Strategies for patients with recurrent nasopharyngeal carcinoma involved internal carotid artery who are intolerant to embolization.

BACKGROUND: The surgical treatment of recurrent nasopharyngeal carcinoma (rNPC) involving the internal carotid artery (ICA) is challenging, as the massive bleeding caused by intraoperative rupture of the ICA is life-threatening. We reported that ICA embolization is an effective pretreatment to avoid fatal bleeding, but some patients cannot tolerate the procedure. We used endovascular vascular protection (ICA stents), vascular sacrifice (bypass grafting) and extravascular vascular protection (transcervical external stent placement) of the ICA to provide alternative options for these patients. METHODOLOGYy: This study enrolled patients with rNPC adjacent to or invading the ICA who were unsuitable for ICA embolization from January 2015 to June 2020. ICA pretreatment combined with endoscopic nasopharyngectomy (ENPG) was performed for the 30 patients. We report the survival outcome and incidence of complications after ICA pretreatment. RESULTS: ICA pretreatment was performed for the 30 enrolled patients, among whom 8 underwent endoscopic-assisted transcervical protection of the parapharyngeal ICA combined with ENPG, 6 underwent bypass grafting, and 16 underwent ICA stent implantation followed by ENPG. After pretreatment, at a median follow-up of 43 months (range, 2-80 months), the 3-year locoregional overall survival (OS), progression-free survival (PFS), locoregional recurrence-free survival (LRRFS), and distant metastasis-free survival (DMFS) were 62.9%, 61.3%, 70.2%, and 71.4%, respectively. CONCLUSIONS: ICA pretreatment combined with salvage ENPG enables the feasible and effective resection of rNPC lesions involving the ICA in patients who cannot tolerate ICA embolization. Therefore, this treatment may be an effective method for improving outcomes. Multidisciplinary therapy is needed to reduce operation-related complications.

The JNK signaling pathway against titanium-particle-induced osteoclastogenesis and bone resorption in vivo.

OBJECTIVE: The c-Jun N-terminal kinases (JNK) signaling pathway may be involved in the regulation of osteoclast development. The purpose of this investigation was to investigate whether SB600125, a JNK inhibitor, could attenuate titanium-particle-induced inflammatory osteolysis in vivo. MATERIALS AND METHODS: A total of 45 mice were randomly divided into a Sham group, a Titanium group, and a Titanium + JNK inhibitor group, 15 mice per group. After establishing an air pouch bone graft model, we injected phosphate-buffered saline (PBS), titanium particles, or titanium particles + JNK inhibitor into the air pouch of the three groups. The pouch membranes containing bone implants were taken for morphological and molecular analysis 14 days after the mice were sacrificed. RESULTS: General morphological structure observation results, Hematoxylin and Eosin (H&E)-Stained Sections, anti-tartaric acid phosphatase (TRAP) staining, and the transmission electron microscope showed that SB600125, by inhibiting the expression of JNK, attenuated titanium particle-induced inflammatory osteolysis (p<0.05). Immunohistochemical appearance results and reverse transcription-polymerase chain reaction (RT-PCR) results showed SB600125 reduced expression of IL-6, and TNF-α in osteolytic sites stimulated with wear debris (p<0.05). The Western blot results showed the expression of the p-JNK protein in the titanium particle + SB600125 group was significantly reduced compared to the titanium particle stimulation group (p<0.05). CONCLUSIONS: Interfering with the JNK signaling pathway may be beneficial in reducing osteolysis, providing a therapeutic target for preventing and treating aseptic loosening caused by debris-induced inflammatory osteolysis.

Stent pretreatment for internal carotid artery exposed to necrotic lesions in nasopharyngeal carcinoma.

BACKGROUND: Post radiation nasopharyngeal necrosis (PRNN) invading the internal carotid artery (ICA) contributes to the death of 69.2-72.7% of PRNN patients. ICA occlusion is an effective treatment to avoid fatal bleeding, while some patients are intolerant. We present a novel method that allows for these patients without interrupting blood flow through the ICA. METHODOLOGY: This study enrolled patients with PRNN-invaded ICA who were not suitable for ICA occlusion from April 2020 to November 2022. ICA stent pretreatment was performed in the 36 patients and followed the endoscopic nasopharyngectomy (ENPG) or conservative treatment for PRNN. We report the survival outcome and incidence of complications after stent implantation and compare the survival outcomes of ENPG and conservative treatment for PRNN followed by stent implantation. RESULTS: ICA stent pretreatment was performed in the 36 enrolled patients, among which 14 underwent ENPG, and 22 received conservative treatment. 27.8% patients died after a median follow-up of 15 months. The Kaplan-Meier estimates of overall survival were higher in the ENPG group than in the conservative treatment group. Karnofsky performance status (KPS) was significantly higher in the ENPG group than in the non-ENPG group. CONCLUSIONS: The innovative application of ICA stents is a promising treatment to improve outcomes in patients with PRNN invading the ICA who are unsuitable for ICA embolization, especially when followed by endoscopic surgery. However, methods to avoid postoperative cerebral ischemia and nasopharyngeal hemorrhage still require further study.

Clinical characteristics of 161 cases of corona virus disease 2019 (COVID-19) in Changsha.

OBJECTIVE: In December 2019, a new type of coronavirus-infected pneumonia broke out in Wuhan and spread rapidly to other parts of the country. The purpose of this study was to investigate the clinical features of coronavirus disease 2019 (COVID-19). MATERIALS AND METHODS: A retrospective analysis was performed on the confirmed cases of COVID-19, who were admitted to the North Hospital of Changsha first Hospital (Changsha Public Health treatment Center) from January 17 to February 7, 2020. RESULTS: The median age of COVID-19 patients was 45 years (range 33.5-57). The male patients accounted for 49.7%, 64.6% of the patients had a history of exposure in Wuhan, and 31.7% had family aggregation. The median days of onset were six, and the incidence of severe illness was 18.6%. Compared with the non-severe group, the severe group showed statistical significance in older age, hypertension, bilateral lung plaque shadow, decrease in lymphocyte count, increase in C-reactive protein (CRP), aspartate aminotransferase (AST), lactate dehydrogenase, and creatine kinase. CONCLUSIONS: Age, combined hypertension, oxygenation index, double lung patch, decreased lymphocyte count, and elevated levels of C-reactive protein, aspartate aminotransferase, lactate dehydrogenase, and creatine kinase can be used as predictors of the disease severity.

Magnetic-charge ordering and phase transitions in monopole-conserved square spin ice.

Magnetic-charge ordering and corresponding magnetic/monopole phase transitions in spin ices are the emergent topics of condensed matter physics. In this work, we investigate a series of magnetic-charge (monopole) phase transitions in artificial square spin ice model using the conserved monopole density algorithm. It is revealed that the dynamics of low monopole density lattices is controlled by the effective Coulomb interaction and the Dirac string tension, leading to the monopole dimerization which is quite different from the dynamics of three-dimensional pyrochlore spin ice. The condensation of the monopole dimers into monopole crystals with staggered magnetic-charge order can be predicted clearly. For the high monopole density cases, the lattice undergoes two consecutive phase transitions from high-temperature paramagnetic/charge-disordered phase into staggered charge-ordered phase before eventually toward the long-range magnetically-ordered phase as the ground state which is of staggered charge order too. A phase diagram over the whole temperature-monopole density space, which exhibits a series of emergent spin and monopole ordered states, is presented.

Estrogen combined with progesterone decreases cell proliferation and inhibits the expression of Bcl-2 via microRNA let-7a and miR-34b in ovarian cancer cells

PURPOSE: This study evaluated the effect of estrogen (E2), progesterone (P4), and the combination of them (E2 + P4) on survival rate, apoptosis, and the expressions of Bcl-2, hsa-let-7a and has-miR-34b in primary ovarian cancer cells to provide new clues for the clinical treatments of ovarian cancer. METHODS: The primary ovarian cancer cells from 60 cases of clinical ovarian cancer tissues were isolated and then cultured. The survival rate of ovarian cancer cells after the treatment of E2, P4 and E2 + P4 was analyzed by MTT assay. Cell apoptosis rate and cell cycle were measured by FACS analysis. Moreover, the relative abundance of Bcl-2 and microRNAs (let-7a, miR-34b) expressions were detected by quantitative real-time PCR (qRT-PCR) and Western blotting. RESULTS: Low concentrations of estrogen (10(-10), 10(-8), 10(-6 )mol/L) did not affect the proliferation of ovarian cancer cells. However, the high concentration of estrogen (10(-4 )mol/L) inhibited survival rate of ovarian cancer cells. Progesterone (10(-4 )mol/L) inhibited the proliferation of cancer cells. The combination of estrogen and progesterone significantly inhibited the survival rate of ovarian cancer cells with a time- and dose-dependent manner. High concentration of estrogen combined with progesterone (E2 + P4) induced apoptosis of ovarian cancer cells. E2 + P4 promoted the expression of let-7a and miR-34b and reduced the expression of Bcl-2 in ovarian cancer cells. When the expression of let-7a or/and miR-34b was inhibited using miRNA inhibitors, E2 + P4 treatment did not change the protein level of Bcl-2. CONCLUSION: E2 + P4 significantly inhibited the cell survival, promoted the cell apoptosis, induced the expression of let-7a and miR-34b, and reduced the expression of Bcl-2 in ovarian cancer cells (AU)

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Palmitic acid in chicken granulosa cell death-lipotoxic mechanisms mediate reproductive inefficacy of broiler breeder hens.

In vivo and in vitro approaches were used to elucidate mechanisms of palmitate-induced cytotoxicity of follicle granulosa cells in fuel-overloaded broiler hens. In contrast to their energy-restricted counterparts, broiler breeder hens fed ad libitum for 2 wk had dyslipidemia, atresia within hierarchical ovarian follicles, and a 34% reduction in egg production (P < 0.05). Based on vital staining of freshly isolated granulosa cells with annexin V/propidium iodide, there were increases in apoptosis consistent with suppressed Akt activation (P < 0.05). Supplementing primary granulosa cell cultures with 0.5 mM palmitate for 48 or 96 h increased apoptosis (P < 0.05). Palmitate-induced cell death was accompanied by increased acyl-CoA oxidase, carnitine palmitoyl transferase-1, serine palmitoyl transferase, and sphingomyelinase transcripts and increased concentrations of proinflammatory interleukin-1ß (P < 0.05). Triacsin-C inhibition of fatty acyl-CoA synthesis blunted interleukin-1ß production and rescued granulosa cultures from palmitate-induced cell death. That there was partial to complete prevention of cell death with addition of the free radical scavenger pyrrolidine dithiocarbamate, the sphingomyelinase inhibitor imipramine, or the de novo ceramide synthesis inhibitor fumonisin B1, supported the notion that palmitate-induced granulosa cell cytotoxicity operated through a palmitate-derived metabolite. Palmitoyl-CoA may be channeled into ß-oxidation and/or into bioactive metabolites that increase free radical generation, an inflammatory response, and ceramide production. In conclusion, palmitate-derived metabolites activated apoptotic machinery in avian granulosa cells, which caused ovarian follicular atresia and reduced egg production in fuel-overloaded broiler breeder hens.

Ceramide accumulation and up-regulation of proinflammatory interleukin-1ß exemplify lipotoxicity to mediate declines of reproductive efficacy of broiler hens.

The study was conducted to delineate fundamental mechanisms that initiate the deleterious effect of fuel overloading on reproductive efficacy of broiler breeder hens. Sixty hens at age 26 wk were fed recommended amounts of feed (160 g/d per hen) or allowed voluntary feeding (approximately 30% more than restriction). At age 35 and 50 wk, hens were sampled for further analyzes. Voluntary feeding resulted in poor egg production, high rate of mortality, and abnormal ovarian structure (mainly overt hierarchical follicle atresia at age 35 wk and ovarian involution at age 50 wk). In contrast to feed-restricted hens, voluntary feeding also induced metabolic dysregulations that comprised enhanced adiposity; hepatic triacylglycerol accumulation; and elevated concentrations of plasma glucose, NEFAs, very low density lipoprotein, triacylglycerol, phospholipids, and sphingomyelin (P < 0.05). Furthermore, hepatic and circulating ceramide and sphingomyelin accumulation, and up-regulation of proinflammatory IL-1ß expression in liver and adipose tissues (P < 0.05) systemically manifested the development of lipotoxicity in feed-satiated hens. Lipotoxicity leading to impaired ovarian dysfunctions, including follicle atresia, ovarian regression, and a decline of circulating estradiol levels (P < 0.05) in feed-satiated hens, was further exemplified by ceramide accumulation and up-regulation of IL-1ß, serine palmitoyltransferase, and sphingomyelinase transcript abundance, but suppressed protein kinase Akt activation (P < 0.1 to 0.05) within the hierarchical follicles. This study provides the first in vivo evidence of the actions of ceramide and IL-1ß in mediating overfeeding-induced follicle atresia and progression of ovarian involution in broiler hens.

Intramolecular disulfide bonds of the prolactin receptor short form are required for its inhibitory action on the function of the long form of the receptor.

The short form (S1b) of the prolactin receptor (PRLR) silences prolactin-induced activation of gene transcription by the PRLR long form (LF). The functional and structural contributions of two intramolecular disulfide (S-S) bonds within the extracellular subdomain 1 (D1) of S1b to its inhibitory function on the LF were investigated. Mutagenesis of the paired cysteines eliminated the inhibitory action of S1b. The expression of the mutated S1b (S1bx) on the cell surface was not affected, indicating native-like folding of the receptor. The constitutive JAK2 phosphorylation observed in S1b was not present in cells expressing S1bx, and JAK2 association was disrupted. BRET(50) (BRET(50) represents the relative affinity as acceptor/donor ratio required to reach half-maximal BRET [bioluminescence resonance energy transfer] values) showed decreased LF/S1bx heterodimeric-association and increased affinity in S1bx homodimerization, thus favoring LF homodimerization and prolactin-induced signaling. Computer modeling based on the PRLR crystal structure showed that minor changes in the tertiary structure of D1 upon S-S bond disruption propagated to the quaternary structure of the homodimer, affecting the dimerization interface. These changes explain the higher homodimerization affinity of S1bx and provide a structural basis for its lack of inhibitory function. The PRLR conformation as stabilized by S-S bonds is required for the inhibitory action of S1b on prolactin-induced LF-mediated function and JAK2 association.