Genomic instabilities in hepatocellular carcinoma: biomarkers and application in immunotherapies.

Hepatocellular carcinoma (HCC) is one of the deadliest cancers. For patients with advanced HCC, liver function decompensation often occurs, which leads to poor tolerance to chemotherapies and other aggressive treatments. Therefore, it remains critical to develop effective therapeutic strategies for HCC. Etiological factors for HCC are complex and multifaceted, including hepatitis virus infection, alcohol, drug abuse, chronic metabolic abnormalities, and others. Thus, HCC has been categorized as a "genomically unstable" cancer due to the typical manifestation of chromosome breakage and aneuploidy, and oxidative DNA damage. In recent years, immunotherapy has provided a new option for cancer treatments, and the degree of genomic instability positively correlates with immunotherapy efficacies. This article reviews the endogenous and exogenous causes that affect the genomic stability of liver cells; it also updates the current biomarkers and their detection methods for genomic instabilities and relevant applications in cancer immunotherapies. Including genomic instability biomarkers in consideration of cancer treatment options shall increase the patients' well-being.

Disguise or surprise: spider antipredator adaptations as a function of the architecture of their webs

Animals exhibit a variety of strategies to avoid predation; spiders are no exception. We explored whether webbuilding spiders that differ in the architecture of their webs exhibit morphologies or behaviors suggestive of antipredator strategies that trade-off with the degree of protection offered by their webs. Spiders build webs of 3 types: the more protected tangles and sheet-and-tangles, which are three-dimensional (3D), and the more exposed orbs, which are two-dimensional (2D), both with or without a refuge. We hypothesize that spiders whose webs offer greater protection—a 3D architecture or a refuge—will be less likely to be armored or brightly colored when compared to spiders without these protections. We collected data on 446 spiders and their webs in 2 lowland tropical rainforest sites. We show that 2D web builders with no refuges tended to be brightly colored (background contrasting) and spiny (spiky), whereas those with refuges tended to blend against the background of their refuges. 3D web builders, on the other hand, were neither cryptic nor brightly colored nor armored but were more likely to drop out of the web upon simulated predator contact. These results support the hypothesis that web-building spiders tend to be protected either through the architecture of their webs or their morphology and behavior, suggesting a trade-off between different types of antipredator strategies.

Influence of small-group experiential learning of integrated traditional Chinese and Western medicine on the oral health knowledge, beliefs, and behaviors of elderly patients with diabetes.

OBJECTIVE: This study aimed at the oral health problems of elderly patients with diabetes. A training course of integrated traditional Chinese and Western medicine was constructed, helping patients improve their oral health quality of life. METHODS: A randomized controlled prospective experimental study was conducted. A total of 190 elderly patients were divided randomly into an observation group and a control group with 95 cases in each. The control group received regular health education, while the observation group was based on the control group to implement the integrated experiential learning of traditional Chinese and Western medicine in small groups. The oral health knowledge, attitude, behavior, and blood glucose control status along with the oral health quality of life of the two groups were compared before the intervention and at 3-month postintervention. RESULTS: Three months after the intervention, the fasting blood glucose control and the 2-h postprandial blood glucose/glycosylated hemoglobin levels in the observation group were significantly better than in the control group, and the difference was statistically significant (p<0.05). The oral health quality of life in the observation group was significantly better than in the control group, and the difference was statistically significant (p<0.05). CONCLUSION: The small-group experiential learning model of integrated Chinese and Western medicine can promote the transformation of knowledge-beliefs-behaviors in elderly patients with diabetes, which is conducive to controlling blood sugar levels and improving the quality of oral health.

Influence of small-group experiential learning of integrated traditional Chinese and Western medicine on the oral health knowledge, beliefs, and behaviors of elderly patients with diabetes

SUMMARY OBJECTIVE: This study aimed at the oral health problems of elderly patients with diabetes. A training course of integrated traditional Chinese and Western medicine was constructed, helping patients improve their oral health quality of life. METHODS: A randomized controlled prospective experimental study was conducted. A total of 190 elderly patients were divided randomly into an observation group and a control group with 95 cases in each. The control group received regular health education, while the observation group was based on the control group to implement the integrated experiential learning of traditional Chinese and Western medicine in small groups. The oral health knowledge, attitude, behavior, and blood glucose control status along with the oral health quality of life of the two groups were compared before the intervention and at 3-month postintervention. RESULTS: Three months after the intervention, the fasting blood glucose control and the 2-h postprandial blood glucose/glycosylated hemoglobin levels in the observation group were significantly better than in the control group, and the difference was statistically significant (p<0.05). The oral health quality of life in the observation group was significantly better than in the control group, and the difference was statistically significant (p<0.05). CONCLUSION: The small-group experiential learning model of integrated Chinese and Western medicine can promote the transformation of knowledge-beliefs-behaviors in elderly patients with diabetes, which is conducive to controlling blood sugar levels and improving the quality of oral health.

Effect of infiltrating nasal packing with local anesthetics in postoperative pain and anxiety following sinonasal surgeries: a systemic review and meta-analysis / Efeito do tamponamento nasal infiltrado com anestésicos locais na dor e ansiedade pós-operatórias após cirurgias nasosinusais: revisão sistêmica e metanálise

Abstract Introduction: Packing of the nasal cavity has traditionally been used for postoperative bleeding control and decreasing synechia formation in patients undergoing nasal surgeries. Although absorbable nasal packing has been gaining popularity in the recent years, nonabsorbable nasal packing is still often used in nasal surgeries in various parts of the world. It is known to be associated with pain and discomfort especially upon and during removal, and previous reviews have only evaluated the effects of local anesthetic infiltration of nasal packing in septal surgeries. Objective: To evaluate the effect of infiltrating nasal packing with local anesthetics in postoperative pain and anxiety following sinonasal surgeries Materials and methods: We searched the PubMed and Embase databases from their earliest record to April 27, 2019, randomized controlled trials and prospective controlled trials for review, and included only randomized controlled trials for data analysis. We included studies using topical anesthetics-infiltrated nasal packing following sinonasal surgeries and evaluated the effectiveness compared to placebo packing in pain reduction during postoperative follow up, as well as the effectiveness in anxiety reduction. Results: Among 15 studies included for review, 9 studies involving 765 participants contributed to the meta-analysis. In terms of pain reduction, our analysis showed significant standard mean differences regarding effectiveness at postoperative 1, 12, 24 h interval for all surgical groups combined, in the sinus surgery group, as well as during nasal packing removal. There was no consistent evidence to support the effectiveness in anxiety reduction. Conclusions: Our study supports anesthetics infiltration of nasal packing as an effective method in managing pain in patients with nasal packing after sinonasal surgeries. However, the level of evidence is low. More high-quality randomized controlled trials are needed to establish its effectiveness in reducing anxiety. We believe this review is of great clinical significance due to the vast patient population undergoing sinonasal surgeries. Postoperative local hemorrhage remains the greatest concern for ear nose and throat surgeons due to the rich vasculature of the nose and sinuses. Sinonasal packing provides structural support and serves as an important measure for hemostasis and synechia formation. Although absorbable packing has been gaining popularity in the recent years, nonabsorable packing materials are still used in many countries due to lower cost. Infiltration of nasal packing with local anesthetic provides a solution to the discomfort, nasal pressure and nasal pain experienced commonly by the patients as evidenced by our analysis.

Resumo Introdução: O tamponamento da cavidade nasal tem sido usado tradicionalmente para controle do sangramento pós-operatório e diminuição da formação de sinéquia em pacientes submetidos a cirurgias nasais. Embora o tamponamento nasal absorvível tenha ganhado popularidade nos últimos anos, o tampão nasal não absorvível ainda é frequentemente usado em várias partes do mundo. Sabe-se que o tamponamento está associado a dor e desconforto, especialmente na sua remoção, e revisões anteriores avaliaram apenas os efeitos do tampão com anestésico local em cirurgias do septo nasal. Objetivo: Avaliar o efeito do tamponamento nasal infiltrado com anestésicos locais na dor e ansiedade pós-operatórias após cirurgias nasosinusais. Material e métodos: Para a revisão, pesquisamos nos bancos de dados PubMed e Embase desde o registro mais antigo até 27 de abril de 2019, incluímos ensaios clínicos controlados e randomizados, a ensaios clínicos prospectivos controlados e apenas ensaios clínicos controlados e randomizados para análise de dados. Incluímos estudos que usaram tamponamento nasal infiltrado com anestésicos tópicos após cirurgias nasosinusais e avaliamos a eficácia em comparação com o tamponamento com placebo na redução da dor durante o acompanhamento pós-operatório, bem como os efeitos na redução da ansiedade. Resultados: Entre os 15 estudos incluídos, 9, que envolveram 765 participantes, contribuíram para a metanálise. Em termos de redução da dor, nossa análise mostrou diferenças médias padrão significantes em relação à eficácia no pós-operatório nos intervalos de 1, 12, 24 horas para todos os grupos cirúrgicos combinados, no grupo da cirurgia sinusal e durante a remoção do tamponamento nasal. Não houve evidências consistentes para apoiar a eficácia na redução da ansiedade. Conclusões: Nosso estudo apoia o uso de tamponamentos nasais infiltrados com anestésicos locais como um método eficaz no tratamento da dor em pacientes após cirurgias nasosinusais. No entanto, o nível de evidência é baixo. São necessários mais ensaios clínicos randomizados de alta qualidade para estabelecer sua eficácia na redução da ansiedade. Acreditamos que esta revisão seja de grande significado clínico devido à vasta população submetida a cirurgias nasosinusais. A hemorragia local pós-operatória continua a ser a maior preocupação para os cirurgiões otorrinolaringológicos devido à rica vasculatura do nariz e seios nasais. O tamponamento nasosinusal fornece suporte estrutural e serve como uma medida importante para a hemostasia e formação de sinéquias. Embora o tamponamento absorvível tenha ganhado popularidade nos últimos anos, os materiais de tamponamento não absorvíveis ainda são usados em muitos países devido ao menor custo. A infiltração do tamponamento nasal com anestésicos locais fornece uma solução para desconforto, pressão e dor nasal comumente referida pelos pacientes, como evidenciado por nossa análise.

Effect of infiltrating nasal packing with local anesthetics in postoperative pain and anxiety following sinonasal surgeries: a systemic review and meta-analysis.

INTRODUCTION: Packing of the nasal cavity has traditionally been used for postoperative bleeding control and decreasing synechia formation in patients undergoing nasal surgeries. Although absorbable nasal packing has been gaining popularity in the recent years, nonabsorbable nasal packing is still often used in nasal surgeries in various parts of the world. It is known to be associated with pain and discomfort especially upon and during removal, and previous reviews have only evaluated the effects of local anesthetic infiltration of nasal packing in septal surgeries. OBJECTIVE: To evaluate the effect of infiltrating nasal packing with local anesthetics in postoperative pain and anxiety following sinonasal surgeries MATERIALS AND METHODS: We searched the PubMed and Embase databases from their earliest record to April 27, 2019, randomized controlled trials and prospective controlled trials for review, and included only randomized controlled trials for data analysis. We included studies using topical anesthetics-infiltrated nasal packing following sinonasal surgeries and evaluated the effectiveness compared to placebo packing in pain reduction during postoperative follow up, as well as the effectiveness in anxiety reduction. RESULTS: Among 15 studies included for review, 9 studies involving 765 participants contributed to the meta-analysis. In terms of pain reduction, our analysis showed significant standard mean differences regarding effectiveness at postoperative 1, 12, 24 h interval for all surgical groups combined, in the sinus surgery group, as well as during nasal packing removal. There was no consistent evidence to support the effectiveness in anxiety reduction. CONCLUSIONS: Our study supports anesthetics infiltration of nasal packing as an effective method in managing pain in patients with nasal packing after sinonasal surgeries. However, the level of evidence is low. More high-quality randomized controlled trials are needed to establish its effectiveness in reducing anxiety. We believe this review is of great clinical significance due to the vast patient population undergoing sinonasal surgeries. Postoperative local hemorrhage remains the greatest concern for ear nose and throat surgeons due to the rich vasculature of the nose and sinuses. Sinonasal packing provides structural support and serves as an important measure for hemostasis and synechia formation. Although absorbable packing has been gaining popularity in the recent years, nonabsorable packing materials are still used in many countries due to lower cost. Infiltration of nasal packing with local anesthetic provides a solution to the discomfort, nasal pressure and nasal pain experienced commonly by the patients as evidenced by our analysis.

Synthetic cathelicidin LL-37 reduces Mycobacterium avium subsp. paratuberculosis internalization and pro-inflammatory cytokines in macrophages.

Mycobacterium avium subsp. paratuberculosis (MAP) causes chronic diarrheic intestinal infections in domestic and wild ruminants (paratuberculosis or Johne's disease) for which there is no effective treatment. Critical in the pathogenesis of MAP infection is the invasion and survival into macrophages, immune cells with ability to carry on phagocytosis of microbes. In a search for effective therapeutics, our objective was to determine whether human cathelicidin LL-37, a small peptide secreted by leuckocytes and epithelial cells, enhances the macrophage ability to clear MAP infection. In murine (J774A.1) macrophages, MAP was quickly internalized, as determined by confocal microscopy using green fluorescence protein expressing MAPs. Macrophages infected with MAP had increased transcriptional gene expression of pro-inflammatory TNF-α, IFN-γ, and IL-1ß cytokines and the leukocyte chemoattractant IL-8. Pretreatment of macrophages with synthetic LL-37 reduced MAP load and diminished the transcriptional expression of TNF-α and IFN-γ whereas increased IL-8. Synthetic LL-37 also reduced the gene expression of Toll-like receptor (TLR)-2, key for mycobacterial invasion into macrophages. We concluded that cathelicidin LL-37 enhances MAP clearance into macrophages and suppressed production of tissue-damaging inflammatory cytokines. This cathelicidin peptide could represent a foundational molecule to develop therapeutics for controlling MAP infection.

Correlation analysis between short-term insulin-like growth factor-I and glucose intolerance status after transsphenoidal adenomectomy in acromegalic patients: a large retrospective study from a single center in China

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.

Correlation analysis between short-term insulin-like growth factor-I and glucose intolerance status after transsphenoidal adenomectomy in acromegalic patients: a large retrospective study from a single center in China.

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.