highly active in Alzheimer's disease (AD). Identification of genetic risk contributed by immune genes to AD may provide essential insight for the prognosis, diagnosis, and treatment of this neurodegenerative disease. In this study, we performed a genetic screening for AD-related top immune genes identified in Europeans in a Chinese cohort, followed by a multiple-stage study focusing on Complement Factor H (CFH) gene. Effects of the risk SNPs on AD-related neuroimaging endophenotypes were evaluated through magnetic resonance imaging scan, and the effects on AD cerebrospinal fluid biomarkers (CSF) and CFH expression changes were measured in aged and AD brain tissues and AD cellular models. Our results showed that the AD-associated top immune genes reported in Europeans (CR1, CD33, CLU, and TREML2) have weak effects in Chinese, whereas CFH showed strong effects. In particular, rs1061170 (P(meta)=5.0 × 10(-4)) and rs800292 (P(meta)=1.3 × 10(-5)) showed robust associations with AD, which were confirmed in multiple world-wide sample sets (4317 cases and 16 795 controls). Rs1061170 (P=2.5 × 10(-3)) and rs800292 (P=4.7 × 10(-4)) risk-allele carriers have an increased entorhinal thickness in their young age and a higher atrophy rate as the disease progresses. Rs800292 risk-allele carriers have higher CSF tau and Aβ levels and severe cognitive decline. CFH expression level, which was affected by the risk-alleles, was increased in AD brains and cellular models. These comprehensive analyses suggested that CFH is an important immune factor in AD and affects multiple pathological changes in early life and during disease progress.

Background: Ovarian clear cell carcinoma (CCC) is an uncommon subtype of ovarian epithelial tumor. The prognostic significance of its clinicopathological parameters is discordant, with the exception of stage as the adverse prognostic factor. The present study aimed to evaluate the prognostic significance of its clinicopathological characteristics and the expression of IMP3 (Insulin-like growth factor-II mRNA-binding protein 3, IMP3 or IGF2BP3) in Chinese patients with primary pure CCC., Methods: We collected clinicopathological data from 73 cases with a minimum of 5 years of follow-up and evaluated the expression of IMP3 by immunohistochemistry., Results: In total, 49.3 % of the patients were in stage I. Advanced stages were closely related to poor prognosis of disease-free survival (DFS) and overall survival (OS) (P < 0.005). Patients with CCC coexisting with endometriosis tended to be younger and to have unilateral involvement but did not exhibit differences in prognosis compared with patients with CCC without endometriosis. Other histological features such as growth pattern, mitosis, and necrosis did not have prognostic significance. IMP3 was positive in 63 % of patients (46 of 73 cases); Thus, positive expression of IMP3 is an adverse prognostic marker in terms of OS (P = 0.012), even in stage I patients (P = 0.038)., Conclusions: The present study demonstrates that IMP3 expression is a prognostic marker, with the exception of stage. IMP3 represents a biomarker of unfavorable prognosis even in stage I patients.

In recent years, genome-wide association studies (GWASs) have identified many novel susceptible genes/loci for Alzheimer's disease (AD). However, most of these studies were conducted in European and populations of European origin, and limited studies have been performed in Han Chinese. In this study, we genotyped 14 single-nucleotide polymorphisms (SNPs) in eight GWAS-reported AD risk genes in 1509 individuals comprising two independent Han Chinese case-control cohorts. Four SNPs (rs11234495, rs592297, rs676733, and rs3851179) in the PICALM gene were significantly associated with late-onset (LO)-AD in populations from Southwest China, whereas SNPs rs744373 (BIN1), rs9331942 (CLU), and rs670139 (MS4A4E) were linked to LO-AD in populations from East China. In the combined Han Chinese population, positive associations were observed between PICALM, CLU, MS4A4E genes, and LO-AD. The association between rs3851179 (PICALM), rs744373 (BIN1), and AD was further confirmed by meta-analysis of Asian populations. Our study verified the association between PICALM, BIN1, CLU, and MS4A4E variants and AD susceptibility in Han Chinese populations. We also discerned some regional differences concerning AD susceptibility SNPs.

Male breast carcinoma is a relatively rare disease. This study retrospectively investigated the clinicopathological features of 73 cases of male breast carcinoma in Chinese population, and classified the molecular subtype based on surrogate immunohistochemical definitions. The expression of GCDFP15, MGB, AR and FOXP1 were evaluated. Invasive carcinoma of no special type was the most common histological type in the study group (71.2%, 52/73). The luminal A and B subtypes were the major types of male breast carcinoma (60.9%, 34.8% respectively). AR and FOXP1 are expressed in 84.2% (48/57) and 71.9% (41/57) of the studied cases. Carcinoma of the luminal A subtype expressed GCDFP15 (73.5%, 25/34) and MGB (58.8%, 20/34) more frequently than cases of the luminal B subtypes (34.8%, 8/23 and 43.5%, 10/23, respectively; P = 0.004, P = 0.255, respectively). In conclusion, invasive carcinoma of no special type was the most common histological type in male breast carcinoma among Chinese population. Our study revealed that the luminal A and B subtypes were the major types of male breast carcinoma. AR and FOXP1 are highly expressed in male breast cancer. The luminal A subtype tends to express GCDFP15 and MGB more frequently than the luminal B subtype.

Purpose: Invasive micropapillary breast carcinoma (IMPC) is a rare pathological finding. Few studies have compared IMPC with invasive ductal breast carcinoma (IDC) according to matched nodal status and age. To better illustrate the difference between IMPC and IDC prognoses, we conducted this cohort study., Methods: 51 mixed or pure IMPC patients and 102 pure IDC patients were matched for nodal status and age. Clinical and biological features as well as disease-free survival (DFS) were compared between groups., Results: More than one-half of IMPC consisted of mostly or exclusively IMPC component (meaning greater than 75%) and these tumors significantly correlated with a higher histologic grade (P = 0.016) and LVI positivity (P = 0.036) compared with mixed IMPC. IMPC displayed a significantly higher rate of estrogen receptor (ER) positivity and lymphovascular invasion (LVI) compared to matched IDC. Women diagnosed with IMPC had a slight, but not significant, reduced frequency for recurrence and metastasis compared to women with IDC (15.7% vs. 21.6%, P = 0.518). In the subgroup analysis, IMPC patients demonstrated significantly reduced survival (P = 0.018) compared to IDC patients in the T1N2-3 subpopulation, whereas IDC patients demonstrated significantly increased recurrence and metastasis (P = 0.024) compared to IMPC patients in the T2N2-3 subgroup. No difference was observed in patients with 3 or less positive lymph nodes (LNs)., Conclusion: Although no difference in DFS was observed between IMPC and LN-matched IDC patients, IMPC patients demonstrated a significantly poorer outcome compared to IDC patients with smaller tumors and 4 or more positive LNs. The opposite results were observed in larger tumors and patients with 4 or more positive LNs. Therefore, we might advise more proactive treatment for IMPC patients with a smaller tumor size and extensive LN involvement. Furthermore, correlative IMPC studies should focus on this subset of patients to elucidate the genetic and/or biologic differences that contribute to metastatic potential.

Carcinoma arising in microglandular adenosis (MGACA) is an extremely rare subtype of breast carcinoma. In this study, clinicopathological analysis of MGACA from 11 Chinese patients was conducted. Microscopically, all cases showed a spectrum of structure and glandular proliferations ranging from microglandular adenosis (MGA) to atypical MGA (AMGA) to MGACA. Carcinoma components were composed of high grade ductal carcinoma in situ (DCIS) in 1 case and invasive carcinoma in 10 cases. Invasive carcinomas were grade 3 in 10 tumors and grade 2 in 1. Invasive components in 5 of 10 cases were composed of invasive carcinoma of no special type (NST), and 1 case showed partially acinic cell differentiation. In 5 cases, invasive components were mixed of NST and matrix-producing carcinoma (MPC). All epitheliums in 11 cases were triple negative (ER-, PR-, HER2-), and diffuse positive for CK and S-100 protein. No myoepithelial cells were demonstrable from MGA to invasive components with immunohistochemical staining for P63 and calponin. PAS or reticulin stain showed the presence of a basement membrane around glands in MGA, AMGA, DCIS, and its absence in invasive components. Follow-up time ranged from 10 to 64 months. One patient developed a lung metastasis 24 months after surgery, 10 patients have been alive without recurrence. Our study revealed that MGACA is a distinct subset of breast carcinoma, with triple negative phenotype, high grade nuclear and variable morphology. Despite histopathologic and immunohistochemical features usually associated with a poor prognosis, MGACA seems to have a relatively favorable outcome.

Background: A novel variant rs2274223 located in the phospholipase C epsilon 1 (PLCE1) gene was found to be associated with risk of esophageal squamous cell carcinoma (ESCC) by 2 large-scale genome-wide association studies (GWASs) in Chinese populations. In this study, we aimed to assess such an association in an eastern Chinese population and to address its possibly functional role in the etiology of ESCC., Methods: A total of 1061 ESCC cases and 1211 controls were recruited and successfully genotyped for 2 single nucleotide polymorphisms (SNPs) (rs2274223 and rs11187870) of the PLCE1 gene by the TaqMan assay. Real-time PCR and immunohistochemical (IHC) analysis were applied to assess mRNA and protein expression levels, respectively, in a subset of tumor samples., Results: SNP rs2274223 was independently associated with risk of ESCC (adjusted odds ratio [OR], 1.49; 95% confidence interval [95% CI], 1.03-2.17 for GG vs AA), and SNP rs11187870 was also found to be associated with risk of ESCC assuming a dominant model (adjusted OR, 1.20; 95% CI, 1.00-1.44 for CG/CC vs GG). The Grs2274223Crs11187870 haplotype increased the risk for ESCC by 1.22-fold (95% CI, 1.04-1.42). Further experiments showed that overall PLCE1 mRNA expression was lower in tumor than in paired normal tissues (0.067±0.016 vs 0.264±0.067, P<.05), and the IHC analysis showed the normal tissues of rs2274223 GG genotype had a lower PLCE1 staining score than that of the AG genotype (0.40±0.22 vs 1.33±0.32, P<.05)., Conclusions: PLCE1 SNP rs2274223 A>G change may reduce gene expression, and the variant G genotypes might contribute to risk of ESCC.