Abstract Introduction: Propofol is a widely used anesthetic and its dose is closely related to aging. Telomere length (TL) is a unique heritable trait, and emerging as a biomarker of aging, health and disease. Telomerase RNA component (TERC) plays an important role in maintaining TL. We proposed a hypothesis that propofol dose in general anesthesia can be predicted by measuring TL before operation, which greatly reduced the risk of anesthesia, especially the elderly. Methods: The association between the propofol dose in anesthesia induction and: TL in the DNA of peripheral blood leukocytes; body weight; sex; difference of the Bispectral Index (BIS) before and after anesthesia induction in patients was evaluated by multivariable linear regression analyses. The mutation at the 5’end or 3’end of TERC was detected. We recruited 100 patients of elective surgery. Results: We found that propofol dose in anesthesia induction was clearly correlated significantly with TL (r = 0.78, p < 0.001), body weight (r = 0.84, p = 0.004), sex (r = 0.83, p= 0.84, p = 0.004), sex (r = 0.83, p = 0.004), and difference of BIS before and after anesthesia induction (r = 0.85, p = 0.029). By comparing the absolute values of standardized regression coefficients (0.58, 0.21, 0.19, and 0.12) of the four variables, it can be seen that TL contributes the most to the propofol dose in anesthesia induction. However, the mutation at the 5’ end or 3’ end of TERC was not found. Conclusions: These findings provide preliminary evidence that the propofol dose in anesthesia induction was clearly correlated with genetically determined TL. TL may be a promising predictor of the propofol dose, which is beneficial to improve the safety of anesthesia and reduce perioperative complications.

ABSTRACT Introduction Main renal artery clamping and selective arterial clamping are two conventional devascularization methods for robot-assisted partial nephrectomy (RAPN) (1, 2). Decreasing warm ischemic (WI) time (3, 4) and improving clear surgical visualization (5) are the main surgically modifiable factors for RAPN, especially in large complex renal cancer (6). In this study, we described our surgical technique, focusing on gradual segmental artery unclamping on patients with large renal tumors. Material and methods Two patients (R.E.N.A.L score 10 and 11) underwent RAPN with gradual segmental artery unclamping (Figures 1 and 2). The unclamping included five key steps. First, all renal segmental arteries were identified as tumor feeding vessel(s) and the vessels for normal kidney parenchyma under the guidance of CT angiography (CTA) 3-division (3D) reconstruction. Second, all segmental arteries were isolated, and the feeding one(s) should be blocked before other arteries were blocked. Third, the tumor was resected outside the pseudocapsule, and the deep resection bed was sutured for initial hemostasis. Fourth, the segmental arteries were reopened except for the tumor feeding one(s), and normal kidney parenchyma restored blood supply. And fifth, the resection bed was completely sutured, and the feeding vessel supplying the tumor was opened after the suture. Warm ischemia time (WIT) was defined as the time measured between clamping and unclamping of the renal artery. WIT1 was the time for normal kidney parenchyma and WIT2 was the time for resection area. Patient demographics, perioperative variables, and warm ischemic time were included in our study. And we presented the details of gradual segmental artery unclamping in the video. Results In both cases, the total operation times were 215 and 130 mins for patient 1 and patient 2, respectively. WIT1 and WIT2 for patient 1 were 15 min and 33 min., and WIT1 and WIT2 for patient 2 were 21 min and 32 min, respectivelly. The maximum diameters of the masses resected were 10.8 and 7.3 cm, and surgical margins were negative. No patient had complications after operation. Preoperative and postoperative eGFR did not change significantly. Pre- and postoperative eGFR were 111 and 108 mL/min for patient 1, 91 and 83 mL/min for patient 2, respectively. Key hints for outcomes optimization during RAPN on patients with large complex renal tumors: 1) Each segmental renal artery is precised clamped before we excise the tumor, and an excellent surgical vision is essential for precising excision and shortening clamping time, 2) Other segmental renal arteries are unclamped except tumor feeding branch after suturing deep layer of parenchyma, and most normal parenchyma restores blood supply, 3) Preoperative high-resolution computed tomography angiography (CTA) and 3D reconstructive renal structure serve as a guide to clear the approach to find the tumor and segmental arteries (7, 8). Conclusions Gradual segmental artery unclamping is feasible and efficient to excise large complex renal cancer. Compared with main renal artery clamping, it can shorten the warm ischemic time of normal parenchyma; On the other hand, compared with selective segmental arterial clamping, the technique can reduce bleeding from the deep resection bed, keep a clear surgical vision, and decrease the incidence of positive margin.

RESUMO Introdução O salto em distância horizontal consiste em quatro partes: corrida de aproximação, impulsão, voo e queda. Objetivo Estudar a influência da ginástica no salto em distância horizontal. Métodos Oito jardins de infância em uma cidade foram selecionados e divididos em um grupo experimental e um grupo de controle. As crianças do grupo experimental atuaram nos módulos de ginástica e de condicionamento físico. Cada módulo foi submetido a um ciclo contínuo de atividades ao ar livre de manhã e à tarde de atividades infantis, de 1º de junho de 2021 a 31 de março de 2010, por um total de 9 meses. Resultados Durante o período de intervenção, não houve diferença significativa entre o grupo experimental e o grupo controle (P > 0,05), mas houve diferença significativa entre o grupo experimental e as meninas antes e depois da intervenção experimental (P < 0,05), enquanto a diferença entre os meninos não foi estatisticamente significativa, indicando que a amplitude do movimento do tornozelo das meninas foi ligeiramente mais afetada do que a dos meninos durante a intervenção de condicionamento físico. Conclusão Com o aumento da idade e do tempo de treinamento, a faixa de variação do ângulo de articulação das crianças mais velhas no grupo experimental foi significativamente maior do que a do grupo de controle. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

ABSTRACT Introduction The standing long jump consists of four parts: pre-swing, take-off, flying, and landing. Objective Analyze the influence of gymnastics game fitness on standing long jump. Methods Eight kindergartens in a city were selected and divided into experimental and control groups. The children in the experimental group were intervened in gymnastics and game fitness modules. Each module was intervened in a rolling cycle in the morning and afternoon outdoor activities of children from June 1, 2021, to March 31, 2010, for nine months. Results During the intervention period, there was no significant difference between the experimental group and the control group (P > 0.05), but there was a significant difference between the experimental group and the girls before and after the experimental intervention (P < 0.05), while the difference between boys was not statistically significant, indicating that the range of ankle movement of girls was slightly more affected than boys during the fitness intervention. Conclusion With the increase in age and training time, the change range of joint angles of older children in the experimental group is significantly higher than that in the control group. Level of evidence II; Therapeutic studies - investigation of treatment results.

RESUMEN Introducción El salto de longitud horizontal consta de cuatro partes: carrera de aproximación, impulsión, vuelo y caída. Objetivo Analizar la influencia de la gimnasia en el salto de longitud de pie. Métodos Se seleccionaron ocho guarderías de una ciudad y se dividieron en un grupo experimental y otro de control. Los niños del grupo experimental realizaron módulos de gimnasia y fitness. Cada módulo intervino en un ciclo continuo de actividades al aire libre por la mañana y por la tarde desde el 1 de junio de 2021 hasta el 31 de marzo de 2010, durante nueve meses. Resultados Durante el período de intervención, no hubo diferencias significativas entre el grupo experimental y el grupo de control (P > 0,05), pero sí entre el grupo experimental y las chicas antes y después de la intervención experimental (P < 0,05), mientras que la diferencia entre los chicos no fue estadísticamente significativa, lo que indica que la amplitud de movimiento del tobillo de las chicas se vio ligeramente más afectada que la de los chicos durante la intervención de acondicionamiento físico. Conclusión Al aumentar la edad y el tiempo de entrenamiento, el rango de variación de los ángulos articulares de los niños mayores del grupo experimental es significativamente mayor que el del grupo de control. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

Abstract Chemotherapy is the main treatment option for advanced osteosarcoma, which is the most common type of primary bone malignancy. However, patients develop resistance rapidly and many succumb to the disease. Niclosamide, an anthelmintic drug, has been recently identified to display potent and selective anti-cancer activity. In this work, we show that niclosamide at sub-micromolar concentrations inhibits proliferation and migration, and induces apoptosis in both parental and chemo-resistant osteosarcoma cells, with much less toxicity in normal osteoblastic cells. Interestingly, chemo-resistant osteosarcoma cells are more sensitive to niclosamide compared to parental cells. We further identify that inhibition of β-catenin is the underlying mechanism of niclosamide’s action in osteosarcoma cells. In addition, we reveal that chemo-resistant osteosarcoma cells display increased β-catenin activity compared to parental cells, which might explain the hypersensitivity of chemo-resistant cells to niclosamide. Our work provides pre-clinical evidence that niclosamide can be repurposed for treating osteosarcoma. Our findings also suggest the therapeutic value of β-catenin to overcome osteosarcoma chemo-resistance. malignancy However disease Niclosamide drug anticancer anti cancer submicromolar sub micromolar migration chemoresistant chemo resistant Interestingly βcatenin β catenin niclosamides s addition preclinical pre clinical chemoresistance. chemoresistance resistance. chemo-resistance

Abstract In this paper, the relationship between Kernel average misorientation (KAM), geometrically necessary dislocation (GND) density and dislocation structures of Nb-bearing austenitic stainless steel under low cycle fatigue (LCF) was studied at 600°C at the total strain amplitude ranged from 0.3% to 1.0%. The results based on EBSD analysis show that the GND density in fatigue specimens gradually increases with the increase of strain amplitude. Under LCF loading, the dislocation structures are mainly planar slip bands (PSBs) and the cell structures. With the increase of strain amplitude, the number of PSBs increases with decrease in width, and the average diameter of cells also decreases. The PSBs originate due to the dynamic strain aging (DSA) effect, and DSA is more significant under high strain amplitude. The average diameter of cell structures has a specific relationship with GND density.

Abstract Polyphenol oxidase (PPO) plays a key role in tea processing. It catalyzes the conversion of tea polyphenols into theaflavin and its derivatives. PPO was partially purified and characterized in both its soluble form (sPPO) and membrane-bound form (mPPO) from tea (Camellia sinensis) leaves. Both forms were purified by three-phase partitioning and membrane ultrafiltration. sPPO and mPPO showed high activity against diphenols as substrate and had the highest affinity for catechol and caffeic acid. The optimum temperatures and pH for enzyme activity were different. mPPO was more stable than sPPO in the acidic pH range. Among the chemical inhibitors studied, oxalic acid exerted the highest inhibitory effect on mPPO, whereas EDTA showed the highest inhibitory effect on sPPO. Both sPPO and mPPO showed similar enzymatic synthesis rates in the formation of theaflavin-3'-gallate and theaflavin-3,3'-gallate. At high concentrations of the substrate, the synthesis of theaflavins was inhibited due to the presence of high levels of ester catechins. However, mPPO showed stronger stability against inhibition by ester catechins than sPPO.

Resumo Introdução: Evidências emergentes indicam que as condições fisiológicas e patológicas do nariz são reguladas pós-transcripcionalmente por microRNAs, uma classe de pequenos RNAs não codificantes. Recentemente, o microRNA-223-3p tem sido cada vez mais implicado na modulação da rinite alérgica. Objetivo: Avaliar o papel e o mecanismo do microRNA-223-3p em um modelo de rinite alérgica em camundongos. Método: O nível de expressão do microRNA-223-3p foi medido no soro de 41 pacientes com rinite alérgica e 39 controles saudáveis com polimerase chain reaction quantitativo em tempo real. Camundongos BALB/c foram usados para estabelecer um modelo de rinite alérgica através de sensibilização intraperitoneal e teste de provocação nasal com ovalbumina. O microRNA-223-3p agomir/antagomir foi então administrado por via intranasal a camundongos após provocação com ovabulmina por mais uma semana. Os sintomas de prurido nasal e espirros foram registrados. A concentração sérica de imunoglobulina E específica para ovalbumina, expressão de microRNA-223-3p e níveis de citocinas pró-inflamatórias (IL-4, IL-5, IFN-γ) na mucosa nasal foram medidos por ELISA e polimerase chain reaction quantitativo, respectivamente. As alterações histopatológicas foram avaliadas com coloração com hematoxilina e eosina. Resultados: Os níveis de microRNA-223-3p aumentaram significativamente em ambos os pacientes e camundongos com rinite alérgica. Além disso, a suprarregulação dos níveis de microRNA-223-3p através da administração nasal de microRNA-223-3p agomir também aumentou significativamente a concentração de IgE específica para ovalbumina, as frequências de prurido nasal e espirros, os níveis de citocinas pró-inflamatórias (IL-4, IL-5, IFN-γ) e infiltração de eosinófilos na mucosa nasal de camundongos com rinite alérgica. Além disso, o microRNA-223-3p antagomir pareceu melhorar significativamente os sintomas e a doença da mucosa nasal. Posteriormente, demonstramos pela primeira vez que o microRNA-223-3p regulou negativamente a expressão de INPP4A ao se ligar à região 3’ não traduzida 3'UTR) do gene INPP4A. Conclusões: Esses achados indicam que o microRNA-223-3p desempenha um papel importante na regulação da doença e dos sintomas da rinite alérgica, tem como alvo o gene INPP4A.

Abstract Introduction: Emerging evidence indicates that physiological and pathological conditions of the nose are posttranscriptionally regulated by microRNAs, a class of small noncoding RNAs. Recently, microRNA-223-3p has been increasingly implicated in the modulation of allergic rhinitis Objective: This study aimed to assess the role and mechanism of microRNA-223-3p in a mouse model of allergic rhinitis. Methods: The expression level of miR-223-3p was measured in the serum of 41 allergic rhinitis patients and 39 healthy controls using quantitative real time polymerase chain reaction. BALB/c mice were used to establish an allergic rhinitis model by intraperitoneal sensitization and intranasal challenge with ovalbumin. MicroRNA-223-3p agomir/antagomir was then intranasally administered to mice after ovalbumin challenge for another week. The symptoms of nasal rubbing and sneezing were recorded. Serum ovalbumin-specific immunoglobulin E concentration, microRNA-223-3p expression and proinflammatory cytokine (IL-4, IL-5, IFN-γ) levels in nasal mucosa were measured by ELISA and quantitative real time polymerase chain reaction, respectively. Histopathologic changes were evaluated using hematoxylin and eosin staining. Results: MicroRNA-223-3p levels increased significantly in both allergic rhinitis patients and allergic rhinitis mice. In addition, upregulation of microRNA-223-3p levels by nasal administration of microRNA-223-3p agomir also markedly increased the concentration of ovalbumin -specific IgE, the frequencies of nasal rubbing and sneezing, the levels of proinflammatory cytokines (IL-4, IL-5, IFN-γ) and eosinophil infiltration in the nasal mucosa of allergic rhinitis mice. Moreover, microRNA-223-3p antagomir appeared to strongly ameliorate the symptoms and pathology in nasal mucosa. Subsequently, we demonstrated for the first time that microRNA-2233p negatively regulated INPP4A expression by binding with the 3 untranslated region 3'UTR) of INPP4A. Conclusions: These findings indicate that microRNA-223-3p plays an important role in regulating the pathology and symptoms of allergic rhinitis by targeting INPP4A.

Recent publications have investigated the potential role of the protein level of matrix metalloproteinase-1 (MMP-1) in the susceptibility to rheumatoid arthritis (RA) and osteoarthritis (OA). However, no unanimous conclusion was obtained. Therefore, we carried out a meta-analysis to explore the association between MMP-1 expression and these two clinical disorders. After database searching and screening, we enrolled a total of eighteen articles for the pooled analysis. We observed a significant association between RA cases and controls in the whole population [SMD (standard mean difference)=1.01, P=0.017]. There were similar positive results in the subgroup analysis of “population-based control” (SMD=1.50, P=0.032) and “synovial fluid” (SMD=1.32, P=0.049). In addition, we observed an increased risk in OA cases, compared with controls, in the overall analysis (SMD=0.47, P=0.004) and subsequent subgroup analysis of “knee OA” (SMD=0.86, P<0.001), “Asian/China” (SMD=0.76, P=0.003), “cartilage-Asian/China” (SMD=1.21, P<0.001), and “synovial fluid-Asian/China” (SMD=0.73, P=0.004). In summary, a high protein level of MMP-1 in synovial fluid may be associated with the susceptibility to RA, and the high MMP-1 level in the cartilage tissue or synovial fluid may be related to the pathogenesis of knee OA in the Chinese population. This should be confirmed by larger sample sizes.

Abstract Clinical endometritis (CE) is a major cause in affecting the reproductive performance of dairy cows. The objectives of this study were to ascertain the prevalence of CE and to evaluate the effect of CE on reproductive performance in dairy cows using vaginal discharge score (VDS) grading system. 803 dairy cows were examined by vaginoscope with 4-point VDS at 26 ± 3 days in milk (DIM) and classified into six groups: non-endometritis with VDS 0 (control; CON), endometritis with VDS 1 (MEM), non-treated endometritis with VDS 2 (NTME), treated endometritis with VDS 2 (TME), non-treated endometritis with VDS 3 (NTPE), and treated endometritis with VDS 3 (TPE). Cows in TME and TPE groups were treated with 200 mL of 50% dextrose solution by intrauterine infusion. The prevalence of CE was 33% at 26 ± 3 DIM. Binary logistic regression analysis revealed cows in MEM, NTME and NTPE groups had a less likelihood of first artificial insemination (AI) pregnancy than those in CON group (P < 0.05). Kaplan-Meier survival curves for days open were statistically different (P = 0.004). In Cox regression model, cows in NTME and NTPE groups had a reduced pregnancy rate than those in CON group (P < 0.05). The hazard of pregnancy in NTME group was lower than that in TME group (P = 0.044). Similarly, it was lower for the hazard of pregnancy in NTPE group than in TPE group (P = 0.048). Cows in MEM, NTME, and NTPE groups required more services per pregnancy than those in CON group (P < 0.05). In conclusion, CE examined by the VDS grading system impaired reproductive performance, and mild endometritis with VDS 1 should be treated in the early postpartum period to ameliorate fertility in dairy herds.

Abstract Pain is a significant problem worldwide that affects the quality of life of patients. Dezocine is a non-addictive analgesic drug with kappa-opioid antagonist activity and has been successfully used to alleviate of postoperative pain. In addition, dezocine has an analgesic effect similar to that of morphine, alleviating moderate to severe pain. Rap guanine nucleotide exchange factor 3 (RAPGEF3) is a guanine nucleotide exchange factor for GTPases Rap1 and Rap2, which could enhance the activity of Rap1 to promote cell adhesion and axon regeneration, as well as promote neurite extension by interacting with nerve growth factors. Here, we first observed that overexpression of RAPGEF3 increased cell viability, as shown by a CCK-8 assay, and recovered brain function in rats. The expression of inflammation-related factors at the mRNA level was detected using qPCR, and the concentration of these factors in a cultured cell medium and rat serum samples were decreased as shown by ELISA after RAPGEF3 overexpression. Through western blotting, we further found that pro-inflammatory proteins were decreased, and these effects might be mediated by inhibition of the Ras/p-38 MAPK signaling pathway. Taken together, we speculated that RAPGEF3overexpression enhances the therapeutic effect of dezocine on neuropathic pain by inhibiting the inflammatory response through inhibition of the Ras/p-38 MAPK signaling pathway.

ABSTRACT Purpose Shen-fu injection (SFI) was used to intervene in the resuscitation of porcine hemorrhagic shock (HS) model to study its protective effects on acute kidney injury. Methods After 60 min of HS, 28 animals were randomly assigned into four groups. The groups were as follows: hemorrhagic shock group (HS); HS resuscitation with shed-blood group (HSR); HS resuscitation with shed-blood and SFI (1 mL·kg–1) group (HSR-SFI); and the sham operation group (Sham). The bloods were analyzed for serum creatinine (sCr), cystatin C (CysC) and neutrophil gelatinase-associated lipocalin (NGAL). BAX, Bcl-2, and caspase-3 protein expressions by Western blot analysis and immunohistochemical staining. The renal tissues were removed and pathologic changes were observed. Results Mean aortic pressure (MAP) in HSR-SFI groups were higher than that in HSR groups after shock. At the 6th hour after shock, the urine volume per hour in the HSR-SFI groups was more than that in the HSR groups. The sCr, NGAL, CysC and cytokine levels of HSR-SFI groups were lower. The Bcl-2 expression was increased in the HSR-SFI groups. The BAX and caspase-3 expressions were reduced. The histopathologic score in the HSR-SFI was lower. Conclusions SFI may reduce the risk of acute kidney injury (AKI) following hemorrhagic shock by attenuating systemic inflammatory responses, and regulating the expression of apoptosis-related proteins.

ABSTRACT Although urological diseases are not directly related to coronavirus disease 2019 (COVID-19), urologists need to make comprehensive plans for this disease. Urological conditions such as benign prostatic hyperplasia and tumors are very common in elderly patients. This group of patients is often accompanied by underlying comorbidities or immune dysfunction. They are at higher risk of COVID-19 infection and they tend to have severe manifestations. Although fever can occur along with urological infections, it is actually one of the commonest symptoms of COVID-19; urologists must always maintain a high index of suspicion in their clinical practices. As a urological surgeon, how we can protect medical staff during surgery is a major concern. Our hospital had early adoption of a series of strict protective and control measures, and was able to avoid cross-infection and outbreak of COVID-19. This paper discusses the effective measures that can be useful when dealing with urological patients with COVID-19.

ABSTRACT Sugarcane (Saccharum L. spp. hybrids) is a globally important crop. While roots contribute to its net primary production, knowledge of sugarcane root growth is incomplete and limited in scope. The objective of this study was to determine cumulative root density (LA), root distribution, effective rooting depth (ERD), and root growth rate for four sugarcane genotypes across three crop cycles (plant cane [PC], first ratoon [FR], and second ratoon [SR]). The experiment was conducted in a rain shelter on four sugarcane genotypes (ROC22, YZ04-241, YZ05-194, and YZ05-51) using minirhizotron tubes to a soil profile depth of 1.08 m. Most roots in were found at 0–0.36 m-depth, and about 85.0% were within a 0–0.72 m depth in PC. In FR and SR, however, > 81.8% of roots were found at 0–0.54 m-depth regardless of genotype. The LA of ROC22 was often significantly higher than that of the other genotypes at depths < 0.54 m regardless of crop cycle. The genotype ROC22 had greater root length and faster root growth rate than YZ05-194 at 0.18–0.36 m in PC and FR, while SR YZ05-194 had slower root growth than the other genotypes at 0–0.18m. Ratooning ability of sugarcane genotypes may be related to these root growth attributes.

Resumo Introdução: A quinase 3 sérica induzida por glicocorticoide, uma serina/treonina quinase que funciona downstream da via de sinalização PI3K, desempenha um papel crítico nos processos neoplásicos. É expressa por vários tumores e contribui para a carcinogênese. Objetivo: Investigar a expressão de quinase 3 sérica induzida por glicocorticoide no carcinoma nasofaríngeo, estudar os efeitos antitumorais do shRNA da quinase 3 sérica induzida por glicocorticoide, que inibem sua expressão em células de carcinoma nasofaríngeo, e discutir as implicações potenciais de nossos achados. Método: A expressão de proteína quinase 3 sérica induzida por glicocorticoide em linhagens de células de carcinoma nasofaríngeo (CNE-1, CNE-2, HNE-1, HONE-1 e SUNE-1) e a linhagem de células humanas imortalizadas do epitélio nasofaríngeo NP69 foram avaliadas por Western blot. A expressão da quinase 3 sérica induzida por glicocorticoide em 42 tecidos de CNF embebidos em parafina foi feita por imuno-histoquímica. Testes com MTT, citometria de fluxo e testes de raspagem foram feitos após as células CNE-2 terem sido transfectadas com o melhor plasmídeo shRNA da quinase 3 sérica induzida por glicocorticoide selecionado por Western blot, com o uso de lipofectamina para estudar seu efeito na proliferação, apoptose e migração celular. Resultados: Foi observada uma sobre-expressão da quinase 3 sérica induzida por glicocorticoide em tecidos e células de carcinoma nasofaríngeo humanas. A expressão de quinase 3 sérica induzida por glicocorticoide diminuiu acentuadamente após as células CNE-2 terem sido transfectadas com o shRNA da quinase 3 sérica induzida por glicocorticoide, conduzindo a forte inibição de proliferação e migração celular. Além disso, a taxa de apoptose aumentou nas células CNE-2 após o knockdown da quinase 3 sérica induzida por glicocorticoide. Conclusão: A expressão de quinase 3 sérica induzida por glicocorticoide foi observada com maior frequência à medida que o epitélio nasofaríngeo progride de tecido normal para carcinoma. Isso sugere que a quinase 3 sérica induzida por glicocorticoide contribui para o processo multietapas da carcinogênese do carcinoma nasofaríngeo. A quinase 3 sérica induzida por glicocorticoide representa um alvo para a terapia do carcinoma nasofaríngeo e há uma base para a investigação adicional dessa modalidade de tratamento adjuvante para o carcinoma nasofaríngeo.

Abstract Introduction: Serum- and glucocorticoid-inducible kinase 3, a serine/threonine kinase that functions downstream of the PI3K signaling pathway, plays a critical role in neoplastic processes. It is expressed by various tumors and contributes to carcinogenesis. Objective: The objective was to investigate serum- and glucocorticoid-inducible kinase 3 expression in nasopharyngeal carcinoma, to study the anti-tumor effects of serum- and glucocorticoid-inducible kinase 3 shRNA by inhibiting its expression in nasopharyngeal carcinoma cells and to discuss the potential implications of our findings. Methods: Serum- and glucocorticoid-inducible kinase 3 protein expression in nasopharyngeal carcinoma cell lines (CNE-1, CNE-2, HNE-1, HONE-1, and SUNE-1) and the human immortalized nasopharyngeal epithelium cell line NP69 were assayed by western blotting. Serum- and glucocorticoid-inducible kinase 3 expression in 42 paraffin-embedded nasopharyngeal carcinoma tissues were performed by immunohistochemistry. MTT assay, flow cytometry, and scratch tests were performed after CNE-2 cells were transfected with the best serum- and glucocorticoid-inducible kinase 3 shRNA plasmid selected by western blotting using lipofectamine to study its effect on cell proliferation, apoptosis, and migration. Results: Serum- and glucocorticoid-inducible kinase 3 was overexpressed in human nasopharyngeal carcinoma tissues and cells. Serum- and glucocorticoid-inducible kinase 3 expression decreased markedly after CNE-2 cells were transfected with the serum- and glucocorticoid-inducible kinase 3 shRNA, leading to strong inhibition of cell proliferation and migration. In addition, the apoptosis rate increased in CNE-2 cells after serum- and glucocorticoid-inducible kinase 3 knockdown. Conclusion: Serum- and glucocorticoid-inducible kinase 3 expression was more frequently observed as the nasopharyngeal epithelium progresses from normal tissue to carcinoma. This suggests that serum- and glucocorticoid-inducible kinase 3 contributes to the multistep process of NPC carcinogenesis. Serum- and glucocorticoid-inducible kinase 3 represents a target for nasopharyngeal carcinoma therapy, and a basis exists for the further investigation of this adjuvant treatment modality for nasopharyngeal carcinoma.

ABSTRACT Objectives: Our study aimed to investigate the associations of glucose tolerance status with insulin-like growth factor-I (IGF-I) and other clinical laboratory parameters of acromegalic patients before and after the patients underwent transsphenoidal adenomectomy (TSA) by conducting a single-center, retrospective study. Subjects and methods: A total of 218 patients with acromegaly who had undergone TSA as the first treatment were retrospectively analyzed. Serum IGF-I, growth hormone (GH) and glucose levels were measured before and after surgery. Results: The follow-up levels for random GH, GH nadir, and the percentage of the upper limit of normal IGF-I (%ULN IGF-I) were decreased significantly. The percentages of normal (39.0%), early carbohydrate metabolism disorders (33.0%) and diabetes mellitus (28.0%) changed to 70.2%, 16.5% and 13.3%, respectively, after TSA. %ULN IGF-I at baseline was higher in the diabetes mellitus (DM) group than in the normal glucose tolerance group and impaired glucose tolerance (IGT) /impaired fasting glucose (IFG) groups before TSA, and the DM group exhibited a greater reduction in %ULN IGF-I value after surgery. The follow-up %ULN IGF-I value after surgery was significantly lower in the improved group, and Pearson's correlation analysis revealed that the reductions in %ULN IGF-I corresponded with the reductions in glucose level. Conclusion: This study examined the largest reported sample with complete preoperative and follow-up data. The results suggest that the age- and sex-adjusted IGF-I level, which reflects altered glucose metabolism, and the change of it are associated with improved glucose tolerance in acromegalic patients both before and after TSA.