Confused subcutaneous nodules in children: Differential diagnosis of pilomatricoma in children.

BACKGROUND: Pilomatricoma is a common but easily misdiagnosed tumor in children. AIMS: To differentiate pilomatricoma from other common subcutaneous nodules in children. PATIENTS/METHODS: Misdiagnosed subcutaneous nodules in four children were recorded. RESULTS: A red mass on a 7-year-old boy's head which had been misdiagnosed pyogenic granuloma was proved to be pilomatricoma. A red mass on an 8-month-old boy's face which had been misdiagnosed infantile hemangioma also turned to be pilomotricoma. A red mass on a 21-month-old girl's breast, which had been misdiagnosed pilomatricoma, was proved to be infantile myofibroma. A subcutaneous nodule under a 13-month-old girl's armpit, which had been misdiagnosed pilomatricoma, turned to be BCG-associated lymphadenitis. CONCLUSIONS: When a child with a subcutaneous nodule attends, pilomatricoma, vascular tumors, fibrous tumors, and BCG-associated lymphadenitis should be considered.

[Design, manufacture and evaluation of a multi-parameter controllable automatic fire-acupuncture instrument].

A multi-parameter controllable automatic fire-acupuncture instrument was developed by integrating traditional fire needling with modern medical device technology. A gun-like appearance was designed for easy hand-held operation, the electromagnetic induction was for heating needle body, a scale knob was for controlling the needle insertion depth, the combination of electromagnetic ejection and spring return was for the precise control of the needle retention time; and the changeable single ste-rile needle or multiple needles were adopted to meet individual demand, obtain high efficiency and prevent infection. All of these designs are associated with the overall process control system to ensure the exact controllability of needle body temperature, needling density, insertion depth and needle retention time. Besides, this device is advantageous at handy and aseptic operation with high efficiency, conformability and visualization. In this research, this instrument was tested in animals for the impacts of automatic fire needling on skin damage and fur growth. It is found that the accurate control of each parameter is of the significant advantage in the safety and effectiveness of treatment, which lays a solid foundation for the subsequent systematic review on safety and effectiveness.

Pharmacodynamic, pharmacokinetic, and phase 1a study of bisthianostat, a novel histone deacetylase inhibitor, for the treatment of relapsed or refractory multiple myeloma.

HDAC inhibitors (HDACis) have been intensively studied for their roles and potential as drug targets in T-cell lymphomas and other hematologic malignancies. Bisthianostat is a novel bisthiazole-based pan-HDACi evolved from natural HDACi largazole. Here, we report the preclinical study of bisthianostat alone and in combination with bortezomib in the treatment of multiple myeloma (MM), as well as preliminary first-in-human findings from an ongoing phase 1a study. Bisthianostat dose dependently induced acetylation of tubulin and H3 and increased PARP cleavage and apoptosis in RPMI-8226 cells. In RPMI-8226 and MM.1S cell xenograft mouse models, oral administration of bisthianostat (50, 75, 100 mg·kg-1·d-1, bid) for 18 days dose dependently inhibited tumor growth. Furthermore, bisthianostat in combination with bortezomib displayed synergistic antitumor effect against RPMI-8226 and MM.1S cell in vitro and in vivo. Preclinical pharmacokinetic study showed bisthianostat was quickly absorbed with moderate oral bioavailability (F% = 16.9%-35.5%). Bisthianostat tended to distribute in blood with Vss value of 0.31 L/kg. This distribution parameter might be beneficial to treat hematologic neoplasms such as MM with few side effects. In an ongoing phase 1a study, bisthianostat treatment was well tolerated and no grade 3/4 nonhematological adverse events (AEs) had occurred together with good pharmacokinetics profiles in eight patients with relapsed or refractory MM (R/R MM). The overall single-agent efficacy was modest, stable disease (SD) was identified in four (50%) patients at the end of first dosing cycle (day 28). These preliminary in-patient results suggest that bisthianostat is a promising HDACi drug with a comparable safety window in R/R MM, supporting for its further phase 1b clinical trial in combination with traditional MM therapies.

Templated-Assisted Synthesis of Structurally Ordered Intermetallic Pt3Co with Ultralow Loading Supported on 3D Porous Carbon for Oxygen Reduction Reaction.

Simple and reliable mass production of platinum-based alloy catalysts with excellent activity and stability is an enormous challenge for the wide commercialization of proton-exchange membrane fuel cells (PEMFC), especially those with ultralow loading of Pt. Herein, an economical, highly durable, and efficient catalyst consisting of structurally ordered intermetallic Pt3Co alloy nanoparticles with ultralow Pt loading (1.4 wt %) supported on hierarchically porous carbon structure (three-dimensional, 3D Pt3Co/C) were synthesized with large-scale production by the NaCl-template-assisted approach. The obtained best sample, 3D Pt3Co/C#1, exhibited mass activities of 11.56 and 0.70 A mgPt-1 for oxygen reduction reactions (ORRs) in alkaline and acidic electrolytes, which are 60.8 and 6.4 times those of commercial Pt/C, respectively. Furthermore, the 3D Pt3Co/C#1 exhibited excellent stability both in acidic and alkaline electrolytes, with almost no decay of the half-wave potential after 5000 potential cycles. This work proposes a new high-yielding, simple, and environmentally friendly method to fabricate excellent Pt-based alloy electrocatalysts with ultralow loading of Pt, which opens up new hopes for the development of PEMFC.

ALDH3B2 Polymorphism Is Associated with Colorectal Cancer Susceptibility.

Colorectal cancer (CRC) is the 5th leading cancer in China. Alcohol consumption has been reported to be one of the risk factors of CRC. However, it remains unclear whether genetic variants of alcohol metabolic genes are associated with CRC risk. In this study, we tested the coding variants in the alcohol metabolic genes and the risk of CRC, by using 485 cases and 516 controls. A total of 16 germline coding variants in 10 alcohol metabolic genes were genotyped. We identified that rs3741178 in ALDH3B2 was significantly associated with CRC risk with odds ratio being 2.13 (95% CI: 1.24-3.68, P=0.0064). Further functional annotation suggested that this variant may damage the protein function of ALDH3B2. Our results suggested that ALDH3B2 in the alcohol metabolism pathway contributed to the development of CRC, which may contribute to the prevention of this disease in the future.

Application of the adenosine triphosphate sensitivity assay in infantile vascular anomalies.

BACKGROUND: The term vascular anomalies include various vascular tumors and vascular malformations, among them infantile hemangiomas and capillary malformations are the most well-known associated diseases in early ages. Multiple drugs have been introduced for intervention, but susceptibility test in vitro were scarcely reported. OBJECTIVE: To evaluate the inhibition effect of different drugs by adenosine triphosphate sensitivity assay in vitro before the treatment of infantile hemangiomas and capillary malformations. METHODS: Specimens were selected from 5 cases of infantile hemangiomas and 11 cases of capillary malformations. Propranolol, rapamycin, sildenafil and itraconazole were tested for their growth inhibition effect by using the adenosine triphosphate sensitivity assay. RESULTS: Propranolol demonstrated inhibitory effects on infantile hemangiomas cells. Rapamycin and itraconazole both showed inhibitory effects on infantile hemangiomas cells and capillary malformations cells. Sildenafil has no growth inhibitory effect on infantile hemangiomas cells or capillary malformations cells. CONCLUSION: Adenosine triphosphate sensitivity assay is a sensitive and useful testing method before the management of vascular anomalies, and individualized medication suggestions for the choice of therapeutic drugs were offered based on the testing result and together with a comprehensive evaluation of each infant.

[Construction of artesunate nanoparticles modified by hyaluronic acid and cell-penetrating peptides and its inhibitory effect on cancer cells in vitro].

Hyaluronic acid (HA) and cell-penetrating peptide (CPP) R6H4-SA modified artesunate nanostructured lipid carrier (HA-R6H4-NLC/ART) for anti-tumor therapy was prepared. The physicochemical properties and in vitro drug release of HA-R6H4-NLC/ART were evaluated, and the uptake and cytotoxicity of liver cancer HepG2 cells were studied. The results showed that HA-R6H4-NLC/ART was spherical like in appearance, and the average particle size was about 160 nm. In vitro release experiments showed that the drug delivery system had sustained release characteristics. Cell results showed that, in slightly acidic environment, pH sensitive CPP R6H4-SA mediated cellular uptake of nanoparticles was significantly higher than that of non-sensitive peptide R8-SA. Meanwhile, HA-R6H4-NLC/ART had a targeting effect on HepG2 cells, and the HA receptor saturation experiment showed that the endocytosis of HA-R6H4-NLC/ART was mediated by the HA receptor on the cell surface. As compared with the unmodified or R6H4-SA single modified group, HA and R6H4-SA co-modified HA-R6H4-NLC/ART significantly improved the cell uptake and had a stronger anti-tumor effect under the conditions of the slightly acid environment and hyaluronidase degradation. The above results showed that hyaluronic acid and CPP R6H4-SA co-modified artesunate nanostructured lipid carrier, which can effectively identify and penetrate the tumor cell membrane into the cell, is a potentially efficient targeting delivery system for anti-tumor drugs.

Dithiolato- and halogenido-bridged nickel-iron complexes related to the active site of [NiFe]-H2ases: preparation, structures, and electrocatalytic H2 production.

A new series of the structural and functional models for the active site of [NiFe]-H2ases has been prepared by a simple and convenient synthetic route. Thus, treatment of diphosphines RN(PPh2)2 (1a, R = p-MeC6H4CH2; 1b, R = EtO2CCH2) with an equimolar NiCl2·6H2O, NiBr2·3H2O, and NiI2 in refluxing CH2Cl2/MeOH or EtOH gave the mononuclear Ni complexes RN(PPh2)2NiX2 (2a, R = p-MeC6H4CH2, X = Cl; 2b, R = EtO2CCH2, X = Cl; 3a, R = p-MeC6H4CH2, X = Br; 3b, R = EtO2CCH2, X = Br; 4a, R = p-MeC6H4CH2, X = I; 4b, R = EtO2CCH2, X = I) in 67-97% yields. Further treatment of complexes 2a,b-4a,b with an equimolar mononuclear Fe complex (dppv)(CO)2Fe(pdt) and NaBF4 resulted in formation of the targeted model complexes [RN(PPh2)2Ni(µ-pdt)(µ-X)Fe(CO)(dppv)](BF4) (5a, R = p-MeC6H4CH2, X = Cl; 5b, R = EtO2CCH2, X = Cl; 6a, R = p-MeC6H4CH2, X = Br; 6b, R = EtO2CCH2, X = Br; 7a, R = p-MeC6H4CH2, X = I; 7b, R = EtO2CCH2, X = I) in 60-96% yields. All the new complexes 3a,b-4a,b and 5a,b-7a,b have been characterized by elemental analysis and spectroscopy, and particularly for some of them (3a,b/4a,b and 5b/6b) by X-ray crystallography. More interestingly, the electrochemical and electrocatalytic properties of such halogenido-bridged model complexes are first studied systematically and particularly they have been found to be pre-catalysts for proton reduction to H2 under CV conditions.

Comorbid Conditions are Associated With Emergency Department Visits, Hospitalizations, and Medical Charges of Patients With Systemic Lupus Erythematosus.

BACKGROUND/OBJECTIVES: In addition to increase mortality, comorbidities can increase medical costs for systemic lupus erythematosus (SLE). Healthcare utilization can dramatically increase medical costs. It is essential to better understand the comorbidities that can lead to healthcare utilization, such as emergency department visit and/or hospitalization, for SLE patients. Therefore, the objective of this study was to examine the associations between comorbidities and healthcare utilization and medical charges of patients with SLE. METHODS: Nebraska statewide emergency departments (ED) discharge and hospitals discharge data from 2007 to 2012 were used to study the comorbid conditions of patients with SLE. SLE was defined using the standard International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) diagnosis codes (710.0). RESULTS: There were more comorbid conditions in patients with SLE than patients without SLE. Comorbid conditions were majorly related to ED visits and hospitalizations of patients with SLE. Chest pain, abdominal pain, injury, acute respiratory infections, symptoms of digestive systems, headache, myalgia and myositis, noninfectious gastroenteritis and colitis, and symptoms of skin and other integumentary systems are common comorbid conditions for ED visits. Infections, cardiovascular diseases, fractures, chronic obstructive pulmonary disease (COPD) and allied conditions, cerebrovascular diseases, and episodic mood disorder are common comorbid conditions for hospitalizations of patients with SLE. In addition, the numbers of comorbid conditions were significantly associated with the length of hospital stay and hospital charges for SLE patients. CONCLUSION: The findings in this study indicated that comorbid conditions are associated with healthcare utilization and medical charges of patients with SLE.

Comorbid conditions are associated with healthcare utilization, medical charges and mortality of patients with rheumatoid arthritis.

This study aims to examine the associations between comorbid conditions and healthcare utilization, medical charges, or mortality of patients with rheumatoid arthritis (RA). Nebraska state emergency department (ED) discharge, hospital discharge, and death certificate data from 2007 to 2012 were used to study the comorbid conditions of patients with RA. RA was defined using the standard International Classification of Diseases (ICD-9-CM 714 or ICD-10-CM M05, M06, and M08). There were more comorbid conditions in patients with RA than in patients without RA. Comorbid conditions were majorly related to healthcare utilization and mortality of patients with RA. In addition to injury, fracture, sprains, and strains, symptoms of cardiovascular and digestive systems, respiratory infection, and chronic obstructive pulmonary disease (COPD) were common comorbid conditions for ED visits. In addition to joint replacement and fracture, infections, COPD and cardiovascular comorbidities were common comorbid conditions for hospitalizations. Cardiovascular, cerebrovascular, and respiratory comorbidities, dementia, malignant neoplasm, and diabetes mellitus were common comorbid conditions for deaths of patients with RA. In addition, the numbers of comorbid conditions were significantly associated with the length of hospital stay and hospital charges for patients with RA. The findings in this study indicated that comorbid conditions are associated with healthcare utilization, medical charges, and mortality of patients with RA.

Lycopene reduces mortality in people with systemic lupus erythematosus: A pilot study based on the third national health and nutrition examination survey.

INTRODUCTION: Persistent inflammation and oxidative stress are the main mechanisms that increase the risks of cardiovascular disease-related morbidity and mortality in systemic lupus erythematosus (SLE). As a natural antioxidant, lycopene can alleviate oxidative stress and suppress inflammation. We hypothesized that lycopene could have the potential to reduce mortality in SLE. METHOD: Thirty-seven participants with SLE from the NHANES III were divided into two groups (higher level group and lower level group) by rank method according to serum lycopene. These participants were followed-up from the date of interview (1988-1994) to 31 December 2006 for mortality. Mortality rate and survival function were compared between the two SLE groups. RESULTS: The mortality rate was significantly lower in the higher level group (5.3%) than that in the lower level group (33.3%). There was a significant survival difference between the higher level group and the lower level group (Log rank p = 0.0436). In addition, cardiovascular disease-related mortality was dramatically lower in the higher level group than that in the lower level group. CONCLUSIONS: These findings from nationally representative samples indicate that higher serum lycopene has the protective effect on mortality in SLE. Further studies with large sample size are needed to confirm these primary results.

Synthetic and Structural Studies of 2-Acylmethyl-6-R-Difunctionalized Pyridine Ligand-Containing Iron Complexes Related to [Fe]-Hydrogenase.

As active site models of [Fe]-hydrogenase, tridentate 2-acylmethyl-6-methoxymethoxy-difunctionalized pyridine-containing complexes η(3)-(2-COCH2-6-MeOCH2OC5H3N)Fe(CO)2(L1) (4, L1 = I; 5, SCN; 6, PhCS2) were prepared via the following multistep reactions: (i) etherification of 2-MeO2C-6-HOC5H3N with ClCH2OMe to give 2-MeO2C-6-MeOCH2OC5H3N (1), (ii) reduction of 1 with NaBH4 to give 2-HOCH2-6-MeOCH2OC5H3N (2), (iii) esterification of 2 with 4-toluenesulfonyl chloride to give 2-TsOCH2-6-MeOCH2OC5H3N (3), (iv) nucleophilic substitution of 3 with Na2Fe(CO)4 followed by treatment of the resulting Fe(0) intermediate Na[(2-CH2-6-MeOCH2OC5H3N)Fe(CO)4] (M1) with I2 to give complex 4, and (v) condensation of 4 with KSCN and PhCS2K to give complexes 5 and 6, respectively. In contrast to the preparation of complexes 4-6, bidentate 2-acylmethyl-6-methoxymethoxy-difunctionalized pyridine-containing model complexes η(2)-(2-COCH2-6-MeOCH2OC5H3N)Fe(CO)2(I)(L2) (7, L2 = PPh3; 8, Cy-C6H11NC) and η(2)-(2-COCH2-6-MeOCH2OC5H3N)Fe(CO)2(L3) (9, L3 = 2-SC5H4N; 10, 8-SC9H6N) were prepared by ligand exchange reactions of 4 with PPh3, Cy-C6H11NC, 2-KSC5H4N, and 8-KSC9H6N, respectively. Particularly interesting is that the tridentate 2,6-bis(acylmethyl)pyridine- and 2-acylmethyl-6-arylthiomethylpyridine-containing model complexes η(3)-[2,6-(COCH2)2C5H3N]Fe(CO)2(L4) (11, L4 = PPh3; 12, CO) and η(3)-2-(COCH2-6-ArSCH2C5H3N)Fe(CO)2(ArS) (13, ArS = PhS; 14, 2-S-5-MeC4H2O) were obtained, unexpectedly, when 2,6-(TsOCH2)2C5H3N reacted with Na2Fe(CO)4 followed by treatment of the resulting mixture with ligands PPh3 and CO or disulfides (PhS)2 and (2-S-5-MeC4H2O)2. Reactions of ligand precursors 3 and 2,6-(TsOCH2)2C5H3N with Na2Fe(CO)4 were monitored by in situ IR spectroscopy, and the possible pathways for producing complexes 4 and 11-14 via intermediates Na[(2-CH2-6-MeOCH2OC5H3N)Fe(CO)4] (M1), Na[(2-CH2-6-TsOCH2C5H3N)Fe(CO)4] (M2), and (2-COCH2-6-CH2C5H3N)Fe(CO)3 (M3) are suggested. New compounds 1-14 were characterized by elemental analysis, spectroscopy, and, for some of them, X-ray crystallography.

Discovery of novel, potent and low-toxicity angiotensin II receptor type 1 (AT1) blockers: Design, synthesis and biological evaluation of 6-substituted aminocarbonyl benzimidazoles with a chiral center.

Novel angiotensin II receptor type 1 (AT1) blockers bearing 6-substituted carbamoyl benzimidazoles with a chiral center were designed and synthesized as the first step to develop new antihypertensive agents and understand their pharmacodynamic and pharmacokinetic properties. The newly synthesized compounds were tested for their potential ability to displace [(125)I] Sar(1) Ile(8)-Ang II, which was specifically bound to human AT1 receptor. Radioligand binding assays revealed nanomolar affinity in several compounds under study. The IC50 values of nine ligands were higher than those of Losartan. The screening of decreased blood pressure in spontaneous hypertensive rats displayed that compound 8S (IC50 = 5.0 nM) was equipotent with Losartan, whereas compounds 13R (IC50 = 7.3 nM), 14R (IC50 = 6.3 nM), and 14S (IC50 = 3.5 nM) were slightly ahead of Losartan, and the most significant activity was demonstrated by compound 8R (IC50 = 1.1 nM). Candidate 8R was identified for its excellent efficacy in antihypertension and fairly low toxicity based on plasma analyses, toxicology studies, and chronic oral tests. Finally, compound 8R exhibited strong and multiple interactions with target active sites of the theoretical AT1 receptor model in docking study.

Nonpeptidic angiotensin II AT1 receptor antagonists derived from 6-substituted aminocarbonyl and acylamino benzimidazoles.

Both 6-substituted aminocarbonyl and acylamino benzimidazole derivatives were designed and synthesized as nonpeptidic angiotensin II AT1 receptor antagonists. Compounds 6f, 6g, 11e, 11f, 11g, and 12 showed nanomolar AT1 receptor binding affinity and high AT1 receptor selectivity over AT2 receptor in a preliminary pharmacological evaluation. Among them, the two most active compounds 6f (AT1 IC50 = 3 nM, AT2 IC50 > 10,000 nM, PA2 = 8.51) and 11g (AT1 IC50 = 0.1 nM, AT2 IC50 = 149 nM, PA2 = 8.43) exhibited good antagonistic activity in isolated rabbit aortic strip functional assay. In addition, they were orally active AT1 receptor antagonists in spontaneous hypertensive rats.

[Prevalence of benign prostatic hyperplasia in Pingliang, Gansu: investigation and clinical analysis].

OBJECTIVE: To investigate the prevalence of benign prostatic hyperplasia (BPH) in Pingliang City of Gansu Province. METHODS: We performed a cross-sectional randomized study of 836 men aged > or = 40 years from 26 communities of Pingliang, obtained their IPSS, measured the prostate volume by transabdominal ultrasonography, recorded the maximum flow (Qmax) by uroflowmetry, and processed the data by one-way analysis of variance. RESULTS: Totally 820 subjects meeting the study criteria were included in the investigation. The men ranged in age from 40 to 83 years, averaging 61.5 years. The mean IPSS, prostate volume and Qmax were 9.3 +/- 7.8, (29.2 +/- 18.6) ml and (15.3 +/- 7.2) ml/s, respectively, all correlated with age. The prevalence of moderate-severe lower urinary tract symptoms (LUTS) was 46.8% (384/820). The prostate volume was > 20 ml in 63.5% (521/820), and Qmax <15 ml/s in 48.5% (398/805) of the subjects. The incidence rate of BPH, defined as IPSS >7, Qmax <15 ml/s and prostate volume > 20 ml, was 23.5% (193/820). CONCLUSION: Among the men aged > or = 40 years in Pingliang, LUTS and prostate volume were correlated positively, while Qmax negatively with age, and the prevalence of BPH was 23.5%.

[The effect on BiP regulation of IRE1a promoter transcription activity and protein expression].

Usually, secreted or transmembrane proteins complete their three-dimension folding within endoplasmic reticulum (ER). Under the conditions of nutrient depletion, cell differentiation, or other stress statuses, misfolded or unfolded proteins aggregate within ER, and consequently cause ER stress and Unfolded Protein Response (UPR). In response to ER stress, BiP (Binding immunoglobulin protein) dissociates with IRE1a (Inositol-requiring kinase 1) and binds to unfolded proteins as a molecular chaperone in helping maintain their correct structure. Co-related to BiP's dissociation, IRE1a oglimerizes and activated its endoribonuclease domain by transautophosphorylation. Activated IRE1a then, by cleaving mRNA of Xbp1 and activating its transcription activity, triggers UPR. In this paper, in order to determine effect of BiP on transcription activity of IRE1a, we cloned promoter region of IRE1a into reporter gene analysis vector and found that BiP could upregulate promoter activity of IRE1a. Then, we constructed another 6 truncated promoter reporter vectors of IRE1a and pinpoint the core promoter activity region. Furthermore, both our RT-PCR and Western blot results showed that BiP could upregulate mRNA transcription level and protein expression level of IRE1a. Base on these findings, we can propose that, in order to alleviate ER stress caused by the misfolded or malfolded proteins, BiP could upregulate expression of IRE1a by increase its promoter activity. This study may suggest a novel signal pathway on IRE1a regulation in ER stress.

[Determination of 16 elements in the different pine pollen by TXRF].

After microwave digestion, 16 elements in pine pollen were simultaneously determined by TXRF. The results show that all the 16 elements were found in all pine pollens. There was a significant difference in the average content of the element such as Ca, Ti, Mn, Zn and Rb between different groups of pine pollen (P < or = 0.01). There was a difference in the average content of the element such as K, V, Fe, Co, Cu and Sr between them (P < or = 0.05). And there was no difference in the average content of the element such as Cr, Ni, As, Pb and Se between them. The results also show that pine pollen has the spectral characteristics of warm property or cold property drug. They were closely related to the tree species and the growth environment or the growth area.