Objective To investigate the temporal changes in pathological damage and macrophage polarization in liver and spleen tissues of mice infected with Angiostrongylus cantonensis, and to preliminarily unravel the peripheral immune responses during the early stage of A. cantonensis infection. Methods Forty female BALB/c mice at ages of 6 to 8 weeks were randomly divided into four groups, including the control group and 7-, 14-, and 21-day infection groups, with 10 mice in each group. Each mouse in the infection groups was inoculated with 30 third-stage (L3) larvae of A. cantonensis by oral gavage, and five mice were randomly selected from each infection group on days 7, 14, and 21 post-infection, while mice in the control group were given the same volume of physiological saline and five mice were randomly selected from the control group on the day of oral gavage. Mouse liver and spleen tissues were sampled. The histopathological changes of mouse liver and spleen tissues were observed using hematoxylin and eosin (HE) staining, and the percentage of positive staining area and the co-localization positive rates of the macrophage surface antigens F4/80, CD86, and CD206 were quantified in mouse liver and spleen tissues using immunohistochemical and immunofluorescence staining. In addition, five mice were collected from each infection group on days 7, 14, and 21 post-infection, and five mice were collected from the control group on the day of oral gavage. Mouse liver and spleen tissues were sampled for detection of macrophage markers CD86 and CD206 and macrophage phenotyping using flow cytometry, and the expression of M1 macrophage markers, including inducible nitric oxide synthase (Nos2), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and M2 markers, including arginase 1 (Arg1), mannose receptor C-type 1 (Mrc1) and chitinase-like protein 3 (Chil3) was quantified in mouse liver and spleen tissues using real-time quantitative PCR (RT-qPCR) assay. Results Proliferative lesions of the hepatocyte were observed in mouse liver tissues and the follicular structures of the mouse spleen white pulp were disrupted 21 days post-infection with A. cantonensis. Immunohistochemical staining showed that there were significant differences in the percentages of F4/80, CD86 and CD206 positive staining areas in the liver and spleen tissues among the four groups of mice (F = 242.40, 197.14, 183.19, 157.65, 242.35 and 146.24; all P values < 0.001), and the percentages of positive staining in the liver and spleen tissues of mice in the 14-day infection group [(4.45 ± 0.51)%, (3.74 ± 0.67)%, (8.32 ± 0.72)%, (16.56 ± 1.14)%, (11.62 ± 0.52)%, and (8.29 ± 0.72)%, respectively] and the 21-day infection group [(3.70 ± 0.11)%, (3.22 ± 0.43)%, (11.53 ± 1.03)%, (12.59 ± 1.05)%, (9.02 ± 0.83)%, and (11.67 ± 1.10)%, respectively] were higher than in the control group [(0.35 ± 0.16)%, (0.40 ± 0.02)%, (0.93 ± 0.05)%, (2.78 ± 0.26)%, (2.33 ± 0.20)%, and (1.85 ± 0.20)%, respectively] (all P values < 0.05). Immunofluorescence staining showed significant differences in the positive rates of F4/80 co-localization with CD86 and CD206 in mouse liver and spleen tissues among the four groups (F = 24.42, 25.28, 54.51 and 130.55; all P values < 0.001). Flow cytometry detected significant differences in the proportions of CD86⁺ and CD206⁺ macrophages in mouse liver and spleen tissues among the four groups (F = 67.98, 18.41, 29.77, 172.80; all P values < 0.001), and the proportions of CD206⁺ macrophages in the liver and spleen of the 21-day infection group were significantly higher than those in the control group [(9.25 ± 2.55)% vs (3.83 ± 0.72)%, and (4.22 ± 0.56)% vs (0.47 ± 0.18)%, respectively] (both P values < 0.05). In addition, RT-qPCR assay quantified significant differences in the relative mRNA expression of M1 macrophage markers (IL-1β, TNF-α and Nos2) and M2 macrophage markers (Arg1, Chil3 and Mrc1) in mouse liver and spleen tissues among the four groups (F = 41.30, 31.82, 199.33, 19.96, 62.01, 119.76, 23.67, 95.90, 72.27, 82.59, 123.41 and 29.75; all P values < 0.05). Conclusions A. cantonensis infection may cause progressive pathological damage in mouse liver and spleen tissues, accompanied by dynamic temporal changes in macrophage polarization. M1 macrophage polarization predominates at the early stage of A. cantonensis infection and shifts towards M2 polarization at the later stages, suggesting that M2 polarization may participate in immune regulation at late stages of A. cantonensis infection by suppressing excessive inflammatory responses and promoting tissue repair.

Cardiac troponin I (cTnI), a widely used biomarker for assessing cardiovascular risk, can provide a window for the evaluation of drug-induced myocardial injury. Label-free biosensors are promising candidates for detecting cell secretomes, since they do not require labor-intensive processes. In this work, a label-free electrochemical aptasensor is developed for in situ monitoring of cardiac cell secretomes in cell culture media based on target-induced strand displacement. The aptasensing system contains an aptamer-functionalized signal nanoprobe facing trimetallic metal-organic framework nanosheets and a gold nanoparticle-based detection working electrode modified with DNA nanotetrahedron-based complementary DNA for indirect target detection. The signal nanoprobes (termed CAHA) consisted of copper-based metal-organic frameworks, AuPt nanoparticles, horseradish peroxidase, and an aptamer. When the aptasensor is exposed to cardiac cell secretomes, cTnI competitively binds to the aptamer, resulting in the release of signal nanoprobes from the biorecognition interface and electrochemical signal changes. The aptasensor exhibited rapid response times, a low detection limit of 0.31 pg/mL, and a wide linear range of 0.001-100 ng/mL. We successfully used this aptasensor to measure cTnI concentrations among secreted cardiac markers during antitumor drug treatment. In general, aptasensors can be used to monitor a variety of cardiac biomarkers in the evaluation of cardiotoxicity.

Objective:To explore the protective mechanism of tea polyphenols (TP) on mouse oral cancer.Methods:A total of 50 mice were divided into control group, model group, TP group, Selisistat group, TP+ Selisistat group, with 10 mice in each group. The control group was gavaged with physiological saline, while the model group, TP group, Selisistat group, and TP+ Selisistat group were gavaged with 300 mg/L 4-NQO to establish a mouse oral cancer model. Physiological saline, 200 mg/kg TP, 0.01 mg/kg Selisistat, and 200 mg/kg TP+ 0.01 mg/kg Selisistat were gavaged respectively. The weight changes of each group of mice were compared; HE staining was used to observe the morphology of mouse oral tumor tissue; Enzyme linked immunosorbent assay was used to detect the levels of malondialdehyde (MDA) and superoxide dismutase (SOD) in serum; Immunoblotting and immunohistochemistry were used to detect the expression of silencing information regulatory factor (Sirt1) and nuclear factor E2 related factor 2 (Nrf2) proteins in mouse oral tissues.Results:Compared with the control group, the model group mice had a decrease in body weight [(23.19±1.36)g], a decrease in serum SOD level [(91.64±8.75)U/ml], an increase in MDA level [(5.18±0.46)nmol/ml], a decrease in Sirt1 (0.38±0.05) and Nrf2 (0.36±0.05) protein expression in oral tissue, and an increase in Nrf2 acetylation level (0.84±0.11) (all P<0.05). Compared with the model group, the TP group mice had an increase in body weight [(25.28±1.25)g], elevated serum SOD levels [(121.24±10.68)U/ml], decreased MDA levels [(3.89±0.42)nmol/ml], increased expression of Sirt1 (0.61±0.09) and Nrf2 (0.58±0.06) proteins in oral tissue, and decreased Nrf2 protein acetylation levels (0.39±0.05); The Selisistat group mice showed a decrease in body weight [(21.41±1.07)g], a decrease in serum SOD levels [(72.16±7.43)U/ml], an increase in MDA levels [(5.87±0.41)nmol/ml], a decrease in Sirt1 (0.23±0.04) and Nrf2 protein (0.24±0.03) expression in oral tissue, and an increase in Nrf2 acetylation levels (1.12±0.14) ( P<0.05). The body weight [(23.32±1.27)g], serum SOD levels [(92.58±8.13)U/ml], and oral Sirt1 (0.41±0.06) and Nrf2 (0.38±0.05) protein expression in the TP+ Selisistat group mice were higher than those in the Selisistat group, while MDA [(5.11±0.38)nmol/ml] and Nrf2 acetylation levels (0.82±0.09) were lower than those in the Selisistat group (all P<0.05). Conclusions:Tea polyphenols can alleviate oral tissue damage and alleviate oxidative stress in mice with oral cancer, and their mechanism may be related to the upregulation of the Sirt1/Nrf2 pathway.

Objective:To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.Methods:Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.Results:6 893 patients in CP ( n=6 453, 93.6%) or AP ( n=440, 6.4%) receiving initial imatinib ( n=4 906, 71.2%), nilotinib ( n=1 157, 16.8%), dasatinib ( n=298, 4.3%) or flumatinib ( n=532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n=1 055, 15.3%), intolerance ( n=248, 3.6%), pursuit of better efficacy ( n=168, 2.4%), economic or other reasons ( n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph + ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph + ACA, poorer TFS; Ph + ACA, poorer OS. Conclusion:At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

Intracranial pressure (ICP) monitoring is an important way to observe the condition of patients with severe neurological diseases; at present, ICP detection mainly relies on mean ICP, but with the progress of scientific and technological means and deepened research in related fields, ICP waveforms and their related derivative indicators have attracted more and more attention from clinicians. Based on the types and morphologies of ICP waveforms and their related derivative indexes, such as pressure response index and pressure amplitude index, relationships of ICP waveforms with brain tissue compliance and brain tissue lesions, and their clinical application are reviewed to provide some references for application of ICP waveforms in patients with severe neurological diseases.

Purpose: The risk stratification of pediatric anaplastic large cell lymphoma (ALCL) has not been standardized. In this study, new risk factors were included to establish a new risk stratification system for ALCL, and its feasibility in clinical practice was explored. Materials and Methods: On the basis of the non-Hodgkin’s lymphoma Berlin–Frankfurt–Munster 95 (NHL-BFM-95) protocol, patients with minimal disseminated disease (MDD), high-risk tumor site (multiple bone, skin, liver, and lung involvement), and small cell/lymphohistiocytic (SC/LH) pathological subtype were enrolled in risk stratification. Patients were treated with a modified NHL-BFM-95 protocol combined with an anaplastic lymphoma kinase inhibitor or vinblastine (VBL). Results: A total of 136 patients were enrolled in this study. The median age was 8.8 years. The 3-year event-free survival (EFS) and overall survival of the entire cohort were 77.7% (95% confidence interval [CI], 69.0% to 83.9%) and 92.3% (95% CI, 86.1% to 95.8%), respectively. The 3-year EFS rates of low-risk group (R1), intermediate-risk group (R2), and high-risk group (R3) patients were 100%, 89.5% (95% CI, 76.5% to 95.5%), and 67.9% (95% CI, 55.4% to 77.6%), respectively. The prognosis of patients with MDD (+), stage IV cancer, SC/LH lymphoma, and high-risk sites was poor, and the 3-year EFS rates were 45.3% (95% CI, 68.6% to 19.0%), 65.7% (95% CI, 47.6% to 78.9%), 55.7% (95% CI, 26.2% to 77.5%), and 70.7% (95% CI, 48.6% to 84.6%), respectively. At the end of follow-up, one of the five patients who received maintenance therapy with VBL relapsed, and seven patients receiving anaplastic lymphoma kinase inhibitor maintenance therapy did not experience relapse. Conclusion This study has confirmed the poor prognostic of MDD (+), high-risk site and SC/LH, but patients with SC/LH lymphoma and MDD (+) at diagnosis still need to receive better treatment (ClinicalTrials.gov number, NCT03971305).

Calcium release-activated calcium(CRAC)channels are non-selective calcium channels that are widely expressed in non-excitable cells.The opening of CRAC channels serves as a primary mechanism for calcium entry in various pancreatic and immune cells.Consequently,CRAC channels are crucial for maintaining Ca2+homeostasis and supporting numerous physiological functions of the exocrine pancreas.Numerous studies have identified CRAC channels as playing a pivotal role in many pathophysiological events that ultimately contribute to both acute and chronic pancreati-tis.In this review,we aim to highlight recent discoveries regarding the involvement of CRAC channels in the pathogenesis of acute and chronic pancreatitis,while also discussing current applications and future directions for CRAC channel-based drug development.

Calcium release-activated calcium(CRAC)channels are non-selective calcium channels that are widely expressed in non-excitable cells.The opening of CRAC channels serves as a primary mechanism for calcium entry in various pancreatic and immune cells.Consequently,CRAC channels are crucial for maintaining Ca2+homeostasis and supporting numerous physiological functions of the exocrine pancreas.Numerous studies have identified CRAC channels as playing a pivotal role in many pathophysiological events that ultimately contribute to both acute and chronic pancreati-tis.In this review,we aim to highlight recent discoveries regarding the involvement of CRAC channels in the pathogenesis of acute and chronic pancreatitis,while also discussing current applications and future directions for CRAC channel-based drug development.

Objective:To explore the value of using risk-stratifcation of mergency department suspected sepsis score(REDS) score in the prognosis of patients with sepsis.Methods:The clinical data of sepsis patients hospitalized in Huangshan Shoukang hospital from January 2018 to February 2020 were collected for retrospective case-control study.The REDS, acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score and mortality in emergency department(MEDS) of all cases were calculated.To evaluate the value of REDS in prognosis of patients with sepsis by comparing REDS with APACHEⅡ and MEDS.Results:Finally 103 patients were enrolled in the study, including 65 males (63.11%) and 38 females (36.89%); the age ranged from 42 to 93 years old, the median (quartile) was 74 (65, 82) years old; 72 patients (69.91%) survived (survival group), 31 patients (30.09%) died (death group). There were significant differences between survival group and death group in REDS((5.28±2.10) score vs.(7.87±2.53) score), MEDS score ((6.64±3.32) score vs.(9.06±3.3) score), APACHE Ⅱ score ((18.96±6.72) score vs.(21.87±6.15) score) (t value were5.404, 3.381 and 2.067, respectively; P value were<0.001, 0.001 and 0.041, respectively). Youden index was biggest(0.381), when REDS was 7.5.The area under the receiver operating characteristic curve was 0.777 (95% CI: 0.678-0.876, P<0.001). When APACHE Ⅱ score was 19.5, Youden index was the largest (0.177), and the area under the ROC of APACHEⅡwas 0.614(95% CI: 0.499-0.729, P=0.068). When the MEDS score was 10.5, Youden index was the largest (0.341), and the area under the receiver operating characteristic curve was 0.696 (95% CI: 0.590-0.802, P=0.002). The area under the curve of working characteristics of the subjects with red score was larger than that of APACHE Ⅱ score ( Z=1.987, P=0.046). Conclusion:REDS has a good effect in judging the condition and prognosis of patients with sepsis, which is equivalent to MEDS score, but better than APACHEⅡ.

Objective To investigate one year survival rate and life quality of patients with non-small cell lung cancer(NSCLC)treated by different arms.Methods One hundred and seventy-nine cases NSCLC patients from January 2013 to December 2014 were selected from the Third Hospital of Tanshan and followed-up,including 57 cases with surgical treatment,70 cases with the use of Navelbine plus cisplatin,52 cases with dendritic cells(DC)and cytokine induced killer cells(CIK)immune based therapy(DC/CIK)treatment.After one year period of radiotherapy and chemotherapy,the SF-36 questionnaire was used to investigate the quality of life of the surviving patients,and the quality of life was assessed from three aspects of the physiological,psychological and social functions.To quantify the quality of life score,the 100 percentage grading system was adopted,logistic regression analysis was used to adjust the influence of age and gender on survival rate,and the data were analyzed by SAS 9.2 statistical software package.Results One hundred and seventy-nine subjects were included in this study,by the end of follow-up on December 2015,there were 119 cases survived,the survival rate was 66.5％(119/179).Survival rate of surgical operation group,DC/CIK group and chemotherapy group orderly decreased(82.5％(47/57),76.9％(40/52)and 45.7％(32/70),P＜0.01).After adjusting age and gender impact,multiple logistic regression model showed that DC/CIK group survival rate was 3.96 times higher than the pure chemotherapy group(95％CI=1.78-8.80),surgical operation group was 5.58 times higher than simple chemotherapy group(95％CI=2.44-12.79).There were no significant differences between DC/CIK group and surgical operation group on physical disease,health status,emotional intelligence,mental health and social function,no significant difference(P＞0.05),but the chemotherapy group was lower(P＜0.05);physiological function in the chemotherapy group,operation group and DC/CIK group showed an increasing trend(P＜0.05).Conclusion The one year survival rate of NSCLC patients treated by different arms is 66.5％,and the life quality of patients with biological immune therapy method is better.