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1.
Cell Death Dis ; 11(1): 1, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31911576

RESUMO

Cubosomes, a product of nanobioengineering, are self-structured lipid nanoparticles that act like drug-loaded theranostic probes. Here, we describe a simple method for the preparation of combinatorial drug-loaded cubosomes with, proof-of-principle, therapeutic effect against cancer cells, along with diagnostic capabilities. Anticancer drugs cisplatin and paclitaxel were loaded in the cubosomes in combination. The cubosomes were coated with a layer of poly-Ɛ-lysine, which helped avoid the initial burst release of drug and allowed for a slow and sustained release for better efficacy. Cubosomes were imaged by transmission electron microscope, and their dispersion analyzed in vitro by differential scanning calorimetric and X-ray diffractogram studies. The microscopic images depicted spherical polyangular structures, which are easily distinguishable. The analyses revealed that the drug is uniformly dispersed all through the cubosomes. Further characterization was carried out by zeta-potential measurement, in vitro release, and entrapment efficiency studies. The in vitro studies established that the coating of cubosomes successfully reduced the burst release of drugs initially and confirmed a slow, sustained release over increased time. Comparative cytotoxicity of coated, uncoated, and blank cubosomes was evaluated, using human hepatoma HepG2 cell line, and the formulations were found to be entirely nontoxic, similar to the blank ones. The therapeutic efficiency of the cubosomes against HeLa cells was confirmed by the impedance measurement and fluorescent imaging. Furthermore, the reduction in impedance in cells treated with coated combinatorial cubosomes proved the impairment of HeLa cells, as confirmed by fluorescence microscopy.

2.
J Cell Physiol ; 235(1): 563-572, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31318050

RESUMO

Sepsis is a severe clinical disease, which is resulted from the excessive host inflammation response to the infection. Growing evidence indicates that Staphylococcus aureus pneumonia is a significant cause of sepsis, which can lead to intestinal injury, inflammation, and apoptosis. Studies have shown that miR-182-5p can serve as a tumor oncogene or a tumor suppressive microRNA in various cancers, however, its biological role in sepsis is still uninvestigated. Here, we reported that miR-182-5p was obviously increased in S. aureus pneumonia mice models. Loss of miR-182-5p inhibited intestinal damage and intestinal apoptosis as indicated by the terminal deoxynucleotidyl transferase dUTP nick end labeling assay. In addition, we observed the lack of miR-182-5p altered the local inflammatory response to pneumonia in the intestine. Elevated tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels were observed in intestinal tissue of pneumonia groups compared with the shams. Furthermore, miR-182-5p knockout (KO) pneumonia group demonstrated decreased levels of intestinal TNF-α and IL-6. Primary murine intestinal epithelial cells were isolated and cultured in our investigation. We exhibited downregulation of miR-182-5p repressed intestinal epithelial cells apoptosis and rescued the cell viability. Meanwhile, miR-182-5p caused elevated cell apoptosis and reduced cell proliferation. Moreover, the surfactant protein D (SP-D) binds with the bacterial pathogens and remove the pathogens and apoptotic bodies, which exhibits important roles in modulating immune responses. It was displayed in our study that SP-D was greatly decreased in pneumonia mice models. SP-D was predicted as a downstream target of miR-182-5p. These data concluded that miR-182-5p promoted intestinal injury in S. aureus pneumonia-induced sepsis via targeting SP-D.

3.
Zhongguo Zhong Yao Za Zhi ; 44(22): 4874-4879, 2019 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-31872595

RESUMO

According to drug design flattening principle and using podophyllotoxin or 4'-demethylepipodophyllotoxin and aldehydes as starting material,a series of podophyllotoxin derivatives containing an imine structure with low toxicity were highly effective synthesized. Nine target compounds were successfully synthesized,and their structures were confirmed by ~1H-NMR,HR-ESI-MS and melting point data analysis. Using etoposide as positive control drug,nine target compounds were screened for cytotoxicity against He La cells in vitro by MTT method. The antitumor activity screening results showed that compound 6 b,6 d,6 e,6 f,6 g,6 i exhibited higher inhibitory rate against He La cells than those of control drug VP-16. It provides some practical reference value for the further development on the structure modification of podophyllotoxin and study on anti-tumor activity.


Assuntos
Antineoplásicos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Podofilotoxina/farmacologia , Desenho de Drogas , Relação Estrutura-Atividade
4.
Sci Rep ; 9(1): 20117, 2019 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-31882839

RESUMO

Transgenic switchgrass overexpressing Lolium perenne L. delta1-pyrroline 5-carboxylate synthase (LpP5CS) in group I (TG4 and TG6 line) and group II (TG1 and TG2 line) had significant P5CS and ProDH enzyme activities, with group I plants (TG4 and TG6) having higher P5CS and lower ProDH enzyme activity, while group II plants had higher ProDH and lower P5CS enzyme activity. We found group II transgenic plants showed stunted growth, and the changed proline content in overexpressing transgenic plants may influence the growth and development in switchgrass. RNA-seq analysis showed that KEGG enrichment included phenylpropanoid biosynthesis pathway among group I, group II and WT plants, and the expression levels of genes related to lignin biosynthesis were significantly up-regulated in group II. We also found that lignin content in group II transgenic plants was higher than that in group I and WT plants, suggesting that increased lignin content may suppress switchgrass growth and development. This study uncover that proline can appropriately reduce lignin biosynthesis to improve switchgrass growth and development. Therefore, appropriate reduction in lignin content and increase in biomass are important for bioenergy crop to lower processing costs for biomass fermentation-derived fuels.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31702523

RESUMO

Due to their unique properties, nanofibers have been widely used in various areas, for example, information industry, pharmaceutical application, environmental industry, textile and clothing, etc. Bubble electrospinning is one of the most important non-needle electrospinning methods for nanofiber fabrication. It usually uses polymers' bubbles for production of nanomaterials by using electrostatic force, flowing air or mechanical force to overcome the surface tension of bubbles. Bubble electrospinning mainly includes the bubble electrospinning and blown bubble electrospinning. A history of the development of bubble electrospinning is briefly introduced in this article. The methods of bubble electrospinning are mainly included single bubble electrospinning, porous bubble electrospinning, blown bubble electrospinning, electrostatic-field-assisted blown bubble spinning and others. These different bubble electrospinning methods are also discussed in this paper.

6.
JCI Insight ; 4(21)2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31672934

RESUMO

Neutrophils play critical roles during the initial phase of hepatic ischemia/reperfusion injury (HIRI). However, the regulation of neutrophil activation, infiltration, and proinflammatory cytokine secretion has not been fully elucidated. In this study, we revealed that OX40 was expressed by neutrophils, its expression in neutrophils was time-dependently upregulated following HIRI, and Ox40 knockout markedly alleviated liver injury. Compared with wild-type neutrophils, the adoptive transfer of Ox40-/- neutrophils decreased HIRI in neutrophil-depleted Rag2/Il2rg-/- or Ox40-/- mice. Moreover, consistently, the in vitro experiments showed that Ox40 not only prolonged neutrophil survival but also promoted proinflammatory cytokines, ROS production, and even neutrophil chemotaxis. Further investigation demonstrated that the knockout of Ox40 in neutrophils inhibited NF-κB signaling via the TRAF1/2/4 and IKKα/IKKß/IκBα pathways. OX40L and OX86 stimulation could enhance neutrophil activation and survival in vitro and in vivo. In conclusion, our study provides a new understanding of OX40, which is expressed not only in adaptive immune cells but also in innate immune cells, i.e., neutrophils, contributing to the activation and survival of neutrophils. These findings provide a novel potential therapeutic target for the prevention of HIRI during liver transplantation or hepatic surgery.

7.
Pharmacol Res Perspect ; 7(6): e00526, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31624634

RESUMO

Dichloroacetate (DCA) is an investigational drug targeting the glycolytic hallmark of cancer by inhibiting pyruvate dehydrogenase kinases (PDK). It is metabolized by GSTZ1, which has common polymorphisms altering enzyme or promoter activity. GSTZ1 is also irreversibly inactivated by DCA. In the first clinical trial of DCA in a hematological malignancy, DiCAM (DiChloroAcetate in Myeloma), we have examined the relationship between DCA concentrations, GSTZ1 genotype, side effects, and patient response. DiCAM recruited seven myeloma patients in partial remission. DCA was administered orally for 3 months with a loading dose. Pharmacokinetics were performed on day 1 and 8. Trough and peak concentrations of DCA were measured monthly. GSTZ1 genotypes were correlated with drug concentrations, tolerability, and disease outcomes. One patient responded and two patients showed a partial response after one month of DCA treatment, which included the loading dose. The initial half-life of DCA was shorter in two patients, correlating with heterozygosity for GSTZ1*A genotype, a high enzyme activity variant. Over 3 months, one patient maintained DCA trough concentrations approximately threefold higher than other patients, which correlated with a low activity promoter genotype (-1002A, rs7160195) for GSTZ1. This patient displayed the strongest response, but also the strongest neuropathy. Overall, serum concentrations of DCA were sufficient to inhibit the constitutive target PDK2, but unlikely to inhibit targets induced in cancer. Promoter GSTZ1 polymorphisms may be important determinants of DCA concentrations and neuropathy during chronic treatment. Novel dosing regimens may be necessary to achieve effective DCA concentrations in most cancer patients while avoiding neuropathy.

8.
Oncol Lett ; 18(5): 4865-4881, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31611997

RESUMO

Surgery as a therapeutic modality for non-small cell lung cancer is widely accepted in clinical practice. However, the role of surgery for small cell lung cancer (SCLC) remains controversial. Therefore, in the present study a period propensity score matching analysis using the Surveillance, Epidemiology and End Results (SEER) Registry database was performed to investigate the role of surgery on survival in patients with SCLC. Patients with SCLC between January 2010 and December 2015 were identified from the SEER database, and individual data for each case regarding general clinical characteristics, surgery of primary site (SPS), cause-specific death classification and survival time were retrieved. Differences of cause-specific survival (CSS) between subgroups were estimated by the log-rank test. Cox regression analysis was used to evaluate the effects of multiple variables on CSS, and differences between the incidences of cause-specific death were examined using a χ2 test. A total of 1,707 records met the inclusion criteria and were retrieved for analysis. There were significant differences of CSS in the clinicopathological features of N (P=0.01), Stage (P<0.01) and Surgery (P<0.01) when comparing non-surgery with surgery, and in N (P<0.001), Stage (P=0.006) and Surgery (P=0.049) when comparing sublobectomy with lobectomy or bilobectomy (lobe/s). Patients who did not receive surgery (P<0.001) or who received sublobectomy (P=0.03) had an increased risk of mortality when compared with patients who received surgery and lobe/s. The findings of the present study indicate that surgery should be taken into consideration when an initial treatment strategy is made in patients for patients with SCLC at clinical stage I-IIA (T1-2,N0,M0), regardless of whether they are >50 years of age, their sex, histology and grade. The results suggest that certain patients with SCLC with stage IIB (N1) can also benefit from lobe/s, although further investigation is required. In addition, lobe/s is preferable to sublobectomy when surgery is performed. However, the present study was unable to comprehensively analyze the efficacy of pneumonectomy for SCLC.

9.
Neurosci Bull ; 2019 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-31520398

RESUMO

α-Synuclein is a soluble monomer abundant in the central nervous system. Aggregates of α-synuclein, consisting of higher-level oligomers and insoluble fibrils, have been observed in many chronic neurological diseases and are implicated in neurotoxicity and neurodegeneration. α-Synuclein has recently been shown to aggregate following acute ischemic stroke, exacerbating neuronal damage. Propofol is an intravenous anesthetic that is commonly used during intravascular embolectomy following acute ischemic stroke. While propofol has demonstrated neuroprotective properties following brain injury, the mechanism of protection in the setting of ischemic stroke is unclear. In this study, propofol administration significantly reduced the neurotoxic aggregation of α-synuclein, decreased the infarct area, and attenuated the neurological deficits after ischemic stroke in a mouse model. We then demonstrated that the propofol-induced reduction of α-synuclein aggregation was associated with increased mammalian target of rapamycin/ribosomal protein S6 kinase beta-1 signaling pathway activity and reduction of the excessive autophagy occurring after acute ischemic stroke.

10.
Nat Commun ; 10(1): 4246, 2019 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-31534137

RESUMO

Allergic asthma is an inflammatory disorder of the airway without satisfactory traditional therapies capable of controlling the underlying pathology. New approaches that can overcome the detrimental effects of immune dysregulation are thus desirable. Here we adoptively transfer ovalbumin (OVA) peptide-primed CD4-CD8- double negative T (DNT) cells intravenously into a mouse model of OVA-induced allergic asthma to find that OVA-induced airway hyperresponsiveness, lung inflammation, mucus production and OVA-specific IgG/IgE production are significantly suppressed. The immunosuppressive function of the OVA-specific DNT cells is dependent on the inhibition of CD11b+ dendritic cell function, T follicular helper cell proliferation, and IL-21 production. Mechanistically, Lag3 contributes to MHC-II antigen recognition and trogocytosis, thereby modulating the antigen-specific immune regulation by DNT cells. The effectiveness of ex vivo-generated allergen-specific DNT cells in alleviating airway inflammation thus supports the potential utilization of DNT cell-based therapy for the treatment of allergic asthma.

11.
Angew Chem Int Ed Engl ; 58(45): 16101-16104, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31483541

RESUMO

Using an external stimulus to modulate the electronic structure of covalent organic frameworks (COFs) is very important because such a response will endow them with additional functions. A two-dimensional (2D) COF, constructed from a photo-responsive unit (1,2-bis(5-formyl-2-methylthien-3-yl)cyclopentene), can reversibly switch its electrical conductivity 200 times from low state (the open form) to high state (the closed form) upon irradiation with UV light and reversible with visible light. This reversible phenomenon can be monitored through a circuit containing a light-emitting diode (LED). Photoinduced ring-closing/opening reactions do not destroy the integrity of the frameworks, and both processes follow logarithmic carrier generation with time. Moreover, the correlation between COFs electronic properties and changes in photoinduced kinetics and absorption curves has been demonstrated.

12.
Int J Infect Dis ; 87: 177-184, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31374344

RESUMO

OBJECTIVES: To explore the long-term effect of exposure to ambient air pollution on the risk of active tuberculosis (TB). METHODS: We constructed a distributed-lag nonlinear model (DLNM) to evaluate the relatively long-term influence of outdoor PM2.5, PM10, SO2 and NO2 exposure on active TB risk in the city of Lianyungang in Jiangsu Province, China. RESULTS: There were 7,282 TB cases reported in the study area during 2014-2017, with annual median (interquartile range) concentrations of PM2.5, PM10, SO2 and NO2 at 45.86 (34.57-64.14) µg/m3, 85.43 (62.86-116.14) µg/m3, 22.00 (15.71-30.86) µg/m3 and 30.00 (23.29-38.57) µg/m3, respectively. The single-pollutant model showed that for each 10 µg/m3 increase in concentration, the cumulative relative risk of TB was 1.12 (lag 0-24 weeks, 95% CI: 1.03-1.22) for PM2.5 with reference to 35 µg/m3; 1.11 (lag 0-21 weeks, 95% CI: 1.06-1.17) for PM10 with reference to 70 µg/m3; 1.37 (lag 0-20 weeks, 95% CI: 1.16-1.62) for SO2 with reference to 60 µg/m3; and 1.29 (lag 0-22 weeks, 95% CI: 1.11-1.49) for NO2 with reference to 40 µg/m3. In the multipollutant model considering both PM10 and NO2, the association remained significant. CONCLUSIONS: Our results revealed a potential association between outdoor exposure to PM2.5, PM10, SO2, and NO2 and active TB. Considering that people from developing countries continue to be exposed to both severe outdoor air pollution and high rates of latent TB infection, the association between worsening air pollution and active TB deserves further attention.

13.
Sci Rep ; 9(1): 11257, 2019 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-31375708

RESUMO

Metastasis is regarded as the fatal hallmark for colon cancer, but molecular mechanisms responsible for it have remained poorly defined. Glucocorticoid receptor (GR) within the tumor microenvironment mediates the effects of stress hormones which are used in clinics for their inflammation-modulatory and immunosuppressive properties. Further, epigenetic activation of GR promotes tumor heterogeneity and metastasis. Here, we sought to investigate the correlation between GR activation and proliferation and invasion in metastatic colon cancer microenvironment. We used proliferation/invasion assays, western blot, RT-qPCR, immunofluorescence staining and quantitative methylation to study glucocorticoid-GR signaling, including the involvement of CDK1, in human colon adenocarcinoma cell lines HT29 and T84 (a representative metastatic cell line). Nuclear expression levels of GR were significantly upregulated in metastatic T84 cells, and glucocorticoid derivative, dexamethasone (DEX) treatment caused increased proliferation and invasion in T84 cell, compared to HT29 cell. DEX treatment induced CDK1 expression which was accompanied by reduced CDK1 methylation, indicating epigenetic regulation. Depletion of GR suppressed proliferation of metastatic colon carcinoma cells and depletion of CDK1 had similar suppressing effects on proliferation as well as invasion of metastatic cells. Our study suggests that glucocorticoid-GR-CDK1 signaling induces proliferation and invasion of colon cancer cells and therapies involving the use of glucocorticoids need to exercise caution and re-evaluation.

14.
J Pharmacol Exp Ther ; 371(2): 385-393, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31420525

RESUMO

Patients with nonalcoholic steatohepatitis (NASH) exhibit altered hepatic protein expression of metabolizing enzymes and transporters and altered xenobiotic pharmacokinetics. The botanical natural product silymarin, which has been investigated as a treatment of NASH, contains flavonolignans that inhibit organic anion-transporting polypeptide (OATP) transporter function. The purpose of this study was to assess the individual and combined effects of NASH and silymarin on the disposition of the model OATP substrate pitavastatin. Male Sprague Dawley rats were fed a control or a methionine- and choline-deficient diet (NASH model) for 8 weeks. Silymarin (10 mg/kg) or vehicle followed by pitavastatin (0.5 mg/kg) were administered intravenously, and the pharmacokinetics were determined. NASH increased mean total flavonolignan area under the plasma concentration-time curve (AUC0-120 min) 1.7-fold. Silymarin increased pitavastatin AUC0-120 min in both control and NASH animals approx. 2-fold. NASH increased pitavastatin plasma concentrations from 2 to 40 minutes, but AUC0-120 min was unchanged. The combination of silymarin and NASH had the greatest effect on pitavastatin AUC0-120 min, which increased 2.9-fold compared with control vehicle-treated animals. NASH increased the total amount of pitavastatin excreted into the bile 2.7-fold compared with control animals, whereas silymarin decreased pitavastatin biliary clearance approx. 3-fold in both control and NASH animals. This double hit of NASH and silymarin on hepatic uptake transporters is another example of a multifactorial pharmacokinetic interaction that may have a greater impact on drug disposition than each hit alone. SIGNIFICANCE STATEMENT: Multifactorial effects on xenobiotic pharmacokinetics are within the next frontier for precision medicine research and clinical application. The combination of silymarin and NASH is a probable clinical scenario that can affect drug uptake, liver concentrations, biliary elimination, and ultimately, efficacy and toxicity.

15.
PLoS One ; 14(7): e0219669, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31310632

RESUMO

In plants, Δ1-pyrroline- 5-carboxylate synthase (P5CS) is the rate-limiting enzyme in proline biosynthesis. In this study, we introduced the LpP5CS (Lolium perenne L.) gene into switchgrass by Agrobacterium-mediated transformation. The transgenic lines (TG) were classified into two groups based on their phenotypes and proline levels. The group I lines (TG4 and TG6) had relatively high proline levels and improved biomass yield. The group II lines (TG1 and TG2) showed low proline levels, severely delayed flowering, stunted growth and reduced biomass yield. Additionally, we used RNA-seq analysis to detect the most significant molecular changes, and we analyzed differentially expressed genes, such as flowering-related and CYP450 family genes. Moreover, the biomass yield, physiological parameters, and expression levels of reactive oxygen species scavenger-related genes under salt stress all indicated that the group I plants exhibited significantly increased salt tolerance compared with that of the control plants, in contrast to the group II plants. Thus, genetic improvement of switchgrass by overexpressing LpP5CS to increase proline levels is feasible for increasing plant stress tolerance.

16.
Chem Commun (Camb) ; 55(59): 8571-8574, 2019 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-31273368

RESUMO

By replacing Lewis acids with Brønsted acids as catalysts, continuous flow synthesis of hypercrosslinked polymers is achieved within 10% of the time required for a typical batch reaction. Compared with batch-synthesised polymers, the flow-produced materials take up 24% more CO2, precluding the need for lengthy reaction protocols to yield high-performance hypercrosslinked polymers for carbon capture.

17.
Zhongguo Zhong Yao Za Zhi ; 44(12): 2532-2537, 2019 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-31359720

RESUMO

According to drug design flattening principle,a series of novel indole podophyllotoxin derivatives which were introduced different indole substituents in C-4 position on the basis of podophyllotoxin nucleus were synthesized with the starting material podophyllotoxin and 1 H-indole-5-carboxylic acid. Its anti-tumor activity in vitro was tested in order to screen for high-efficiency and low-toxic compounds. Six target compounds were synthesized,and were confirmed by~1 H-NMR,~(13)C-NMR,HR-ESI-MS and melting point determination analysis. All these target compounds were not reported by previous literature. Using etoposide as positive control drug,all the target compounds were screened for cytotoxicity against He La cells,K562 cells and K562/A02 cell in vitro by MTT method. The antitumor activity screening results showed that compounds 4 b,4 e,4 f exhibited higher inhibitory rate against He La cells and K562 cells than those of control drug VP-16. This route has the advantages on simple operation and reasonable design,provides some practical reference value for the further development on the structure modification of podophyllotoxin and study on anti-tumor activity.


Assuntos
Antineoplásicos/farmacologia , Indóis/farmacologia , Podofilotoxina/farmacologia , Antineoplásicos/síntese química , Ensaios de Seleção de Medicamentos Antitumorais , Células HeLa , Humanos , Indóis/síntese química , Células K562 , Podofilotoxina/síntese química , Relação Estrutura-Atividade
18.
Nat Commun ; 10(1): 2883, 2019 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-31253768

RESUMO

A substantial number of mouse genes, about 25%, are embryonically lethal when knocked out. Using current genetic tools, such as the CRISPR-Cas9 system, it is difficult-or even impossible-to produce viable mice with heritable embryonically lethal mutations. Here, we establish a one-step method for microinjection of CRISPR reagents into one blastomere of two-cell embryos to generate viable chimeric founder mice with a heritable embryonically lethal mutation, of either Virma or Dpm1. By examining founder mice, we identify a phenotype and role of Virma in regulating kidney metabolism in adult mice. Additionally, we generate knockout mice with a heritable postnatally lethal mutation, of either Slc17a5 or Ctla-4, and study its function in vivo. This one-step method provides a convenient system that rapidly generates knockout mice possessing lethal phenotypes. This allows relatively easy in vivo study of the associated genes' functions.


Assuntos
Sistemas CRISPR-Cas , Embrião de Mamíferos/fisiologia , Animais , Desenvolvimento Embrionário , Feminino , Edição de Genes/métodos , Engenharia Genética/métodos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos ICR , Camundongos Knockout , Mutação , RNA Guia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
19.
Medicine (Baltimore) ; 98(24): e16077, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31192970

RESUMO

RATIONALE: Secondary hyperparathyroidism (SHPT) is often complicated with chronic renal failure. Though the total parathyroidectomy (TPTX) with forearm autotransplantation (FAT) has been commonly used to treatment refractory renal SHPT, the recurrence of SHPT is not infrequent, resulting from hyperplastic autograft, remnant parathyroid tissues, and supernumerary parathyroid gland (SPG). PATIENT CONCERNS: A 67-year-old man undergoing TPTX+FAT 4 years previously for renal SHPT, who received regular hemodialysis with active vitamin D supplements of Rocaltrol treatment postoperatively, was admitted to our hospital with progressively elevated serum intact parathyroid hormone (iPTH) from 176 to 1266 pg/mL for 8 months and bilateral ankle joints pain for 1 month. Tc-sestamibi dual-phase imaging with single positron emission tomography (SPECT)/computed tomography (CT) revealed a nodule in suprasternal fossa, besides a nodule in autografted site, accompanied with intense radioactivity. DIAGNOSIS: Recurrent SHPT was easily diagnosed based on previous medical history, painful joints, increased serum iPTH level and positive findings of Tc-sestamibi imaging. Routine postoperative pathology showed that the nodules were consistent with an adenomatoid hyperplasic autograft and a supernumerary parathyroid adenoma in suprasternal fossa, respectively. INTERVENTIONS: Reoperation for removing nodules in suprasternal fossa and autografted site was performed 1 month later. Then regular hemodialysis 3 times a week with Rocaltrol was continued. OUTCOMES: During 12 months of follow-up, the joints pain improved obviously and the serum iPTH level ranged from 30.1 to 442 pg/mL. LESSONS: Although rare, recurrent renal SHPT may be caused by a coexistence of both hyperfunctional autograft and SPG after TPTX+FAT. The Tc-sestamibi parathyroid imaging with SPECT/CT is helpful to locate the culprits of recurrent renal SHPT before reoperation. To prevent recurrence of renal SHPT, the present initial surgical procedures should be further optimized in patient on permanent hemodialysis.


Assuntos
Adenoma/complicações , Autoenxertos , Hiperparatireoidismo Secundário/etiologia , Nefropatias/complicações , Neoplasias das Paratireoides/complicações , Adenoma/diagnóstico por imagem , Adenoma/patologia , Adenoma/cirurgia , Idoso , Autoenxertos/patologia , Antebraço , Humanos , Hiperparatireoidismo Secundário/diagnóstico por imagem , Hiperparatireoidismo Secundário/patologia , Hiperparatireoidismo Secundário/cirurgia , Hiperplasia , Nefropatias/diagnóstico por imagem , Nefropatias/patologia , Nefropatias/cirurgia , Masculino , Neoplasias das Paratireoides/diagnóstico por imagem , Neoplasias das Paratireoides/patologia , Neoplasias das Paratireoides/cirurgia , Recidiva , Reoperação
20.
Ann Transl Med ; 7(9): 202, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31205920

RESUMO

Background: At present, there are no randomized trial or higher levels of evidence than case studies to guide thoracic surgeons in the field of thoracic deformities, typically for pectus excavatum. This study investigates the current clinical practices amongst the Chinese Association of Thoracic Surgeon (CATS) members in order to seek potential consensus and divergence. Methods: A web-based questionnaire was designed by a subgroup of CATS Pectus Excavatum Management Working Group and was sent to all of the CATS members. The questionnaire was composed of 27 questions concerning debatable sections, including preoperative evaluations, indications, timings of surgery, anesthesia and analgesia methods, rehabilitations. Results: A total of 385 questionnaires were mailed to available CATS members. Moreover, 208 questionnaires were retrieved, of them 170 were finally available for analysis. Results of high consensus were extracted. Besides well-known factors such as complaints of symptoms, a moderate to severe deformity by physical exam, a Haller CT index >3.2, pulmonary function deviance, and cardiology evaluation abnormality, cosmetic requests and severe social-psychological problems from deformity come to be the most common reasons (17.34% and 56.89%) for PE patients' demands for surgery, and also occupy high percentages (49.41% and 89.41%) in indications of surgery. Concerning CT scan, 3D reconstruction of the chest is performed additionally by two thirds (64.12%) of the investigated cohort. Two surgeons out of three (66.47%) responders consider the optimal age for surgery is 6-12 years old. After the Nuss procedure, the majority of responders (79.41%) agree on the removal of the bar 2-3 years after surgery. To deal with complicated or severe deformities, 84.71% of surgeons utilize the double bar or multiple bar techniques. The majority of responders (92.35%) prefer general anesthesia combined with intubation in PE surgery, as well as in the procedure of the Nuss bar removal (72.35%). Conclusions: The survey reveals a remarkable consistency of practice patterns in several aspects. Adequate preoperative evaluations are needed. Cosmetic request and psychological discomfort from deformity are crucial indications for surgery. We had better perform PE surgery before patients' puberty and bar removal 3 years after surgery. Several surgical skills are fully debated to enhance orthopedic effect and diminish complications. General anesthesia combined with intubation is considered as a standard maneuver. Surgeons now pay more and more attention to perioperative rehabilitations. The given results can be used as evidence in guiding clinical practice in circumstances where no evidence of higher levels exists, although divergences exist. Future studies, especially randomized trials, are needed to establish clinical practice guidelines for thoracic surgeons in PE surgery.

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