Study on the relationship between hyperthyroidism and vascular endothelial cell damage.

The aim of the research is to explore the relationship between hyperthyroidism, iodine, antithyroid drugs (propylthiouracil) and vascular endothelial injury. In total, 136 SD rats were randomly allocated into the control group, the hyperthyroidism group, the hyperthyroidism propylthiouracil group, the hyperthyroidism low iodine group, the high iodine group, and the endothelial injury group. Rats were raised for 60 days. Afterward, indicators concerning endothelial damage were determined, including the von Willebrand Factor (vWF), thrombomodulin (TM), nitric oxide (NO), endothelin 1 (ET-1), and P-selectin, as well as the plant hemagglutinin sample type oxidized low-density lipoprotein receptor 1 (LOX-1) from the aorta and the number of endothelial progenitor cells (EPCs) in whole blood. The hyperthyroidism group had significantly higher values for vWF, TM, NO, ET-1, and P-selectin in serum and a higher number of EPCs in whole blood compared with the control group, similar to the LOX-1 expression in abdominal aorta. The hyperthyroidism low iodine group had significantly higher values for vWF, ET-1, and P-selectin in serum and a higher number of EPCs in whole blood compared with those of the control group, as was the case for LOX-1 expression in the abdominal aorta. The hyperthyroidism propylthiouracil group had significantly higher values for FT4 in the serum compared with those in the control group. The electron microscope showed that hyperthyroidism caused a certain degree of endothelial injury to the abdominal aorta in rats. Hyperthyroidism can damage the vascular endothelium and is a high-risk factor for cardio-cerebrovascular disease. Propylthiouracil could be used in the treatment of hyperthyroidism, thus protecting endothelial cells from damage.

Exogenous obestatin decreases beta-cell apoptosis and alfa-cell proliferation in high fat diet and streptozotocin induced type 2 diabetic rats.

Type 2 diabetes is a chronic metabolic disease characterized by progressive decrease of islet cell function. Delaying the process of islet failure remains a challenging goal in diabetes care. Previous studies have confirmed the role of obestatin, a gut peptide that belongs to ghrelin family, in the mediation of glucose metabolism. This study aimed to observe the long term effects of exogenous obestatin on glucose metabolism in type 2 diabetes rat model. Type 2 diabetic rat model was set up by high-fat diet (60%) followed by a low dose of streptozotocin intra-peritoneal injection. Exogenous obestatin was administered at a dose of 20 nmol/kg for 12 weeks by intraperitoneal injection. Compared to placebo group (saline intraperitoneal injection), obestatin treatment decreased the glucagon levels and increased the c-peptide levels. Furthermore, obestatin treatment led to a significant restoration of islet morphology, increasing insulin and reducing glucagon expressions. Apoptosis assay showed a reduction in the number of TUNEL positive-cells. The up-regulation of Akt and GSK3ß in pancreas was confirmed by Real-Time PCR. These results demonstrated that obestatin might have a potential therapeutic relevance in improving islet cell function, including increasing insulin secretion through inhibiting beta cell apoptosis and decreasing glucagon secretion by inhibiting alfa cell proliferation in type 2 diabetes. In spite of its role in these phenomena, it is necessary to further discuss, especially regarding the role of obestatin on glucagon.

Dual-Stimuli Responsive Bismuth Nanoraspberries for Multimodal Imaging and Combined Cancer Therapy.

Development of stimuli-responsive theranostics is of great importance for precise cancer diagnosis and treatment. Herein, bovine serum albumin (BSA) modified bismuth nanoraspberries (Bi-BSA NRs) are developed as cancer theranostic agents for multimodal imaging and chemo-photothermal combination therapy. The Bi-BSA NRs are synthesized in aqueous phase via a facile reduction method using Bi2O3 nanospheres as the sacrificial template. The morphology, biocompatibility, photothermal effect, drug loading/releasing abilities, chemotherapy effect, synergistic chemo-photothermal therapy efficacy, and multimodal imaging capacities of Bi-BSA NRs have been investigated. The results show that the NRs possess multiple unique features including (i) raspberry-like morphology with high specific surface area (∼52.24 m2·g-1) and large cavity (total pore volume ∼0.30 cm3·g-1), promising high drug loading capacity (∼69 wt %); (ii) dual-stimuli responsive drug release, triggered by acidic pH and NIR laser irradiation; (iii) infrared thermal (IRT), photoacoustic (PA) and X-ray computed tomography (CT) trimodality imaging with the CT contrast enhanced efficiency as high as ∼66.7 HU·mL·mg-1; (iv) 100% tumor elimination through the combination chemo-photothermal therapy. Our work highlights the great potentials of Bi-BSA NRs as a versatile theranostics for multimodal imaging and combination therapy.

Liquid Exfoliation of Colloidal Rhenium Disulfide Nanosheets as a Multifunctional Theranostic Agent for In Vivo Photoacoustic/CT Imaging and Photothermal Therapy.

Near-infrared light-mediated theranostic agents with superior tissue penetration and minimal invasion have captivated researchers in cancer research in the past decade. Herein, a probe sonication-assisted liquid exfoliation approach for scalable and continual synthesis of colloidal rhenium disulfide nanosheets, which is further explored as theranostic agents for cancer diagnosis and therapy, is reported. Due to high-Z element of Re (Z = 75) and significant photoacoustic effect, the obtained PVP-capped ReS2 nanosheets are evaluated as bimodality contrast agents for computed tomography and photoacoustic imaging. In addition, utilizing the strong near-infrared absorption and ultrahigh photothermal conversion efficiency (79.2%), ReS2 nanosheets could also serve as therapeutic agents for photothermal ablation of tumors with a tumor elimination rate up to 100%. Importantly, ReS2 nanosheets show no obvious toxicity based on the cytotoxicity assay, serum biochemistry, and histological analysis. This work highlights the potentials of ReS2 nanosheets as a single-component theranostic nanoplatform for bioimaging and antitumor therapy.

Natural Humic-Acid-Based Phototheranostic Agent.

Humic acids, a major constituent of natural organic carbon resources, are naturally formed through the microbial biodegradation of animal and plant residues. Due to numerous physiologically active groups (phenol, carboxyl, and quinone), the biomedical applications of humic acid have been already investigated across different cultures for several centuries or even longer. In this work, sodium humate, the sodium salt of humic acid, is explored as phototheranostic agent for light-induced photoacoustic imaging and photothermal therapy based on intrinsic absorption in the near-infrared region. The purified colloidal sodium humate exhibits a high photothermal conversion efficiency up to 76.3%, much higher than that of the majority of state-of-the-art photothermal agents including gold nanorods, Cu9 S5 nanoparticles, antimonene quantum dots, and black phosphorus quantum dots, leading to obvious photoacoustic enhancement in vitro and in vivo. Besides, highly effective photothermal ablation of HeLa tumor is achieved through intratumoral injection. Impressively, sodium humate reveals ultralow toxicity at the cellular and animal levels. This work promises the great potential of humic acids as light-mediated theranostic agents, thus expanding the application scope of traditional humic acids in biomedical field.

Multimodal Imaging-Guided Antitumor Photothermal Therapy and Drug Delivery Using Bismuth Selenide Spherical Sponge.

Elaborately designed biocompatible nanoplatforms simultaneously having diverse therapeutic and imaging functions are highly desired for biomedical applications. Herein, a Bi2Se3 nanoagent with a special morphology as a nanoscale spherical sponge (NSS) has been fabricated and investigated in vitro and in vivo. The highly porous NSS exhibits strong, steady, and broad-band absorbance in the near-infrared range as well as high efficiency and stability of photothermal conversion, resulting in high antitumor efficacy for photothermal therapy (PTT). Together with a high X-ray attenuation coefficient (218% that of the clinically used iopromide), the NSS shows excellent performance on triple-modal high-contrast imaging, including X-ray-computed tomography, multispectral optoacoustic tomography, and infrared thermal imaging. Furthermore, the high surface area and porous structure impart the NSS a competent drug loading capability as high as 600% of that on Bi2Se3 nanoplates, showing a bimodal pH/photothermal sensitive drug release and pronounced synergetic effects of thermo-chemotherapy with a tumor inhibition ratio even higher than that of PTT alone (∼94.4% vs ∼66.0%). Meanwhile, the NSS is highly biocompatible with rather low in vitro/in vivo toxicity and high stability, at variance with easily oxidized Bi2Se3 nanoagents reported previously. Such biocompatible single-component theranostic nanoagents produced by a facile synthesis and highly integrated multimodal imaging and multiple therapeutic functions may have substantial potentials for clinical antitumor applications. This highly porous nanostructure with a large fraction of void space may allow versatile use of the NSS, for example, in catalysis, gas sensing, and energy storage, in addition to accommodating drugs and other biomolecules.

Highly porous PEGylated Bi2S3 nano-urchins as a versatile platform for in vivo triple-modal imaging, photothermal therapy and drug delivery.

Biocompatible single-component nanoplatforms simultaneously integrating multiple therapeutic functions with multiple imaging modes are desirable for anticancer treatments. Herein, elaborately-designed highly porous PEGylated bismuth sulfide nano-urchins (Bi2S3-PEG NUs) have been successfully synthesized by using Bi2O3 nanospheres as the sacrificial template via the hydrothermal process. It is demonstrated that the Bi2S3-PEG NUs possess high compatibility, stability, X-ray attenuation ability, near-infrared (NIR) absorbance and photothermal conversion capability, without noticeable toxicity. Based on both in vitro and in vivo results, the product shows excellent performance in highly effective photothermal therapy (PTT) guided by triple-modal imaging, including X-ray computed tomography (CT), and photoacoustic (PA) and infrared thermal (IRT) imaging, without noticeable toxicity in vivo. Importantly, the NUs are highly porous with a high specific surface area and copious mesopores, providing high loading capacity to accommodate drugs (or guest biomolecules) for further applications in chemotherapy and other additional functions. Doxorubicin is loaded as an example, showing a rather high loading capacity (∼37.9%) together with a bimodal on-demand pH/photothermal-sensitive drug release property. Such fascinating multifunctional nanoagents may have considerable applications in antitumor diagnosis and therapy in the clinic.

Analysis of Specific IgE Level in 1,215 Patients with Allergic Diseases in Harbin, China.

BACKGROUND: As the incidence of allergic diseases increases, the detection of serum-specific immunoglobulin E (sIgE) becomes important for the diagnosis and management of allergic disease. This study aimed to investigate the diagnostic value of sIgE level in north east Chinese patients with allergic disease and provide more information for rational use of the sIgE results METHODS: A total of 1,215 patients with positive allergens by an sIgE assay were enrolled from the Second Affiliated Hospital of Harbin Medical University, China. Serum levels of sIgE to fourteen allergens were detected by AllergyScreen. RESULTS: Age of the subjects ranged from 0 to 86 years old, and 49.1% of them (597) were less than 18 years old. sIgE levels were grade 1 in 51.5% of them, grade 2 in 84.2%, grade 3 in 29.5%, and grade 4 and above in 13.2%. There was a significant difference in the positive rank of the house dust mite mix and mixing mold between the group of 4 to 12 year-old boys and the group of 0 to 3 year-olds and the group of over 30 year-olds. 280 patients were positive at grade 1; if grade 2 was taken as the critical, 23% patients would be negative. CONCLUSIONS: The positive rank of sIgE was grade 1-3 in most cases and few patients were over grade 4. If grade 2 was taken as a positive judgment basis, 23% of patients would be mistakenly judged as negative. Serum sIgE levels may have value for the prevention and management for allergic disease.

Analysis of total immunoglobulin E and specific immunoglobulin E of 3,721 patients with allergic disease.

Due to the increase in the prevalence and incidence of allergic diseases, improving the sensitivity and specificity of screening indexes is critical. Total immunoglobulin E (IgE) is a traditional index for judging allergic diseases, while its specificity is relatively poor. Serum-specific IgE (sIgE) is an objective index with high specificity in the diagnosis of allergic diseases. In the present research, the total IgE and sIgE of 3,721 patients with allergic diseases were analyzed to further illuminate the association between them. The data were derived from 3,721 patients. The serum-sIgE to 14 types of common allergens and total IgE were detected. A total of 2,419 cases (65.0%) of 3,721 patients exhibited increasing total IgE and 1,215 patients (32.7%) exhibited positive sIgE. The consistency rate of the two indexes was 60.4%, and the κ-value was 0.28. In 135 patients with normal total IgE, 82.2% exhibited one sIgE positive and 17.8% exhibited two or more sIgE positive. While the number of positive sIgE increased and the detecting level enhanced, the number of positive total IgE markedly increased. Patients (84.1%) with increasing total IgE were associated with positive sIgE, but the increase of total IgE could not be completely explained by the total accumulation of sIgE. Total IgE may play an important role on screening allergic disease while sIgE could be used as crucial evidence for allergy diagnosis. Although the consistency of the two methods was poor, neither total IgE nor sIgE could replace each other. Combining the two indexes with clinical manifestations together will improve the method.

Intraportal infusion of ghrelin could inhibit glucose-stimulated GLP-1 secretion by enteric neural net in Wistar rat.

As a regulator of food intake and energy metabolism, the role of ghrelin in glucose metabolism is still not fully understood. In this study, we determined the in vivo effect of ghrelin on incretin effect. We demonstrated that ghrelin inhibited the glucose-stimulated release of glucagon-like peptide-1 (GLP-1) when infused into the portal vein of Wistar rat. Hepatic vagotomy diminished the inhibitory effect of ghrelin on glucose-stimulated GLP-1 secretion. In addition, phentolamine, a nonselective α receptor antagonist, could recover the decrease of GLP-1 release induced by ghrelin infusion. Pralmorelin (an artificial growth hormone release peptide) infusion into the portal vein could also inhibit the glucose-stimulated release of GLP-1. And growth hormone secretagogue receptor antagonist, [D-lys3]-GHRP-6, infusion showed comparable increases of glucose stimulated GLP-1 release compared to ghrelin infusion into the portal vein. The data showed that intraportal infusion of ghrelin exerted an inhibitory effect on GLP-1 secretion through growth hormone secretagogue receptor 1α (GHS1α receptor), which indicated that the downregulation of ghrelin secretion after food intake was necessary for incretin effect. Furthermore, our results suggested that the enteric neural net involved hepatic vagal nerve and sympathetic nerve mediated inhibition effect of ghrelin on incretin effect.

Hashimoto encephalopathy associated with hyperthyroidism: A case report.

Hashimoto's encephalopathy (HE) is an acute encephalopathy associated with Hashimoto's thyroiditis. The majority of reported cases have been associated with hypothyroidism, while cases with hyperthyroidism are rare. The current study reported on a 56-year old female patient with HE, who was found to have progressively aggregated dysarthria, gait disturbance, somniloquy and delirium. Thyroid function tests revealed that the patient had hyperthyroidism, with high levels of anti-thyroid antibodies. Following treatment with corticosteroids, the neurological/psychiatric symptoms of the patient were relieved quickly. The one-year follow-up investigation indicated that there was no recurrence of the disease, demonstrating that the treatment administered for this rare case was effective.

The HIV/AIDS epidemic characteristics in a northeast province of China--men who have sex with men have made a tremendous contribution to the growth of the HIV epidemic.

OBJECTIVE: To investigate the characteristics and trends of the HIV epidemic in Heilongjiang province of China between 1993 and 2012. METHODS: Data from the provincial surveillance system for HIV infections and AIDS were reviewed. Local health staff reviewed medical records, including dates of HIV/AIDS diagnoses and deaths, exposure category, treatment, laboratory testing, and demographics. RESULTS: By 31 October 2012, a total of 3062 HIV-infections were detected with 426 deaths and 206 who presently live outside Heilongjiang province, 38.1% of whom were diagnosed as AIDS. Since 2007, homosexual transmission has increased and become the dominant route of HIV transmission, accounting for 57.9% of cases during 2009-2010, and 69.0% during 2011-2012. Men who have sex with men (MSM) with HIV-infections had the following characteristics: 21-30 year age group (42.4%); unmarried (61.6%); urban residents (46.7%); and college or higher education (36.8%). In addition, the proportion of MSM ≤ 30 years of age and rural residents showed an uptrend across the study years. CONCLUSIONS: The HIV/AIDS epidemic has continued to increase in Heilongjiang province, and has shown an explosive growth since 2008, with MSM making a tremendous contribution to the HIV outbreak. Homosexual contact has become the dominant route of HIV transmission. Urgent intervention is needed to recognize this target population, especially those ≤30 years of age, unmarried, and urban residents.

Subtype B was the dominant strain among HIV type 1 infections except for the population of men who have sex with men in Harbin City, China.

We sought to identify the prevalent subtypes and study the genetic variation of HIV-1 circulating in HIV infections in Harbin City, China. Forty-seven samples from the env V3-V4 region were successfully sequenced and analyzed, which involved thirty-one men who have sex with men (MSM), eight heterosexuals, seven former plasma donors (FPD)/blood transfusion recipients (BT), and one injection drug user (IDU). In all, 46.8% of CRF01_AE, 40.4% of subtype B, and 12.8% of CRF07_BC were identified. CRF01_AE (64.5%) was the dominant strain in MSM, and subtype B (81.2%) was the chief strain in other infected subjects except for the MSM population. Among all the genotypes, the B subtype possesses greater diversity of the tetramer on the tip of V3 loop than CRF07_BC and CRF01_AE, in which the peculiar GWGR was commonly found. Because nationwide there is a trend toward the increasing presence of CRF01_AE, a consecutive surveillance campaign was necessary among all HIV vulnerable populations in this locality.