The transcriptional repressor Hes1 attenuates inflammation by regulating transcription elongation.

Most of the known regulatory mechanisms that curb inflammatory gene expression target pre-transcription-initiation steps, and evidence for post-initiation regulation of inflammatory gene expression remains scarce. We found that the transcriptional repressor Hes1 suppressed production of CXCL1, a chemokine that is crucial for recruiting neutrophils. Hes1 negatively regulated neutrophil recruitment in vivo in a manner that was dependent on macrophage-produced CXCL1, and it attenuated the severity of inflammatory arthritis. Mechanistically, inhibition of Cxcl1 expression by Hes1 did not involve modification of transcription initiation. Instead, Hes1 inhibited signal-induced recruitment of the positive transcription-elongation complex P-TEFb and thereby prevented phosphorylation of RNA polymerase II at Ser2 and productive elongation. Thus, our results identify Hes1 as a homeostatic suppressor of inflammatory responses that exerts its suppressive function by regulating transcription elongation.

Burden and Trends of IBD in 5 Asian Countries From 1990 to 2019: A Comparison With the United States and the United Kingdom.

BACKGROUND: IBD is becoming a global health challenge, with substantial variations in incidence and death rates between Eastern and Western countries. OBJECTIVE: This study aimed to investigate the burden and trends of IBD in 5 Asian countries, the United States, and the United Kingdom. DESIGN: This was a cross-sectional study. SETTING: Data were obtained from Global Burden of Disease 2019 Study. PATIENTS: Patients with IBD were included. MAIN OUTCOME MEASURES: Incidence, death, and age-standardized rates of IBD were measured. RESULTS: The age-standardized incidence and rates of death from IBD gradually decreased worldwide from 1990 to 2019. The age-standardized incidence rate in the United States decreased from 1990 to 2000 and then increased gradually from 2000 to 2019; the age-standardized incidence rates in the United Kingdom, Mongolia, and China increased gradually from 1990 to 2019, whereas in the Democratic People's Republic of Korea, it decreased from 1990 to 1995 and increased gradually from 1995 to 2019. The age-standardized death rate in the Republic of Korea exhibited a rising trend until 1995, fell significantly up to 2015, and then stabilized from 2015 to 2019. The age-standardized death rate in the United States showed a rising trend until 2007, and then decreased gradually from 2007 to 2019, whereas the rate in the United Kingdom showed a rising trend until 2010 and decreased from 2010 to 2019. The age-standardized death rates in China, Mongolia, the Democratic People's Republic of Korea, and Japan decreased gradually from 1990 to 2019. The age-standardized incidence and death rates in the United States and United Kingdom in recent decades were higher than those in the 5 Asian countries. The peak age-standardized incidence rates in the 7 countries were among people of 20 to 60 years of age. The age-standardized death rates in all 7 countries exhibited rising trends with increasing age, with older individuals, particularly those aged ≥70 years, accounting for the most deaths. LIMITATIONS: Limitations of this study include data from different countries with different quality and accuracy. CONCLUSIONS: There have been large variations in the burdens and trends of IBD between 5 Asian countries, the United States, and the United Kingdom during the past 3 decades. These findings may help policymakers to make better public decisions and allocate appropriate resources. See Video Abstract at http://links.lww.com/DCR/B996 . CARGA Y TENDENCIAS DE LA ENFERMEDAD INFLAMATORIA INTESTINAL EN CINCO PASES ASITICOS DESDE HASTA UNA COMPARACIN CON LOS ESTADOS UNIDOS Y EL REINO UNIDO: ANTECEDENTES:La enfermedad inflamatoria intestinal se está convirtiendo en un desafío en la salud mundial, con variaciones sustanciales en las tasas de incidencia y mortalidad entre los países orientales y occidentales.OBJETIVO:Investigar la carga y las tendencias de la enfermedad inflamatoria intestinal en cinco países asiáticos, EE. UU. y el Reino Unido.DISEÑO:Estudio transversal.ESCENARIO:Estudio de carga global de morbilidad 2019.PACIENTES:Enfermedad inflamatoria intestinal.PRINCIPALES MEDIDAS DE RESULTADO:Incidencia, muerte y tasas estandarizadas por edad de enfermedad inflamatoria intestinal.RESULTADOS:Las tasas de incidencia y muerte estandarizadas por edad de la enfermedad inflamatoria intestinal disminuyeron gradualmente en todo el mundo desde 1990 hasta 2019. La tasa de incidencia estandarizada por edad en los EE. UU. disminuyó de 1990 a 2000 y luego aumentó gradualmente de 2000 a 2019, las tasas en el Reino Unido, Mongolia y China aumentaron gradualmente de 1990 a 2019, mientras que la tasa en la República Popular Democrática de Corea disminuyó de 1990 a 1995 y aumentó gradualmente de 1990 a 2019. La tasa de mortalidad estandarizada por edad en la República de Corea exhibió un tendencia ascendente hasta 1995, cayó significativamente hasta 2015 y luego se estabilizó de 2015 a 2019. La tasa de mortalidad estandarizada por edad en los EE. UU. mostró una tendencia ascendente hasta 2007 y luego disminuyó gradualmente de 2007 a 2019, mientras que la tasa en el Reino Unido mostró una tendencia ascendente hasta 2010 y disminuyó de 2010 a 2019. Las tasas de mortalidad estandarizadas por edad en China, Mongolia, la República Popular Democrática de Corea y Japón disminuyeron gradualmente de 1990 a 2019. La tasa de incidencia estandarizada por edad y mortalidad en los EE. UU. y el Reino Unido en la última década fueron más altas que las de los cinco países asiáticos. Las tasas máximas de incidencia estandarizadas por edad en los siete países se dieron entre personas de 20 a 60 años. Las tasas de mortalidad estandarizadas por edad en los siete países exhibieron tendencias crecientes con el aumento de la edad, y las personas mayores, en particular las de ≥70 años, representaron la mayoría de las muertes.LIMITACIONES:Datos de diferentes países con diferente calidad y precisión.CONCLUSIONES:Ha habido grandes variaciones en las cargas y tendencias de la enfermedad inflamatoria intestinal entre cinco países asiáticos, EE. UU. y el Reino Unido durante las últimas tres décadas. Estos hallazgos pueden ayudar a los formuladores de políticas a tomar mejores decisiones públicas y asignar los recursos apropiados. Consulte Video Resumen en http://links.lww.com/DCR/B996 . (Traducción- Dr. Francisco M. Abarca-Rendon ).

Characteristics of H7N9 avian influenza pneumonia: a retrospective analysis of 17 cases.

BACKGROUND: H7N9 avian influenza is an infection of public health concern, in part because of its high mortality rate and pandemic potential. AIMS: To describe the clinical features of H7N9 avian influenza and the response to treatment. METHODS: Clinical, radiological and histopathological data, and treatment-related of H7N9-infected patients hospitalised during 2014-2017 were extracted and analysed. RESULTS: A total of 17 H7N9 patients (three females; mean age, 58.4 ± 13.7 years) was identified; of these six died. All patients presented with fever and productive cough; four patients had haemoptysis and 13 had chest distress and/or shortness of breath. Early subnormal white blood cell count and elevation of serum liver enzymes were common. Multilobar patchy shadows, rapid progression to ground-glass opacities, air bronchograms and consolidation were the most common imaging findings. Histopathological examination of lung tissue of three patients who died showed severe alveolar epithelial cell damage, with inflammatory exudation into the alveolar space and hyaline membrane formation; widened alveolar septae, prominent inflammatory cell infiltration; and hyperplasia of pneumocytes. Viral inclusions were found in the lung tissue of two patients. All patients received antiviral drugs (oseltamivir ± peramivir). Four patients carried the rs12252-C/C interferon-induced transmembrane protein-3 (IFITM3) genotype, while the others had the C/T genotype. CONCLUSIONS: H7N9 virus infection causes human influenza-like symptoms, but may rapidly progress to severe pneumonia and even death. Clinicians should be alert to the possibility of H7N9 infection in high-risk patients. The presence of the IFITM3 rs12252-C genotype may predict severe illness.

Retrospective study of Langerhans cell histiocytosis in ear, nose and neck.

OBJECTIVE: Langerhans cell histiocytosis (LCH) is a rare clinical disorder. We retrospectively analysed the clinical manifestations, treatments and prognoses of LCH cases involving the ear, nose, and neck. MATERIALS AND METHODS: 28 cases with confirmed LCH in ear, nose or neck were reviewed. We recorded patient age, sex, chief complaints, accompanying symptoms, lesional sites, radiological data, treatments and pathologies. Whole-exome sequencing was performed on the patient diagnosed with LCH and Treacher-Collins syndrome (TCS). RESULTS: The mean age was 14.86 years. Most LCH was in the ear (93%), usually in the mastoid. The most common symptoms were an ear mass and a purulent discharge. Imaging was not very useful. Treatments included surgery, chemotherapy, and radioactive particle implantation. Some cases exhibited multisystem involvement. Most patients enjoyed good prognoses. One patient was diagnosed with both temporal LCH and TCS. Whole-exome sequencing revealed a heterozygous c.261_272delAGGTACCCTTCC(p.87_91delRGTLPinsR) mutation in exon 2 of the POLR1D gene (NM_015972). CONCLUSION: LCH mostly occurs in children. In head and neck it affects principally the mastoid part of the temporal bone. Treatments include surgery, chemotherapy, and irradiation. Most patients enjoy good prognoses. LCH accompanied by TCS is rare and increases the difficulty of diagnosis; molecular data aid in TCS identification.

Far-infrared ray for treating chronic lower extremity lymphedema with dermatolymphangioadenitis: a postoperative complication of gynecological tumor resection.

PURPOSE: Lower extremity lymphedema is regarded as a relatively common postoperative complication and is often accompanied with dermatolymphangioadenitis (DLA). This study combines clinical assessment and laboratory investigation to explore therapeutic effects of far-infrared radiation (FIR) therapy for chronic lower extremity lymphedema accompanied with DLA, occurring after gynecological tumor resection. METHODS: Patients who met inclusion and exclusion criteria would be enrolled. They received regular sessions using the FIR therapy machine over the 4-week treatment course. Clinical and laboratory outcome measures were carried out before and after treatment. Clinical outcome measures included DLA seizure frequency (episodes/year), patients' subjective feedback for lymphedema-related symptoms and quality of life (QOL). Laboratory outcome measures included bacterial cultures and concentrations of inflammatory cytokines: IL-1ß, IL-2, IL-4, IL-10, IL-12, IL-18, TNF-α, TNF-ß, caspase-1 and INF-γ, detected in serum and local lymphedema tissue fluid samples using protein microarray and ELISA. RESULTS: Between 2012 and 2016, a total of 120 female patients were screened for study enrollment. Sixty-four recruited patients underwent clinical evaluation both before FIR radiation therapy and 1 year after a single course of FIR radiation therapy. Eleven patients (17.2%), randomly chosen from the study group, underwent additional laboratory analysis of blood and local lymphedema tissue fluid samples. The frequency of DLA decreased following treatment (p < 0.001). Fifty patients (78%) did not experience a single episode of DLA recurrence in the year subsequent to treatment. The efficiency rate calculated using DLA frequencies was greater than 50% for 63 (98%) patients following treatment. Patients reported a subjective decrease in lymphedema-related symptoms (p < 0.05). Patients' QOL scores were higher after treatment (p < 0.001). Laboratory analysis showed an elevation in serum concentration of IL-1ß after FIR therapy (p < 0.05) and reduced local tissue fluid concentrations of inflammatory cytokines IL-2, IL-10 and IL-18 (p < 0.05). Bacterial culture results before and after treatment were both negative. CONCLUSION: FIR radiation therapy provides an effective treatment modality for patients with chronic lymphedema accompanied with DLA that develops secondarily to treatment of gynecological malignancies, whose therapeutic effects may be due to reduced immune dysfunction within local lymphedema tissues.

Efficacy and safety of far infrared radiation in lymphedema treatment: clinical evaluation and laboratory analysis.

Swelling is the most common symptom of extremities lymphedema. Clinical evaluation and laboratory analysis were conducted after far infrared radiation (FIR) treatment on the main four components of lymphedema: fluid, fat, protein, and hyaluronan. Far infrared radiation is a kind of hyperthermia therapy with several and additional benefits as well as promoting microcirculation flow and improving collateral lymph circumfluence. Although FIR therapy has been applied for several years on thousands of lymphedema patients, there are still few studies that have reported the biological effects of FIR on lymphatic tissue. In this research, we investigate the effects of far infrared rays on the major components of lymphatic tissue. Then, we explore the effectiveness and safety of FIR as a promising treatment modality of lymphedema. A total of 32 patients affected by lymphedema in stage II and III were treated between January 2015 and January 2016 at our department. After therapy, a significant decrease of limb circumference measurements was noted and improving of quality of life was registered. Laboratory examination showed the treatment can also decrease the deposition of fluid, fat, hyaluronan, and protein, improving the swelling condition. We believe FIR treatment could be considered as both an alternative monotherapy and a useful adjunctive to the conservative or surgical lymphedema procedures. Furthermore, the real and significant biological effects of FIR represent possible future applications in wide range of the medical field.

Abnormal mural cell recruitment in lymphatic capillaries: a common pathological feature in chronic lymphedematous skin?

OBJECTIVES: This study aimed to explore the structural and functional characteristics of dermal lymphatic capillaries in patients with chronic LE, specifically focused on the mural cells that are associated with skin lymphatics. METHODS: Forty-four patients (30 primary LE and 14 secondary LE) and eight healthy controls were enrolled in this study. Genetic analysis of the FOXC2 was performed in 18 patients with primary LE. Full-thickness skin was excised and immunohistologically stained for podoplanin and α-SMA. The proportions of α-SMA+ Lv (α-SMA+ Lv%) were calculated. Lymphatic vascular function was assessed by indocyanine green lymphography. RESULTS: Analysis of FOXC2 revealed two mutations in two patients with LDs. Histologically, thirty-nine patients exhibited increased α-SMA+ mural cell coverage of lymphatic capillaries. The α-SMA+ Lv% values in the superficial and deep dermis in patients with primary and secondary LE were significantly higher than in the control group. Compared with imaging findings in healthy limbs, in which the collecting lymphatics were clearly visualized, lymphedematous extremities all exhibited dermal backflow. CONCLUSIONS: Abnormal recruitment of mural cells in dermal lymphatic capillaries is a common pathological event in chronic LE, and may play a role in disease evolution.

Clonal integration ameliorates the carbon accumulation capacity of a stoloniferous herb, Glechoma longituba, growing in heterogenous light conditions by facilitating nitrogen assimilation in the rhizosphere.

BACKGROUND AND AIMS: Enhanced availability of photosynthates increases nitrogen (N) mineralization and nitrification in the rhizosphere via rhizodeposition from plant roots. Under heterogeneous light conditions, photosynthates supplied by exposed ramets may promote N assimilation in the rhizosphere of shaded, connected ramets. This study was conducted to test this hypothesis. METHODS: Clonal fragments of the stoloniferous herb Glechoma longituba with two successive ramets were selected. Mother ramets were subjected to full sunlight and offspring ramets were subjected to 80 % shading, and the stolon between the two successive ramets was either severed or left intact. Measurements were taken of photosynthetic and growth parameters. The turnover of available soil N was determined together with the compostion of the rhizosphere microbial community. KEY RESULTS: The microbial community composition in the rhizosphere of shaded offspring ramets was significantly altered by clonal integration. Positive effects of clonal integration were observed on NAGase activity, net soil N mineralization rate and net soil N nitrification rate. Increased leaf N and chlorophyll content as well as leaf N allocation to the photosynthetic machinery improved the photosynthetic capability of shaded offspring ramets when the stolon was left intact. Clonal integration improved the growth performance of shaded, connected offspring ramets and whole clonal fragments without any cost to the exposed mother ramets. CONCLUSIONS: Considerable differences in microbial community composition caused by clonal integration may facilitate N assimilation in the rhizosphere of shaded offspring ramets. Increased N content in the photosynthetic machinery may allow pre-acclimation to high light conditions for shaded offspring ramets, thus promoting opportunistic light capture. In accordance with the theory of the division of labour, it is suggested that clonal integration may ameliorate the carbon assimilation capacity of clonal plants, thus improving their fitness in temporally and spatially heterogeneous habitats.

Clonal integration of stress signal induces morphological and physiological response of root within clonal network.

Clonal integration of defense or stress signal induced systemic resistance in leaf of interconnected ramets. However, similar effects of stress signal in root are poorly understood within clonal network. Clonal fragments of Centella asiaticas with first-young, second-mature, third-old and fourth-oldest ramets were used to investigate transportation or sharing of stress signal among interconnected ramets suffering from low water availability. Compared with control, oxidative stress in root of the first-young, second-mature and third-old ramets was significantly alleviated by exogenous ABA application to the fourth-oldest ramets as well as enhancement of antioxidant enzyme (SOD, POD, CAT and APX) activities and osmoregulation ability. Surface area and volume in root of the first-young ramets were significantly increased and total length in root of the third-old ramets was significantly decreased. POD activity in root of the fourth-oldest and third-old ramets was significantly enhanced by exogenous ABA application to the first-young ramets. Meanwhile, total length and surface area in root of the fourth-oldest and third-old ramets were significantly decreased. Ratio of belowground to aboveground biomass in the whole clonal fragments was significantly increased by exogenous ABA application to the fourth-oldest or first-young ramets. It is suggested that transportation or sharing of stress signal may induce systemic resistance in root of interconnected ramets. Specially, transportation or sharing of stress signal against phloem flow was observed in the experiment. Possible explanation is that rapid recovery of foliar photosynthesis in first-young ramets subjected to exogenous ABA application can partially reverse phloem flow within clonal network. Thus, our experiment provides insight into ecological implication on clonal integration of stress signal.

EFFNet: A skin cancer classification model based on feature fusion and random forests.

Computer-aided diagnosis techniques based on deep learning in skin cancer classification have disadvantages such as unbalanced datasets, redundant information in the extracted features and ignored interactions of partial features among different convolutional layers. In order to overcome these disadvantages, we propose a skin cancer classification model named EFFNet, which is based on feature fusion and random forests. Firstly, the model preprocesses the HAM10000 dataset to make each category of training set images balanced by image enhancement technology. Then, the pre-training weights of the EfficientNetV2 model on the ImageNet dataset are fine-tuned on the HAM10000 skin cancer dataset. After that, an improved hierarchical bilinear pooling is introduced to capture the interactions of some features between the layers and enhance the expressive ability of features. Finally, the fused features are passed into the random forests for classification prediction. The experimental results show that the accuracy, recall, precision and F1-score of the model reach 94.96%, 93.74%, 93.16% and 93.24% respectively. Compared with other models, the accuracy rate is improved to some extent and the highest accuracy rate can be increased by about 10%.

High triglyceride-glucose index is associated with poor cardiovascular outcomes in Chinese acute coronary syndrome patients without diabetes mellitus who underwent emergency percutaneous coronary intervention with drug-eluting stents.

Background: Previous research has supported the association between the triglyceride-glucose index (TyG index) and the incidence and prognosis of cardiovascular disease. However, the association between the TyG index and the prognosis of patients with acute coronary syndrome (ACS) without diabetes mellitus (DM) who underwent emergency percutaneous coronary intervention (PCI) with drug-eluting stents (DESs) has not been thoroughly investigated, and these patients may easily be neglected. Therefore, this study aimed to investigate the association between the TyG index and major adverse cardiovascular and cerebrovascular events (MACCEs) in Chinese ACS patients without DM who underwent emergency PCI with DES. Methods: The total number of ACS patients without DM who underwent emergency PCI with DES for this study was 1650. Ln [fasting triglycerides (mg/dL) ×fasting plasma glucose (mg/dL)/2] is the formula used to calculate the TyG index. According to the TyG index, we classified the patients into two groups. The frequency of the following endpoint events was calculated and compared between the two groups: all-cause death, non-fatal myocardial infarction (MI), non-fatal ischemia stroke, ischemia-driven revascularization and cardiac rehospitalization. Results: After a median of 47 months of follow-up [47 (40, 54)], 437 (26.5%) endpoint events were recorded in total. The TyG index was further demonstrated to be independent of MACCE by multivariable Cox regression analysis (hazard ratio [HR], 1.493; 95% confidence interval [CI], 1.230-1.812; p<0.001). The TyG index≥7.08 group had a considerably greater incidence of MACCE (30.3% vs. 22.7% in the TyG index<7.08 group, p<0.001), cardiac death (4.0% vs. 2.3% in the TyG index<7.08 group, p=0.047), and ischemia-driven revascularization (5.7% vs. 3.6% in the TyG index<7.08 group, p=0.046) than the TyG index<7.08 group. Between the two groups, there was no discernible difference in all-cause death (5.6% vs. 3.8% in the TyG index<7.08 group, p=0.080), non-fatal MI (1.0% vs. 0.2% in the TyG index<7.08 group, p=0.057), non-fatal ischemic stroke (1.6% vs. 1.0% in the TyG index<7.08 group, p=0.272), and cardiac rehospitalization (16.5% vs. 14.1% in the TyG index<7.08 group, p=0.171). Conclusion: For ACS patients without DM who received emergency PCI with DES, the TyG index might be an independent predictor of MACCE.

Prolonged dual antiplatelet therapy for Chinese ACS patients undergoing emergency PCI with drug-eluting stents: Benefits and risks.

Background: In patients with acute coronary syndrome (ACS), prolonged dual antiplatelet therapy (DAPT) may reduce ischemic events and increase the risks of bleeding events differently in different ethnic groups. However, whether prolonged DAPT in Chinese patients with ACS following emergency percutaneous coronary intervention (PCI) with drug-eluting stents (DES) will be beneficial or dangerous remains unclear. This study aimed to examine the potential benefits and risks of prolonged DAPT in Chinese patients with ACS who have undergone emergency PCI with DES. Methods: This study included 2,249 patients with ACS who underwent emergency PCI. If DAPT was continued for 12 or 12-24 months, it was classified as the standard (n = 1,011) or prolonged (n = 1,238) DAPT group, respectively. The incidence of the following endpoint events was determined and compared between the two groups: composite bleeding event (BARC 1 or 2 types of bleeding and BARC 3 or 5 types of bleeding) and major adverse cardiovascular and cerebrovascular events (MACCEs) [ischemia-driven revascularization, non-fatal ischemia stroke, non-fatal myocardial infarction (MI), cardiac death, and all-cause death]. Results: After a median period of 47 months of follow-up [47 (40, 54)], the rate of composite bleeding events was 13.2% (n = 163) in the prolonged DAPT group and 7.9% (n = 80) in the standard DAPT group [odds ratio (OR) 1.765, 95% confidence interval (CI) 1.332-2.338, p < 0.001]. The rate of MACCEs was 11.1% (n = 138) in the prolonged DAPT group and 13.2% (n = 133) in the standard DAPT group (OR 0.828, 95% CI 0.642-1.068, p = 0.146). The DAPT duration was further shown to be insignificantly correlated with MACCEs as per the multivariable Cox regression model (HR, 0.813; 95% CI, 0.638-1.036; p = 0.094). No statistically significant difference was observed between the two groups. However, the DAPT duration was a separate predictor of composite bleeding events according to the multivariable Cox regression model (HR 1.704, 95% CI 1.302-2.232, p < 0.001). Compared with the standard DAPT group, the prolonged DAPT group had substantially more BARC 3 or 5 types of bleeding events (3.0 vs. 0.9% in those with standard DAPT, OR 3.430, 95% CI 1.648-7.141, p < 0.001) and BARC 1 or 2 types of bleeding events (10.2 vs. 7.0% in those with standard DAPT, OR 1.500, 95% CI 1.107-2.032, p = 0.008). Conclusion: The prolonged DAPT group had a considerably greater incidence of composite bleeding events than the standard DAPT group. No statistically significant difference was observed in the incidence of MACCEs between the two groups.

Identification and initial validation of maximal tumor area as a novel prognostic factor for overall and disease-free survival in patients with resectable colon cancer: a retrospective study.

BACKGROUND: The tumor area may be a potential prognostic indicator. The present study aimed to determine and validate the prognostic value of tumor area in curable colon cancer. METHODS: This retrospective study included a training and validation cohorts of patients who underwent radical surgery for colon cancer. Independent prognostic factors for overall survival (OS) and disease-free survival (DFS) were identified using Cox proportional hazards regression models. The prognostic discrimination was evaluated using the integrated area under the receiver operating characteristic curves (iAUCs) for prognostic factors and models. The prognostic discrimination between tumor area and other individual factors was compared, along with the prognostic discrimination between the tumor-node-metastasis (TNM) staging system and other prognostic models. Two-sample Wilcoxon tests were carried out to identify significant differences between the two iAUCs. A two-sided P <0.05 was considered statistically significant. RESULTS: A total of 3051 colon cancer patients were included in the training cohort and 872 patients in the validation cohort. Tumor area, age, differentiation, T stage, and N stage were independent prognostic factors for both OS and DFS in the training cohort. Tumor area had a better OS and DFS prognostic discrimination characteristics than T stage, maximal tumor diameter, differentiation, tumor location, and number of retrieved lymph nodes. The novel prognostic model of T stage + N stage + tumor area (iAUC for OS, 0.714, P <0.001; iAUC for DFS, 0.694, P <0.001) showed a better prognostic discrimination than the TNM staging system (T stage + N stage; iAUC for OS, 0.664; iAUC for DFS, 0.658). Similar results were observed in an independent validation cohort. CONCLUSIONS: Tumor area was identified as an independent prognostic factor for both OS and DFS in curable colon cancer patients, and in cases with an adequate number of retrieved lymph nodes. The novel prognostic model of combining T stage, N stage, and tumor area may be an alternative to the current TNM staging system.

Association between hospital surgical case volume and postoperative mortality in patients undergoing gastrectomy for gastric cancer: a systematic review and meta-analysis.

BACKGROUND: Postoperative mortality is an important indicator for evaluating surgical safety. Postoperative mortality is influenced by hospital volume; however, this association is not fully understood. This study aimed to investigate the volume-outcome association between the hospital surgical case volume for gastrectomies per year (hospital volume) and the risk of postoperative mortality in patients undergoing a gastrectomy for gastric cancer. METHODS: Studies assessing the association between hospital volume and the postoperative mortality in patients who underwent gastrectomy for gastric cancer were searched for eligibility. Odds ratios were pooled for the highest versus lowest categories of hospital volume using a random-effects model. The volume-outcome association between hospital volume and the risk of postoperative mortality was analyzed. The study protocol was registered with Prospective Register of Systematic Reviews (PROSPERO). RESULTS: Thirty studies including 586 993 participants were included. The risk of postgastrectomy mortality in patients with gastric cancer was 35% lower in hospitals with higher surgical case volumes than in their lower-volume counterparts (odds ratio: 0.65; 95% CI: 0.56-0.76; P <0.001). This relationship was consistent and robust in most subgroup analyses. Volume-outcome analysis found that the postgastrectomy mortality rate remained stable or was reduced after the hospital volume reached a plateau of 100 gastrectomy cases per year. CONCLUSIONS: The current findings suggest that a higher-volume hospital can reduce the risk of postgastrectomy mortality in patients with gastric cancer, and that greater than or equal to 100 gastrectomies for gastric cancer per year may be defined as a high hospital surgical case volume.

Transcutaneous Electrical Acupoint Stimulation Improves Postoperative Sleep Quality in Patients Undergoing Laparoscopic Gastrointestinal Tumor Surgery: A Prospective, Randomized Controlled Trial.

INTRODUCTION: This study was conducted to observe the effect of transcutaneous electrical acupoint stimulation (TEAS) on the postoperative sleep quality of patients undergoing gastrointestinal tumor surgery and to verify the possible mechanism. METHODS: Eighty-three patients were allocated to the TEAS or Sham group. Patients in the TEAS group received TEAS treatment (disperse-dense waves; frequency, 2/100 Hz) on bilateral Shenmen (HT7), Neiguan (PC6) and Zusanli (ST36) points for 30 min each time, total three times in the perioperative period. In the Sham group, electrodes were placed; however, no current was given. Sleep quality was assessed on the day before surgery (P1) and the first and third days after surgery (D1 and D3) using the Pittsburgh Sleep Quality Index (PSQI) and Athens Insomnia Scale (AIS). Postoperative pain was assessed using visual analog scale (VAS) 72 h postoperatively. The incidences of abdominal distension, dizziness, postoperative nausea and vomiting (PONV) and pulmonary complications were recorded. Serum levels of inflammatory cytokines and the expression of key factors of oxidative stress and key molecules of the nuclear factor erythroid 2-related factor 2/antioxidant response element (Nrf2/ARE) signal pathway were measured. RESULTS: TEAS ameliorated sleep quality at D1 and D3 (PSQI P < 0.05, AIS P < 0.05) and decreased postoperative pain as demonstrated by lower VAS scores compared to the Sham group (P < 0.05). The incidences of abdominal distension and PONV were also lower in the TEAS group. Markers of oxidative stress were increased (P < 0.05), and the serum concentration of interleukin-6 (IL-6) was significantly lower in the TEAS group. The key mediators of the Nrf2/ARE pathway were enhanced after TEAS. CONCLUSION: Perioperative TEAS improved postoperative sleep quality, reduced postoperative pain and alleviated postoperative adverse effects in patients undergoing laparoscopic gastrointestinal tumor surgery resection. This may be associated with activating Nrf2/ARE signal pathway and decreasing its inflammatory actions. TRIAL REGISTRATION: Chinese Clinical Trial Registry ( http://www.chictr.org.cn/index.aspx ), ChiCTR2100054971.

Vascularized lymph node flaps can survive on venous blood without an arterial inflow: an experimental model describing the dynamics of venous flow using indocyanine green angiography (With video).

Background: Several surgeons have described studies of free-tissue transfers using veins instead of arteries. These innovative microsurgical techniques can offer several advantages, such as an easier dissection during flap harvesting, and represent an alternative during an accidental surgical mistake or development of new surgical procedures. The purpose of this study was to describe and explore different constructs of vascularized lymph node transfer (VLNT) only based on venous blood flow in a mouse model, evaluate their blood flow microcirculation through indocyanine green (ICG) angiography and investigate the lymphatic drainage function and the lymph nodes' structures. Methods: Five types of venous lymph node flaps (LNF) were created and investigated: Types IA, IB, IC, IIA and IIB were developed by ICG intraoperatively (with videos in the article). Seven weeks later, by applying methylene blue, the recanalization of the lymphatic vessels between the LNF and the recipient site was detected. Lymph nodes were collected at the same time and their structures were analyzed by hematoxylin and eosin staining analysis. Results: All of the venous LNFs developed except Type IC. Seven weeks later, methylene blue flowed into Types IA, IB, IIA and IIB from recipient sites. When comparing with arteriovenous lymph node, the medullary sinus was diffusely distributed in venous lymph nodes. The proportion of cells was significantly reduced (p < 0.05). The artery diameters were significantly smaller (p < 0.05). The veins diameters and lymphatic vessels output in Types IA, IB, IIA and IIB were more dilated (p < 0.05). Conclusions: This research demonstrated that Type IA, IB, IIA and IIB venous LNFs can retrogradely receive venous blood supply; they can survive, produce a lymphatic recanalization and integrate with the surrounding tissue, despite lymph node structural changes. Our results will improve the understanding of the survival mechanism of venous LNFs and will help researchers to design new studies or lymphatic models and eventually find an alternative procedure for the surgical treatment of lymphedema.

Angiopoietin-2 promotes inflammatory lymphangiogenesis and its effect can be blocked by the specific inhibitor L1-10.

Angiopoietin (Ang)-2, a ligand of the receptor tyrosine kinase Tie2, is known to be involved in the regulation of embryonic lymphangiogenesis. However, the role of Ang-2 in postnatal pathological lymphangiogenesis, such as inflammation, is largely unknown. We used a combination of imaging, molecular, and cellular approaches to investigate whether Ang-2 is involved in inflammatory lymphangiogenesis. We observed strong and continuous expression of Ang-2 on newly generated lymphatic vessels for 2 wk in sutured corneas of BALB/c mice. This expression was concurrent with an increased number of lymphatic vessels. TNF-α expression also increased, with peak TNF-α expression occurring before peak Ang-2 expression was reached. In vitro experiments showed that TNF-α stimulates Ang-2 and Tie2 and ICAM-1 expression on human lymphatic endothelial cells (LECs) and blood vascular endothelial cells (BECs). Ang-2 alone did not affect the biological behavior of LECs, whereas Ang-2 combined with TNF-α significantly promoted the proliferation of LECs but not BECs. In mouse models, blockade of Ang-2 with L1-10, an Ang-2-specific inhibitor, significantly inhibited lymphangiogenesis but promoted angiogenesis. These results clearly indicate that Ang-2 acts as a crucial regulator of inflammatory lymphangiogenesis by sensitizing the lymphatic vasculature to inflammatory stimuli, thereby directly promoting lymphangiogenesis. The involvement of Ang-2 in inflammatory lymphangiogenesis provides a strong rationale for the exploitation of anti-Ang-2 treatment in the prevention and treatment of tumor metastasis and transplant rejection.

Global, Regional, and National Burdens with Temporal Trends of Early-, Intermediate-, and Later-Onset Gastric Cancer from 1990 to 2019 and Predictions up to 2035.

BACKGROUND: Evidence for estimating and predicting the temporal trends of gastric cancer in different age groups is lacking. METHODS: Data of early-, intermediate-, and later-onset gastric cancer (EOGC, IOGC, LOGC) was from the Global Burden of Diseases Study 2019. The incidences and deaths due to EOGC, IOGC, and LOGC were analyzed by period, sex, geographic location, and sociodemographic incidence. Temporal trends were evaluated by estimated annual percentage changes (EAPCs). The incidences and temporal trends were predicted until 2035. RESULTS: There were substantial differences in the incidence and death rates of the three populations at global, regional and national levels in 2019. From 1990 to 2019, EOGC (EAPC, -0.84) showed a slower decrease in incidence rate worldwide than IOGC (EAPC, -1.77) and LOGC (EAPC, -1.10), whereas EOGC and LOGC showed slower decreases in mortality than IOGC. The worldwide incidence rate of EOGC (EAPC, 1.44) was predicted to increase substantially from 2020 to 2035, while that for LOGC (EAPC, 0.43) was predicted to increase slightly and that for IOGC (EAPC, -0.01) was predicted to remain stable over the same period. CONCLUSIONS: This study revealed differences in the burdens and temporal trends of EOGC, IOGC, and LOGC, and highlighted the importance of tailored cancer-control measures in neglected subpopulations, especially in patients with EOGC.

The burden and trend of gastric cancer and possible risk factors in five Asian countries from 1990 to 2019.

The burdens and trends of gastric cancer are poorly understood, especially in high-prevalence countries. Based on the Global Burden of Disease Study 2019, we analyzed the incidence, death, and possible risk factors of gastric cancer in five Asian countries, in relation to year, age, sex, and sociodemographic index. The annual percentage change was calculated to estimate the trends in age-standardized incidence rate (ASIR) and age-standardized death rate (ASDR). The highest ASIR per 100,000 person-years in 2019 was in Mongolia [44 (95% uncertainty interval (UI), 34 to 55)], while the lowest was in the Democratic People's Republic of Korea (DPRK) [23 (95% UI, 19 to 29)]. The highest ASDR per 100,000 person-years was in Mongolia [46 (95% UI, 37 to 57)], while the lowest was in Japan [14 (95% UI, 12 to 15)]. Despite the increase in the absolute number of cases and deaths from 1990 to 2019, the ASIRs and ASDRs in all five countries decreased with time and improved sociodemographic index but increased with age. Smoking and a high-sodium diet were two possible risk factors for gastric cancer. In 2019, the proportion of age-standardized disability-adjusted life-years attributable to smoking was highest in Japan [23% (95% UI, 19 to 28%)], and the proportions attributable to a high-sodium diet were highest in China [8.8% (95% UI, 0.21 to 33%)], DPRK, and the Republic of Korea. There are substantial variations in the incidence and death of gastric cancer in the five studied Asian countries. This study may be crucial in helping policymakers to make better decisions and allocate appropriate resources.

Effects of nutrient supply on leaf stoichiometry and relative growth rate of three stoloniferous alien plants.

Different nutrient supply brings about changes in leaf stoichiometry, which may affect growth rate and primary production of plants. Invasion of alien plants is a severe threat to biodiversity and ecosystem worldwide. A pot experiment was conducted by using three stoloniferous alien plants Wedelia trilobata, Alternanther philoxeroides and Hydrocotyle vulgaris to investigate effects of nutrient supply on their leaf stoichiometry and relative growth rate. Different nitrogen or phosphorus supply was applied in the experiment (N1:1 mmol L-1, N2:4 mmol L-1, and N3:8 mmol L-1, P1:0.15 mmol L-1, P2:0.6 mmol L-1 and P3:1.2 mmol L-1). Nitrogen and phosphorus concentrations in leaves of the three alien plants significantly increased with increase of nitrogen supply. With increase of phosphorus supply, nitrogen or phosphorus concentration of leaf was complex among the three alien plants. N:P ratio in leaf of the three alien plants subjected to different levels of nutrient supply was various. A positive correlation between relative growth rate and N:P ratio of the leaf is observed in W. trilobata and A. philoxeroides suffering from N-limitation. A similar pattern was not observed in Hydrocotyle vulgaris. We tentatively concluded that correlations between relative growth rate and N: P ratio of the leaf could be affected by species as well as nutrient supply. It is suggested that human activities, invasive history, local abundance of species et al maybe play an important role in the invasion of alien plants as well as relative growth rate.