Clinicopathological Features and Long-Term Prognostic Role of Human Epidermal Growth Factor Receptor-2 Low Expression in Chinese Patients with Early Breast Cancer: A Single-Institution Study.

Objective: This study aimed to comprehensively analyze and compare the clinicopathological features and prognosis of Chinese patients with human epidermal growth factor receptor 2 (HER2)-low early breast cancer (BC) and HER2-IHC0 BC. Methods: Patients diagnosed with HER2-negative BC ( N = 999) at our institution between January 2011 and December 2015 formed our study population. Clinicopathological characteristics, association between estrogen receptor (ER) expression and HER2-low, and evolution of HER2 immunohistochemical (IHC) score were assessed. Kaplan-Meier method and log-rank test were used to compare the long-term survival outcomes (5-year follow-up) between the HER2-IHC0 and HER2-low groups. Results: HER2-low BC group tended to demonstrate high expression of ER and more progesterone receptor (PgR) positivity than HER2-IHC0 BC group ( P < 0.001). The rate of HER2-low status increased with increasing ER expression levels (Mantel-Haenszel χ 2 test, P < 0.001, Pearson's R = 0.159, P < 0.001). Survival analysis revealed a significantly longer overall survival (OS) in HER2-low BC group than in HER2-IHC0 group ( P = 0.007) in the whole cohort and the hormone receptor (HR)-negative group. There were no significant differences between the two groups in terms of disease-free survival (DFS). The discordance rate of HER2 IHC scores between primary and metastatic sites was 36.84%. Conclusion: HER2-low BC may not be regarded as a unique BC group in this population-based study due to similar clinicopathological features and prognostic roles.

Prevalence and molecular characterization of Cryptosporidium spp. in dairy cattle in Central Inner Mongolia, Northern China.

BACKGROUND: Cryptosporidium is a gastrointestinal protozoan that widely exists in nature, it is an established zoonotic pathogen. Infected cattle are considered to be associated with cryptosporidiosis outbreaks in humans. In the present study, we aimed to assess the prevalence and species distribution of Cryptosporidium in dairy cattle in Central Inner Mongolia. METHODS: We focused on the small subunit ribosomal RNA gene (SSU rRNA) of Cryptosporidium and 60-kDa glycoprotein gene (gp60) of Cryptosporidium parvum. We collected 505 dairy cattle manure samples from 6 sampling sites in Inner Mongolia in 2021; the samples were divided into 4 groups based on age. DNA extraction, polymerase chain reaction (PCR), sequence analysis, and restriction fragment length polymorphism (RFLP) using SspI and MboII restriction endonucleases were performed. RFLP analysis was performed to determine the prevalence and species distribution of Cryptosporidium. RESULTS: SSU rRNA PCR revealed that the overall prevalence of Cryptosporidium infection was 29.90% (151/505), with a prevalence of 37.67% (55/146) and 26.74% (96/359) in diarrheal and nondiarrheal samples, respectively; these differences were significant. The overall prevalence of Cryptosporidium infection at the 6 sampling sites ranged from 0 to 47.06% and that among the 4 age groups ranged from 18.50 to 43.81%. SSU rRNA sequence analysis and RFLP analysis revealed the presence of 4 Cryptosporidium species, namely, C. bovis (44.37%), C. andersoni (35.10%), C. ryanae (21.85%), and C. parvum (11.92%), along with a mixed infection involving two or three Cryptosporidium species. Cryptosporidium bovis or C. andersoni was the most common cause of infection in the four age groups. The subtype of C. parvum was successfully identified as IIdA via gp60 analysis; all isolates were identified as the subtype IIdA19G1. CONCLUSIONS: To the best of our knowledge, this is the first report of dairy cattle infected with four Cryptosporidium species in Inner Mongolia, China, along with a mixed infection involving two or three Cryptosporidium species, with C. bovis and C. andersoni as the dominant species. Moreover, this is the first study to identify C. parvum subtype IIdA19G1 in cattle in Inner Mongolia. Our study findings provide detailed information on molecular epidemiological investigation of bovine cryptosporidiosis in Inner Mongolia, suggesting that dairy cattle in this region are at risk of transmitting cryptosporidiosis to humans.

Prevalence and molecular characterization of Giardia duodenalis in dairy cattle in Central Inner Mongolia, Northern China.

Giardia duodenalis is a gastrointestinal protozoan ubiquitous in nature. It is a confirmed zoonotic pathogen, and cattle are considered a source of giardiasis outbreaks in humans. This study aimed to evaluate the prevalence and multilocus genotype (MLG) of G. duodenalis in dairy cattle in Central Inner Mongolia. This study was based on the small subunit ribosomal RNA (SSU rRNA), glutamate dehydrogenase (gdh), triosephosphate isomerase (tpi), and beta-giardin (bg) genes of G. duodenalis. DNA extraction, polymerase chain reaction (PCR), and sequence analysis were performed on 505 dairy cattle fecal samples collected in 2021 from six sampling sites and four age groups in Central Inner Mongolia to determine the prevalence and MLG distribution of G. duodenalis. The PCR results of SSU rRNA revealed that the overall prevalence of G. duodenalis was 29.5% (149/505) and that the overall prevalence of the diarrhea and nondiarrhea samples was 31.5% (46/146) and 28.5% (103/359), respectively; the difference was not significant (p > 0.05). SSU rRNA sequence analysis revealed that G. duodenalis assemblage E (91.1%, 133/146) was primarily detected and that assemblage A (8.9%, 13/146) was detected in 13 samples. The G. duodenalis-positive samples were PCR amplified and sequenced for gdh, tpi, and bg, from which 38, 47, and 70 amplified sequences were obtained, respectively. A combination of G. duodenalis assemblages A and E were detected in seven samples. Multilocus genotyping yielded 25 different assemblage E MLGs, which formed six subgroups. To the best of our knowledge, this is the first report regarding G. duodenalis infection in dairy cattle in Inner Mongolia, China. This study revealed that Inner Mongolian cattle pose a risk of giardiasis transmission to humans and that the distribution of local cattle G. duodenalis assemblage E MLGs is diverse. The findings of this study can bridge the knowledge gap in the molecular epidemiological investigation of giardiasis in Central Inner Mongolia.

Comparative analysis of microbial communities in different growth stages of Dermacentor nuttalli.

Ticks were identified as arthropods that are pathogenic vectors. Dermacentor nuttalli is one of the dominant tick species in Inner Mongolia, and it carries and transmits a wide range of pathogenic microorganisms. However, at present, only the detection of D. nuttalli adult ticks and D. nuttalli different developmental stages carrying one specific pathogen, or the next-generation sequencing of D. nuttalli adult ticks were available. In this study, we investigated the microbial community structures of D. nuttalli in different growth stages under laboratory artificial feeding conditions. Total DNA was extracted from seven growth stages (female adult ticks, eggs, larval ticks, engorged larval ticks, nymphal ticks, engorged nymphal ticks, and second-generation adult ticks) obtained from laboratory artificial feeding of engorged D. nuttalli female ticks in Inner Mongolia. Then, the 16S rDNA V3-V4 hypervariable region was amplified to construct an Illumina PE250 library. Finally, 16S rRNA sequencing was performed on Illumina Novaseq 6000 platform. The sequencing data were analyzed using molecular biology software and platforms. The Illumina PE250 sequencing results showed that the egg stage had the highest diversity and number of species (28.74%, 98/341), while the engorged nymph stage had the lowest diversity and number of species (9.72%, 21/216). A total of 387 genera of 22 phyla were annotated in D. nuttalli, with 9 phyla and 57 genera found throughout all 7 growth stages. The dominant phylum was Proteobacteria; the dominant genera were Arsenophonus and Rickettsia; and the genera with the highest relative abundance in the 7 growth stages were Pseudomonas, Paenalcaligenes, Arsenophonus, Arsenophonus, Pseudomonas, Arsenophonus, and Rickettsia, respectively. Among the 23 exact species annotated, Brucella melitensis exhibits pathogeny that poses a serious threat to humans and animals. In this study, the microbial community composition at different growth stages of D. nuttalli was comprehensively analyzed for the first time.

First determination of DNA virus and some additional bacteria from Melophagus ovinus (sheep ked) in Tibet, China.

Melophagus ovinus (sheep ked) is one of the common ectoparasites in sheep. In addition to causing direct damage to the host through biting and sucking blood, sheep ked is a potential vector of helminths, protozoa, bacteria, and viruses. Sheep M. ovinus samples from three regions in Tibet were selected for DNA extraction. The 16S rDNA V3-V4 hypervariable region was amplified, after genomic DNA fragmentation, Illumina Hiseq libraries were constructed. The 16S rRNA sequencing and viral metagenomics sequencing were separately conducted on the Illumina Novaseq 6000 platform and molecular biology software and platforms were employed to analyze the sequencing data. Illumina PE250 sequencing results demonstrated that the dominant bacteria phylum in M. ovinus from Tibet, China was Proteobacteria, where 29 bacteria genera were annotated. The dominant bacterial genera were Bartonella, Wolbachia, and Arsenophonus; Bartonella chomelii, Wolbachia spp., and Arsenophonus spp. were the dominant bacterial species in M. ovinus from Tibet, China. We also detected Kluyvera intermedia, Corynebacterium maris DSM 45190, Planomicrobium okeanokoites, and Rhodococcus erythropolis, of which the relative abundance of Kluyvera intermedia was high. Illumina Hiseq sequencing results demonstrated that 4 virus orders were detected in M. ovinus from Tibet, China, and 3 samples were annotated into 29 families, 30 families, and 28 families of viruses, respectively. Virus families related to vertebrates and insects mainly included Mimiviridae, Marseilleviridae, Poxviridae, Ascoviridae, Iridoviridae, Baculoviridae, Hytrosaviridae, Nudiviridae, Polydnaviridae, Adomaviridae, Asfarviridae, Hepeviridae, Herpesviridae, and Retroviridae; at the species level, the relative abundance of Tupanvirus_soda_lake, Klosneuvirus_KNV1, and Indivirus_ILV1 was higher. African swine fever virus and many poxviruses from the family Poxviridae were detected, albeit their relative abundance was low. The dominant bacterial phylum of M. ovinus from Tibet, China was Proteobacteria, and the dominant bacterial genera were Bartonella, Wolbachia, and Arsenophonus, where 23 out of 29 annotated bacteria genera were first reported in M. ovinus. Kluyvera intermedia, Corynebacterium maris DSM 45190, Planomicrobium okeanokoites, and Rhodococcus erythropolis were detected for the first time. All DNA viruses detected in this study have been reported in M. ovinus for the first time.

Anlotinib combined with TQB2450 in patients with platinum-resistant or -refractory ovarian cancer: A multi-center, single-arm, phase 1b trial.

This is a phase Ib study of anlotinib plus a programmed death-ligand 1 (PD-L1) inhibitor TQB2450 for platinum-resistant or -refractory ovarian cancer. Thirty-four patients are enrolled and receive treatment. The objective response rate (ORR) is 47.1%, and the disease control rate is 97.1%. The median duration of response (DOR) has not been reached, and 61.3% of patients have a DOR of at least 8 months. The median progression-free survival (PFS) is 7.8 months, and the median overall survival (OS) has not been reached. The PD-L1-positive group has an ORR of 25.0%, whereas the PD-L1-negative group has an ORR of 92.9%. Treatment-related grade 3 or 4 adverse events (AEs) occur in 70.6% of patients, with the most common being hypertension (29.4%) and palmar-plantar erythrodysesthesia syndrome (29.4%). Anlotinib plus TQB2450 show promising antitumor activity and manageable toxicities in patients with platinum-resistant or -refractory ovarian cancer. A phase 3 randomized controlled trial to further validate our findings is ongoing.

Serological investigation and genotyping of Mycobacterium avium subsp. paratuberculosis in sheep and goats in Inner Mongolia, China.

Paratuberculosis a contagious and chronic disease in domestic and wild ruminants, is caused by Mycobacterium avium subspecies paratuberculosis (MAP). Typical clinical signs include intractable diarrhea, progressive emaciation, proliferative enteropathy, and mesenteric lymphadenitis. Paratuberculosis is endemic to many parts of the world and responsible for considerable economic losses. In this study, different types of paratuberculosis and MAP in sheep and goats were investigated in Inner Mongolia, a northern province in China contiguous with two countries and eight other provinces. A total of 4434 serum samples were collected from six cities in the western, central, and eastern regions of Inner Mongolia and analyzed using the ELISA test. In addition, tissue samples were collected from seven animals that were suspected to be infected with MAP. Finally, these tissues samples were analyzed by histopathological examination followed by polymerase chain reaction (PCR), IS1311 PCR-restriction enzyme analysis (PCR-REA), and a sequence analysis of five genes. Among all 4434 ruminant serum samples collected from the six cities in the western, central, and eastern regions of Inner Mongolia, 7.60% (337/4434) measured positive for the MAP antibody. The proportions of positive MAP antibody results for serum samples collected in the western, central, and eastern regions were 5.10% (105/2058), 6.63% (85/1282), and 13.44% (147/1094), respectively. For the seven suspected infected animals selected from the herd with the highest rate of positivity, the gross pathology and histopathology of the necropsied animals were found to be consistent with the pathological features of paratuberculosis. The PCR analysis further confirmed the diagnosis of paratuberculosis. The rest of the results demonstrated that herds of sheep and goats in Inner Mongolia were infected with both MAP type II and type III. To the best of our knowledge, this is the first study of the two subtypes of MAP strains in sheep and goats in Inner Mongolia.

Diagnostic accuracy of novel folate receptor-mediated staining solution detection (FRD) for CIN2+: A systematic review and meta analysis.

BACKGROUND: Early detection and diagnosis of high-grade cervical intraepithelial neoplasia grade 2 or higher (CIN2+) is critical for a good prognosis and appropriate treatment. The chief aim of our study was to evaluate the diagnostic performance of folate receptor-mediated staining solution detection (FRD) for CIN2+. METHODS: We conducted a systematic review and meta-analysis by searching the PubMed and EMBASE databases for studies published until May 2020, which assessed the diagnostic accuracy of FRD, human papilloma virus (HPV) testing, and ThinPrep cytology test (TCT) for the detection of CIN2+. Bivariate models were used to compare the diagnostic performance of FRD, HPV, and TCT. RESULTS: Six studies involving 2817 patients were included in this meta-analysis. The pooled specificity of FRD was higher than that of HPV and TCT for detecting CIN2+ (0.65, 0.12, and 0.39, respectively). The summary area under the receiver operating characteristic curve values using FRD, HPV, and TCT for detecting CIN2+ were 0.79, 0.95, and 0.77, respectively, indicating that FRD was superior to TCT. The diagnostic odds ratios of FRD, HPV, and TCT were 6 (95% CI: 5-7), 3 (95% CI: 2-5), and 3 (95% CI: 2-4), respectively, demonstrating that FRD had good diagnostic accuracy. CONCLUSION: FRD showed good diagnostic accuracy and higher specificity than HPV and TCT for detecting CIN2+. Based on our results, we propose that FRD could be a candidate for cervical screening, especially in underdeveloped countries.

[Combined Effects of Erythromycin and Nutrients on Microalgae in Seawater].

A large number of antibiotics and their metabolites eventually enter the ocean, and their potential threat to marine ecosystems demands attention. In this study, Karenia mikimotoi, Prorocentrum donghaiense, and Skeletonema costatum were selected to investigate the effects of different concentrations of erythromycin and nutrients on microalgae biomass, photosynthetic pigment contents, protein contents, superoxide dismutase (SOD) activity, and malondialdehyde (MDA) content. The possibility of whether erythromycin and nutrient limitation can have combined effects on microalgae was explored, and under different nutritional conditions, the impact of erythromycin on marine ecology was evaluated. The study found that nutrient limitation reduces the tolerance of Karenia mikimotoi, Prorocentrum donghaiense, and Skeletonema costatum to erythromycin. Erythromycin in the experimental range (0-1000 µg·L-1) had no significant effect on the growth of Karenia mikimotoi. However, high concentrations of erythromycin (≥100 µg·L-1)significantly inhibited the growth of Prorocentrum donghaiense and Skeletonema costatum. The sensitivity of Skeletonema costatum was the most pronounced.

125 I interstitial brachytherapy in management of pediatric skull base tumors.

BACKGROUND: The purpose of this study was to present our preliminary assessment of the safety and efficacy of 125 I interstitial brachytherapy (IBT) in the management of pediatric skull base tumors. METHODS: Thirty pediatric patients with skull base tumors treated with 125 I IBT from April 2007 to May 2017 were included in this study. The probabilities of local control (LC) and overall survival (OS) were calculated by the Kaplan-Meier method. RESULTS: The one- and two-year LC rates were 96.7% and 74.8%, respectively. The one- and two-year OS rates were 93.3% and 72.2%, respectively. No severe acute toxicity was observed. Severe late toxicities were observed in one (3.33%) of 30 patients. CONCLUSION: 125 I IBT is effective and safe in the management of pediatric skull base tumors, with satisfactory cosmetic and functional outcomes.

Membrane-Bound CD40L Promotes Senescence and Initiates Senescence-Associated Secretory Phenotype via NF-κB Activation in Lung Adenocarcinoma.

BACKGROUND/AIMS: Cellular senescence acts as a barrier against tumorigenesis. The CD40L transgene, expressed in some tumor cells, not only becomes visible to antigen-presenting cells but also actively catalyzes its own termination. Here, we evaluated the effect of a membrane-bound mutant form of human CD40L (CD40L-M) on senescence and the senescence-associated secretory phenotype (SASP) in non-small cell lung cancer (NSCLC). METHODS: CD40 expression levels in the NSCLC cell lines A549/TR, A549/DDP and H460 were examined by flow cytometry. Senescent cells and tissues were identified via SA-ß-gal activity. Cell proliferation was visualized by EdU labeling. qRT-PCR, Western blotting, and immunofluorescence staining were conducted to assess mRNA and protein expression levels of CD40L, γ-H2A.X, p65, p-p65, IκBα, p53, p21 and p16. Cytokines secreted from transfected cells were tested by ELISA and cell migration assay. Capsid tyrosine-modified rAAV5-CD40L-M was packaged and carried out in vivo. RESULTS: Overexpression of CD40L-M promoted senescence, inhibited proliferation, increased DNA damage-associated γ-H2A.X, and initiated the SASP in CD40-positive NSCLC cells. NF-κB signaling was activated by CD40L-M overexpression in these cells. Knockdown of NF-κB partially overcame senescence and failed to induce SASP. Furthermore, increased p53 and p21 protein levels induced by CD40L-M were also reduced following NF-κB suppression. CONCLUSIONS: These data showed that the membrane-bound CD40L mutant may promote cellular senescence and initiate the SASP of NSCLC cells in an NF-κB-dependent manner. Therefore, CD40L-M-induced senescence may be a potential approach to protect against lung adenocarcinoma.

[A rhabdomyosarcoma patient from a Li-Fraumeni syndrome family: a case report and literature review].

Li-Fraumeni syndrome (LFS) is a hereditary cancer predisposition syndrome, with the characteristics of early onset of cancer and high cancer incidence. TP53 is widely accepted as a pathogenic gene of LFS. A 2 years and 6 months old boy is reported in this article, who was diagnosed with embryonal rhabdomyosarcoma (RMS) in the left submandibular region. His brother died of RMS, and his grandmother was diagnosed with breast cancer. TP53 gene mutation detection was performed in this patient and some family members, indicating a missense mutation in exon 8 of the patient: c.844C>T (p.Arg282Trp, heterozygous). TP53 mutation was also found in his mother and sister. The boy met the diagnostic criteria for LFS. Among pediatric patients, the most common LFS diseases include osteosarcoma, adrenocortical cancer, central nervous system tumor, and soft tissue tumor. Additionally, leukemia and lymphoma are also involved. LFS patients have a high risk to suffer secondary or even multiple cancers. Therefore, it is necessary to perform genetic detection for pediatric cancer patients, especially those with hereditary predisposition cancers. TP53 mutation often indicates poor prognosis, so it is important to take active treatment and systematic monitoring for LFS family.

Distinct EphB4-mediated mechanisms of apoptotic and resistance to dasatinib in human chronic myeloid leukemia and K562 cell lines.

OBJECTIVE: To determine the role and mechanism of EphB4 in dasatinib (DAS) resistance in advanced chronic myeloid leukemia (CML), we explored the EphB4-mediated apoptotic and matrix microenvironment pathway in human CML and K562 cell lines. METHOD: Heparinized bone marrow samples were obtained from enrolled five patients (identified as A to E and visits identified by number) at initial diagnosis (A1-E1) and in the DAS-resistance advanced phase (A2-E2). Meanwhile, highly DAS-resistant cells, named K562-R cells, were obtained from K562-W cells with increasing concentrations of DAS. Stable under-expressing EphB4 cells (K562-R-EphB4-sh) were obtained from K562-R cells by RNA interference. K562-W, K562-R and K562-R-EphB4-sh cells (108) were respectively injected subcutaneously on the dorsal surface of BALB/C female nude mice to establish the xenografts models. RESULT: The mRNA/protein of EphB4 was overexpressed in the DAS-resistant A2-E2 in comparison with the A1-E1 human cell lines. Further, compared with K562-R cells, the expressions of EphB4 and p-Rac1/Cdc42 protein/mRNA were significantly downregulated in K562-R-EphB4-sh cells (P<0.01). K562-R cells showed the highest DAS resistance (IC50 10.54±0.67µg/ml), but K562-R-EphB4-sh cells became sensitive to DAS (IC50 1.02±0.1µg/ml, P<0.01). The expression of EphB4/p-RhoA/MCL-1 protein was gradually increased in the stimulating of EphrinB2-Fc, which partly made K562-R-EphB4-sh cells restore sensitivity to DAS (4.18±0.30µg/ml). Meanwhile, the K562-R-EphB4-sh xenografts group had relatively good efficacy compared to K562-R xenografts nude mice receiving the same dose of DAS. The analysis of xenografts tissue also suggested parallel results with the overexpression of EphB4/RhoA/ROCK1/PTEN/MCL-1 in K562-R xenografts, which decreased in the A2-R-EphB4-sh xenografts (P<0.01). CONCLUSIONS: The present study found that a new DAS resistance pathway of EphB4 overexpression was triggered by EphrinB2-Fc, which induced the resistance to DAS by activating RhoA/ROCK1/PTEN/MCL-1 signaling.

Novel cycloneolignans from Vernicia fordii with inhibitory effects on over-activation of BV2 cells in vitro.

Novel natural products 7R, 8R, 7'R, 9'S-verniciasin A (1a), 7S, 8S, 7'S, 9'R- verniciasin A (1b), 7R, 8R, 7'R, 9'S-7'-methoxylverniciasin A (2a) and 7S, 8S, 7'S, 9'R-7'-methoxylverniciasin A (2b) were characterized from the seed capsule of Vernicia fordii. And the unique 9-O-9'-7, 9'-cyclo-8, 1'-neolignan skeleton with a seven-membered ring, was identified by extensive spectroscopic analysis. Further the possible biosynthetic pathway was briefly discussed. Interestingly, 1a, 2a, 1b and 2b all exhibited significant stereoselective inhibitory effects on NO production in LPS-induced BV2 microglia cell. Then the primary mechanism of the bioactivities and stereoselectivity was explored by means of bioassay and molecular docking.

[Adverse effects of high-dose methotrexate therapy].

OBJECTIVE: To investigate the adverse effects of high-dose methotrexate (HDMTX) therapy, and to provide a theoretical basis for optimizing clinical treatment. METHODS: A retrospective analysis was performed for the clinical data of 120 children with acute lymphoblastic leukemia or non-Hodgkin lymphoma who underwent 601 times of HDMTX therapy. The adverse effects of various systems were analyzed according to the WHO criteria for the classification of adverse effects of anticancer drugs. RESULTS: Almost all the children experienced bone marrow suppression, and 93.3% had granulocytopenia. The most common adverse effects in the digestive system and urinary system were elevated glutamic-pyruvic transaminase (60.4%) and proteinuria (9.2%) respectively. For skin symptoms, skin erythema had the highest incidence rate (7.2%). The adverse effects in the nervous system (hyperpathia, numbness of extremities, or headache) were only observed in 7 cases. Serious adverse effects were only seen in the blood system and digestive system. Compared with the 3 g/m2 methotrexate (MTX) group, the 5 g/m2 HDMTX group had a significantly higher 24-hour plasma MTX concentration, significant reductions in hemoglobin and platelet count, and significantly higher incidence rates of oral mucositis, proteinuria, and skin symptoms (P<0.05). CONCLUSIONS: Serious adverse effects of HDMTX therapy mainly involve the blood system and digestive system, and the adverse effects such as bone marrow suppression, oral mucositis, proteinuria, and skin symptoms occur in a dose-dependent manner.

Clinical presentation and outcome of pediatric patients with hemophagocytic lymphohistiocytosis in China: A retrospective multicenter study.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a heterogeneous disease with major diagnostic and therapeutic difficulties. A large-scale multicenter study of pediatric HLH is still lacking in China. PROCEDURE: The Histiocytosis Study Group of the Chinese Pediatric Society conducted this retrospective study in 2014. A total of 323 patients diagnosed with HLH between 2011 and 2013 from 12 hospitals were registered. RESULTS: The median age at diagnosis was 2.2 years (range, 0-14.6 years), with a peak age of HLH onset at 0 to 3 years (63%). Mutations in HLH-related genes were found in 27.9% (24/86) patients who underwent genetic testing. PRF1, UNC13D, STXBP2 and LYST were the predominant genes involved. Sixteen patients (66.7%) presented with only monoallelic mutations in one gene. Epstein-Barr virus (EBV) infection was the major condition related to HLH, which was documented in 74.4% (201/270) of the patients who underwent EBV detection. Of 252 evaluable patients, 64.7% (163) achieved non-active disease at the eighth week and patients treated with a protocol containing etoposide presented higher remission rates (75.6% vs. 46.8%, P < 0.001). In multivariate analysis, a younger age at diagnosis (<12 months), platelet count less than 80×109 /L, central nervous system involvement, and initial treatment using a protocol without etoposide (not HLH-94/04) were independent prognostic factors indicating resistant disease. DISCUSSION: This study first multicenter assessment of HLH in China shows some different features in Chinese children with HLH compared with those in western countries, including older age, vulnerability to EBV infection, and a high proportion of patients with single monoallelic genetic mutations.

c-myc Gene Copy Number Variation in Cervical Exfoliated Cells Detected on Fluorescence in situ Hybridization for Cervical Cancer Screening.

PURPOSE: This study assessed the clinical significance of c-myc gene copy number gain detected by fluorescence in situ hybridization (FISH) in the prediction of cervical intraepithelial neoplasia (CIN) progression. METHODS: We retrospectively investigated 140 Thinprep cytologic test (TCT) specimens that were histopathologically diagnosed with various stages of cervical neoplasia or malignancy. The specimens were subjected to TCT, human papillomavirus (HPV) testing, and FISH analysis with a c-myc-specific probe. The diagnostic reliability of these methods in determining progression was assessed according to sensitivity, specificity, and κ coefficients. RESULTS: The gene copy number gain of c-myc was significantly higher in the cervical lesion of advanced histologic grade (p < 0.001). For CIN2+ lesions, the sensitivities of TCT, HPV DNA testing, and FISH analysis were 72.3, 92.1, and 64.5%, respectively; the specificities were 81.3, 57.8, and 93.8%, respectively (p < 0.001). The κ coefficients between the c-myc gene test and either the TCT or the HPV DNA test were 0.538 and 0.399, respectively (p < 0.001). CONCLUSIONS: FISH analysis of the c-myc oncogene could be a useful adjunct screening method for the early diagnosis of high-grade cervical lesions. Moreover, c-myc may be a new molecular biomarker for the early diagnosis of cervical lesion progression.

[Studied on Colored Dissolved Organic Matter of Spring in North Yellow Sea with Three-Dimensional Fluorescence Spectroscopy Combined with Parallel Factor Analysis].

This paper conducted fluorescent spectra of dissolved organic matter of Spring China North Yellow Sea by using three-dimensional fluorescence spectroscopy (EEMs) combined with parallel factors analysis (PARAFAC). The results showed that the fluorescent dissolved organic matter (FDOM) in colored dissolved organic matter (CDOM) of North Yellow Sea could be resolved to four components. Two components, c1 (260,315/425) and c2 (295,355/490) were identified as humic-like fluorescence components while c3 (275/310) and c4 (230,290/345) were protein-like components. The different linear correlations showed different degrees of similarities in the source or the chemical constitution, the relationship of the humic-like fluorescence components were most closely, followed by protein-like components. Four fluorescent components and total fluorescence intensity (TFI) in the horizontal and vertical directions had a higher intensity in coastal area than that of the area far away from the coast. Additionally, besides terrestrial input, the seawater mass movement also affects the distribution of CDOM in North Yellow Sea. Cluster analysis not only further illustrated the TFI characteristics of different areas of the North Yellow Sea, but also reflects the overall uniformity of the CDOM. Fluorescence Index (FI), Humification Index (HIX) and Biological Index (BIX) at some extent indicated the source of North Yellow Sea CDOM and the conclusion was that the near shore side gets greater influence from terrigenous sources while the sea side is more impacted by biological activity, which matched with the prior distribution patterns of fluorescence components.

[Autoimmune lymphoproliferative syndrome: a case report and literature review].

We described 1 case of autoimmune lymphoproliferative syndrome (ALPS), first diagnosed in our hospital, and reviewed the recent literature. The 11-month old male patient presented with a history of splenomegaly and hepatomegaly since 1 month after birth. He suffered recurrent infectious diseases including cytomegalovirus infection, parvovirus B19 infection and chronic diarrhea disease. Besides, his symptoms included hemolytic anemia and thrombocytopenia. The laboratory abnormality indicated an expanded population of alpha/beta double-negative T cells (DNTs) (27.18% of lymphocytes, 35.16% of CD3+ T lymphocytes) in peripheral blood, and autoantibodies including antinuclear antibody, double-stranded DNA and rheumatic factor were positive. Hyper gamma globulinemia and positive direct Coombs tests were seen in the patient. His parents were both healthy and denied autoimmune diseases. We identified a heterozygous point mutation in exon 3 of the FAS gene carrying c.309 A>C, resulting in a single base pair substitution in exon 3 of FAS gene which changed the codon of Arg103 to Ser103. Unfortunately, we were unable to obtain the gene results of the child's parents. The patient was treated with glucocorticoids in our hospital and with mycophenolatemofetil in other hospital. And we were informed that his anemia condition relieved through the telephone follow-up, but he still suffered recurrent infections, hepatomegaly and splenomegaly still existed. As we all know ALPS is characterized by defective lymphocyte apoptosis, and thus cause lymphoproliferative disease and autoimmune disease, and increase the risk of lymphoma. It is more likely to be misdiagnosed as other diseases. ALPS should be suspected in the case of chronic lymphadenopathy, splenomegaly and autoimmune features. Flow cytometry approach is helpful for the diagnosis. Immunosuppressive drugs are the necessary treatment.

Risk factors for ectopic pregnancy: a multi-center case-control study.

BACKGROUND: Ectopic pregnancy (EP) is the leading cause of maternal death during the first trimester of pregnancy. A better understanding of EP risk can help prevent its occurrence. We carried out a multi-center, large-sample, case-control study to evaluate the risk factors for EP in Shanghai, China. METHODS: Women who were diagnosed with EP (n = 2411) and women with intrauterine pregnancies (n = 2416) were recruited from five hospitals in Shanghai, China. Information regarding the sociodemographic characteristics; reproductive, gynecological and surgical history; and previous and current use of contraceptives was collected from all participants. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated and adjusted for potential confounding factors via multivariate logistic regression analysis. RESULTS: The study revealed that the risk of EP was associated with the traditional risk factors including previous EP (Adjusted odds ratio [AOR] = 2.72, 95% CI: 1.83-4.05), previous Chlamydia trachomatis infection (Adjusted OR = 3.18, 95% CI: 2.64, 3.84), previous infertility (AOR = 2.18, 95% CI: 1.66-2.88), previous adnexal surgery (AOR = 2.09, 95% CI: 1.49-2.93), previous appendectomy (AOR = 1.64, 95% CI: 1.13-2.37), and previous use of intrauterine devices (IUDs) (AOR = 1.72, 95% CI: 1.39-2.13). Additionally, EP risk was increased following the failure of most contraceptives used in the current cycle including IUDs (AOR = 16.43, 95% CI: 10.42-25.89), oral contraceptive pills (AOR = 3.02, 95% CI: 1.16-7.86), levonorgestrel emergency contraception (AOR = 4.75, 95% CI: 3.79-5.96), and female sterilization (AOR = 4 .73, 95% CI: 1.04-21.52). Stratified analysis showed that in vitro fertilization and embryo transfer (IVF-ET) was the main risk factor for EP in women with tubal infertility (AOR = 8.99, 95% CI: 1.98-40.84), although IVF-ET showed no association with EP in women with non-tubal infertility (AOR = 2.52, 95% CI: 0.14-44.67). CONCLUSION: In addition to the traditional risk factors, IVF-ET and current IUD use play dominant roles in the occurrence of EP. Attention should be given to women with tubal infertility who have undergone IVE-ET treatment.