Diagnostic accuracy and cellular origin of pleural fluid CXCR3 ligands for tuberculous pleural effusion.

BACKGROUND: Pleural biomarkers represent potential diagnostic tools for tuberculous pleural effusion (TPE) due to their advantages of low cost, short turnaround time, and less invasiveness. This study evaluated the diagnostic accuracy of two CXCR3 ligands, C-X-C motif chemokine ligand 9 (CXCL9) and CXCL11, for TPE. In addition, we investigated the cellular origins and biological roles of CXCL9 and CXCL11 in the development of TPE. METHODS: This double-blind study prospectively enrolled patients with undiagnosed pleural effusion from two centers (Hohhot and Changshu) in China. Pleural fluid on admission was obtained and levels of CXCL9 and CXCL11 were measured by an enzyme-linked immunosorbent assay (ELISA). The receiver operating characteristic (ROC) curve and the decision curve analysis (DCA) were used to evaluate their diagnostic accuracy and net benefit, respectively. THP-1 cell-derived macrophages were treated with Bacillus Calmette-Guérin (BCG), and quantitative real-time PCR (qRT-PCR) and ELISA were used to determine the mRNA and protein levels of CXCL9 and CXCL11. The chemoattractant activities of CXCL9 and CXCL11 for T helper (Th) cells were analyzed by a transwell assay. RESULTS: One hundred and fifty-three (20 TPEs and 133 non-TPEs) patients were enrolled in the Hohhot Center, and 58 (13 TPEs and 45 non-TPEs) were enrolled in the Changshu Center. In both centers, we observed increased CXCL9 and CXCL11 in TPE patients. The areas under the ROC curves (AUCs) of pleural CXCL9 and CXCL11 in the Hohhot Center were 0.70 (95 % CI: 0.55-0.85) and 0.68 (95 % CI: 0.52-0.84), respectively. In the Changshu Center, the AUCs of CXCL9 and CXCL11 were 0.96 (95 % CI: 0.92-1.00) and 0.97 (95 % CI: 0.94-1.00), respectively. The AUCs of CXCL9 and CXCL11 decreased with the advancement of age. The decision curves of CXCL9 and CXCL11 showed net benefits in both centers. CXCL9 and CXCL11 were upregulated in BCG-treated macrophages. Pleural fluid from TPE and conditioned medium from BCG-treated macrophages were chemotactic for Th cells. Anti-CXCL9 or CXCL11 neutralizing antibodies could partly block the chemotactic activity. CONCLUSIONS: Pleural CXCL9 and CXCL11 are potential diagnostic markers for TPE, but their diagnostic accuracy is compromised in elderly patients. CXCL9 and CXCL11 can promote the migration of peripheral Th cells, thus representing a therapeutic target for the treatment of TPE.

CircMAT2B facilitates the progression of head and neck squamous cell carcinoma via sponging miR-491-5p to trigger ASCT2-mediated glutaminolysis.

Circular RNAs (circRNAs) are well-known to exert significant roles in regulating the pathological processes, including human carcinogenesis. Currently, less is known about their exact roles in head and neck squamous cell carcinoma (HNSCC). Herein, we aimed to investigate and validate the role of a novel circRNA, circMAT2B, as well as its potential molecular mechanism in HNSCC progression. A cohort of 41 paired of HNSCC tumor tissues and adjacent normal tissues from HNSCC patients were collected. Further, we characterized circMAT2B expression patterns in HNSCC tissues and cell lines, as well as exploring its association with the prognosis of HNSCC patients. Biological functions on cell proliferation, apoptosis, migration, and invasion were assessed using Cell Counting Kit-8, EdU incorporation, TUNEL, wound healing, and transwell assays. Glutaminolysis was evaluated by measuring glutamine, glutamate, and α-ketoglutarate (α-KG) levels. The regulatory network of circMAT2B/miR-491-5p/ASCT2 axis was verified by RNA immunoprecipitation and luciferase reporter assays. Western blot was conducted to detect the level of ASCT2 and GLS1. Remarkably overexpressed circMAT2B was observed in HNSCC tissues and cell lines, of which high abundance was positively correlated with patients' poor prognosis. Silencing of circMAT2B inhibited cell proliferation, migration, and invasion, as well as glutaminolysis. miR-491-5p, interacted with ASCT2, was identified to be a downstream target of circMAT2B, thereby involving in circMAT2B-mediated biological effects. In summary, we draw a conclusion that circMAT2B could modulate the processes of cell proliferation, migration, invasion, and glutaminolysis of HNSCC cells partly via the miR-491-5p/ASCT2 axis by a molecular mechanism of competing endogenous RNA (ceRNA), implying an underlying circRNA-targeted therapy for HNSCC treatment.

A Circular RNA, hsa_circ_0018180 (circPARD3), Triggers Glycolysis and Promotes Malignancy of Head and Neck Squamous Cell Carcinoma Through the miR-5194/ENO1 Axis.

Emerging evidence has demonstrated the pivotal roles of circular RNAs (circRNAs) in the modulation of malignancy and pathological progression among multiple human cancers. Glucose metabolism reprogramming is a widely identified characteristic for contributing to facilitate tumorigenesis. Nonetheless, their contributions to head and neck squamous cell carcinoma (HNSCC) cell glycolysis remain to be further elucidated. Herein, we aim to investigate the role of circRNA, hsa_circ_0018180 (also named as circPARD3) in HNSCC. Expression patterns of circPARD3 in HNSCC tissues and different cell lines were determined by qRT-PCR assay, as well as its correlation with the prognosis of survival. CCK-8, EdU incorporation, and transwell assays were carried out to assess the cell viability, proliferation, migration, and invasion, respectively. Glucose uptake and lactate production were evaluated by preforming glycolysis. Mechanistically, the circPARD3/miR-5194/ENO1 axis was verified by RNA immunoprecipitation (RIP) and luciferase reporter assays. Western blot analysis was employed to measure the epithelial-mesenchymal transition (EMT)-associated biomarkers. Upregulated circPARD3 observed in HNSCC tissues and cell lines indicated the poor prognosis of patients. Stable knockdown of circPARD3 dramatically exerted the suppressive effects on cell viability, proliferation, migration, and invasion, as well as glucose uptake and lactate production. Mechanistically, circPARD3 harbored miR-5194, serving as a miRNA sponge, thereby increasing ENO1 expression. Moreover, ENO1 evidently reversed miR-5194-mediated attenuated malignant behaviors. Collectively, our study identified an oncogenic role of circPARD3 in HNSCC through a novel machinery of circPARD3/miR-5194/ENO1 and provided a promising therapeutic target for HNSCC.

Relationships of prenatal organophosphate ester exposure with pregnancy and birth outcomes: A systematic scoping review of epidemiological studies.

Exposure to organophosphate esters (OPEs) during pregnancy has been suggested to be associated with adverse pregnancy and birth outcomes. However, relevant investigations are scarce, and the findings are inconsistent. We aimed to conduct a scoping review to provide an overview of these associations. Electronic databases, including MEDLINE (through PubMed), Web of Science, and CNKI (China National Knowledge Infrastructure), were searched from inception to March 2022 and updated in July 2022. A total of 8 studies (1860 participants) were included. Limited evidence indicates that OPE exposure during pregnancy may be negatively associated with both maternal and neonatal triiodothyronine and tetraiodothyronine concentrations but positively associated with thyroid-stimulating hormone concentrations. OPE exposure during pregnancy may be associated with lower insulin concentrations. OPE exposure during pregnancy was associated with gestational age in a sex-specific manner. Intrauterine OPE exposure might increase the risk of preterm birth in female infants but decrease the risk of preterm birth in male infants. Prenatal OPE exposure might be associated with an increased risk of low birth weight. The current scoping review suggests that OPE exposure during pregnancy may disturb pregnancy and birth health, including adverse thyroid function and birth size. Because of the limited evidence obtained for most associations, additional studies followed by a traditional systematic review are needed to confirm these findings.

Efficacy and safety of pomalidomide and low-dose dexamethasone in Chinese patients with relapsed or refractory multiple myeloma: a multicenter, prospective, single-arm, phase 2 trial.

BACKGROUND: Pomalidomide in combination with dexamethasone has demonstrated positive results in patients with relapsed or refractory multiple myeloma (RRMM), but no data are available in China. We conducted a multicenter, single-arm trial to examine the efficacy and safety of bioequivalent generic pomalidomide plus low-dose dexamethasone in Chinese RRMM patients. METHODS: Adult (≥ 18 years of age) RRMM patients who progressed after at least two previous treatments, including bortezomib and lenalidomide, were eligible. Pomalidomide was given orally at 4 mg/day on days 1 to 21 of a 28-day cycle. Dexamethasone was given at 40 mg/day (either orally or intravenously; 20 mg/day at 75 years or older) on days 1, 8, 15, and 22 of each cycle. Treatment continued until disease progression or intolerable adverse events (AEs). The primary end point was objective response rate (ORR). RESULTS: Seventy-four patients were enrolled between February 2017 and February 2019. All patients had progressed within 60 days of their last therapy. 74.3% of the patients were resistant to lenalidomide, 31.1% had renal insufficiency and 33.8% had high-risk cytogenetic RRMM. The median follow-up duration was 33.0 months (range 31.1-34.8 months). The ORR was 37.8% in the overall analysis, 32.7% in lenalidomide-refractory patients, 36.0% in patients with high-risk cytogenetics and 34.8% in RRMM patients with renal impairment. The median progression-free survival was 5.7 months (95% CI 3.7-8.8 months). The median overall survival was 24.3 months (95% CI 14.4-41.1 months). The most common grade 3 and 4 treatment-emergent adverse events (TEAEs) were neutropenia (63.5%), leukopenia (37.8%), thrombocytopenia (28.4%), and anemia (31.1%). Pulmonary infection (27.0%) was the most frequent grade 3 and 4 nonhematologic TEAE. No previously unreported AEs were observed. No venous thromboembolism was reported. CONCLUSIONS: Pomalidomide in combination with low-dose dexamethasone is effective and safe in Chinese RRMM patients. TRIAL REGISTRATION: The study is registered at Chinese Clinical Trial Registry (ChiCTR) ( ChiCTR-OIC-17013234 , first registered on 03/11/2017).

Prenatal phthalate exposure associated with age-specific alterations in markers of adiposity in offspring: A systematic review.

Childhood obesity and metabolic disorders are of concern and are public health problems globally. Environmental endocrine disruptors, including phthalates, are well known as "obesogens" and "metabolic disruptors". Several studies have investigated the relationships between prenatal phthalate exposure and childhood obesity with inconsistent conclusions. Given the child growth trajectory/pattern as a possible early marker of metabolic disorders, we aimed to assess the effect of prenatal phthalate exposure on offspring growth trajectory. A systematic literature search was conducted using MEDLINE (accessed through PubMed), Web of Science, and CNKI (Chinese National Knowledge Infrastructure) until July 2021. We evaluated the risk of bias for adherence to the prespecified criteria. Fourteen eligible articles were finally included in this systematic review according to the defined PECOS statement. The risk of bias of the included studies was "low" or "probably low", and few were "probably high" and "high". These studies were mostly carried out in the United States (N = 6); others were conducted in China (N = 2), Mexico (N = 2), France (N = 1), Spain (N = 1), Greece (N = 1), and Australia (N = 1) and published from 2015 to 2021. The combined subjects of the 14 studies were 10,396 mother-child pairs. Except for 3 studies not reporting the sex ratio, at least 4001 boys and 3366 girls were included. For the association of prenatal phthalate exposure with an absolute adiposity marker (at a specific visit timepoint), only a few studies were using the same obesity marker as the outcome endpoint and using the same statistical method to explore their associations. However, MEP appeared to be positively associated with several obesity markers, such as the absolute BMI z score, weight-for-age z score, waist circumference, and overweight status. For the association of prenatal phthalate exposure with a repeated measurement of the adiposity marker over the age range, neither associations of adiposity markers with a specific phthalate metabolite nor relationships of a specific adiposity marker with prenatal phthalate exposure were of a consistent result. All four articles reported that phthalate metabolite exposure during pregnancy was associated with children's growth trajectory. Three suggested a sex-specific association between prenatal phthalate exposure and obesity trajectory. In conclusion, the current articles did not show any relationship between prenatal phthalate exposure and children's age-specific outcomes, except for positive associations of prenatal MEP exposure with absolute adiposity markers. However, epidemiological data supported a weak relationship between prenatal phthalate exposure and children's obesity trajectory in a sex-specific manner.

circKIF4A promotes tumorogenesis of glioma by targeting miR-139-3p to activate Wnt5a signaling.

BACKGROUND: Glioma has the characteristics of high incidence and mortality, and is a common malignant tumor of the central nervous system. Circular RNAs (circRNAs) have been reported to play vital roles in progression of cancer including glioma, and circKIF4A is up-regulated in glioma tissues. However, its role and mechanisms in gliomas are unclear. METHODS: circKIF4A and miR-139-3p were determined by qRT-PCR. Transwell assay, wound-healing assay, cell colony formation and flow cytometry were performed to measure cell invasion, migration, proliferation and apoptosis. Western blotting was used to evaluate Wnt/ß-catenin pathway-related protein. Luciferase reporter assays confirmed the relationship among circKIF4A, miR-139-3p and Wnt5a. Sphere formation was performed to measure the ability of glioma-initiating cells (GICs) spheroid formation. A nude mouse xenograft model was established and immunohistochemical staining was used to detect Ki-67 and Wnt5a levels. RESULTS: circKIF4A and Wnt5a were up-regulated and miR-139-3p was down-regulated in both glioma cells and tissues. circKIF4A promoted Wnt5a expression by sponging miR-139-3p. Knockdown of circKIF4A inhibited the colony formation ability, migration and invasion, and promoted the apoptosis of glioma cells by regulating miR-139-3p. Knockdown of circKIF4A inhibited Wnt/ß-catenin signaling pathway and proliferation-related signal via miR-139-3p. Furthermore, knockdown of circKIF4A or overexpression of miR-139 suppressed the ability of sphere formation of GICs and inhibitd Wnt/ß-catenin signaling pathway and proliferation-related signal in GICs. Additionally, depletion of circKIF4A decreased the expression level of Wnt5a and Ki-67, inhibited tumorigenesis in xenograft modes. CONCLUSION: circKIF4A was overexpressed in glioma, and knockdown of circKIF4A suppressed glioma progression via miR-139-3p/Wnt5a axis. The results indicated that circKIF4A may be a potential target for clinical treatment of glioma.

A comparative study of clinical effect of total knee arthroplasty in the treatment of primary osteoarthritis and osteoarthritis of Kashin-Beck disease.

OBJECTIVE: To evaluate the clinical efficacy of total knee arthroplasty (TKA) in the treatment of primary osteoarthritis (OA) and osteoarthritis of Kashin-Beck disease (KBD). METHODS: This study enrolled 77 KBD patients (77 knees, KBD-TKA) and 75 OA patients (75 knees, OA-TKA) who underwent TKA from September 2008 to June 2018. Clinical assessments for each patient were performed pre-operatively and last follow-up. The efficacy measures included the visual analogue scale (VAS) pain score, range of motion (ROM), Hospital for Special Surgery (HSS) score, and short form 36 Health Survey (SF-36) as well as related influencing factors between the two groups. RESULTS: All patients were followed up; the follow-up time of KBD-TKA was 14-132 months, with an average of 72.68 ± 37.55 months; OA-TKA was 15-120 months, with an average of 49.2 ± 28.91 months. There was no difference in pre-operative VAS score (7.29 vs. 7.24) and SF-36 (PCS) score (4.87 vs. 5.49) between KBD-TKA and OA-TKA (P > 0.05), while compared with OA, KBD-TKA had significantly worse pre-operative ROM (75.48° vs. 82.87°), HSS score (36.40 vs. 41.84), and SF-36 (MCS) score (26.28 vs. 28.73) (P < 0.05). At the final follow-up, there was no significant difference in VAS score (1.13 vs. 1.16), ROM (105.79 vs. 105.79), and HSS score (92.06 vs. 92.25) between KBD-TKA and OA-TKA (P > 0.05), while compared with OA, KBD-TKA had significantly worse SF-36 (PCS) score (36.90 vs. 42.00) and SF-36 (MCS) score (55.16 vs. 59.70) (P < 0.05). In a multivariate regression, controlling for multiple potential confounders, diagnosis of KBD was associated with poor quality of life after surgery, whereas pre-operative pain was specifically associated with post-operative pain. However, preoperative gender, age, BMI, and the angles of knee prosthesis (before and after surgery) were not associated with post-operative outcome. CONCLUSION: Patients with KBD undergoing primary TKA have excellent outcomes, comparable with OA at the final follow-up, in spite of worse pre-operative ROM, HSS score, and SF-36(MCS) score. However, KBD patients are worse than OA in terms of general health. Pre-operative age, gender, BMI, and the angles of knee prosthesis were not the factors influencing the clinical efficacy of TKA. The diagnosis of KBD was an independent risk factor for poor quality of life after TKA. Pre-operative pain was a clinically important predictor of outcome.

Prenatal phthalate exposure in relation to gestational age and preterm birth in a prospective cohort study.

This study enrolled 3266 pregnant women, to explore the relationship of prenatal phthalate exposure with the risk of preterm birth and gestational age. All participants filled questionnaires and provided with up to three urine samples during three trimesters. Seven phthalate metabolites in urines were measured. The incidences of very preterm, late preterm, early-term, late-term and postterm births were 0.58%, 3.52%, 24.22%, 10.53%, and 0.34%, respectively. Non-linear relationships were shown between phthalate metabolites and gestational age. Except for monomethyl phthalate (OR = 1.65, 95%CI = 1.17-2.34), the average concentrations of phthalate metabolites were associated with a slightly and insignificantly increased risk of overall preterm birth (<37+0 gestational weeks). Through a restricted cubic spline regression, phthalate metabolites were found to be related to the risk of overall preterm birth in a linear manner (p-value >0.05) or a non-linear manner (p-value <0.05). All curves indicated the overall preterm birth risk rose with the increase of phthalate metabolite concentrations. Finally, compared with full-term birth (39+0 to 40+6 gestational weeks), phthalate metabolites were associated with the elevated risks of very preterm, late preterm and postterm births, although some relationships were not statistically significant. In conclusion, these findings suggested non-linear associations between phthalate metabolites and gestational age. Exposure to some phthalate metabolites was associated with increased risks of overall preterm birth and postterm birth.

[Analysis of ISSR Amplification Results of Six Species in Sect. Cruciata Gaudin].

OBJECTIVE: To identify and analyze the genetic relationship of four species of Gentiana (G. macrophylla, G. straminea, G. dahurica and G. crassicaulis) recorded as Gentianae Macrophyllae Radix in the Chinese Pharmacopoeia, and two other Gentiana species (G. officinalis and G. siphonantha) often used as substitutes by ISSR, in order to estimate the reasonability of G. officinalis and G. siphonantha used as substitutes from the DNA level. METHODS: Eight primers ivere screened to amplify all the samples and agarose gel electrophoresis were analyzed. NTSYSpc-2. 10E software was used to calculate similarity coefficient and draw dendrogram. Results: Nine characteristic bands were found in different species on the ISSR fingerprints and which could be used to identify five species except G. dahurica. The substitute G. officinalis firstly clustered with G. dahurica and G. siphonantha showed closer genetic relationship with G. straminea and G. dahurica. G. crassicaulis showed a far genetic relationship with the other five species. CONCLUSION: The dendrogram based on the ISSR data supports that G. officinalis and G. siphonantha can be used as substitutes of Gentianae Macrophyllae Radix.

Pleural carbohydrate antigen 50 and malignant pleural effusion: a prospective, double-blind diagnostic accuracy test.

Background: Serum carbohydrate antigen 50 (CA50) is an auxiliary diagnostic marker for various solid tumors, but it remains unclear whether CA50 in pleural fluid can assist in the diagnosis of malignant pleural effusion (MPE). This study aimed to evaluate the diagnostic accuracy of pleural fluid CA50 for MPE in pleural effusion patients with undetermined causes. Methods: This study prospectively recruited pleural effusion patients with undetermined causes who visited the Affiliated Hospital of Inner Mongolia Medical University between September 2018 and July 2021. We measured pleural fluid CA50 level with an electrochemiluminescence assay. We analyzed the diagnostic accuracy of CA50 and carcinoembryonic antigen (CEA) for MPE with the receiver operating characteristic (ROC) curve. The net benefits of CA50 and CEA were analyzed using the decision curve analysis (DCA). Results: We enrolled 66 MPEs and 87 benign pleural effusions (BPEs). MPE patients had significantly higher CA50 and CEA than BPE patients. The area under the ROC curve (AUC) of CA50 was 0.72 (95% CI: 0.63-0.80). CA50 had a sensitivity of 0.30 (95% CI: 0.19-0.41) and a specificity of 1.00 (95% CI: 1.00-1.00) at the threshold of 15 IU/mL. The decision curve of CA50 was above the reference line at the calculated risk probability of between 0.30 and 1.00. Venn diagram indicated that some patients with low CEA (<50 or <150 ng/mL) and/or negative cytology can be identified by positive CA50 (>15 IU/mL). Conclusions: Pleural fluid CA50 has moderate accuracy and net benefit for detecting MPE. CA50 >15 IU/mL can be used to diagnose MPE. The combination of CA50 and CEA improves the diagnostic sensitivity for MPE.

Inhibition of Bcl-6 Expression Ameliorates Asthmatic Characteristics in Mice.

OBJECTIVE: The function of Bcl-6 in T follicular helper (Tfh) cell maturation is indispensable, and Tfh cells play a pivotal role in asthma. This study investigated the impact of Bcl-6 on asthmatic traits. METHODS: The microscopic pathological alterations, airway resistance (AR), and lung compliance (LC) were determined in asthmatic mice and Bcl-6 interference mice. The surface molecular markers of Tfh cells and the Bcl-6 mRNA and protein expression were determined by flow cytometry, RT-qPCR, and Western blotting, respectively. The relationships between the Tfh cell ratio and the IgE and IgG1 concentrations in peripheral blood mononuclear cells (PBMCs) and bronchoalveolar lavage fluid (BALF) were determined. RESULTS: Asthmatic inflammatory changes were observed in the lung tissue and were attenuated by Bcl-6 siRNA and dexamethasone (DXM). Asthmatic mice exhibited an increased AR and a decreased LC, while Bcl-6 siRNA or DXM mitigated these changes. The percentages of Tfh cells and eosinophils were significantly increased in the asthmatic mice, and they significantly decreased after Bcl-6 inhibition or DXM treatment. RT-qPCR and Western blotting analyses revealed that the Bcl-6 expression level in PBMCs was significantly higher in asthmatic mice, and it decreased following Bcl-6 inhibition or DXM treatment. The IgE expression in the serum and BALF and the B cell expression in PBMCs exhibited a similar trend. In asthmatic mice, the ratio of Tfh cells in the peripheral blood showed a strong positive correlation with the IgE levels in the serum and BALF, but not with the IgG1 levels. CONCLUSION: The amelioration of airway inflammation and airway hyper-responsiveness is achieved through Bcl-6 suppression, which effectively hinders Tfh cell differentiation, ultimately resulting in a concurrent reduction in IgE production.

Impact of periconceptional multi-micronutrient supplementation on gestation: a population-based study.

OBJECTIVE: To examine the effect of periconceptional multi-micronutrient supplementation on gestation and birth outcomes. METHODS: A population-based community intervention program was conducted in 18 counties in China. Participants were divided into an intervention group, who received multi-micronutrient supplementation from at least 3 months before pregnancy throughout the first trimester, and a control group. Pregnant women were followed up to record information about birth outcomes. Maternal socio-economic characteristics and main birth outcomes were evaluated. Gestational age was further analyzed using survival analysis, to determine the time distribution of delivery. RESULTS: Periconceptional multi-micronutrient supplementation was associated with higher birth weight, birth length and occipitofrontal head circumference, and with lower incidence rates for stillbirth, low birth weight, and preterm birth. Moreover, periconceptional multi-micronutrient supplementation changed the time distribution of delivery, making the deliveries more clustered in the period between day 275 and day 295 of gestation. CONCLUSION: Our study shows that periconceptional multi-micronutrient supplementation is beneficial for fetal development and optimizes all measured aspects of health in neonates in socioeconomically disadvantaged areas in China. The change in time distribution of deliveries caused by multi-micronutrient supplementation needs further clarification.

[Comparison of the targeting properties of 2-deoxy-D-glucose-conjugated nanoparticles to breast cancer MDA-MB-231 cells and breast fibroblasts cells].

OBJECTIVE: To compare the differences in uptake of 2-deoxy-D-glucose (2-DG)-conjugated nanoparticles between breast carcinoma MDA-MB-231 cells with high metabolism and breast fibroblasts with normal metabolism, and investigate the feasibility of using the coated nanoparticles as a MRI-targeted contrast agent for highly metabolic carcinoma cells. METHODS: The γ-Fe2O3@DMSA-DG was prepared. The glucose metabolism level of both cell lines was determined. The targeting efficacy of γ-Fe2O3@DMSA-DG and γ-Fe2O3@DMSA NPs to breast carcinoma MDA-MB-231 cells and breast fibroblasts at 10 min, 30 min, 1 h and 2 h was measured with Prussian blue staining and UV colorimetric assay. MRI was performed to visualize the changes of T2WI signal intensity. RESULTS: Prussian blue staining showed more intracellular blue granules in the MDA-MB-231 cells of γ-Fe2O3@DMSA-DG NPs group than that in the γ-Fe2O3@DMSA NPs group, and the γ-Fe2O3@DMSA-DG uptake was greatly competed by free D-glucose. As revealed by UV colorimetric assay, MDA-MB-231 cells also showed that the cellular iron amount of γ-Fe2O3@DMSA-DG group was significantly higher than that of the γ-Fe2O3@DMSA group and γ-Fe2O3@DMSA-DG + D-glucose group, statistically with a significant difference between them. MRI showed that the signal intensity of γ-Fe2O3@DMSA-DG group was decrease significantly, the T2 signal intensity was decreased by 10.5%, 37.5%, 72.9%, 92.0% for 10 min, 30 min, 1 h and 2 h, respectively. In contrast, the signal intensity did not show obvious decrease in the γ-Fe2O3@DMSA-DG group, the T2 signal intensity was decreased by 8.5%, 11.4%, 32.0%, 76.7% for 10 min, 30 min, 1 h and 2 h, respectively. However, HUM-CELL-0056 cells did not produce apparent difference for positive staining in the γ-Fe2O3@DMSA-DG group, γ-Fe2O3@DMSA group and γ-Fe2O3@DMSA-DG+D-glucose group, and the signal intensity also did not produce apparent difference. CONCLUSIONS: γ-Fe2O3@DMSA-DG has good targeting ability to highly metabolic breast carcinoma (MDA-MB-231) cells. It is feasible to serve as a specific MRI-targeted contrast agent for highly metabolic carcinoma cells, and deserves further studies in vivo.

[Optimization extraction conditions of triphyllin A in Pronephrium triphyllum].

OBJECTIVE: To optimize the extraction conditions for triphyllin A in Pronephrium triphyllum. METHODS: The content of triphyllin A in the Pronephrium triphyllum was determined by HPLC. Concentration and volume of the alcohol,time and times of the extraction were assayed by orthogonal test to detect their influences on the extraction rate of triphyllin A in the Pronephrium triphyllum. RESULTS: Alcohol volume and extraction times had significant influence on the process (P < 0.05) while alcohol concentration and extraction time had no effect. The optimal extraction conditions were as follows:50 fold 60% alcohol, extraction for 3 times and 50 min for each time. CONCLUSION: The extration rate of triphyllin A is higher,and the process can be used for the development and production of Pronephrium triphyllum.

The effects of health education and exercise style changes on the maturation of autologous arteriovenous fistula in hemodialysis patients: A randomized controlled trial.

BACKGROUND: Upper limb exercise has long been considered to be the main means to promote autogenous arteriovenous fistula (AVF) maturation, but in practice exercise intensity and compliance are both typically lacking. Several randomized controlled trials (RCTs) have demonstrated the good effects of functional resistance or pressure exercise in patients with AVF. However, many patients' have difficulty complying with upper limb exercise programs without systematic health education. Therefore, we argue that resistance and pressure exercise supported by health education is actually the most beneficial for AVF patients. METHODS: We randomly divided 114 patients into a control group and an experimental group of 57 patients each. In the control group, conventional care was used, and in the experimental group, online health education based on the IMB (Information-Motivation-Behavior skills) model and functional resistance and pressure upper limb exercises was implemented with the AVF side arm. The failure rate of AVF maturation, clinical maturation time, cephalic venous blood flow, vessel diameter, and vessel skin thickness were compared between the two groups. RESULTS: Fifty-five cases were included for each in the final study. The primary outcome of this study was the failure rate of AVF maturation. Secondary outcomes included clinical maturation time, cephalic vein flow, vessel diameter, and vessel thickness. The failure rate of AVF maturation in the experimental group was significantly lower than that in the control group, and the clinical maturation time in the experimental group was significantly shorter than that in the control group. For the remaining three indicators, there were between-group effects, time effects, and interaction effects in both groups. Comparison between groups showed that there was no statistical difference in the observed indicators of cephalic vein flow, vessel diameter, or vessel thickness between the two groups before the intervention but that there was a statistical difference at the end of the 4th, 8th, and 12th weeks of the intervention. A 2 × 2 comparison also showed that there was a statistical difference between the three indicators at each time point within the two groups. CONCLUSION: IMB model-based online health education combined with functional resistance and pressure exercises can improve AVF maturation status and accelerate AVF maturation within 12 weeks of surgery.

Long-term stability of pleural fluid carcinoembryonic antigen and its effect on the diagnostic accuracy for malignant pleural effusion.

BACKGROUND: The in vitro stability assessment is essential for investigating the diagnostic accuracy of pleural biomarkers. This study aimed to investigate the long-term stability of pleural fluid carcinoembryonic antigen (CEA) at -80°C to -70°C. In addition, we analyzed the effects of frozen storage on the diagnostic accuracy of CEA for malignant pleural effusion (MPE). METHODS: Pleural fluid CEA of participants in two prospective cohorts were stored at -80°C to -70°C for 1-3 years. The CEA level in the stored specimen was measured with an immunoassay, and its level in the fresh specimen was extracted from medical records. The Bland-Altman method, Passing-Bablok regression, and Deming regression were used to analyze the agreement of CEA between the fresh and frozen pleural fluid. In addition, we used receiver operating characteristic (ROC) curves to evaluate the diagnostic accuracy of CEA in the fresh and frozen specimens for MPE. RESULTS: A total of 210 participants were enrolled. The median CEA levels in frozen and fresh pleural fluid specimens were similar (frozen, 2.32 ng/mL; fresh, 2.59 ng/mL; p < 0.01). The slopes and intercepts in the Passing-Bablok regression (intercept 0.01, slope 1.04) and Deming regression (intercept 0.65; slope 1.00) were not statistically significant (p > 0.05 for all). No significant difference was observed between the area under the ROC curves of CEA in the fresh and frozen specimens (p > 0.05 for all). CONCLUSION: Pleural fluid CEA is seemingly stable when stored at -80°C to -70°C for 1-3 years. Frozen storage does not significantly affect the diagnostic accuracy of CEA for MPE.

Diagnostic accuracy of pleural fluid to serum carcinoembryonic antigen ratio and delta value for malignant pleural effusion: findings from two cohorts.

BACKGROUND: Pleural fluid (PF) carcinoembryonic antigen (CEA) is a widely used diagnostic marker for malignant pleural effusion (MPE). Recent studies revealed that PF to serum CEA was also a promising diagnostic parameter for MPE. OBJECTIVE: We aimed to investigate whether PF to serum CEA ratio and delta CEA (PF minus serum CEA) provided added value to PF CEA in diagnosing MPE. METHODS: Patients with pleural effusion in a retrospective cohort (BUFF) and a prospective cohort (SIMPLE) were included. The clinical characteristics of the patients were extracted from their medical records. The diagnostic value of CEA ratio and delta CEA was estimated by a receiver operating characteristics (ROC) curve, net reclassification improvement (NRI), and integrated discrimination improvement (IDI). RESULTS: A total of 148 patients in the BUFF cohort and 164 patients in the SIMPLE cohort were enrolled. The BUFF cohort had 46 MPE patients and 102 benign pleural effusion (BPE) patients, and the SIMPLE cohort had 85 MPE patients and 79 BPE patients. In both cohorts, MPE patients had significantly higher PF CEA, serum CEA, CEA ratio, and delta CEA. The area under ROC curves (AUCs) of PF CEA, CEA ratio, and delta CEA were 0.78 (95% CI: 0.67-0.88), 0.80 (95% CI: 0.72-0.89) and 0.83 (95% CI: 0.75-0.91) in the BUFF cohort, and 0.89 (95% CI: 0.83-0.94), 0.86 (95% CI: 0.80-0.92), and 0.84 (95% CI: 0.78-0.91) in the SIMPLE cohort. The differences between the AUCs of PF CEA, CEA ratio, and delta CEA did not reach statistical significance. The continuous NRI and IDI of CEA ratio and delta CEA were <0. CONCLUSION: CEA ratio and delta value cannot provide added diagnostic value to PF CEA. The simultaneous determination of serum and PF CEA should not be adopted in clinical practice.

Inhalation of hydrogen gas attenuates ouabain-induced auditory neuropathy in gerbils.

AIM: Auditory neuropathy (AN) is a hearing disorder characterized by abnormal auditory nerve function with preservation of normal cochlear hair cells. This study was designed to investigate whether treatment with molecular hydrogen (H(2)), which can remedy damage in various organs via reducing oxidative stress, inflammation and apoptosis, is beneficial to ouabain-induced AN in gerbils. METHODS: AN model was made by local application of ouabain (1 mmol/L, 20 mL) to the round window membrane in male Mongolian gerbils. H(2) treatment was given twice by exposing the animals to H(2) (1%, 2%, and 4%) for 60 min at 1 h and 6 h after ouabain application. Before and 7 d after ouabain application, the hearing status of the animals was evaluated using the auditory brainstem response (ABR) approach, the hear cell function was evaluated with distortion product otoacoustic emissions (DPOAE). Seven days after ouabain application, the changes in the cochleae, especially the spiral ganglion neurons (SGNs), were morphologically studied. TUNEL staining and immunofluorescent staining for activated caspase-3 were used to assess the apoptosis of SGNs. RESULTS: Treatment with H(2) (2% and 4%) markedly attenuated the click and tone burst-evoked ABR threshold shift at 4, 8, and 16 kHz in ouabain-exposed animals. Neither local ouabain application, nor H(2) treatment changed the amplitude of DPOAE at 4, 8, and 16 kHz. Morphological study showed that treatment with H(2) (2%) significantly alleviated SGN damage and attenuated the loss of SGN density for each turn of cochlea in ouabain-exposed animals. Furthermore, ouabain caused significantly higher numbers of apoptotic SGNs in the cochlea, which was significantly attenuated by the H(2) treatment. However, ouabain did not change the morphology of cochlear hair cells. CONCLUSION: The results demonstrate that H(2) treatment is beneficial to ouabain-induced AN via reducing apoptosis. Thus, H(2) might be a potential agent for treating hearing impairment in AN patients.

[Clinical features and outcome analyses of newly-diagnosed multiple myeloma with extramedullary involvements].

OBJECTIVE: To explore the clinical features and prognostic factors of newly-diagnosed multiple myeloma (MM) with extramedullary (EM) involvements. METHODS: The clinical features, efficacies, survival rates and prognostic factors were retrospectively analyzed in 46 MM patients with EM (group A) from January 2000 to October 2011. And another 53 MM patients without EM (group B) were selected as the controls. RESULTS: The median age of Group A was 58 years. Compared with group B, the incidence of EM was associated with a higher level of ß2-microglobulin (ß2-MG) and extensive bone disease. The most common location of EM was soft tissues. And the total effective rates of groups A and B were 58.5% (24/41) and 78.8% (41/52) respectively. The difference was statistically significant (P = 0.042). The median follow-up time was 28(2-88) months. The estimated overall survival (OS) of the patients with EM was significantly shorter than those without EM (42.6 vs 53.9 months, P = 0.009). Log-rank univariate analysis showed that the number of osteolytic lesions ≥ 3, ß2-MG ≥ 5.5 mg/L, hemoglobin ≤ 110 g/L and albumin ≤ 30 g/L were poor prognostic factors in MM patients with EM. Multivariate analysis with Cox model showed only the number of osteolytic lesions ≥ 3 (OR = 2.327, 95%CI: 1.282 - 4.224) and ß2-MG ≥ 5.5 mg/L (OR = 2.677, 95%CI: 1.092 - 6.566) were statistically significant. CONCLUSIONS: Multiple EM lesions may be involved in MM patients. For the patients with EM, the response to conventional chemotherapy is poor and the prognosis is unfavorable, especially for those with a high level of ß2-MG or the number of osteolytic lesions ≥ 3.