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1.
Int Urol Nephrol ; 2019 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-31679137

RESUMO

PURPOSE: To compare differences in clinical characteristics and outcomes between patients with and without human immunodeficiency virus (HIV) infection in light of robot-assisted laparoscopic radical prostatectomy (RALRP) as the most common surgical technique for prostate cancer. Previous data on perioperative complication rates of RALRP in HIV(+) patients are limited by small sample size. METHODS: The National Inpatient Sample database from 2008 to 2014 was used to query prostate cancer patients who underwent RALRP. HIV(+) patients were identified through ICD9 codes 042, 043, 044, V08 and 079.53. Intraoperative and postoperative complications, rate of blood transfusion, in-hospital mortality, prolonged length of stay and total cost were compared by univariate, multivariate regression and 1:4 propensity score matched analyses. RESULTS: Overall, 270,319 weighted patients undergoing RALRP were identified, among whom 546 (0.20%) patients were diagnosed with HIV. Patients with HIV were younger, less likely to be white and had more comorbidities. Multivariable regression analysis revealed that HIV(+) patients had significantly increased genitourinary complications (odds ratio [OR]: 3.31; 95% confidence interval [CI]: 1.03-10.68) and miscellaneous surgical events (OR 3.19; 95% CI 1.26-8.08). There were no differences in potentially life-threatening cardiac, respiratory and vascular events between patients with and without HIV after RALRP. Propensity score matched analysis yielded similar results. CONCLUSIONS: Our findings suggest that patients who underwent RALRP with HIV did not experience higher risk of potentially life-threatening postoperative complications. RALRP could be safely considered as a surgical treatment for HIV(+) patients with prostate cancer.

2.
Fitoterapia ; 139: 104394, 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31669719

RESUMO

Naturally occurring monoterpenes are known for their various pharmacological activities including anti-inflammation. KV1.3 ion channel is a voltage-gated potassium channel and has been validated as a drug target for autoimmune and chronic inflammatory diseases like psoriasis. Here we experimentally test the direct interaction between monoterpenes and KV1.3 ion channel. Our electrophysiological analysis determined that monoterpenes (geraniol, nerol, ß-citronellol, citral and linalool) have inhibitory effects on KV1.3 ion channel. Representatively, geraniol reversibly blocked KV1.3 currents in a voltage-dependent manner with an IC50 of 490.50 ±â€¯1.04 µM at +40 mV in HEK293T cells. At the effective concentrations, geraniol also inhibited cytokine secretion of activated human T cells, including IL-2, TNF-α and IFN-γ. In an imiquimod-induced psoriasis-like animal model, geraniol administration significantly reduced psoriasis area and severity index scores, ameliorated the deteriorating histopathology and decreased the degree of splenomegaly. Together, our findings not only suggest that monoterpenes may serve as lead molecules for the development of KV1.3 inhibitors, but also indicate that geraniol could be considered as a promising therapeutic candidate to treat autoimmune diseases.

3.
Microb Pathog ; 138: 103808, 2019 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-31634530

RESUMO

Iron plays a central role at the interface of pathogen and host. The ability to sequester iron from a host not only reduces host immune defenses but also promotes pathogen virulence, leading to the occurrence of infectious disease. Recently, outer membrane protein OmpW was shown to protect bacteria against harsh environmental conditions and to play a role in infectious disease. The expression of this versatile protein is controlled by iron, but the underlying mechanism of iron regulation has not been elucidated. In this study, the relation between OmpW expression and iron was investigated. Our results demonstrated that expression of OmpW is responsive to iron. Iron uptake analysis showed that an ompW mutant strain has a strong requirement for iron as compared to wild type and the ompW complemented strain. Moreover, ferric uptake regulation protein Fur, an iron binding transcriptional factor, was downregulated under iron limitation conditions and had a similar expression profile to OmpW in the presence or absence of iron. Based on these results, we suggest that iron regulates OmpW by binding to Fur. Furthermore, SoxS, a transcriptional factor involved in oxidative stress, was found to negatively regulate OmpW. We found that downregulating or knocking out OmpW results in bacterial resistance to oxidative stress. These findings provide new insight into the regulation of OmpW expression by iron, and may represent a new mechanism contributing to iron-mediated infectious disease.

4.
J Clin Neurosci ; 69: 250-256, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31477463

RESUMO

Electroacupuncture (EA) is an adjuvant therapy for peripheral nerve injury (PNI). Both peripheral and central alterations contribute to the rehabilitation process. We employed diffusion tensor imaging (DTI) to investigate the diffusion plasticity of afferent and efferent pathways caused by EA in model of peripheral nerve injury and reparation. Twenty-four rats were divided into three groups: normal group, model group and intervention group. Rats of the model group and the intervention group underwent sciatic nerve transection and anastomosis. EA intervention was performed on the intervention group at ST-36 and GB-30 for three months. Gait assessment and DTI were conducted at days post-operative (DPO) 30, 60 and 90. We selected corticospinal tract, spinothalamic tract and internal capsule as regions of interest and analyzed diffusion metrics including fractional anisotropy (FA), axial diffusivity (AD) and radial diffusivity (RD). FA values and RD values displayed significant differences or obvious tendency while AD values maintained a stable level. RD values displayed better indicative performance than FA in internal capsule. The intervention group presented significant correlation between RD values and Regularity Index (RI) during the intervention period. The effect of EA on peripheral nerve injury repairing rats appeared to be accelerated recovery process of sensory and motor neural pathway. We proposed that RD was a potential in vivo indicator for structural plasticity caused by EA and PNI.

5.
Am J Physiol Renal Physiol ; 317(5): F1331-F1341, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31509007

RESUMO

Posttranslational modifications are essential for the regulation of urea transporter-A1 (UT-A1), among which ubiquitination is a rather attractive and complex issue. Previously, our group reported that murine double minute 2 (MDM2) is one of the E3 ubiquitin ligases for UT-A1, and, later, we showed that ubiquitination contributes to the subcellular trafficking and stability of UT-A1. In the present study, we discovered that MDM2 interacts with UT-A1 in an AP50 (a component of the clathrin-coated pit)-dependent manner. However, their binding is irrelevant to the phosphorylatory status of UT-A1. Next, our findings indicated that MDM2 decreases the stability of either total or membrane UT-A1. On the cell membrane, MDM2 and ubiquitinated UT-A1 are both distributed in the lipid raft domain, and their linkage is obviously enhanced under forskolin (FSK) stimulation. In line with these results, in the diabetic rat, not only MDM2 but also ubiquitinated UT-A1 are intensified. Also, in vitro high glucose and angiotensin II play similar roles as FSK does on the association of MDM2 with UT-A1. In conclusion, MDM2 binds with UT-A1 and mediates its ubiquitination and degradation in an AP50-dependent manner, and their binding capacity is strengthened under FSK and diabetic milieu.

6.
Angew Chem Int Ed Engl ; 58(41): 14462-14466, 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31469211

RESUMO

3-(2-Formylphenyl)-1-pyrazol-1-yl-propenones undergo an asymmetric photorearrangement to benzo[d]cyclopropa[b]pyranones with up to >99 % ee, which is catalyzed by a bis-cyclometalated rhodium catalyst in the presence of visible light. Mechanistic experiments and DFT calculations support a mechanism in which a photoexcited catalyst/substrate complex triggers an intramolecular hydrogen-atom transfer followed by a highly stereocontrolled hetero-Diels-Alder reaction. In this reaction scheme, the rhodium catalyst fulfills multiple functions by 1) enabling visible-light π→π* excitation of the catalyst-bound enone substrate, 2) facilitating the hydrogen-atom transfer, and 3) providing the asymmetric induction for the hetero-Diels-Alder reaction.

7.
Asian J Androl ; 2019 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-31417010

RESUMO

Hypoxia-induced erythropoietin signaling plays an important role in tumor growth and invasion. In the present study, we investigated the contribution of erythropoietin signaling pathway to castration-resistant prostate cancer and the development of a neuroendocrine phenotype. Immunohistochemical staining showed that the erythropoietin and erythropoietin receptor scores in castration-resistant prostate cancer and androgen-dependent prostate cancer were 7.55 versus 4.5 and 7.45 versus 5.9,respectively (P < 0.001). Furthermore, a cell proliferation assay was conducted, and the differential expression of erythropoietin and erythropoietin receptor in LNCaP cells and hypoxia-induced LNCaP cells was evaluated using western blot and quantitative real-time PCR. The proliferation capacity of hypoxia-induced LNCaP cells was similar in cultures of both fetal bovine serum and charcoal-stripped fetal bovine serum, suggesting that LNCaP cells acquired hypoxia-induced androgen-independent growth. After 2 weeks of hypoxic culture, LNCaP cells showed a neuroendocrine cell change and increased expression of neuron-specific enolase, erythropoietin, and erythropoietin receptor; knockdown of erythropoietin receptor reversed the hypoxia-induced upregulation of neuron-specific enolase in the LNCaP cells. In conclusion, the concurrent upregulation of erythropoietin and erythropoietin receptor in castration-resistant prostate cancer suggests that the erythropoietin/erythropoietin receptor autocrine loop plays an important role in the progression of castration resistance and is responsible for the development of a neuroendocrine phenotype.

8.
Sci Adv ; 5(8): eaaw7286, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31453328

RESUMO

While benefiting greatly from electronics, our society also faces a major problem of electronic waste, which has already caused environmental pollution and adverse human health effects. Therefore, recyclability becomes a must-have feature in future electronics. Here, we demonstrate an erasable and recreatable two-dimensional electron gas (2DEG), which can be easily created and patterned by depositing a water-dissolvable overlayer of amorphous Sr3Al2O6 (a-SAO) on SrTiO3 (STO) at room temperature. The 2DEG can be repeatedly erased or recreated by depositing the a-SAO or dissolving in water, respectively. Photoluminescence results show that the 2DEG arises from the a-SAO-induced oxygen vacancy. Furthermore, by gradually depleting the 2DEG, a transition of nonlinear to linear Hall effect is observed, demonstrating an unexpected interfacial band structure. The convenience and repeatability in the creation of the water-dissolvable 2DEG with rich physics could potentially contribute to the exploration of next generation electronics, such as environment-friendly or water-soluble electronics.

9.
Gut ; 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31462556

RESUMO

OBJECTIVE: Insulinomas and non-functional pancreatic neuroendocrine tumours (NF-PanNETs) have distinctive clinical presentations but share similar pathological features. Their genetic bases have not been comprehensively compared. Herein, we used whole-genome/whole-exome sequencing (WGS/WES) to identify genetic differences between insulinomas and NF-PanNETs. DESIGN: The mutational profiles and copy-number variation (CNV) patterns of 211 PanNETs, including 84 insulinomas and 127 NF-PanNETs, were obtained from WGS/WES data provided by Peking Union Medical College Hospital and the International Cancer Genome Consortium. Insulinoma RNA sequencing and immunohistochemistry data were assayed. RESULTS: PanNETs were categorised based on CNV patterns: amplification, copy neutral and deletion. Insulinomas had CNV amplifications and copy neutral and lacked CNV deletions. CNV-neutral insulinomas exhibited an elevated rate of YY1 mutations. In contrast, NF-PanNETs had all three CNV patterns, and NF-PanNETs with CNV deletions had a high rate of loss-of-function mutations of tumour suppressor genes. NF-PanNETs with CNV alterations (amplification and deletion) had an elevated risk of relapse, and additional DAXX/ATRX mutations could predict an increased relapse risk in the first 2-year period. CONCLUSION: These WGS/WES data allowed a comprehensive assessment of genetic differences between insulinomas and NF-PanNETs, reclassifying these tumours into novel molecular subtypes. We also proposed a novel relapse risk stratification system using CNV patterns and DAXX/ATRX mutations.

11.
Crit Care Med ; 47(10): 1371-1379, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31306176

RESUMO

OBJECTIVES: Assess patient outcomes in patients with suspected infection and the cost-effectiveness of implementing a quality improvement program. DESIGN, SETTING, AND PARTICIPANTS: We conducted an observational single-center study of 13,877 adults with suspected infection between March 1, 2014, and July 31, 2017. The 18-month period before and after the effective date for mandated reporting of the sepsis bundle was examined. The Sequential Organ Failure Assessment score and culture and antibiotic orders were used to identify patients meeting Sepsis-3 criteria from the electronic health record. INTERVENTIONS: The following interventions were performed as follows: 1) multidisciplinary sepsis committee with sepsis coordinator and data abstractor; 2) education campaign; 3) electronic health record tools; and 4) a Modified Early Warning System. MAIN OUTCOMES AND MEASURES: Primary health outcomes were in-hospital death and length of stay. The incremental cost-effectiveness ratio was calculated and the empirical 95% CI for the incremental cost-effectiveness ratio was estimated from 5,000 bootstrap samples. RESULTS: In multivariable analysis, the odds ratio for in-hospital death in the post- versus pre-implementation periods was 0.70 (95% CI, 0.57-0.86) in those with suspected infection, and the hazard ratio for time to discharge was 1.25 (95% CI, 1.20-1.29). Similarly, a decrease in the odds for in-hospital death and an increase in the speed to discharge was observed for the subset that met Sepsis-3 criteria. The program was cost saving in patients with suspected infection (-$272,645.7; 95% CI, -$757,970.3 to -$79,667.7). Cost savings were also observed in the Sepsis-3 group. CONCLUSIONS AND RELEVANCE: Our health system's program designed to adhere to the sepsis bundle metrics led to decreased mortality and length of stay in a cost-effective manner in a much larger catchment than just the cohort meeting the Centers for Medicare and Medicaid Services measures. Our single-center model of interventions may serve as a practice-based benchmark for hospitalized patients with suspected infection.

12.
Appl Microbiol Biotechnol ; 103(18): 7703-7717, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31359103

RESUMO

G protein-coupled receptors (GPCRs), also known as seven-transmembrane domain receptors, are among the most important targets against which many small molecule drugs have been developed. However, only two antibody drugs targeting GPCRs have been approved for clinical use although many antibody drugs against non-GPCR protein targets have been successfully developed for various disease indications. One of the challenges for developing anti-GPCR drugs is the high difficulty to perform affinity maturation due to their insolubility in aqueous solutions. To address this issue, CHO cell display libraries of single-chain variable fragments (scFvs) and full-length antibodies were maturated directly against vesicle probes prepared from CHO cells displaying the endothelin A receptor (ETaR) GPCR. The probe in the vesicle form ensures the physiological conformation and functional activity of the protein and avoids issues with membrane protein insolubility. The size of the vesicle had a clear effect on protein-ligand interaction; we used small-sized vesicles with low expression levels of GPCRs for the affinity maturation. Four rounds of affinity maturation combining vesicles as probes with the CHO cell display platform improved affinity by 13.58-fold for scFvs and 5.05-fold for full-length antibodies. We expect that this method will not only be used for the affinity maturation of antibodies against GPCRs but will also be used to mature antibodies for other types of proteins where the conformation/activity of which depends on the proper membrane environment.

13.
Sensors (Basel) ; 19(13)2019 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-31284502

RESUMO

The development of accurate, reliable devices for glucose detection has drawn much attention from the scientific community over the past few years. Here, we report a single-step method to fabricate Ni nanoparticle-modified graphene-diamond hybrid electrodes via a catalytic thermal treatment, by which the graphene layers are directly grown on the diamond surface using Ni thin film as a catalyst, meanwhile, Ni nanoparticles are formed in situ on the graphene surface due to dewetting behavior. The good interface between the Ni nanoparticles and the graphene guarantees efficient charge transfer during electrochemical detection. The fabricated electrodes exhibit good glucose sensing performance with a low detection limit of 2 µM and a linear detection range between 2 µM-1 mM. In addition, this sensor shows great selectivity, suggesting potential applications for sensitive and accurate monitoring of glucose in human blood.

14.
J Ethnopharmacol ; 243: 112078, 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31301369

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Rhododendron molle G. Don (Ericaceae) (RM) is a natural medicinal plant. Its root extracts have been applied in clinic and proved to be effective in chronic glomerulonephritis and rheumatoid arthritis in China. Surprising, little is understood about the key compound of RM and the exact mechanisms underlying its treatment on kidney diseases. In this study, we will explore whether rhodojaponin II (R-II), as the important compound of RM, also exerts the major effect. MATERIALS AND METHODS: Mouse model of focal segmental glomerulosclerosis was induced by single dose of adriamycin injection. Induced adriamycin nephropathy (ADRN) mice were treated individually with RM root extract (5 mg/kg, n = 5), RM root extract (60 mg/kg, n = 5), R-II (0.04 mg/kg, n = 6) or captopril (30 mg/kg, n = 5) for five weeks. Podocyte marker (nephrin and podocin) expressions were examined by immunohistochemical staining and Western Blot analysis. Fibronectin level was evaluated by immunohistochemical staining and Western Blot analysis. Interstitial infiltrated inflammatory cells (CD4+ T cells, CD8+ T cells, and CD68+ macrophages) were examined with immunohistochemical staining. The expressions of NF-ĸB p-p65 and TGF-ß1/Smad pathway associated key proteins, such as TGF-ß1, Smad3, phosphorylated-Smad3 (p-Smad3), and Smad7, were analyzed respectively by Western Blot analysis. RESULTS: RM root extract (5 mg/kg) and its important compound R-II (0.04 mg/kg) significantly ameliorated proteinuria, podocyte injury, and glomerulosclerosis, meanwhile, they hampered interstitial fibrosis in mice with ADRN. R-II significantly reduced NF-ĸB p65 phosphorylation, interstitial infiltrated CD4+ T cells, CD8+ T cells, and CD68+ macrophages, at the same time, down-regulated TGF-ß1 and p-Smad3 protein expressions in mice with ADRN. CONCLUSION: RM root extract, R-II, could effectively ameliorate proteinuria and kidney injury in ADRN, related to its anti-inflammatory effects, as well as suppression of TGF-ß1/Smad signaling pathway.

15.
Nat Commun ; 10(1): 3108, 2019 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-31311932

RESUMO

Pulmonary lymphoepithelioma-like carcinoma (LELC) is a rare and distinct subtype of primary lung cancer characterized by Epstein-Barr virus (EBV) infection. Herein, we reported the mutational landscape of pulmonary LELC using whole-exome sequencing, targeted deep sequencing and single-nucleotide polymorphism arrays. We identify a low degree of somatic mutation but widespread existence of copy number variations. We reveal predominant signature 2 mutations and frequent loss of type I interferon genes that are involved in the host-virus counteraction. Integrated analysis shows enrichment of genetic lesions affecting several critical pathways, including NF-κB, JAK/STAT, and cell cycle. Notably, multi-dimensional comparison unveils that pulmonary LELC resemble NPC but are clearly different from other lung cancers, natural killer/T-cell lymphoma or EBV-related gastric cancer in terms of genetic features. In all, our study illustrates a distinct genomic landscape of pulmonary LELC and provides a road map to facilitate genome-guided personalized treatment.

16.
World J Urol ; 2019 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-31292732

RESUMO

OBJECTIVES: To evaluate the feasibility and safety of the application of robotic enucleation of adrenal masses (REAM). METHODS: Thirteen patients at Shanghai Changhai Hospital who underwent robotic enucleation of adrenal mass from February 2017 to March 2018 were reviewed. After mobilizing the adrenal gland and clamping the feeding blood vessels, the tumor was enucleated and reconstruction was performed. Relevant clinical data were recorded including baseline patient and tumor characteristics, and perioperative outcomes (operating time, ischemic time, estimated blood loss, complications, and so on). RESULTS: All cases were successfully completed without conversion to total adrenalectomy or open surgery. The mean operative time was 75 min (range 60-95), with a mean warm ischemia time of 12 min (range 8-17). The estimated blood loss was 20 mL (range 10-50). No intraoperative complications were observed, and no steroid replacement was given post-operatively. After a median follow-up period of 12 months (range 9-15), no evidence of disease recurrence was detected. CONCLUSIONS: Robotic enucleation of adrenal masses is a safe and feasible procedure with excellent short-term functional and oncologic outcomes. Steroid supplementation is not necessary and recurrence is not usual with limited follow-up. Long-term follow-up and larger studies should be conducted to further evaluate outcomes of this robotic adrenal-sparing approach.

17.
Pain Physician ; 22(3): E215-E224, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31151344

RESUMO

BACKGROUND: Approximately 30% to 80% of patients with brachial plexus avulsion (BPA) developed neuropathic pain. It is an intolerable neuropathic pain, which brings heavy burden to family and society. In addition to motor and sensory deficits, neuropathic pain can be another serious sequela that equally influences the patient. The development of a microsurgical technique has promoted the treatment and rehabilitation of brachial plexus injury, but pain relief after BPA is still a difficult problem. OBJECTIVES: The present study aimed to semi-quantify changes in the behavior, spinal cord and cerebral metabolism in a neuropathic pain model following BPA injury in rats. STUDY DESIGN: Controlled animal study. SETTING: Institute of Rehabilitation Medicine, Shanghai, China. METHODS: A total of 15 Sprague-Dawley rats, weighing 200 to 220 g, were randomly divided into 2 groups: experimental group (n = 10) and control group (n = 5). In the experimental group, neuropathic pain induced by BPA was established by directly avulsing the C5, C6, C7, C8, and T1 roots on the right side from the spinal cord. Rats in the control group only received open-close surgery. The autotomic behavior of biting their own digits was recorded and scored at 2 months after the surgery. Small animal positron emission tomography/computed tomography (PET/CT) images after injection of a 2-[18F]-fluoro-2-deoxy-D-glucose (18F-FDG) tracer were acquired to evaluate glucose metabolism in pain-related brain regions before and after the surgery, respectively. Semi-quantitative values of cortical to cerebellum standardized uptake value (SUV) ratios were calculated. Then, the animals were euthanized and the cervical segments of the spinal cord were removed for detection of glial fibrillary acidic protein (GFAP) expression in the astrocytes by immunohistochemical assay. RESULTS: Nine of the 10 rats (90%) in the experimental group showed autotomic behavior at 2 months after the surgery. Slight autotomic behavior was noted only in one of 5 rats (20%) from the control group. The autotomic score in the experimental group was significantly higher than that in the control group (5.4 ± 1.0 vs. 0.2 ± 0.4, P < 0.05). The experimental group showed significantly higher SUV ratio in both the right and left thalamus, compared to the control group (P < 0.05). Immunohistochemical assay demonstrated that GFAP positive astrocytes in the dorsal horn at the injured side significantly increased compared to the control group (P < 0.05). LIMITATIONS: There are differences between small animals and human beings, and the structure and function of the human brain is more complex than in rodents. Therefore, extrapolation of the present conclusion should be cautious. CONCLUSIONS: The present study reported a unique model of neuropathic pain following total BPA in rodents, which was demonstrated by a higher rate and score of autotomic behavior. More astrocytes were found activated in the spinal cord at the corresponding level of C5 and C6 spinal cord. In the small animal PET/CT imaging, significantly higher standardized glucose metabolic activity was found in both the right and left thalamus in the experimental group. The present study semi-quantified the neuropathic pain behavior in rats and explored the plastic changes in the spinal and brain metabolism. KEY WORDS: Brachial plexus avulsion, small animal PET/CT, glucose metabolism, neuropathic pain, astrocyte, 18F-FDG.

18.
Asian J Surg ; 2019 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-31253384

RESUMO

OBJECTIVE: To evaluate the possibility and efficiency of a modified margin strategy in laparoscopic partial nephrectomy with selective renal artery clamping. METHODS: Seventy-six cases of laparoscopic partial nephrectomy with segmental renal artery clamping in Shanghai Changhai Hospital between July 2014 and September 2017 were retrospectively reviewed. Relevant clinical data were recorded including baseline patient and tumor characteristics, and surgical outcomes (segmental artery mobilization time, operating time, warm ischemic time, estimated blood loss, complications, and so on). A comparative analysis between standard technique and margin strategy was performed. RESULTS: In 38 cases, margin strategy to mobilize segmental artery was successfully performed. In the other 38 cases, the surgery was performed in traditional method. The use of new strategy led to a shortened segmental artery mobilization time (5 min vs 12 min, p < 0.001). There was no difference in terms of perioperative complications between the two techniques. CONCLUSIONS: The margin strategy is a practical method in laparoscopic partial nephrectomy with selective renal artery clamping. It provides a simplified way of finding segmental arteries. Further studies are needed to confirm these preliminary findings.

19.
Bioorg Med Chem Lett ; 29(15): 1918-1921, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31176700

RESUMO

A low level of high density lipoprotein (HDL) is an independent risk factor for cardiovascular disease. HDL reduces inflammation and plays a central role in reverse cholesterol transport, where cholesterol is removed from peripheral tissues and atherosclerotic plaque. One approach to increase plasma HDL is through inhibition of endothelial lipase (EL). EL hydrolyzes phospholipids in HDL resulting in reduction of plasma HDL. A series of benzothiazole sulfone amides was optimized for EL inhibition potency, lipase selectivity and improved pharmacokinetic profile leading to the identification of Compound 32. Compound 32 was evaluated in a mouse pharmacodynamic model and found to show no effect on HDL cholesterol level despite achieving targeted plasma exposure (Ctrough > 15 fold over mouse plasma EL IC50 over 4 days).

20.
Oper Neurosurg (Hagerstown) ; 17(6): 580-587, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31089696

RESUMO

BACKGROUND: Radical resection is the first-line option in managing cervical primary chondrosarcoma. Favorable anterior reconstruction is challenging after multilevel total spondylectomy in the cervical spine. OBJECTIVE: To illustrate the application of piezoelectric surgery and three-dimensional (3D) printing techniques in spine surgery. METHODS: A 27-yr-old patient was referred to our center with complaints of nocturnal neck pain and right upper extremity weakness. A 2-stage radical tumor resection was conducted using piezoelectric surgery with pathologically tumor-free margins. A 3D-printed titanium microporous prosthesis (3D-PTMP) was designed to reconstruct the anterior column of the cervical spine between C1 and T1 for stability. RESULTS: The whole intraoperative blood loss was 2300 mL over the 2 procedures. The patient had an uneventful recovery, regaining ambulatory status 3 wk after the 2 operations without ventilator support or other severe complications. By the final 14-mo follow-up, the patient had achieved marked pain relief and favorable neurological improvement; a postoperative computed tomography scan indicated a good position of the 3D-printed construct between the endplates with no sign of tumor recurrence or implant subsidence. CONCLUSION: The applications of piezosurgery in total spondylectomy and in 3D-PTMP in reconstruction can be a favorable alternative for managing multilevel cervical spinal tumors. Further studies are warranted to validate this surgical strategy.

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