[Rethinking the scope of lymphadenectomy after neoadjuvant immunotherapy for locally advanced gastric cancer].

Radical gastrectomy is the core of comprehensive treatment for patients with locally advanced gastric cancer,while reasonable and standardized lymphadenectomy is the key to radical gastrectomy.With the continuous development of treatment methods and therapeutic drugs for advanced gastric cancer, it is worth exploring whether the scope of lymphadenectomy needs to be changed. Neoadjuvant immunotherapy has brought a new breakthrough for locally advanced gastric cancer, increased pathological complete response rate, reduced clinical stage of tumors, and increased radical surgical resection rate, but it has not brought long-term benefits to patients. Lymph nodes play an important role in human anti-tumor immune response, and some basic studies suggest that preserving some normal lymph nodes may be more helpful to enhance the efficacy of immunotherapy. Thus, in the era of immunotherapy, the extent of lymph node dissection for locally advanced gastric cancer needs to balance continuous drug benefits, patient quality of life, and survival benefits, awaiting further high-quality clinical research for determination. Questions such as how to differentiate between normal and metastatic lymph nodes, how to rationally preserve normal lymph nodes, and whether preserving partial lymph node function can lead to greater benefits for patients from immunotherapy warrant further exploration.

[Antioxidant activity of Euryale ferox seed shell extract and its therapeutic effects on oral ulcer in rats].

OBJECTIVE: To investigate the therapeutic effect of Euryale ferox seed shell extract on oral ulcer in rats and its underlying mechanism. METHODS: The contents of polyphenols and flavonoids in Euryale ferox seed shells were determined by Folin-phenol assay and aluminum nitrate colorimetry, respectively. DPPH·, ABTS+·, ·OH and·O2- scavenging experiments were performed to evaluate the antioxidant activities of Euryale ferox seed shell extract in vitro. In a rat model of oral ulcer induced by burning with glacial acetic acid, the therapeutic effect of Euryale ferox seed shell extract was assessed by detecting changes in serum levels of oxidative factors by enzyme-linked immunosorbent assay (ELISA) and observing pathological changes of the ulcerous mucosa using HE staining; the therapeutic mechanism of the extract was explored by detecting the expression levels of Keap1, Nrf2, Nes-Nrf2 and HO-1 proteins in ulcerous mucosa using Western blotting. RESULTS: The ethyl acetate extract of Euryale ferox seed shells contained 306.74±1.04 mg/g polyphenols and 23.43±0.61 mg/g flavonoids and had IC50 values for scavenging DPPH· and ABTS+· free radicals of 3.42 ± 0.97 µg/mL and 3.32 ± 0.90 µg/mL, respectively. In the rat models, the ethyl acetate extract significantly ameliorated oral mucosal ulcer, increased serum CAT level, and decreased serum MDA level. The protein expression levels of Nes-Nrf2 and HO-1 were increased and Keap1 protein expression was lowered significantly in the ulcerous mucosa of the rats after treatment with the extract (P<0.05 or 0.01). CONCLUSION: The therapeutic effect of Euryale ferox seed shell extract on oral ulcers in rats is mediated probably by activation of the Keap1/Nrf2/HO-1 signaling pathway.

[Clinical and electrophysiological characteristics and treatment outcomes of anti-neutrophil cytoplasmic antibody ANCA-associated vasculitic neuropathy].

Objective: To investigate the clinical and electrophysiological characteristics of ANCA-associated vasculitic neuropathy (VN) and analyze the predictors of treatment outcomes. Methods: Retrospective case series. In all, 652 consecutive patients with ANCA-associated vasculitis were admitted to the First Medical Center of the Chinese PLA General Hospital between January 2006 and December 2022. Peripheral neuropathy occurred in 91 patients. Patients were excluded if other known causes of neuropathy were present. Sixty-one patients were eventually enrolled, including 17 with eosinophilic granulomatosis with polyangiitis (EGPA), 11 with granulomatosis polyangiitis (GPA), and 33 with microscopic polyangiitis (MPA). Their clinical data were collected and clinical characteristics, VN manifestations, electrophysiological findings (including interside amplitude ratio [IAR]), and treatment outcomes were compared among the three subsets of AAV. Then, factors influencing the treatment outcomes were analyzed using multivariable logistic regression analysis. Results: Peripheral neuropathy occurred in 62.1%(18/29) of EGPA, 8.3%(15/180) of GPA, and 13.1%(58/443) of MPA patients. The age at onset and examination was higher in patients with MPA than those with EGPA or GPA (P<0.01). The occurrence of VN was later in patients with GPA than those with EGPA (P<0.01), and the GPA group had fewer affected nerves than the other two groups (P<0.016). The abnormal IARs of motor nerves in lower limbs were more detected in the EGPA than the MPA group (P<0.01). Logistic regression analysis suggested that higher Birmingham vasculitis activity score-version 3 (BVAS-V3) (OR=6.85, 95%CI 1.33-35.30) was associated with better treatment outcomes of VN. However, central nervous system involvement was a risk factor for poor treatment outcomes (OR=0.13, 95%CI 0.02-0.89). Conclusions: The clinical and electrophysiological characteristics of VN were slightly different among subsets of AAV. Patients with GPA often presented with polyneuropathy and had fewer nerves affected; mononeuritis multiplex was more common in EGPA than GPA and MPA. Higher BVAS-V3 and central nervous system involvement might predict the treatment outcome of VN.

Comprehensive genomic profiling to identify actionable alterations for breast cancer brain metastases in the Chinese population.

BACKGROUND: Breast cancer brain metastasis (BCBM) is a crucial issue in the treatment of breast cancer and is associated with poor prognosis. Therefore, novel therapeutic targets are urgently needed in clinical practice. In this study, we aimed to identify potential actionable targets in brain metastases (BMs) utilising the FoundationOne® CDx (F1CDx). PATIENTS AND METHODS: Formalin-fixed paraffin-embedded archived specimens including 16 primary breast tumours (PTs), 49 BCBMs and 7 extracranial metastases (ECMs) from 54 patients who underwent surgery for BCBM were tested using F1CDx. Tumour-infiltrated lymphocytes (TILs) of BMs were also tested using haematoxylin-eosin staining. RESULTS: The median tumour mutational burden (TMB) and TILs in BMs were 5.0 (range 0-29) mut/Mb and 1.0% (range 0%-5.0%), respectively. High TMB (≥10 mut/Mb) was detected in four cases (8%). Genomic alterations (GAs) were detected in all samples. The top-ranked somatic mutations in BMs were TP53 (82%), PIK3CA (35%), MLL2 (22%), BRCA2 (14%) and ATM (14%) and the most prevalent copy number alterations were ERBB2 (64%), RAD21 (36%), CCND1 (32%), FGF19 (30%) and FGF3 (30%). The most prevalent GAs were relatively consistent between paired PTs and BMs. Actionable GAs were detected in 94% of all BMs. Consistent rate in actionable GAs was 38% (6/16) between paired PTs/ECMs and BMs. Compared to matched PTs/ECMs, additional actionable GAs (BRAF, FGFR1, PTEN, KIT and CCND1) were discovered in 31% (5/16) of the BMs. CONCLUSIONS: TMB and TILs were relatively low in BCBMs. Comparable consistency in actionable GAs was identified between BCBMs and matched PTs/ECMs. It was, therefore, logical to carry out genomic testing for BCBMs to identify potential new therapeutic targets when BCBM specimens were available, as ∼31% of samples carried additional actionable GAs.

Identification and validation of a novel cuproptosis signature for stratifying different prognostic, immune, metabolic, and therapeutic landscapes in pancreatic adenocarcinoma.

OBJECTIVE: Pancreatic adenocarcinoma (PAAD) is a highly malignant cancer that urgently needs more effective therapeutic strategies. The discovery of cuproptosis brings great inspiration for the treatment and clinical assessment of cancers. MATERIALS AND METHODS: A novel cuproptosis-related (CR) risk signature was constructed using the Lasso regression analysis. Its prognostic value was assessed via a series of survival analyses and validated in four GEO cohorts. The effects of CR risk signature on tumor immune microenvironment (TIM) were explored through CIBERSORT, ESTIMATE, and ssGSEA algorithms. Using GESA, we investigated its associations with various patterns of programmed cell death (PCD) and the metabolism process. The somatic mutation features of each CR-risk group were also probed using 'maftools' R package and cBioPortal database. The potential linkages between CR risk score and the efficacy of multiple therapeutic approaches were elucidated using tumor mutation burden, the expressions of immune checkpoints, the TIDE score, and the GDSC database. Finally, we ascertained the biofunctions of LIPT1 (Lipoyltransferase 1) in pancreatic cancer (PC) cells through immunohistochemistry, qPCR (quantitative polymerase chain reaction), colony formation, and Transwell assays. RESULTS: LIPT1, LIAS (lipoyl synthase), PDP1 (Pyruvate dehydrogenase phosphatase1), and GCSH (Glycine cleavage system H protein) constituted the CR risk signature. The CR risk signature possessed a high prognostic value and could improve the traditional prognostic model. Moreover, the CR risk score was indicative of the changes in infiltration levels of CD8+T cells and macrophages, whereas it was not associated with the enrichment of various PCD patterns and multiple metabolic processes. As for therapeutic correlation, CR risk score was a potential biomarker for predicting the efficacy of ICBs but failed in targeted drugs and chemotherapeutic agents. Through qPCR and immunohistochemistry detection in clinical samples, we confirmed that LIPT1 was significantly downregulated in pancreatic adenocarcinoma (PAAD) samples. Experiments in vitro revealed that silencing LIPT1 promoted the proliferation, migration, and invasion of PANC-1 and SW1990 cells. CONCLUSIONS: The novel CR risk signature contributed to the risk stratification of PAAD patients. Cuproptosis regulatory genes, well represented by LIPT1, provided new insights into PAAD treatment and assessment.

[Respiratory virus infection and its influence on outcome in children with septic shock].

Objective: To investigate respiratory virus infection in children with septic shock in pediatric care units (PICU) in China and its influence on clinical outcomes. Methods: The clinical data of children with septic shock in children's PICU from January 2018 to December 2019 in 10 Chinese hospitals were retrospectively collected. They were divided into the pre-COVID-19 and post-COVID-19 groups according to the onset of disease, and the characteristics and composition of respiratory virus in the 2 groups were compared. Matching age, malignant underlying diseases, bacteria, fungi and other viruses, a new database was generated using 1∶1 propensity score matching method. The children were divided into the respiratory virus group and non-respiratory virus group according to the presence or absence of respiratory virus infection; their clinical characteristics, diagnosis, and treatment were compared by t-test, rank sum test and Chi-square test. The correlation between respiratory virus infection and the clinical outcomes was analyzed by logistic regression. Results: A total of 1 247 children with septic shock were included in the study, of them 748 were male; the age was 37 (11, 105) months. In the pre-and post-COVID-19 groups, there were 530 and 717 cases of septic shock, respectively; the positive rate of respiratory virus was 14.9% (79 cases) and 9.8% (70 cases); the seasonal distribution of septic shock was 28.9% (153/530) and 25.9% (185/717) in autumn, and 30.3% (161/530) and 28.3% (203/717) in winter, respectively, and the corresponding positive rates of respiratory viruses were 19.6% (30/153) and 15.7% (29/185) in autumn, and 21.1% (34/161) and 15.3% (31/203) in winter, respectively. The positive rates of influenza virus and adenovirus in the post-COVID-19 group were lower than those in the pre-COVID-19 group (2.1% (15/717) vs. 7.5% (40/530), and 0.7% (5/717) vs. 3.2% (17/530), χ2=21.51 and 11.08, respectively; all P<0.05). Rhinovirus virus were higher than those in the pre-Covid-19 group (1.7% (12/717) vs. 0.2% (1/530), χ2=6.51, P=0.011). After propensity score matching, there were 147 cases in both the respiratory virus group and the non-respiratory virus group. Rate of respiratory failure, acute respiratory distress, rate of disseminated coagulation dysfunction, and immunoglobulin usage of the respiratory virus group were higher than those of non-respiratory virus group (77.6% (114/147) vs. 59.2% (87/147), 17.7% (26/147) vs. 4.1% (6/147), 15.6% (25/147) vs. 4.1% (7/147), and 35.4% (52/147) vs. 21.4% (32/147); χ2=11.07, 14.02, 11.06 and 6.67, all P<0.05); and PICU hospitalization of the former was longer than that of the later (7 (3, 16) vs. 3 (1, 7)d, Z=5.01, P<0.001). Univariate logistic regression analysis showed that the presence of respiratory viral infection was associated with respiratory failure, disseminated coagulation dysfunction, the use of mechanical ventilation, and the use of immunoglobulin and anti-respiratory viral drugs (OR=2.42, 0.22, 0.25, 0.56 and 1.12, all P<0.05). Conclusions: The composition of respiratory virus infection in children with septic shock is different between pre and post-COVID-19. Respiratory viral infection is associated with organ dysfunction in children with septic shock. Decreasing respiratory viral infection through respiratory protection may improve the clinical outcome of these children.

[Research progress on physical activity of childhood cancer survivors].

Many childhood cancer survivors are suffering serious and long-lasting complications or sequelae, taking a significant toll on their health. Adequate physical activity can be effective in mitigating the negative effects of these complications or sequelae. However, low levels of physical activity are prevalent among childhood cancer survivors. Due to the lack of guidelines on physical activity for childhood cancer survivors, there are many difficulties in correctly guiding childhood cancer survivors to participate in physical activity. Therefore, it is necessary to summarize the relevant studies on the physical activity of childhood cancer survivors. This article provides a review of the concept and measurement of physical activity, recommended amount, and the participation of childhood cancer survivors both domestically and internationally, in order to provide a reference for promoting the physical activity level of Chinese childhood cancer survivors.

Testosterone promotes the migration, invasion and EMT process of papillary thyroid carcinoma by up-regulating Tnnt1.

PURPOSE: To explore the key genes and molecular pathways in the progression of thyroid papillary carcinoma (PTC) promoted by testosterone using RNA-sequencing technology, and to provide new drug targets for improving the therapeutic effect of PTC. METHODS: Orchiectomy (ORX) was carried out to construct ORX mouse models. TPC-1 cells were subcutaneously injected for PTC formation in mice, and the tumor tissues were collected for RNA-seq. The key genes were screened by bioinformatics technology. Tnnt1 expression in PTC cells was knocked down or overexpressed by transfection. Cell counting kit-8 (CCK-8), colony formation assay, scratch assay and transwell assay were adopted, respectively, for the detection of cell proliferation, colony formation, migration and invasion. Besides, quantification real-time polymerase chain reaction (qRT-PCR) and western blot were utilized to determine the mRNA and protein expression levels of genes in tissues or cells. RESULTS: Both estradiol and testosterone promoted the growth of PTC xenografts. The key gene Tnnt1 was screened and obtained by bioinformatics technology. Functional analysis revealed that overexpression of Tnnt1 could markedly promote the proliferation, colony formation, migration, invasion, and epithelial-to-mesenchymal transition (EMT) process of PTC cells, as well as could activate p38/JNK pathway. In addition, si-Tnt1 was able to inhibit the cancer-promoting effect of testosterone. CONCLUSION: Based on the outcomes of bioinformatics and basic experiments, it is found that testosterone can promote malignant behaviors such as growth, migration, invasion and EMT process of PTC by up-regulating Tnnt1 expression. In addition, the function of testosterone may be achieved by activating p38/JNK signaling pathway.

[Outcomes and care practices of extremely preterm infants at 22-25 weeks' gestation age from the Chinese Neonatal Network].

Objective: To describe the current status and trends in the outcomes and care practices of extremely preterm infants at 22-25 weeks' gestation age from the Chinese Neonatal Network (CHNN) from 2019 to 2021. Methods: This cross-sectional study used data from the CHNN cohort of very preterm infants. All 963 extremely preterm infants with gestational age between 22-25 weeks who were admitted to neonatal intensive care units (NICU) of the CHNN from 2019 to 2021 were included. Infants admitted after 24 hours of life or transferred to non-CHNN hospitals were excluded. Perinatal care practices, survival rates, incidences of major morbidities, and NICU treatments were described according to different gestational age groups and admission years. Comparison among gestational age groups was conducted using χ2 and Kruskal-Wallis tests. Trends by year were evaluated by Cochran-Armitage and Jonckheere-Terpstra tests for trend. Results: Of the 963 extremely preterm infants enrolled, 588 extremely preterm infants (61.1%) were male. The gestational age was 25.0 (24.4, 25.6) weeks, with 29 extremely preterm infants (3.0%), 88 extremely preterm infants (9.1%), 264 extremely preterm infants (27.4%), and 582 extremely preterm infants (60.4%) at 22, 23, 24, and 25 weeks of gestation age, respectively. The birth weight was 770 (680, 840) g. From 2019 to 2021, the number of extremely preterm infants increased each year (285, 312, and 366 extremely preterm infants, respectively). Antenatal steroids and magnesium sulfate were administered to 67.7% (615/908) and 51.1% (453/886) mothers of extremely preterm infants. In the delivery room, 20.8% (200/963) and 69.5% (669/963) extremely preterm infants received noninvasive positive end-expiratory pressure support and endotracheal intubation. Delayed cord clamping and cord milking were performed in 19.0% (149/784) and 30.4% (241/794) extremely preterm infants. From 2019 to 2021, there were significant increases in the usage of antenatal steroids, antenatal magnesium sulfate, and delivery room noninvasive positive-end expiratory pressure support (all P<0.05). Overall, 349 extremely preterm infants (36.2%) did not receive complete care, 392 extremely preterm infants (40.7%) received complete care and survived to discharge, and 222 extremely preterm infants (23.1%) received complete care but died in hospital. The survival rates for extremely preterm infants at 22, 23, 24 and 25 weeks of gestation age were 10.3% (3/29), 23.9% (21/88), 33.0% (87/264) and 48.3% (281/582), respectively. From 2019 to 2021, there were no statistically significant trends in complete care, survival, and mortality rates (all P>0.05). Only 11.5% (45/392) extremely preterm infants survived without major morbidities. Moderate to severe bronchopulmonary dysplasia (67.3% (264/392)) and severe retinopathy of prematurity (61.5% (241/392)) were the most common morbidities among survivors. The incidences of severe intraventricular hemorrhage or periventricular leukomalacia, necrotizing enterocolitis, and sepsis were 15.3% (60/392), 5.9% (23/392) and 19.1% (75/392), respectively. Overall, 83.7% (328/392) survivors received invasive ventilation during hospitalization, with a duration of 22 (10, 42) days. The hospital stay for survivors was 97 (86, 116) days. Conclusions: With the increasing number of extremely preterm infants at 22-25 weeks' gestation admitted to CHNN NICU, the survival rate remained low, especially the rate of survival without major morbidities. Further quality improvement initiatives are needed to facilitate the implementation of evidence-based care practices.

[Tumor Mechanomedicine].

Malignant tumors represent a significant health challenge, critically impacting human well-being. Historically, the focus has been on leveraging the biochemical cues of tumors for both diagnosis and treatment. While valuable, this strategy does not capture the full complexity of tumor diagnosis and management. Recently, the integration of biomechanics and mechanobiology with oncology has highlighted the importance of mechanical cues, which have emerged as new hallmarks of tumors, opening potential novel routes for cancer diagnosis and therapeutic interventions. Despite the advances, a thorough literature review suggests a pronounced gap in our understanding of the mechanical properties of tumors. The clinical community has not yet completely recognized the diagnostic and therapeutic relevance of the mechanical cues of tumors. To bridge this knowledge gap, we propose and introduce the paradigm of "Tumor Mechanomedicine". We provide a comprehensive overview of the multi-scale mechanical characteristics of tumors, exploring their influence on tumor biology, from the aspects of tumor biomechanics, tumor mechanobiology, tumor mechanodiagnostics, and tumor mechanotherapeutics. By elucidating the diagnostic and therapeutic potential of these mechanical cues, we aim to furnish the oncology community with fresh insights, paving the way for innovative solutions to persistent clinical conundrums.

[Chest hemorrhage after left total pulmonary resection for secondary rifampin-resistant tuberculosis:a case report].

The patient had received five courses of anti-tuberculosis treatment for recurrent tuberculosis. The drug sensitivity test results of the first three courses showed drug-sensitive pulmonary tuberculosis, and the fourth diagnosis was rifampin-resistant tuberculosis (RR-TB), complicated by chronic obstructive pulmonary disease, type Ⅱ respiratory failure, pulmonary heart disease, and heart failure (grade Ⅲ). The patient stopped taking the anti-tuberculosis drugs on his own in the eighth month of receiving the resistant treatment. After admission, the symptoms improved temporarily after receiving oxygen therapy, anti-infection, and anti-tuberculosis treatment. Because of hemoptysis, the patient underwent arterial embolization by catheterization, but a large amount of hemoptysis occurred shortly thereafter. Emergency left total lung resection and gauze packing for hemostasis were performed. After surgery, the patient's vital signs were maintained with mechanical ventilation and vasopressors. Forty-eight hours after surgery, the gauze was removed, and the patient underwent tracheotomy, enteral nutrition, and anti-tuberculosis treatment. After discharge, the patient underwent rehabilitative exercise and anti-resistant tuberculosis therapy. The patient's condition remained stable for more than six months of follow-up.

[The value of aspirin challenge tests in the diagnosis of non-steroidal anti-inflammatory drugs-exacerbated respiratory disease].

Objective: To investigate the value of aspirin challenge tests in the diagnosis of non-steroidal anti-inflammatory drugs-exacerbated respiratory disease (NERD). Methods: Fifty patients (22 males and 28 females; aged 16-61 years) who were diagnosed with chronic rhinosinusitis with nasal polyps (CRSwNP) with/without asthma, and underwent NERD standardized diagnosis in the Allergy Centre of West China Hospital, Sichuan University from December 2021 to November 2022 were included in the study. The first step was asking about the history of exacerbation respiratory symptoms after intake of any non-steroidal anti-inflammatory drug, including aspirin; the second step was performing intranasal aspirin challenge (IAC); and the third step was performing oral aspirin challenge (OAC). The diagnosis of NERD was made if any of the above steps was positive, and the subsequent steps were not performed, otherwise the diagnosis was made to OAC. If OAC was negative, the diagnosis was non-NERD. All patients completed the sino-nasal outcome test 22 (SNOT 22) score, Lund-Kennedy score by nasal endoscopic, allergen skin prick test, blood routine and serum total IgE test. SPSS version 20.0 was used for statistical analysis. Results: The diagnosis of NRED was confirmed in 27 patients (27/50, 54%). Seven (7/50, 14%) of them were diagnosed by clinical history and 20 (20/50, 40%) were diagnosed by aspirin challenge tests, of which 17 (17/20, 85%) were positive to IAC and 3 (3/20, 15%) to OAC. Of the 43 patients who underwent IAC testing, only 2 (2/43, 5%) developed asthma attacks during challenge. Comparing the clinical characteristics of patients in NERD and non-NERD group, there were significant differences between the two groups in gender (P=0.001), hyposmia (P=0.003), history of repeated CRSwNP surgeries (P=0.028), comorbid asthma (P=0.013), SNOT-22 score (P=0.004) and the percentage of peripheral blood eosinophil (P=0.043). Conclusions: Patients may be underdiagnosed if the diagnosis of NERD is made only by medical history, and it is necessary to carry out aspirin challenge tests. IAC is an important means to diagnose NERD with high accuracy and good safety. However, If IAC is negative, further OAC is required.

Multi-dimensional radiomics analysis to predict visceral pleural invasion in lung adenocarcinoma of ≤3 cm maximum diameter.

AIM: To explore the value of radiomics analysis in preoperatively predicting visceral pleural invasion (VPI) of lung adenocarcinoma (LAC) with ≤3 cm maximum diameter and to compare the performance of two-dimensional (2D) and three-dimensional (3D) computed tomography (CT) radiomics models. MATERIALS AND METHODS: A total of 391 LAC patients were enrolled retrospectively, of whom 142 were VPI (+) and 249 were VPI (-). Radiomics features were extracted from 2D and 3D regions of interest (ROIs) of tumours in CT images. 2D and 3D radiomics models were developed combining the optimal radiomics features by using the logistic regression machine-learning method and radiomics scores (rad-scores) were calculated. Nomograms were constructed by integrating independent risk factors and rad-scores. The performance of each model was evaluated by using the receiver operator characteristic (ROC) curve, decision curve analysis (DCA), clinical impact curve (CIC), and calculating the area under the curve (AUC). RESULTS: There was no difference in the VPI prediction between 2D and 3D radiomics models (training group: 2D AUC=0.835, 3D AUC=0.836, p=0.896; validation group: 2D AUC=0.803, 3D AUC=0.794, p=0.567). The 2D and 3D nomograms performed similarly regarding discrimination (training group: 2D AUC=0.867, 3D AUC=0.862, p=0.409, validation group: 2D AUC=0.835, 3D AUC=0.827, p=0.558), and outperformed their corresponding radiomics models and the clinical model. DCA and CIC revealed that the 2D nomogram had slightly better clinical utility. CONCLUSION: The 2D radiomics model has a similar discrimination capability compared with the 3D radiomics model. The 2D nomogram performs slightly better for individual VPI prediction in LAC.

[Efficacy of arteriovenous argatroban versus heparin flush anticoagulation after cardiovascular surgery].

Objective: To compare the effects of arteriovenous argatroban and heparin flushes on platelet count and assess the occurrence of heparin-induced thrombocytopenia (HIT) and other complications in patients undergoing cardiovascular surgeries. Methods: A single-center, prospective randomized control study was conducted. Patients who underwent cardiovascular surgery at Fuwai Hospital, Chinese Academy of Medical Sciences from March to December 2019 were randomly divided into the argatroban group (250 ml normal saline plus 2.5 mg of argatroban) and the heparin group (250 ml normal saline plus 10 mg of heparin). Platelet count, hemorrhage, and thrombosis were assessed. The 4T scores of HIT, the incidences of HIT and other complications were also evaluated. Results: A total of 491 patients (307 males and 184 females) were included in the study, with a mean age of (52.3±13.7) years. There were 245 cases in the argatroban group and 246 cases in the heparin group, respectively. There was no statistically significant difference in the preoperative platelet count between the argatroban and heparin groups [198.0 (161.0, 248.0)×109/L vs 194.0 (157.2, 243.8)×109/L, P=0.498]. Likewise, there were no statistically significant differences in the platelet count between the argatroban and heparin groups at 12 h, 1 day, and 5 days after operation [127.0 (100.0, 154.0)×109/L vs 121.5 (90.2, 149.0)×109/L, 126.0 (97.0, 162.0)×109/L vs 123.5 (88.0, 151.0)×109/L, 168.0 (130.0, 215.0) ×109/L vs 161.0 (101.0, 210.5)×109/L] (repeated measures ANOVA between groups: F=3.327, P=0.069; time comparison: F=532.523, P<0.001; time interaction between groups: F=0.675, P=0.512). The proportion of 4T scores of medium and high scores (≥4)[9.8% (24/245) vs 10.6% (26/246), P=0.777] and incidence of HIT antibody positive [1.63% (4/245) vs 1.63% (4/246), P=0.726] were similar between argatroban group and the heparin group. Mechanical ventilation time was shorter in the argatroban group than that in the heparin group [13.0 (11.0, 21.0) vs 15.5 (12.0, 21.0) h, P=0.020]. Conclusion: Compared with heparin, routine management with argatroban for arteriovenous flush in patients undergoing cardiovascular surgery does not affect the HIT incidence.

[Abnormal expression of CXCR5+CD8+ T cells and CXCL13 in severe aplastic anemia patients and their correlation with hematological parameters].

Objective: To analyze the expression of C-X-C chemokine receptor 5 (CXCR5)+CD8+ T cells and plasma C-X-C motif chemokine 13 (CXCL13) in severe aplastic anemia (SAA) patients and their correlations with hematological parameters. Methods: The clinical data of 35 SAA patients in the Hematology Department of Tianjin Medical University General Hospital from January 2018 to September 2021 were retrospectively analyzed. The patients were divided into two groups according to whether they had received the medication: untreated SAA group and recovery SAA group. In untreated group, there were 18 patients who had not received any medication, with 9 males and 9 females, and aged 51 (18-76) years. In recovery SAA group, there were 17 patients who were separated from component blood transfusion after the immunosuppressive treatment with anti-thymocyte globulin (ATG) combined with cyclosporine A (CsA), with 7 males and 10 females, and aged 46 (16-70) years. Meanwhile, 20 healthy controls were also selected, including 8 males and 12 females, and aged 45(15-72) years. Peripheral blood and bone marrow samples were collected from SAA patients, while peripheral blood samples were obtained from healthy controls. Flow cytometry was used to detect the percentage of CXCR5+CD8+ T cells in peripheral blood and bone marrow samples. The concentration of plasma CXCL13 was measured by enzyme-linked immunosorbent assay (ELISA). The correlations between the percentage of CXCR5+CD8+ T cells and the concentration of CXCL13, as well as the correlations between these two parameters and the hematological parameters were analyzed by Spearman correlation analysis. Results: The proportion of CXCR5+CD8+ T cells in the bone marrow of untreated SAA group was (4.9±2.9)%, which was higher than that of recovery SAA group (2.7±1.5)%, with a statistically significant difference (t=2.34, P=0.027). The proportion of CXCR5+CD8+ T cells in peripheral blood of untreated SAA group, recovery SAA group and healthy control group was (8.4±4.2)%, (3.8±2.3)% and (2.6±2.0)% respectively. The proportion of CXCR5+CD8+ T cells in peripheral blood of untreated SAA group was higher than that of recovery SAA group and healthy control group (both P<0.05). The plasma CXCL13 concentration in untreated SAA group was (97.2±46.8) ng/L, which was significantly higher than that in recovery SAA group [(54.9±20.9) ng/L] and healthy control group [(47.6±17.3) ng/L] (both P<0.05). The proportion of CXCR5+CD8+ T cells in peripheral blood of SAA patients was positively correlated with the concentration of plasma CXCL13 (r=0.545, P<0.001). The proportion of peripheral blood CXCR5+CD8+ T cells in SAA patients was negatively correlated with white blood cell count, platelets count, percentage of neutrophils, absolute neutrophils count, percentage of reticulocytes, absolute reticulocytes count, bone marrow myeloid cells, bone marrow erythroid cells and megakaryocytes count (r=-0.556, -0.392, -0.617, -0.615, -0.395, -0.543, -0.432, -0.484 and -0.523, all P<0.05). The proportion of peripheral blood CXCR5+CD8+ T cells was positively correlated with the percentage of peripheral blood lymphocytes and bone marrow lymphoid cells (r=0.593 and 0.556, both P<0.05). Meanwhile, the concentration of plasma CXCL13 in SAA patients was negatively correlated with white blood cell count, absolute neutrophils count, percentage of reticulocytes, absolute reticulocytes count and bone marrow myeloid cells (r=-0.447, -0.446, -0.498, -0.407 and -0.456, all P<0.05), but positively correlated with bone marrow lymphoid cells (r=0.384, P<0.05). Conclusions: The proportion of CXCR5+CD8+ T cells and the concentration of plasma CXCL13 increases in SAA patients. The proportion of CXCR5+CD8+ T cells in peripheral blood is positively correlated with the concentration of CXCL13. Moreover, the proportion of CXCR5+CD8+ T cells and the concentration of CXCL13 are correlated with many hematological parameters, which may play a critical role in the immune pathogenesis of SAA.

Risk prediction of second primary malignancies in primary colorectal neuroendocrine neoplasms patients: a population-based study.

PURPOSE: In this study, we aimed to identify risk factors for developing second primary malignancies (SPMs) in colorectal neuroendocrine neoplasms (NENs) patients and develop a competing-risk nomogram to predict SPMs' probabilities quantitatively. METHODS: Patients with colorectal NENs were retrospectively collected from the Surveillance, Epidemiology, and End Results (SEER) database during 2000-2013. Potential risk factors for SPMs' occurrence in colorectal NENs' patients were identified by the Fine and Gray's proportional sub-distribution hazards model. Then, a competing-risk nomogram was constructed to quantify SPMs' probabilities. The discriminative abilities and calibrations of this competing-risk nomogram were assessed by the area under the receiver-operating characteristic (ROC) curves (AUC) and calibration curves. RESULTS: We identified 11,017 colorectal NENs' patients, and randomly divided them into training (n = 7711 patients) and validation (n = 3306 patients) cohorts. In the whole cohort, 12.4% patients (n = 1369) had developed SPMs during the maximum follow-up of approximately 19 years (median 8.9 years). Sex, age, race, primary tumor location, and chemotherapy were identified as risk factors for SPMs' occurrence in colorectal NENs' patients. Such factors were selected to develop a competing-risk nomogram and showed excellent predictive ability for SPMs' occurrence (the 3-, 5-, and 10-year AUC values were 0.631, 0.632, and 0.629 in the training cohort and 0.665, 0.639, 0.624 in the validation cohort, respectively). CONCLUSIONS: This research identified risk factors for SPMs' occurrence in colorectal NENs' patients. Competing-risk nomogram was constructed and proved to have good performance.

[Tumor necrosis factor-related apoptosis-inducing ligand gene polymorphism and its plasma phenotype in relation to Crohn's disease].

Objectives: To investigate the associations of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) gene polymorphism and plasma soluble TRAIL level (sTRAIL) with Crohn's disease (CD) and to retrospectively analyze the effects of TRAIL gene variants and plasma sTRAIL levels on clinical response to infliximab (IFX). Methods: From January 2012 to January 2021, 312 CD patients [205 males, 107 females, average age (33.9±9.8) years] and 514 age-and gender-matched healthy controls [304 males, 210 females, average age (34.9±9.4) years] were recruited from the Department of Gastroenterology, the Second Affiliated Hospital of Wenzhou Medical University. Among them, 72 patients with active CD who were ineffective or intolerant to traditional drug therapy regularly received IFX (5 mg/kg) treatment. According to the changes in the Harvey-Bradshaw index (HBI) and the Simplified Endoscopic Score for Crohn's Disease (SES-CD) in the 14th week, these patients were classified into response group (a decrease in HBI≥3 or a decrease in SES-CD≥50%) and non-response group. TRAIL (rs1131568) gene polymorphism was analyzed by matrix-assisted laser desorption/ionization time of flight mass spectrometry technique. The plasma sTRAIL level was examined by enzyme-linked immunosorbent assay (ELISA). Based on the Montreal CD classification criteria, all CD patients were divided into different subgroups. Finally, a comprehensive analysis was performed to investigate the relationship between TRAIL (rs1131568) gene polymorphism, the plasma sTRAIL level and the risk of CD, the clinicopathological characteristics of CD patients, and the clinical response to IFX. Results: The recessive model analysis showed that the homozygous variant genotype (CC) was more prevalent in patients with moderately to severely active CD than in those with mildly active CD (45.34% vs 29.23%, P=0.005). Both variant allele (C) and homozygous variant genotype (CC) in patients with stricturing and penetrating CD were more frequent than those in patients with non-stricturing and non-penetrating CD (65.48% vs 57.53%, P=0.046; 49.21% vs 31.18%, P=0.001). The dominant model analysis showed that variant allele (C) and variant genotype (TC+CC) was higher in CD patients with perianal lesions than in those without perianal lesions (66.83% vs 58.17%, P=0.037; 92.31% vs 78.37%, P=0.002). The average plasma sTRAIL level was higher in CD patients than in healthy controls [(243.04±42.74) ng/L vs (194.16±31.14) ng/L, P<0.001]. Compared with the patients with mildly active CD, the plasma sTRAIL level was increased in those with moderately to severely active CD [263.47(242.09, 281.91) ng/L vs 231.13(211.11, 247.11) ng/L, P<0.001]. The same conclusion was also drawn for the patients with stricturing and penetrating CD in contrast to those with non-stricturing and non-penetrating CD [266.18 (246.68, 289.91) ng/L vs 227.19 (204.57, 249.59) ng/L, P<0.001]. The plasma sTRAIL level was also higher in patients with perianal disease than in those without perianal disease [(261.40±41.51) ng/L vs (233.86±40.41) ng/L, P<0.001]. Multiple linear regression analysis further showed that disease activity (ß=22.640, P<0.001) and homozygous variant genotype (CC) (ß=16.814, P<0.001) may be positively related to the plasma sTRAIL level in CD patients independently. At the 14th week of IFX treatment, the plasma sTRAIL level in the response group was lower than that in the non-response group [205.98(190.72, 214.56) ng/L vs (238.33±29.38) ng/L, P<0.001]. Compared with week 0, the plasma sTRAIL level was decreased in the response group in the 14th week [(205.98 (190.72, 214.56) ng/L vs (239.89±42.43) ng/L, P<0.001]. Non-conditional logistic regression analysis showed that variant allele (C) and variant genotype (TC+CC) were less frequent in the response group than in the non-response group (53.33% vs 70.83%, P=0.037; 70.00% vs 91.67%, P=0.036). Conclusions: The increased plasma sTRAIL level may be a risk factor for CD. TRAIL (rs1131568) gene variation and the increase of plasma sTRAIL level may be associated with the increased disease activity of CD and may be the risk factors for stenosis, penetration, and perianal lesions in CD patients. In addition, TRAIL (rs1131568) gene variation or the increase of plasma sTRAIL level may be related to no response to IFX treatment in CD patients.

Three first records of stick insects attacking plants (Inseect: Phasmida) in Tibet / Três primeiros registros de insetos-pau atacando plantas (Inseect: Phasmida) no Tibet

Except for a few stick insects that are economically valuable, most species be considered to be forest pests, so it is extremely important to obtain plant host-use information of more stick insects. In this paper, the plant hosts of three species of stick insects were recorded for the first time. We also discovered these stick insects can feed upon the flowers or leaves of plants. Lopaphus unidentatus (Chen & He, 1995) (Phasmida: Lonchodidae) attacked Hypericum choisianum Wall. ex N. Robson, 1973 (Hypericaceae), Leurophasma dolichocercum Bi, 1995 (Phasmida: Aschiphasmatidae) attacked Antenoron filiforme (Thunb.) Roberty & Vautier, 1964 (Polygonaceae) and Megalophasma granulatum Bi, 1995 (Phasmida: Lonchodidae) attacked Debregeasia orientalis C. J. Chen, 1991 (Urticaceae). Finally, we were lucky enough to also obtain photographs of them mating and feeding.

Exceto por alguns insetos-pau que são economicamente valiosos, a maioria das espécies pode ser considerada praga florestal, por isso é extremamente importante obter informações sobre o uso de hospedeiros de plantas de mais insetos-pau. Neste artigo, as plantas hospedeiras de três espécies de bicho-pau foram registradas pela primeira vez. Também descobrimos que esses bichos-pau podem se alimentar de flores ou folhas de plantas. Lopaphus unidentatus (Chen & He, 1995) (Phasmida: Lonchodidae) atacou a parede de Hypericum choisianum. ex N. Robson, 1973 (Hypericaceae), Leurophasma dolichocercum Bi, 1995 (Phasmida: Aschiphasmatidae) atacou Antenoron filiforme (Thunb.) Roberty & Vautier, 1964 (Polygonaceae) e Megalophasma granulatum Bi, 1995 (Phasmida: Lonchodidae orientaled) atacou Chen, 1991 (Urticaceae). Finalmente, tivemos a sorte de também obter fotos deles se acasalando e se alimentando.