GLYR1 transcriptionally regulates PER3 expression to promote the proliferation and migration of multiple myeloma.

Period circadian regulator 3 (PER3) functions as a tumor suppressor in various cancers. However, the role of PER3 in multiple myeloma (MM) has not been reported yet. Through this study, we aimed to investigate the potential role of PER3 in MM and the underlying mechanisms. RT-qPCR and western blotting were used to determine the mRNA and protein expression levels of PER3. Glyoxylate reductase 1 homolog (GLYR1) was predicted to be a transcription factor of PER3. The binding sites of GLYR1 on the promoter region of PER3 were analyzed using UCSC and confirmed using luciferase and chromatin immunoprecipitation assays. Viability, apoptosis, and metathesis were determined using CCK-8, colony formation, TUNEL, and transwell assays. We found that PER3 expression decreased in MM. Low PER3 levels may predict poor survival rates; PER3 overexpression suppresses the viability and migration of MM cells and promotes apoptosis. Moreover, GLYR1 transcriptionally activates PER3, and the knockdown of PER3 alleviates the effects of GLYR1 and induces its malignant behavior in MM cells. To conclude, GLYR1 upregulates PER3 and suppresses the aggressive behavior of MM cells, suggesting that GLYR1/PER3 signaling may be a potential therapeutic target for MM.

CALCRL knockdown suppresses cancer stemness and chemoresistance in acute myeloid leukemia with FLT3-ITD and DNM3TA-R882 double mutations.

Acute myeloid leukemia (AML) patients with FLT3 internal tandem duplication (FLT3-ITD) and DNA methyltransferase 3A (DNMT3A) R882 double mutations had a worse prognosis compared with AML with FLT3-ITD or DNMT3A R882 single mutation. This study was designed to explore the specific role of Calcitonin Receptor Like (CALCRL) in AML with FLT3-ITD and DNMT3A R882 double mutations. MOLM13 cells were transduced with CRISPR knockout sgRNA constructs to establish the FTL3-ITD and DNMT3A-R882 double-mutated AML cell model. Quantitative real-time PCR and Western blot assay were carried out to examine corresponding gene and protein expression. Methylation of CALCRL promoter was measured by methylation-specific PCR (MSP). Cell viability, colony formation, flow cytometry, and sphere formation assays were conducted to determine cell proliferation, apoptosis, and stemness. MOLM13 cells were exposed to stepwise increasing concentrations of cytarabine (Ara-C) to generate MOLM13/Ara-C cells. An in vivo AML  animal model was established, and the tumor volume and weight were recorded. TUNEL assay was adopted to examine cell apoptosis in tumor tissues. DNMT3A-R882 mutation upregulated the expression of CALCRL while downregulated the DNA methylation level of CALCRL in MOLM13 cells. CALCRL knockdown greatly inhibited cell proliferation, promoted apoptosis and repressed cell stemness, accompanied with the downregulated Oct4, SOX2, and Nanog in DNMT3A-R882-mutated MOLM13 cells and MOLM13/Ara-C cells. Furthermore, CALCRL knockdown restricted tumor growth and the chemoresistance of AML in vivo, as well as inducing cell apoptosis in tumor tissues. Together, these data reveal that CALCRL is a vital regulator of leukemia cell survival and resistance to chemotherapy, suggesting CALCRL as a promising therapeutic target for the treatment of FTL3-ITD and DNMT3A-R882 double-mutated AML.

CALCRL induces resistance to daunorubicin in acute myeloid leukemia cells through upregulation of XRCC5/TYK2/JAK1 pathway.

Chemotherapy is the main treatment option for acute myeloid leukemia (AML), but acquired resistance of leukemic cells to chemotherapeutic agents often leads to difficulties in AML treatment and disease relapse. High calcitonin receptor-like (CALCRL) expression is closely associated with poorer prognosis in AML patients. Therefore, this study was performed by performing CALCRL overexpression constructs in AML cell lines HL-60 and Molm-13 with low CALCRL expression. The results showed that overexpression of CALCRL in HL-60 and Molm-13 could confer resistance properties to AML cells and reduce the DNA damage and cell cycle G0/G1 phase blocking effects caused by daunorubicin (DNR) and others. Overexpression of CALCRL also reduced DNR-induced apoptosis. Mechanistically, the Cancer Clinical Research Database analyzed a significant positive correlation between XRCC5 and CALCRL in AML patients. Therefore, the combination of RT-PCR and Western blot studies further confirmed that the expression levels of XRCC5 and PDK1 genes and proteins were significantly upregulated after overexpression of CALCRL. In contrast, the phosphorylation levels of AKT/PKCε protein, a downstream pathway of XRCC5/PDK1, were significantly upregulated. In the response study, transfection of overexpressed CALCRL cells with XRCC5 siRNA significantly upregulated the drug sensitivity of AML to DNR. The expression levels of PDK1 protein and AKT/PKCε phosphorylated protein in the downstream pathway were inhibited considerably, and the expression of apoptosis-related proteins Bax and cleaved caspase-3 were upregulated. Animal experiments showed that the inhibitory effect of DNR on the growth of HL-60 cells and the number of bone marrow invasions were significantly reversed after overexpression of CALCRL in nude mice. However, infection of XCRR5 shRNA lentivirus in HL-60 cells with CALCRL overexpression attenuated the effect of CALCRL overexpression and upregulated the expression of apoptosis-related proteins induced by DNR. This study provides a preliminary explanation for the relationship between high CALCRL expression and poor prognosis of chemotherapy in AML patients. It offers a more experimental basis for DNR combined with molecular targets for precise treatment in subsequent studies.

Adoption value of support vector machine algorithm-based computed tomography imaging in the diagnosis of secondary pulmonary fungal infections in patients with malignant hematological disorders.

This study aimed to assess the feasibility of diagnosing secondary pulmonary fungal infections (PFIs) in patients with hematological malignancies (HM) using computerized tomography (CT) imaging and a support vector machine (SVM) algorithm. A total of 100 patients with HM complicated by secondary PFI underwent CT scans, and they were included in the training group. Concurrently, 80 patients with the same underlying disease who were treated at our institution were included in the test group. The types of pathogens among different PFI patients and the CT imaging features were compared. Radiomic features were extracted from the CT imaging data of patients, and a diagnostic SVM model was constructed by integrating these features with clinical characteristics. Aspergillus was the most common pathogen responsible for PFIs, followed by Candida, Pneumocystis jirovecii, Mucor, and Cryptococcus, in descending order of occurrence. Patients typically exhibited bilateral diffuse lung lesions. Within the SVM algorithm model, six radiomic features, namely the square root of the inverse covariance of the gray-level co-occurrence matrix (square root IV), the square root of the inverse covariance of the gray-level co-occurrence matrix, and small dependency low gray-level emphasis, significantly influenced the diagnosis of secondary PFIs in patients with HM. The area under the curve values for the training and test sets were 0.902 and 0.891, respectively. Therefore, CT images based on the SVM algorithm demonstrated robust predictive capability in diagnosing secondary PFIs in conjunction with HM.

Fecal microbiota transplantation inhibited neuroinflammation of traumatic brain injury in mice via regulating the gut-brain axis.

Introduction: Recent studies have highlighted the vital role of gut microbiota in traumatic brain injury (TBI). Fecal microbiota transplantation (FMT) is an effective means of regulating the microbiota-gut-brain axis, while the beneficial effect and potential mechanisms of FMT against TBI remain unclear. Here, we elucidated the anti-neuroinflammatory effect and possible mechanism of FMT against TBI in mice via regulating the microbiota-gut-brain axis. Methods: The TBI mouse model was established by heavy object falling impact and then treated with FMT. The neurological deficits, neuropathological change, synaptic damage, microglia activation, and neuroinflammatory cytokine production were assessed, and the intestinal pathological change and gut microbiota composition were also evaluated. Moreover, the population of Treg cells in the spleen was measured. Results: Our results showed that FMT treatment significantly alleviated neurological deficits and neuropathological changes and improved synaptic damage by increasing the levels of the synaptic plasticity-related protein such as postsynaptic density protein 95 (PSD-95) and synapsin I in the TBI mice model. Moreover, FMT could inhibit the activation of microglia and reduce the production of the inflammatory cytokine TNF-α, alleviating the inflammatory response of TBI mice. Meanwhile, FMT treatment could attenuate intestinal histopathologic changes and gut microbiota dysbiosis and increase the Treg cell population in TBI mice. Conclusion: These findings elucidated that FMT treatment effectively suppressed the TBI-induced neuroinflammation via regulating the gut microbiota-gut-brain axis, and its mechanism was involved in the regulation of peripheral immune cells, which implied a novel strategy against TBI.

Expression properties, structural features and functional analysis of CALR E381A in MPN patients.

OBJECTIVE: To investigate the expression properties, structural features and function of CALR E381A in myeloproliferative neoplasms (MPN) patients. METHODS: In this retrospective study, 435 MPN patients admitted to the Department of Hematology, Ningbo First Hospital from July 2015 to July 2021 were selected as the study subjects. Mutations in CALR exon 9 from genomic DNA samples were identified by PCR, followed by Sanger sequencing. The physicochemical properties of the wild-type calreticulin and the p.E381A variant, and the structural information of the p.E381A variant were analyzed by using the bioinformatics databases. Growth assay of UT-7/mpl cells with CALR E381A was used for the functional analysis of CALR E381A. RESULTS: The predominant types of CALR variants were identified as follows: p.L367fs*46 (38.1%), p.K385fs*47 (25.8%) and p.E381A (19.6%). Notably, the frequency of the p.E381A variant (c.1142A >C) in polycythemia vera or essential thrombocythemia was significantly higher than the frequency of that as a single nucleotide polymorphism (SNP) in the East Asian population. Furthermore, CALR E381A coexisted with other genetic variants, of which JAK2 V617F was more common. Bioinformatics analysis confirmed that CALR E381A did not change the physicochemical properties of the calreticulin protein, but did change the electrical charge, energy state and steric hindrance of amino acid residues at site 381. UT-7/mpl cells harboring CALR E381A overexpression did not exhibit altered cell growth, which is distinctly different from the stereotypical frameshift mutation. CONCLUSION: CALR E381A is not a driver mutation for the development of MPN but may be a risk SNP implying an inherited predisposition for MPN disease in East Asian populations.

The gut microbiota correlate with the disease characteristics and immune status of patients with untreated diffuse large B-cell lymphoma.

Background: Gut microbiota characteristics in patients with diffuse large B-cell lymphoma (DLBCL) are reportedly different when compared with the healthy population and it remains unclear if the gut microbiota affects host immunity and clinical disease features. This research investigated the gut microbiota in patients with untreated DLBCL and analyzed its correlation with patient clinical characteristics, humoral, and cell immune status. Methods: Thirty-five patients with untreated DLBCL and 20 healthy controls (HCs) were recruited to this study and microbiota differences in stool samples were analyzed by 16S rDNA sequencing. Absolute ratios of immune cell subset counts in peripheral blood were detected by flow cytometry and peripheral blood cytokine levels were detected by enzyme-linked immunosorbent assay. Relationships between changes in patient microbiomes and clinical characteristics, such as clinical stage, international prognostic index (IPI) risk stratification, cell origin, organ involved and treatment responses were investigated and correlations between differential microbiota and host immune indices were analyzed. Results: The alpha-diversity index of intestinal microecology in DLBCL patients was not significantly different when compared with HCs (P>0.05), nonetheless beta-diversity was significantly decreased (P=0.001). p_Proteobacteria were dominant in DLBCL, while p_Bacteroidetes abundance was significantly decreased when compared with HCs (P<0.05). Gut microbiota characteristics were identified that were associated with clinical features, such as tumor load, risk stratification and cell origin, and correlation analyses were performed between differential flora abundance associated with these clinical features and host immune status. The p_Firmicutes was positively correlated with absolute lymphocyte values, g_Prevotella_2 and s_un_g_Prevotella_2 were negatively correlated with absolute lymphocyte values, T cell counts and CD4 cell counts, while g_Pyramidobacter, s_un_g_Pyramidobacter, and f_Peptostreptococcaceae were negatively correlated with IgA. Conclusions: Dominant gut microbiota, abundance, diversity, and structure in DLBCL were influenced by the disease, correlated with patient immune status and this suggested that the microecology-immune axis may be involved in regulating lymphoma development. In the future, it may be possible to improve immune function in patients with DLBCL by regulating the gut microbiota, improve treatment response rates and increase patient survival rates.

Identification of MKNK1 and TOP3A as ovarian endometriosis risk-associated genes using integrative genomic analyses and functional experiments.

The risk of endometriosis (EM), which is a common complex gynaecological disease, is related to genetic predisposition. However, it is unclear how genetic variants confer the risk of EM. Here, via Sherlock integrative analysis, we combined large-scale genome-wide association studies (GWAS) summary statistics on EM (N = 245,494) with a blood-based eQTL dataset (N = 1490) to identify EM risk-related genes. For validation, we leveraged two independent eQTL datasets (N = 769) for integration with the GWAS data. Thus, we prioritised 14 genes, including GIMAP4, TOP3A, and NMNAT3, which showed significant association with susceptibility to EM. We also utilised two independent methods, Multi-marker Analysis of GenoMic Annotation and S-PrediXcan, to further validate the EM risk-associated genes. Moreover, protein-protein interaction network analysis showed the 14 genes were functionally connected. Functional enrichment analyses further demonstrated that these genes were significantly enriched in metabolic and immune-related pathways. Differential gene expression analysis showed that in peripheral blood samples from patients with ovarian EM, TOP3A, MKNK1, SIPA1L2, and NUCB1 were significantly upregulated, while HOXB2, GIMAP5, and MGMT were significantly downregulated compared with their expression levels in samples from the controls. Immunohistochemistry further confirmed the increased expression levels of MKNK1 and TOP3A in the ectopic and eutopic endometrium compared to normal endometrium, while HOBX2 was downregulated in the endometrium of women with ovarian EM. Finally, in ex vivo functional experiments, MKNK1 knockdown inhibited ectopic endometrial stromal cells (EESCs) migration and invasion. TOP3A knockdown inhibited EESCs proliferation, migration, and invasion, while promoting their apoptosis. Convergent lines of evidence suggested that MKNK1 and TOP3A are novel EM risk-related genes.

Gastrointestinal Bleeding Secondary to High-Dose Melphalan Pretreatment in Patients with Multiple Myeloma Was Associated with the Mode of Melphalan Administration.

Objective: To analyze the characteristics of gastrointestinal bleeding secondary to high-dose melphalan pretreatment in patients with multiple myeloma. Methods: Between 1 January 2016 and 31 October 2021, 26 patients with multiple myeloma after autologous peripheral blood hematopoietic stem cell transplantation with high-dose melphalan pretreatment were recruited. They were assigned to either the oral administration group or the intravenous administration group according to the administration modes, or to either the gastrointestinal bleeding group or the nongastrointestinal bleeding group. Analyses were performed based on the differences in general gastrointestinal symptoms and hemorrhage between different administration modes and on the differences in the general gastrointestinal symptoms, platelet alterations, and the intestinal microecology before pretreatment between patients with and without gastrointestinal bleeding. Results: Of the 26 included patients, heavy secondary gastrointestinal bleeding was found in 6 patients with intravenous pretreatment. In patients given intravenous melphalan, those with gastrointestinal bleeding showed more pronounced general symptoms such as nausea and vomiting versus those without. There was no significant difference in platelet alterations between the two groups. Gastrointestinal bleeding was associated with more significant microecological disturbances than no bleeding. Conclusion: Gastrointestinal bleeding secondary to high-dose melphalan pretreatment in patients with multiple myeloma was associated with the mode of melphalan administration, adverse symptoms at pretreatment, and the intestinal microecology prior to pretreatment. Thus, improvement of the intestinal microecology prior to pretreatment and mitigation of adverse gastrointestinal symptoms during pretreatment may contribute to a lower incidence of secondary gastrointestinal bleeding and enhanced transplantation safety.

Do methylenetetrahydrofolate dehydrogenase, cyclohydrolase, and formyltetrahydrofolate synthetase 1 polymorphisms modify changes in intelligence of school-age children in areas of endemic fluorosis?

BACKGROUND: Excessive exposure to fluoride can reduce intelligence. Methylenetetrahydrofolate dehydrogenase, cyclohydrolase, and formyltetrahydrofolate synthetase 1 ( MTHFD1 ) polymorphisms have important roles in neurodevelopment. However, the association of MTHFD1 polymorphisms with children's intelligence changes in endemic fluorosis areas has been rarely explored. METHODS: A cross-sectional study was conducted in four randomly selected primary schools in Tongxu County, Henan Province, from April to May in 2017. A total of 694 children aged 8 to 12 years were included in the study with the recruitment by the cluster sampling method. Urinary fluoride (UF) and urinary creatinine were separately determined using the fluoride ion-selective electrode and creatinine assay kit. Children were classified as the high fluoride group and control group according to the median of urinary creatinine-adjusted urinary fluoride (UF Cr ) level. Four loci of MTHFD1 were genotyped, and the Combined Raven's Test was used to evaluate children's intelligence quotient (IQ). Generalized linear model and multinomial logistic regression model were performed to analyze the associations between children's UF Cr level, MTHFD1 polymorphisms, and intelligence. The general linear model was used to explore the effects of gene-environment and gene-gene interaction on intelligence. RESULTS: In the high fluoride group, children's IQ scores decreased by 2.502 when the UF Cr level increased by 1.0 mg/L (ß = -2.502, 95% confidence interval [CI]:-4.411, -0.593), and the possibility for having "excellent" intelligence decreased by 46.3% (odds ratio = 0.537, 95% CI: 0.290, 0.994). Children with the GG genotype showed increased IQ scores than those with the AA genotype of rs11627387 locus in the high fluoride group ( P   <  0.05). Interactions between fluoride exposure and MTHFD1 polymorphisms on intelligence were observed (Pinteraction < 0.05). CONCLUSION: Our findings suggest that excessive fluoride exposure may have adverse effects on children's intelligence, and changes in children's intelligence may be associated with the interaction between fluoride and MTHFD1 polymorphisms.

Interaction of fluoride exposure and CREB1 gene polymorphisms on thyroid function in school-age children.

OBJECTIVES: To evaluate the effects of CREB1 gene polymorphisms and long-term exposure to fluoride on thyroid function of children. STUDY DESIGN: A total of 424 children (including 226 boys and 198 girls) aged 7-12 years old were enrolled in Kaifeng, China by cross-sectional study in 2017. The concentrations of urinary fluoride (UF) and creatinine (UCr) were measured using fluoride ion-selective electrode assay and creatinine assay kit (picric acid method), respectively. The concentration of UCr-adjusted UF (CUF) was calculated. Children were divided into high fluoride exposure group (HFG, CUF >1.41 mg/L) and low fluoride exposure group (LFG, CUF ≤1.41 mg/L) according to the median concentration of CUF (1.41 mg/L). The serum thyroid-stimulating hormone (TSH), total triiodothyronine (TT3) and total thyronine (TT4) levels were detected by the radiation immunoassay. The B-mode ultrasound was performed to test the thyroid volume (Tvol). Genotyping of CREB1 gene was conducted by a custom-by-design 48-plex SNPscan™ Kit. Associations between CUF concentration, CREB1 single nucleotide polymorphisms (SNPs) and thyroid function were assessed by multiple linear regression models. RESULTS: Negative and positive associations between serum TT4 level (ß = -0.721, 95%CI: -1.209, -0.234) and Tvol (ß = 0.031, 95%CI: 0.011, 0.050) and CUF concentration were observed respectively. Children carrying CREB1 rs11904814 TG and rs2254137 AC genotypes had lower TT3 levels (P < 0.05). Children in HFG carrying rs11904814 TT, rs2253206 GG genotypes and rs6740584 C allele easily manifested lower serum TT4 levels (P < 0.05). Moreover, interactions between excessive fluoride exposure and CREB1 SNPs on Tvol were observed, and the interaction among different loci of CREB1 gene could modify serum TT3 level (P < 0.05, respectively). CONCLUSIONS: Fluoride could alter children's serum TT4 levels and Tvol. Interactions between fluoride exposure and CREB1 polymorphisms may modify thyroid volume of children.

Effects of SNPs in SOD2 and SOD3 interacted with fluoride exposure on the susceptibility of dental fluorosis.

A total of 649 children aged 7-13 years of age were recruited in a cross-sectional study in Tongxu County, China (2017) to assess the effects of interaction between single nucleotide polymorphisms (SNPs) in SOD2 and SOD3 gene and fluoride exposure on dental fluorosis (DF) status. Associations between biomarkers and DF status were evaluated. Logistic regression suggested that the risk of DF in children with rs10370 GG genotype and rs5746136 TT genotype was 1.89-fold and 1.72-fold than that in children with TT/CC genotype, respectively. Increased T-SOD activity was associated with a lower risk of DF (OR = 0.99). The rs2855262*rs10370*UF model was regarded as the optimal interaction model in generalized multifactor dimensionality reduction analyses. Our findings suggested that rs4880 and rs10370 might be useful genetic markers for DF, and there might be interactions among rs10370 in SOD2, rs2855262 in SOD3, and fluoride exposure on DF status.

Fluoride Stimulates Anxiety- and Depression-like Behaviors Associated with SIK2-CRTC1 Signaling Dysfunction.

Using Sprague-Dawley rats and rat PC12 cells treated with sodium fluoride (NaF), we investigated the effects of SIK2-CRTC1 signaling on the neurobehavioral toxicity induced by fluoride. The in vivo results demonstrated that NaF treatment induced anxiety- and depression-like behaviors in juvenile rats, resulting in histological and ultrastructural abnormalities in the rat hippocampus and medial prefrontal cortex. Moreover, NaF exposure induced neuronal loss and excessive apoptosis. We also found that NaF elevated the expression of SIK2 and reduced the expression of CRTC1, brain-derived neurotrophic factor (BDNF), and VGF. The in vitro results showed that NaF suppressed cell viability, induced SIK2-CRTC1 signaling dysfunction, and caused excessive apoptosis in PC12 cells. Notably, targeted knockout of SIK2 with SIK2-siRNA or blocking of SIK2-CRTC1 signaling with 7,8-dihydroxyflavone (7,8-DHF) (as well as venlafaxine) can reduce apoptosis and increase cell viability in vitro. These findings suggest that neuronal death resulting from abnormal SIK2-CRTC1 signaling contributes to neurobehavioral toxicity induced by fluoride.

Inhibition of NF-κB/IL-33/ST2 Axis Ameliorates Acute Bronchiolitis Induced by Respiratory Syncytial Virus.

BACKGROUND/AIM: Bronchiolitis is a common acute lower respiratory tract infectious disease in infants. Respiratory syncytial virus (RSV) infection is one of the main causes. Bronchiolitis can lead to a significant increase in the incidence of asthma in young children, but the mechanism of bronchiolitis transforming into asthma is still unclear. The study was aimed at investigating the role of NF-κB/IL-33/ST2 axis on RSV-induced acute bronchiolitis. METHODS: A total of 40 infants diagnosed with acute bronchiolitis infected by RSV, and 20 normal infants were included in this study. BALB/c mice (6-8 weeks old, 20 ± 1.1 g) were used as study models. Enzyme-linked immunosorbent assay (ELISA), quantitative real time PCR, western blot analysis, immunohistochemical staining, and flow cytometry analysis were performed to examine relevant indicators. RESULTS: IL-33 level was significantly elevated, and Th1/Th2 ratio is imbalance after in infants with acute bronchiolitis. In vivo study, we found that NF-κB/IL-33/ST2 axis is mediated the Th2 cytokine levels and BAL cell number induced by RSV. Acute bronchiolitis induced by RSV in a mouse model is attenuated after inhibition of NF-κB/IL-33/ST2 pathway. Moreover, we also confirmed that macrophages are important sources of IL-33 and are regulated by NF-κB pathway in RSV-induced mice. CONCLUSION: We confirmed that inhibition of NF-κB/IL-33/ST2 axis could attenuate acute bronchiolitis by RSV infected. Our findings not only demonstrate the potential role of IL-33 antibody in attenuating RSV-induced lung damage but also provide a new insight into better prevention of RSV-induced asthma by mediating NF-κB/IL-33/ST2 axis.

Optimal Dose of Pituitrin in Laparoscopic Uterine Myomectomy: A Double-Blinded, Randomized Controlled Trial.

STUDY OBJECTIVE: To determine the optimal effective dose of pituitrin in laparoscopic myomectomy for uterine leiomyoma. DESIGN: Double-blinded, randomized controlled trial. SETTING: Tertiary women's hospital in China. PATIENTS: Total of 118 patients who underwent laparoscopic myomectomy. INTERVENTIONS: Patients randomly received 0, 2, 4, or 6 units of pituitrin injected into the myometrium surrounding the myoma. MEASUREMENTS AND MAIN RESULTS: Rate of satisfactory surgical condition, hemodynamic changes, total surgical time, and blood loss were recorded. The rates of satisfactory surgical conditions were 6.7%, 72.4%, 89.7%, and 93.3% in groups 0U, 2U, 4U, and 6U, respectively; they were higher in groups 2U, 4U, and 6U than those in group 0U, but there were no significant differences among the groups 2U, 4U, and 6U. The blood loss was higher in group 0U than that in groups 2U, 4U, and 6U (p < .01). Pituitrin was associated with a transient decrease in blood pressures and an increase in heart rate in a dose-dependent fashion, with more pronounced changes in groups 4U and 6U, and these groups also required a higher amount of vasoactive drug to correct hemodynamic changes (p < .05). CONCLUSION: Two units of pituitrin could provide a satisfactory surgical field with minimal hemodynamic changes for laparoscopic uterine myomectomy.

Sexual function in patients with endometriosis: a prospective case-control study in China.

OBJECTIVE: Endometriosis is a common disease in women of childbearing age, leading to sexual dysfunction or loss of libido. We aimed to evaluated the effect of endometriosis on women's sexual function. METHODS: We performed a prospective case-control study to determine the effect of endometriosis on women's sexual function using a self-administered questionnaire from September 2017 to August 2018. The simplified Chinese version of the Female Sexual Function Index (FSFI) was used to assess sexual function. RESULTS: We found that sexual function of women in the endometriosis group (n=77) in all dimensions was significantly lower compared with that in the control group (n=63). The total FSFI score in patients was 25.5, which tended to be lower than that in the control group (26.7). Sexual arousal, sexual pain, and satisfaction were significantly different between the two groups. Sexual arousal and sexual pain scores were significantly lower in the endometriosis group than in the control group at the ages of 31 to 40 years. CONCLUSION: Women with endometriosis suffer from sexual dysfunction, especially those aged 31 to 40 years. Our findings suggest that the quality of sexual life in this subpopulation needs to be improved.

[Corrigendum] Anticancer effect of quinacrine on diffuse large B­cell lymphoma via inhibition of MSI2­NUMB signaling pathway.

Subsequently to the publication of this paper, an interested reader drew to the authors' attention that, in Fig. 1A on p. 524, the images selected to represent the Control experiments for the SU­DHL­8 and OCI­Ly01 cell lines bore some striking similarities. After having examined their original data, the authors realized that they uploaded the wrong images during the process of compiling this figure. The corrected version of Fig. 1, showing the correct data for Fig. 1A, is shown on the next page. Note that the replacement of the erroneous data does not affect either the results or the conclusions reported in this paper, and all the authors agree to this Corrigendum. The authors are grateful to the Editor of Molecular Medicine Reports for granting them this opportunity to publish a Corrigendum, and apologize to the readership for any inconvenience caused. [the original article was published in Molecular Medicine Reports 17: 522­530, 2018; DOI: 10.3892/mmr.2017.7892].

Identification of key genes and pathways in endometriosis by integrated expression profiles analysis.

The purpose of this study was to integrate the existing expression profile data on endometriosis (EM)-related tissues in order to identify the differentially expressed genes. In this study, three series of raw expression data were downloaded from GEO database. Differentially expressed genes (DEGs) in three tissue types were screened. GO, KEGG pathway enrichment analysis, core differential genes (CDGs) protein-protein interaction (PPI) network and weighted gene co-expression network analysis (WGCNA) were performed, finally, the dysregulation of Hippo pathway in ectopic endometrium (EC) was detected by Western blotting. A total of 1,811 DEGs between eutopic (EU) and normal endometrium (NE), 5,947 DEGs between EC and EU, and 3,192 DEGs between EC and NE datasets were identified. After screening, 394 CDGs were obtained, and 5 hub genes identified in the PPI network. CDGs enrichment and WGCNA network analysis revealed cell proliferation, differentiation, migration and other biological processes, Hippo and Wnt signaling pathways, and a variety of tumor-related pathways. Western blotting results showed that YAP/TAZ was upregulated, and MOB1, pMOB1, SAV1, LATS1 and LATS2 were downregulated in EC. Moreover, CDGs, especially the hub genes, are potential biomarkers and therapeutic targets. Finally, the Hippo pathway might play a key role in the development of endometriosis.

Fluoride exposure and intelligence in school-age children: evidence from different windows of exposure susceptibility.

BACKGROUND: The intellectual loss induced by fluoride exposure has been extensively studied, but the association between fluoride exposure in different susceptibility windows and children's intelligence is rarely reported. Hence, we conducted a cross-sectional study to explore the association between fluoride exposure in prenatal and childhood periods and intelligence quotient (IQ). METHODS: We recruited 633 local children aged 7-13 years old randomly from four primary schools in Kaifeng, China in 2017. The children were divided into four groups, of which included: control group (CG, n = 228), only prenatal excessive fluoride exposure group (PFG, n = 107), only childhood excessive fluoride exposure group (CFG, n = 157), both prenatal and childhood excessive fluoride exposure group (BFG, n = 141). The concentrations of urinary fluoride (UF) and urinary creatinine (UCr) were determined by fluoride ion-selective electrode assay and a creatinine assay kit (picric acid method), respectively. The concentration of UCr-adjusted urinary fluoride (CUF) was calculated. IQ score was assessed using the second revision of the Combined Raven's Test-The Rural in China (CRT-RC2). Threshold and saturation effects analysis, multiple linear regression analysis and logistic regression analysis were conducted to analyze the association between fluoride exposure and IQ. RESULTS: The mean IQ score in PFG was respectively lower than those in CG, CFG and BFG (P < 0.05). The odds of developing excellent intelligence among children in PFG decreased by 51.1% compared with children in CG (OR = 0.489, 95% CI: 0.279, 0.858). For all the children, CUF concentration of ≥1.7 mg/L was negatively associated with IQ scores (ß = - 4.965, 95% CI: - 9.198, - 0.732, P = 0.022). In children without prenatal fluoride exposure, every 1.0 mg/L increment in the CUF concentration of ≥2.1 mg/L was related to a reduction of 11.4 points in children's IQ scores (95% CI: - 19.2, - 3.5, P = 0.005). CONCLUSIONS: Prenatal and childhood excessive fluoride exposures may impair the intelligence development of school children. Furthermore, children with prenatal fluoride exposure had lower IQ scores than children who were not prenatally exposed; therefore the reduction of IQ scores at higher levels of fluoride exposure in childhood does not become that evident.