Application of Genetic Origin Analysis of Copy Number Variations in Non-Invasive Prenatal Testing.

OBJECTIVE: This study aimed to assess the application of origin analysis of copy number variations (CNVs) in non-invasive prenatal testing (NIPT) and provide a basis for expanding the clinical application of NIPT. METHOD: We enrolled 35,317 patients who underwent NIPT between January 2019 and March 2023. Genome sequencing of copy number variation (CNV-Seq) analysis was performed using the CNV calling pipeline to identify subchromosomal abnormalities in maternal plasma. Genetic origin was determined by comparing the chimaerism ratio of CNV and the concentration of cell-free foetal DNA (cffDNA). All pregnant women with a high risk of CNV, as indicated by the NIPT, were informed of their genetic origins. Amniocentesis was recommended for detecting the CNVs in foetal chromosomes, and pregnancy outcomes were tracked. RESULTS: A total of 109 pregnancies showed clinically significant positive results for CNV after NIPT, including 65 cases of maternal/foetal (M/F)-CNVs and 44 cases of F-CNVs. The occurrence of M/F-CNVs was independent of age, screening (serological or ultrasound) indications for abnormalities, and mode of pregnancy. The incidence of pathogenic/likely pathogenic (P/LP)-F-CNVs was high in cases where serological screening indicated intermediate, high-risk, or abnormal US findings (p < 0.05). In the M/F-CNV group, most of the P/LP-CNVs were small fragments with low penetrance; 55 (84.62%) were less than 5 Mb in size, and nine (13.85%) were between 5 and 10 Mb. In the F-CNV group, foetal P/LP-CNV was detected in 36 of 42 cases undergoing prenatal diagnosis, and no significant bias was noted in the size distribution of P/LP-F-CNV fragments. The prenatal diagnostic rate and positive predictive value in the F-CNV group were 95.45% and 85.71%, respectively, which were significantly different from those in the M/F group (26.15% and 52.95%), respectively (p < 0.05). CONCLUSIONS: Genetic origin analysis of CNV can effectively improve adherence to prenatal diagnosis in pregnant women and the accuracy of prenatal diagnosis.

Socioeconomic status influences on bone mineral density in American men: findings from NHANES 2011-2020.

The association between socioeconomic status (SES) and bone mineral density (BMD) in men remains controversial. We showed that SES was positively associated with BMD in American men. Confounding factors like race/ethnicity and age could affect the association. INTRODUCTION: Based on the data from the National Health and Nutrition Examination Survey (NHANES), 2011-2020, this article aims to investigate the association of SES (poverty income ratio (PIR) and education level) with the BMD in American men. METHODS: We evaluated the association of SES with BMD in 4446 men aged ≥ 20 years (mean age, 41.0 ± 13.4 years) from the NHANES 2011-2020. BMD was measured by dual-energy X-ray absorptiometry (DXA) at the lumbar spine. We used multivariate linear regression models to examine the relationship between SES and total spine BMD, adjusted for a large range of confounding factors. RESULTS: Compared with other PIR quarters, individuals in the highest quarter of PIR were more likely to be older and white and had fewer smoking or drinking behaviors. After adjusting for race/ethnicity, age, drinking and smoking behavior, body mass index (BMI), total protein, serum calcium, serum uric acid, cholesterol, serum phosphorus, and blood urea nitrogen, PIR was positively correlated with total spine BMD (ß = 0.004 95% CI: 0.001-0.007, P = 0.006). Individuals with the highest degree (college degree or above) had a 0.057 g/cm2 greater BMD than that of the lowest degree (less than 9th grade) (ß = 0.057 95% CI: 0.037-0.077, P < 0.001). CONCLUSIONS: Our study indicates that SES was positively associated with the lumbar BMD among American men. Clinicians, healthcare providers, and policymakers should consider the unequal SES of men when implementing osteoporosis prevention and treatment strategies.

Radiofrequency ablation for primary hyperparathyroidism and risk factors for postablative eucalcemic parathyroid hormone elevation.

OBJECTIVE: To investigate the efficacy of radiofrequency ablation (RFA) as a treatment option for primary hyperparathyroidism (pHPT) and risk factors for postablative eucalcemic parathyroid hormone elevation (ePTH). METHODS: This retrospective study included 51 patients with pHPT who underwent RFA. The patients were divided into the ePTH and normal PTH groups, based on the serum intact parathyroid hormone (iPTH) level one month after ablation. Serum iPTH, calcium, and phosphorus levels, and the volume reduction rates (VRR) of the parathyroid glands were compared between the groups at each follow-up point. Risk factors for ePTH at one month after ablation were examined. RESULTS: After RFA, one (2%) patient had persistent pHPT, and 50 (98%) patients were cured. The incidence rates of ePTH at 1, 3, 6, and 12 months were 48%, 30%, 20%, and 16%, respectively. Serum iPTH levels in the ePTH group were higher than those in the normal PTH group at each follow-up point (all p < 0.05), except 1 day after ablation (p > 0.05). Serum calcium and phosphorus levels, and the VRR of the glands were comparable in both groups at each follow-up point (all p > 0.05), except for calcium levels 3 days after RFA (p < 0.05). Baseline iPTH (odds ratio, 1.067; p = 0.045) and calcium (odds ratio, 3.923; p = 0.038) levels were independent risk factors for ePTH 1 month after RFA. CONCLUSIONS: RFA is safe and effective for the treatment of pHPT. Moreover, ePTH occurrence after RFA was associated with baseline iPTH and calcium levels and did not increase the risk of recurrent pHPT.

Characterization of Plasmodium berghei Homologues of T-cell Immunomodulatory Protein as a New Potential Candidate for Protecting against Experimental Cerebral Malaria.

The pathogenesis of cerebral malaria is biologically complex and involves multi-factorial mechanisms such as microvascular congestion, immunopathology by the pro-inflammatory cytokine and endothelial dysfunction. Recent data have suggested that a pleiotropic T-cell immunomodulatory protein (TIP) could effectively mediate inflammatory cytokines of mammalian immune response against acute graft-versus-host disease in animal models. In this study, we identified a conserved homologue of TIP in Plasmodium berghei (PbTIP) as a membrane protein in Plasmodium asexual stage. Compared with PBS control group, the pathology of experimental cerebral malaria (ECM) in rPbTIP intravenous injection (i.v.) group was alleviated by the downregulation of pro-inflammatory responses, and rPbTIP i.v. group elicited an expansion of regulatory T-cell response. Therefore, rPbTIP i.v. group displayed less severe brain pathology and feverish mice in rPbTIP i.v. group died from ECM. This study suggested that PbTIP may be a novel promising target to alleviate the severity of ECM.

High-dose dexamethasone vs prednisone for treatment of adult immune thrombocytopenia: a prospective multicenter randomized trial.

This study compared the efficacy and safety of high-dose dexamethasone (HD-DXM) and conventional prednisone (PDN) on the largest cohort to date as first-line strategies for newly diagnosed adult primary immune thrombocytopenia (ITP). Patients enrolled were randomized to receive DXM 40 mg/d for 4 days (n = 95, nonresponders received an additional 4-day course of DXM) or prednisone 1.0 mg/kg daily for 4 weeks and then tapered (n = 97). One or 2 courses of HD-DXM resulted in a higher incidence of overall initial response (82.1% vs 67.4%, P = .044) and complete response (50.5% vs 26.8%, P = .001) compared with prednisone. Time to response was shorter in the HD-DXM arm (P < .001), and a baseline bleeding score ≥8 was associated with a decreased likelihood of initial response. Sustained response was achieved by 40.0% of patients in the HD-DXM arm and 41.2% in the PDN arm (P = .884). Initial complete response was a positive indicator of sustained response, whereas presence of antiplatelet autoantibodies was a negative indicator. HD-DXM was generally tolerated better. We concluded that HD-DXM could be a preferred corticosteroid strategy for first-line management of adult primary ITP. This study is registered at www.clinicaltrials.gov as #NCT01356511.

Treatment and outcomes of tumor-induced osteomalacia associated with phosphaturic mesenchymal tumors: retrospective review of 12 patients.

BACKGROUND: Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome characterized by severe hypophosphatemia and osteomalacia. Nonspecific symptoms make the diagnosis elusive. In addition, locating the responsible tumor(s) is challenging. The aim of this study was to investigate the clinical management and outcomes of TIO. METHODS: The clinical features, diagnostic procedures, treatment, and outcomes of 12 patients were reviewed retrospectively. RESULTS: The cohort comprised six men and six women (mean age 45.5 ± 9.9 years, range 23-61 years). The mean duration of disease was 3.7 ± 2.6 years. All patients manifested progressive bone pain, muscle weakness, and/or difficulty walking. Serum phosphorus concentrations were low in all patients (mean 0.42 ± 0.12 mmol/L). Technetium-99m octreotide scintigraphy was performed in 11 patients and showed lesions in the right distal femur, left femoral head, and right tibial plateau, respectively, in three patients. Magnetic resonance imaging (MRI) was negative for lesions in one patient. Two patients underwent biopsies that showed negative histopathology. Two patients, at 2 years and 8 months, respectively, after having negative technetium-99m octreotide studies, underwent 18F-fluorodeoxyglucose positron emission tomography/computed tomography (CT), which revealed lesions in the sacrum and soft tissue of the left palm, respectively. One tumor was detected by CT and MRI. Overall, lesion sites were the head (two patients, 16.7%), thoracic and lumbar region (two, 16.7%), pelvis (three, 25%), lower limbs (four, 33.3%), and upper limbs (one, 8.3%). All patients underwent surgery, and histopathology showed phosphaturic mesenchymal tumors in each. Postoperatively, serum phosphorus concentrations normalized within 2-7 days in 11 patients. With follow-ups of 1-41 months, surgery was effective in 10 patients. One patient developed local recurrence and another had metastases. CONCLUSIONS: Locating tumors responsible for tumor-induced osteomalacia is often challenging. Although complete tumor resection confers a good prognosis in most patients, surveillance for recurrence and metastasis is necessary. Before surgery or when surgery is not indicated, oral phosphate can alleviate symptoms and metabolic imbalance.

Association of chronic hepatitis B virus infection with preterm birth: our experience and meta-analysis.

OBJECTIVES: To assess the association of chronic hepatitis B virus (HBV) infection with preterm birth (PTB). METHODS: A cohort of 20,498 pregnant women (497 HBV carriers with 20,001 non-HBV controls) with normal alanine aminotransferase (ALT) levels was selected from the Obstetrics & Gynecology Hospital of Nantong University. The clinical parameters and PTB incidence were compared between HBV carriers and non-HBV subjects. For the meta-analysis, we searched the PubMed, Ovid and Cochrane Library databases for studies comparing PTB incidence between individuals with chronic HBV infection and non-HBV subjects. RESULTS: HBV carriers were slightly older and had slightly higher ALT levels within normal limits. The body mass index, education and history of pregnancy between HBV carrier and non-HBV groups were comparable. PTB incidence was not associated with HBV carrier status [relative risk (RR) 0.98, 95% confidence interval (CI) 0.71-1.37] in our cohort. However, the meta-analysis involving eight published studies and our study revealed a significant association between chronic HBV infection and PTB incidence (pooled RR 1.26, 95% CI 1.19-1.33). CONCLUSION: While maternal HBV carriers did not have a higher incidence of PTB in our cohort, the meta-analysis indicates that individuals with chronic HBV infection appeared to be at risk of PTB as a whole.

Maternal hepatitis B virus carrier status and pregnancy outcomes: a prospective cohort study.

BACKGROUND: Infection with hepatitis B virus (HBV) in pregnant women may be a threat for both mothers and fetuses. This study was performed to explore the impact of maternal HBV carrier status on pregnancy outcomes. METHODS: We conducted a prospective cohort study at the Obstetrics & Gynecology Hospital of Nantong University between January 1, 2012 and September 30, 2015. A consecutive sample of 21,004 pregnant women, 513 asymptomatic HBV carriers and 20,491 non-HBV controls, was included in this study. The main outcomes of interest were selected pregnancy outcomes including miscarriage, stillbirth, preterm birth (PTB), gestational diabetes (GDM), intrahepatic cholestasis of pregnancy (ICP), preterm premature rupture of the membrane (PPROM), low birth weight (LBW), small for gestational age (SGA) and Apgar scores. The incidence of adverse pregnancy outcomes between asymptomatic HBV carriers and non-HBV controls were compared using the chi-square test and logistic regression. P values were two sided, and P <0.05 was considered to indicate statistical significance. RESULTS: The incidences of stillbirth, PTB, GDM, ICP, PPROM, LBW, and SGA were similar between the HBV carrier and non-HBV groups. The proportion of miscarriage was significantly higher among the HBV carriers than the controls (9.36% vs 5.70%; P <0.001). After using multivariate modelling to adjust for possible socio-demographical variables and obstetric complications, women with HBV carrier status were still more likely to have miscarriage (adjusted OR 1.71, 95% CI 1.23-2.38). In addition, the incidences of other maternal and neonatal outcomes were similar between the two groups. CONCLUSION: Maternal HBV carrier status may be an independent risk factor for miscarriage and careful surveillance is warranted.

Slow magnetization relaxation in Ni(II)Dy(III)Fe(III) molecular cycles.

Two cyano- and phenoxo-bridged hexanuclear Ni(II)2Dy(III)2Fe(III)2 (1) and octanuclear Ni(II)4Dy(III)2Fe(III)2 (2) trimetallic cyclic complexes have been obtained. They are the first trimetallic metallocycles. Magnetic studies reveal that 1 and 2 exhibit single-molecule-magnet behavior with an energy barrier of 17.9 K for complex 1 in a 2000 Oe static field and 25.0 K for complex 2 in a zero static field.

Recruitment of IL-27-Producing CD4(+) T Cells and Effect of IL-27 on Pleural Mesothelial Cells in Tuberculous Pleurisy.

BACKGROUND: The numbers of IL-27-producing CD4(+) T cells and the concentration of soluble IL-27 have been found to be increased in tuberculous pleural effusion (TPE). The objective of the present study was to explore the mechanism by which IL-27(+)CD4(+) T cells are recruited into the pleural space, and to explore the impact of IL-27 on pleural mesothelial cells (PMCs). METHODS: The expression profiles of chemokine receptor (CCR) were determined by flow cytometry. The chemoattractant activity of chemokines CCL20 and CCL22 for IL-27(+)CD4(+) T cells in vitro was observed. Effects of IL-27 on wound healing, proliferation and apoptosis of PMCs were also investigated. RESULTS: IL-27(+)CD4(+) T cells in TPE expressed high level of CCR6, medium level of CCR4, and low levels of CCR2, CCR3, CCR5, CCR7, CCR10, and CXCR3. Recruitment of IL-27(+)CD4(+) T cells into TPE could be induced by pleural CCL20 and CCL22. By activating STAT3 signaling, IL-27 significantly improved wound healing and promoted proliferation of PMCs, and completely prevented apoptosis of PMCs induced by IFN-γ. CONCLUSIONS: After being recruited into pleural space by CCL20 or/and CCL22, these pleural IL-27-producing CD4(+) T cells may play important roles in tuberculosis immunity by affecting PMC functions.

Toward higher nuclearity: tetranuclear cobalt(II) metallogrid exhibiting spin crossover.

Supramolecular strategy was employed to achieve the highest nuclearity Co(II) cluster exhibiting spin-crossover (SCO) behavior. Magnetic susceptibility characterization of the Co4(II) complex shows that two different spin-transition processes occur. The SCO behavior is directed by the partially deprotonated polydentate ligand, which favors the structural distortion required by the spin transition.

Efficient allocation of heterogeneous response times in information spreading process.

Recently, the impacts of spatiotemporal heterogeneities of human activities on spreading dynamics have attracted extensive attention. In this paper, we intend to understand how the heterogeneous distribution of response times at the individual level influences information spreading. Based on the uncorrelated scale-free networks without degree-degree correlation, we study the susceptible-infected spreading dynamics with adjustable power-law response time distribution, and find that the stronger the heterogeneity of response times is, the faster the information spreading is in the early and middle stages. Following a given heterogeneity, the procedure of reducing the correlation between the response times and degrees of individuals can also accelerate the spreading dynamics in the early and middle stages. However, the dynamics in the late stage is slightly more complicated, and there is an optimal value of the full prevalence time (i.e., the time for full infection on a network) changing with the heterogeneity of response times and the response time-degree correlation, respectively. The optimal phenomena result from the efficient allocation of heterogeneous response times.

Humanin rescues cultured rat cortical neurons from NMDA-induced toxicity not by NMDA receptor.

Excitatory neurotoxicity has been implicated in many pathological situations and there is no effective treatment available. Humanin is a 24-aa peptide cloned from the brain of patients with Alzheimer's disease (AD). In the present study, excitatory toxicity was induced by N-methyl-D-aspartate (NMDA) in primarily cultured rat cortical neurons. MTT assessment, lactate dehydrogenase (LDH) release, and calcein staining were employed to evaluate the protective activity of humanin on NMDA induced toxicity. The results suggested that NMDA (100 µmol/L, 2.5 hr) triggered neuronal morphological changes, lactate dehydrogenase (LDH) release (166% of the control), reduction of cell viability (about 50% of the control), and the decrease of living cell density (about 50% of the control). When pretreated with humanin, the toxicity was suppressed. The living cells' density of humanin treated group was similar to that of control. The cell viability was attenuated dose-dependently (IC50 = 0.132 nmol/L). The LDH release was also neutralized in a dose-dependent manner. In addition, the intracellular Ca(2+) overloading triggered by NMDA reverted quickly and humanin could not inhibit it. These findings indicate that humanin can rescue cortical neurons from NMDA-induced toxicity in rat but not through interfering with NMDA receptor directly.

Solitary Submandibular Schwannoma Mimicking a Salivary Gland Tumor in a Child.

Tumors occurring in the submandibular space are infrequent among pediatric patients, and benign peripheral nerve tumors in this region are exceptionally rare. This study describes the uncommon occurrence of a schwannoma in the submandibular space in a child and describes its management. A 7-year-old child presented with a gradually enlarging swelling over a 7-month period in the submandibular region, clinically resembling a salivary gland tumor. There were no associated marginal mandibular, lingual, or hypoglossal nerve palsy. The mass was excised completely, and histopathological examination revealed it to be a schwannoma. It is appropriate to consider benign peripheral nerve tumors, such as schwannoma, in the differential diagnosis of submandibular space tumors in children.

Spin transitions in Fe(II) metallogrids modulated by substituents, counteranions, and solvents.

Two bis(tridentate) Schiff base ligands H2L(x) were used to construct three 2×2 grid-type tetranuclear Fe(II) complexes 1-3 to obtain polynuclear spin-crossover materials. Magnetic susceptibility measurements show that the spin states of the complexes are related to the substituents of H2L(x), and that spin transition occurs only in complexes 1 and 2, which are derived from a bulky ligand, whereas complex 3 is diamagnetic. The transition temperatures of complexes 1 and 2 are close to room temperature and are dependent on counteranions. The spin transition of complex 1 can be reversibly tuned by the dehydration and hydration process.

Amygdalin induces apoptosis in human cervical cancer cell line HeLa cells.

Amygdalin, a naturally occurring substance, has been suggested to be efficacious as an anticancer substance. The effect of amygdalin on cervical cancer cells has never been studied. In this study, we found that the viability of human cervical cancer HeLa cell line was significantly inhibited by amygdalin. 4,6-Diamino-2-phenyl indole (DAPI) staining showed that amygdalin-treated HeLa cells developed typical apoptotic changes. The development of apoptosis in the amygdalin-treated HeLa cells were confirmed by double staining of amygdalin-treated HeLa cells with annexin V-FITC and propidium iodide (PI) along with increase in caspase-3 activity in these cells. Further studies indicated that antiapoptotic protein Bcl-2 was downregulated whereas proapoptotic Bax protein was upregulated in the amygdalin-treated HeLa cells implying involvement of the intrinsic pathway of apoptosis. In vivo, amygdalin administration inhibited the growth of HeLa cell xenografts through a mechanism of apoptosis. The results in the present study suggest that amygdalin may offer a new therapeutic option for patients with cervical cancer.

10-(3,5-Dinitro-phen-yl)-5,5-difluoro-1,3,7,9-tetra-methyl-5H-dipyrrolo-[1,2-c:2',1'-f][1,3,2]diaza-borinin-4-ium-5-uide.

In an effort to discover new potential boron-dipyrromethene (BODIPY) dyes, the title compound, C19H17BF2N4O4, was prepared from 2,4-dimethyl-pyrrole, 3,5-dinitro-benzaldehyde and boron trifluoride in a one-pot reaction. The BODIPY fragment is nearly planar, with a maximum deviation from the least-squares plane of 0.251 (2) Å, and the benzene ring is inclined at a dihedral angle of 86.8 (6)° to the BODIPY mean plane. In the crystal, pairs of C-H⋯F hydrogen bonds connect neighbouring mol-ecules into inversion dimers, which are linked by further strong C-H⋯F inter-actions, forming a supra-molecular layered array parallel to the bc plane.

[Exploration of the association of H. pylori and EBV infection with cardiac and distal gastric adenocarcinoma among residents in Cixian County, a high-risk area of esophgeal cancer in Hebei province].

OBJECTIVE: To evaluate the H. pylori and Epstein-Barr virus infection in cardiac and distal gastric adenocarcinoma tissues in residents in Cixian county, a high risk area of esophageal cancer in Hebei province, and to explore the putative role of H. pylori and Epstein-Barr virus infection in the carcinogenesis of adenocarcinoma at different subsites of stomach. METHODS: H. pylori and Epstein-Barr virus latent membrane protein 1 (EBV-LMP1) immunopositivities were determined by Elivision(TM) plus immunohistochemical staining in 190 gastric adenocarcinoma tissues including 144 cases of cardiac adenocarcinoma and 46 cases of distal gastric adenocarcinoma. The relationship between H. pylori and Epstein-Barr virus infection and the subsite, Laurén type as well as other clinicopathological features of gastric adenocarcinoma were analyzed. RESULTS: No significant difference was found between the H. pylori detection rates in cardiac and distal gastric adenocarcinomas(56.9% vs. 65.2%, P > 0.05). The detection rate of H. pylori in intestinal type was significantly higher than that in the diffuse type distal gastric adenocarcinomas (71.8% vs. 28.6%, P < 0.05). No positive expression of EBV-LMP1 was found in the gastric adenocarcinomas in this study. CONCLUSIONS: No significant differences in H. pylori and EBV-LMP1 infections were found between cardiac and distal gastric adenocarcinomas in Cixian county. H. pylori infection is related with the intestinal type of distal gastric adenocarcinoma.

{2-[(3,5-Dimethyl-2H-pyrrol-2-yl-idene-κN)(4-nitro-phen-yl)meth-yl]-3,5-dimethyl-1H-pyrrol-1-ido-κN}difluoridoboron.

In an effort to discover novel and potential boron-dipyrromethene (BODIPY) dyes, the title compound, C(19)H(18)BF(2)N(3)O(2), was prepared from 2,4-dimethyl-pyrrole, 4-nitro-benzaldehyde and BF(3)·Et(2)O in a one-pot reaction. There are two independent mol-ecules, A and B, in the asymmetric unit in which the dihedral angles between the benzene ring and boron-dipyrromethene mean plane have significantly different values [82.71 (8)° for mol-ecule A and 73.16 (8)° for mol-ecule B]. Inter-molecular C-H⋯π inter-actions help to stabilize the crystal structure.