A real-world observation on thrombopoietic agents for patients with cancer treatment-induced thrombocytopenia in China: A multicenter, cross-sectional study.

BACKGROUND: Studies on various thrombopoietic agents for cancer treatment-induced thrombocytopenia (CTIT) in China are lacking. This study aimed to provide detailed clinical profiles to understand the outcomes and safety of different CTIT treatment regimens. METHODS: In this retrospective, cross-sectional study, 1664 questionnaires were collected from 33 hospitals between March 1 and July 1, 2021. Patients aged >18 years were enrolled who were diagnosed with CTIT and treated with recombinant interleukin 11 (rhIL-11), recombinant thrombopoietin (rhTPO), or a thrombopoietin receptor agonist (TPO-RA). The outcomes, compliance, and safety of different treatments were analyzed. RESULTS: Among the 1437 analyzable cases, most patients were treated with either rhTPO alone (49.3%) or rhIL-11 alone (27.0%). The most common combination regimen used was rhTPO and rhIL-11 (10.9%). Platelet transfusions were received by 117 cases (8.1%). In multivariate analysis, rhTPO was associated with a significantly lower proportion of platelet recovery, platelet transfusion, and hospitalization due to chemotherapy-induced thrombocytopenia (CIT) than rhIL-11 alone. No significant difference was observed in the time taken to achieve a platelet count of >100 × 109/L and chemotherapy dose reduction due to CIT among the different thrombopoietic agents. The outcomes of thrombocytopenia in 170 patients who received targeted therapy and/or immunotherapy are also summarized. The results show that the proportion of platelet recovery was similar among the different thrombopoietic agents. No new safety signals related to thrombopoietic agents were observed in this study. A higher proportion of physicians preferred to continue treatment with TPO-RA alone than with rhTPO and rhIL-11. CONCLUSIONS: This survey provides an overview of CTIT and the application of various thrombopoietic agents throughout China. Comparison of monotherapy with rhIL-11, rhTPO, and TPO-RA requires further randomized clinical trials. The appropriate application for thrombopoietic agents should depend on the pretreatment of platelets, treatment variables, and risk of bleeding. PLAIN LANGUAGE SUMMARY: To provide an overview of the outcome of cancer treatment-induced thrombocytopenia in China, our cross-sectional study analyzed 1437 cases treated with different thrombopoietic agents. Most of the patients were treated with recombinant interleukin 11 (rhIL-11) and recombinant thrombopoietin (rhTPO). rhTPO was associated with a significantly lower proportion of platelet recovery and platelet transfusion compared with rhIL-11.

Optimal Sequential Strategies for Antibody-Drug Conjugate in Metastatic Breast Cancer: Evaluating Efficacy and Cross-Resistance.

BACKGROUND: The optimal sequential strategy for antibody-drug conjugates (ADCs) in breast cancer remains uncertain. This study aimed to evaluate the efficacy and potential resistance of second ADC (ADC2) following the first ADC (ADC1) in human epidermal growth factor receptor 2 (HER2)-positive and HER2-low MBC. METHODS: This retrospective, multicenter, real-world study enrolled patients with MBC who received at least 2 different types of ADCs in 3 hospitals in China between July 1, 2017 and May 1, 2023. Outcomes included the objective response rate (ORR) for ADC1 and ADC2, progression free survival 2 (PFS2), defined as the time from initiation of ADC2 to progression, and overall survival (OS). RESULTS: Seventy-nine female patients were included, 64 of whom had HER2-positive disease. The ORR for ADC2 with similar payload of ADC1 was found to be 5.3%. When switching to a different payload, the ORR of ADC2 increased to 22.6%. The PFS2 for ADC2 remained similar regardless of whether the payload was similar or different. Switching to different payload showed a higher ORR in patients with rapid progression and a durable response longer than 6 months (41.2% vs 15.0%). Specifically, significantly longer PFS2 and OS were seen in patients treated with trastuzumab deruxtecan (T-Dxd) compared to those treated with disitamab vedotin (RC48) after progression from trastuzumab emtansine (T-DM1; median PFS2 5.37 months vs 3.30 months, HR = 0.40, 95% CI 0.17-0.93, P = .034; median OS 50.6 months vs 20.2 months, HR = 0.27, 95% CI 0.08-0.91, P = .034). For patients who progressed after T-Dxd, the median PFS2 was 6.05 months for those treated with RC48 versus 0.93 months for those treated with T-DM1 (HR = 0.03, 95% CI 0.002-0.353, P = .0093). Genomic analysis revealed that alternation of retinoblastoma1 was significantly associated with superior PFS. CONCLUSION: The alternation of payload achieves different responses in different settings. T-Dxd followed by RC48 may be a potentially beneficial strategy in HER2-positive disease. Further research is needed to elucidate the mechanism of cross-resistance.

The coinfection of ALVs causes severe pathogenicity in Three-Yellow chickens.

The coinfection of ALVs (ALV-J plus ALV-A or/and ALV-B) has played an important role in the incidence of tumors recently found in China in local breeds of yellow chickens. The study aims to obtain a better knowledge of the function and relevance of ALV coinfection in the clinical disease of avian leukosis, as well as its unique effect on the pathogenicity in Three-yellow chickens. One-day-old Three-yellow chicks (one day old) were infected with ALV-A, ALV-B, and ALV-J mono-infections, as well as ALV-A + J, ALV-B + J, and ALV-A + B + J coinfections, via intraperitoneal injection, and the chicks were then grown in isolators until they were 15 weeks old. The parameters, including the suppression of body weight gain, immune organ weight, viremia, histopathological changes and tumor incidence, were observed and compared with those of the uninfected control birds. The results demonstrated that coinfection with ALVs could induce more serious suppression of body weight gain (P < 0.05), damage to immune organs (P < 0.05) and higher tumor incidences than monoinfection, with triple infection producing the highest pathogenicity. The emergence of visible tumors and viremia occurred faster in the coinfected birds than in the monoinfected birds. These findings demonstrated that ALV coinfection resulted in considerably severe pathogenic and immunosuppressive consequences.

HER2-targeting antibody-drug conjugate RC48 alone or in combination with immunotherapy for locally advanced or metastatic urothelial carcinoma: a multicenter, real-world study.

BACKGROUND: Phase II trials showed the efficacy of anti-HER2 RC48-ADC (disitamab vedotin) for HER2-positive metastatic urothelial carcinoma (UC). This study evaluated RC48 alone verses in combination with immunotherapy for locally advanced or metastatic UC using real-world data. METHODS: This retrospective, multicenter, real-world study included patients with locally advanced or metastatic UC who received RC48 in five hospitals in China between July 2021 and April 2022. The outcomes were progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and adverse events. RESULTS: Thirty-six patients were included. The patients were 47-87 years, and 26 (72.2%) were male. Eighteen patients received RC48 alone, and 18 received RC48 combined with a programmed death-1 antibody. The median PFS was 5.4 months. The median OS was not reached. The 6-month and 1-year PFS rates were 38.8% and 15.5%, respectively. The 1-year OS rate was 79.6%. Fourteen (38.9%) patients achieved a partial response, and the ORR was 38.9%. Eleven patients had stable disease, and the DCR was 69.4%. The median PFS for patients who received RC48 combined with immunotherapy and those who received RC48 alone was 8.5 and 5.4 months, respectively. The main treatment-related adverse events included anemia, hypoesthesia, fatigue, and elevated transaminase. No treatment-related death occurred. CONCLUSION: RC48 alone or combined with immunotherapy might benefit patients with locally advanced or metastatic UC, regardless of impaired renal function.

"Moderate" adjuvant chemotherapy-induced leukopenia is beneficial for survival of patients with early breast cancer: a retrospective study.

BACKGROUND: The association between chemotherapy-induced leukopenia (CIL) and survival for patients with early breast cancer (EBC) is not known. We investigated the relationship between different grades of CIL and survival in patients with EBC receiving adjuvant chemotherapy. METHODS: A total of 442 patients with EBC receiving a regimen containing an anthracycline (A) and taxane (T) were included into our analysis. Survival analyses were undertaken using Kaplan-Meier curves. The P-value was calculated using the log rank test. Subgroup analysis was conducted to investigate the correlation of CIL grade and survival based on the clinicopathological characteristics of patients. Afterwards, univariate and multivariate analyses screened out independent prognostic factors to construct a prognostic model, the robustness of which was verified. RESULTS: Patients with EBC who experienced grade 2-4 ("moderate" and "severe") CIL were associated with longer overall survival (OS) than those with grade 0-1 (mild) CIL (P = 0.021). Compared with patients with mild CIL, OS was longer in patients with severe CIL (P = 0.029). Patients who suffered from moderate CIL tended to have longer OS than those with mild CIL (P = 0.082). Nevertheless, there was no distinguishable difference in OS between moderate- or severe-CIL groups. Subgroup analysis revealed that patients with moderate CIL had longer OS than those with mild CIL among patients who were premenstrual, or with human epidermal growth factor receptor 2-positive (HER2+), > 3 lymph nodes with metastases, a tumor diameter > 5 cm. A prognostic model based on menstrual status, N stage, and CIL grade showed satisfactory robustness. CONCLUSION: The grade of CIL was strongly associated with the prognosis among patients with EBC who received a regimen containing both anthracyclines and taxanes. Patients with a "moderate" CIL grade tended to have better survival outcomes.

Effect of chemotherapy alone or combined with immunotherapy for locally advanced or metastatic genitourinary small cell carcinoma: a real-world retrospective study.

BACKGROUND: Genitourinary small cell carcinoma is rare, and has a poor prognosis. However, effective treatment options for this disease are limited. We present a study to assess the efficacy of chemotherapy alone or combined with immunotherapy for locally advanced or metastatic genitourinary small cell carcinoma (GSCC). METHODS: We performed a retrospective analysis of patients with locally advanced or metastatic GSCC from Jan 2013 to September 2022 at Sun Yat-sen University Cancer Center. The survival and safety profiles were analyzed. RESULTS: Forty-two GSCC patients were enrolled, which included 20 with chemotherapy plus immunotherapy and 22 with chemotherapy alone. The median follow-up time was 15.13 months (95% CI, 8.84-21.42). The addition of immunotherapy to chemotherapy demonstrated no significant difference in median progression-free survival (p = 0.37). However, the median overall survival (OS) was 22.97 and 14.03 months with immunotherapy plus chemotherapy and chemotherapy alone, respectively (HR = 0.69, 95%CI 0.08-0.55, p = 0.017). Two patients with immunotherapy plus chemotherapy achieved clinical complete remission. The overall response rate for patients receiving chemotherapy combined with immunotherapy was 65%, which was higher in comparison to those treated with chemotherapy alone (50%). Univariate and multivariate analyses demonstrated that chemotherapy combined with immunotherapy independently achieved favorable OS. Four patients experienced immunotherapy-related adverse events, with one developing grade 3 hypothyroidism. CONCLUSIONS: Among patients with locally advanced or metastatic GSCC, immunotherapy combined with chemotherapy might be thought of as a potentially effective treatment option for patients with GSCC.

Gemcitabine/nab-paclitaxel vs gemcitabine/carboplatin for advanced urothelial carcinoma.

OBJECTIVE: To compare in a phase III trial the efficacy and safety of nanoparticle albumin-bound (nab)-paclitaxel plus gemcitabine (GA) with that of carboplatin plus gemcitabine (GCb) as a first-line treatment for patients with cisplatin-ineligible metastatic urothelial cancer (mUC). PATIENTS AND METHODS: Treatment-naive, cisplatin-ineligible patients with mUC were assigned randomly to either the GA (both nab-paclitaxel 125 mg/m2 and gemcitabine 1000 mg/m2 on Days 1 and 8, every 21 days) or GCb group (carboplatin area under the free carboplatin plasma concentration versus time curve of 4.5 on Day 1, gemcitabine 1000 mg/m2 on Days 1 and 8, every 21 days). The primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), safety, and patient-reported outcomes (PROs). RESULTS: The trial was terminated early because of slow accrual after 54 patients were enrolled: 26 in in the GA group and 28 in the GCb groups. The median PFS was 6.7 vs 5.9 months for the GA and GCb groups, respectively (P = 0.248). The median OS time was 12.1 vs 10.7 months for the GA and GCb groups, respectively (P = 0.837). The ORR and DCR were 40% vs 46.4% (P = 0.637) and 72% vs 68% (P = 0.188) in the GA and GCb groups, respectively. Patients treated with GA showed significantly lower incidence of Grade 3-4 thrombocytopenia and does reduction and delay. Although peripheral sensory neuropathy was higher in the GA arm, no Grade 3 neuropathy occurred. There was no difference in the PROs between the two groups. CONCLUSION: While not powered for comparison, first-line GA showed similar efficacy and better tolerability and might be considered a rational alternative to GCb.

Risk assessment of rectal anastomotic leakage (RAREAL) after DIXON in non-emergency patients with rectal cancer.

BACKGROUND: The routine establishment of a diverting stoma (DS) remains controversial in every patient undergoing Dixon operation. We aimed to establish a model for the risk assessment of rectal anastomotic leak (RAREAL) after Dixon in non-emergency patients with rectal cancer, using routinely available variables, by which surgeons could individualize their approach to DS. METHODS: 323 patients who underwent Dixon operation for rectal cancer from January 2015 to December 2018 were taken as the model group for retrospective study. Univariable and multivariable logistic regression analysis was used to determine the independent risk factors associated with anastomotic leakage. We constructed the RAREAL model. 150 patients who underwent Dixon operation due to rectal cancer from January 2019 to December 2020 were collected according to the uniform criteria as a validation group to validate the RAREAL model. RESULTS: In the model group, multivariable analysis identified the following variables as independent risk factors for AL: HbA1c (odds ratio (OR) = 4.107; P = 0.044), Left colic artery (LCA) non preservation (OR = 4.360; P = 0.026), Tumor distance from the anal margin (TD) (OR = 6.373; P = 0.002). In the model group, the area under the curve (AUC) of the receiver operating characteristic (ROC) for evaluating AL with RAREAL was 0.733, and when RAREAL score = 2.5, its sensitivity, specificity and Youden index were 0.385, 0.973, 0.358, respectively. The AUC was 0.722 in the validation group and its sensitivity and specificity were 0.333 and 0.985, respectively, when RAREAL score = 2.5. CONCLUSION: The RAREAL score can be used to assess the risk of AL after Dixon operation for rectal cancer, and prophylactic DS should be proactively done when the score is greater than 2.5.

Callicarpanes A-L, Twelve New Clerodane Diterpenoids with NLRP3 Inflammasome Inhibitory Activity from Callicarpa integerrima.

Twelve new clerodane diterpenoids named callicarpanes A-L (1-12), together with eight known compounds (13-20), were isolated from Callicarpa integerrima. Their structures were determined by comprehensive spectroscopic data. The calculated chemical shifts were used to identify relative configurations using DP4+ analysis. The absolute configurations (AC) were assigned based on quantum chemical calculations and X-ray single-crystal diffraction methods. Compounds 1, 3, 5, 9, 10, 12, 15, 16, and 19 showed significant inhibitory activity for NLRP3 inflammasome activation, with the IC50 against lactate dehydrogenase (LDH) release ranging from 0.08 to 4.78 µM. Further study revealed that compound 10 repressed IL-1ß secretion and caspase-1 maturation in J774A.1 cell as well as blocked macrophage pyroptosis.

Optimal first-line treatment for platinum-eligible metastatic urothelial carcinoma: Comparison of chemo-immunotherapy, immunotherapy, and chemotherapy- A systematic review and meta-analysis.

BACKGROUND: The role of first-line of immunotherapy in metastatic urothelial carcinoma (mUC) remains unclear. This meta-analysis aimed to explore an optimal first-line treatment strategy for mUC patients. METHODS: We carried out a meta-analysis between chemo-immunotherapy, immunotherapy, and chemotherapy in mUC based on randomized trials. The outcomes included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and treatment-related adverse events (AEs). A fixed-effect or random-effects model was adopted depending on between-study heterogeneity. RESULTS: Three trials involving 3238 patients were included. PD-1/PD-L1 inhibitor plus platinum-based chemotherapy was associated with the improvements of OS (HR, 0.85; 95% CI 0.75-0.99), PFS (HR, 0.80; 95% CI 0.71-0.90) and ORR (OR, 1.32; 95% CI 1.07-1.63) when compared with platinum-based chemotherapy, but not with better DCR (OR, 1.07; 95% CI 0.78-1.46). PD-1/PD-L1 inhibitor alone was associated with worse ORR (OR, 0.38; 95% CI 0.17-0.87) and DCR (OR, 0.20; 95% CI 0.16-0.25) when compared with platinum-based chemotherapy while it did not statistically reduce the risk of mortality (HR 0.97 for entire cohort; 0.90 for PD-L1 high cohort). In safety analyses, the incidence of adverse events (AEs) between regimens showed no difference, but the frequency of AEs of grade 3 or severity was higher in chemo-immunotherapy compared to chemotherapy. CONCLUSIONS: Compared with platinum-based chemotherapy, chemo-immunotherapy is associated with significantly improved PFS, OS, and ORR in the first-line therapy for mUC at the expanse of increased toxicity.

Effect of Capecitabine Maintenance Therapy Using Lower Dosage and Higher Frequency vs Observation on Disease-Free Survival Among Patients With Early-Stage Triple-Negative Breast Cancer Who Had Received Standard Treatment: The SYSUCC-001 Randomized Clinical Trial.

Importance: Among all subtypes of breast cancer, triple-negative breast cancer has a relatively high relapse rate and poor outcome after standard treatment. Effective strategies to reduce the risk of relapse and death are needed. Objective: To evaluate the efficacy and adverse effects of low-dose capecitabine maintenance after standard adjuvant chemotherapy in early-stage triple-negative breast cancer. Design, Setting, and Participants: Randomized clinical trial conducted at 13 academic centers and clinical sites in China from April 2010 to December 2016 and final date of follow-up was April 30, 2020. Patients (n = 443) had early-stage triple-negative breast cancer and had completed standard adjuvant chemotherapy. Interventions: Eligible patients were randomized 1:1 to receive capecitabine (n = 222) at a dose of 650 mg/m2 twice a day by mouth for 1 year without interruption or to observation (n = 221) after completion of standard adjuvant chemotherapy. Main Outcomes and Measures: The primary end point was disease-free survival. Secondary end points included distant disease-free survival, overall survival, locoregional recurrence-free survival, and adverse events. Results: Among 443 women who were randomized, 434 were included in the full analysis set (mean [SD] age, 46 [9.9] years; T1/T2 stage, 93.1%; node-negative, 61.8%) (98.0% completed the trial). After a median follow-up of 61 months (interquartile range, 44-82), 94 events were observed, including 38 events (37 recurrences and 32 deaths) in the capecitabine group and 56 events (56 recurrences and 40 deaths) in the observation group. The estimated 5-year disease-free survival was 82.8% in the capecitabine group and 73.0% in the observation group (hazard ratio [HR] for risk of recurrence or death, 0.64 [95% CI, 0.42-0.95]; P = .03). In the capecitabine group vs the observation group, the estimated 5-year distant disease-free survival was 85.8% vs 75.8% (HR for risk of distant metastasis or death, 0.60 [95% CI, 0.38-0.92]; P = .02), the estimated 5-year overall survival was 85.5% vs 81.3% (HR for risk of death, 0.75 [95% CI, 0.47-1.19]; P = .22), and the estimated 5-year locoregional recurrence-free survival was 85.0% vs 80.8% (HR for risk of locoregional recurrence or death, 0.72 [95% CI, 0.46-1.13]; P = .15). The most common capecitabine-related adverse event was hand-foot syndrome (45.2%), with 7.7% of patients experiencing a grade 3 event. Conclusions and Relevance: Among women with early-stage triple-negative breast cancer who received standard adjuvant treatment, low-dose capecitabine maintenance therapy for 1 year, compared with observation, resulted in significantly improved 5-year disease-free survival. Trial Registration: ClinicalTrials.gov Identifier: NCT01112826.

Adjuvant chemotherapy for small, lymph node-negative, triple-negative breast cancer: A single-center study and a meta-analysis of the published literature.

BACKGROUND: Current guidelines recommend adjuvant chemotherapy for patients with small, lymph node-negative, triple-negative breast cancer (TNBC) measuring >5 mm (T1b disease), but clinical evidence to support this recommendation is lacking. Thus, the current study aimed to evaluate the survival benefit of adjuvant chemotherapy in patients with T1N0M0 (measuring ≤2 cm) TNBC with different tumor sizes. METHODS: The authors retrospectively evaluated consecutive patients with pT1N0M0 TNBC who were diagnosed between 2000 and 2016 at Sun Yat-Sen University Cancer Center. For the meta-analysis, electronic medical databases were searched for all relevant studies regarding the effect of adjuvant chemotherapy on the target population. RESULTS: Of the 351 enrolled patients, 309 (88%) received adjuvant chemotherapy and 42 patients (12%) did not. The distribution by T classification was T1a in 19 patients (5.4%), T1b in 67 patients (19.1%), and T1c in 265 patients (75.5%). Adjuvant chemotherapy significantly improved recurrence-free survival (RFS) in the patients with T1c disease, but not those with T1b and T1a disease. Meanwhile, there was no difference in RFS noted according to the chemotherapy regimen among patients with T1c disease. Seven eligible studies comprising 1525 patients with T1N0M0 (941 with T1a/bN0M0) were included in the meta-analysis. The meta-analysis demonstrated that adjuvant chemotherapy significantly reduced the rate of disease recurrence for patients with T1a/b disease as a group, but the population driving that was only patients with T1b disease, not those with T1a disease. CONCLUSIONS: Although the retrospective analysis demonstrated a survival benefit of adjuvant chemotherapy only for patients with T1cN0 TNBC, the meta-analysis showed it also is beneficial for individuals with T1bN0 TNBC. For patients with T1cN0M0 TNBC, less intensive chemotherapy regimens achieve an excellent survival outcome similar to that of intensive anthracycline and taxane combination chemotherapy.

Evaluation of the safety and protection efficacy of an attenuated genotype vii newcastle disease virus strain as a candidate vaccine.

Newcastle disease (ND) is a serious avian infectious disease, causing severe economic loss worldwide. Its prevention depends on comprehensive vaccination scheme against Newcastle disease virus (NDV). However, current vaccine strains are of different genotypes with prevalent circulating strains (genotype VII), with significant genetic distance. Our team previously generated a genotype matched attenuated NDV strain (rmNA-1). In this study, its safety and immunization efficacy were evaluated. Its lentogenic characteristic was stable for 25 generations in embryonated chicken eggs and for six generations in SPF chickens. Overdosed administration did not cause any clinical signs or pathogenic changes in chickens. As to its immunization effect, rmNA-1 stimulated a comparable serum NDV specific antibody level to a LaSota (genotype II) strain based commercial vaccine, and provided full protection against virulent genotype VII strain challenge, with significantly reduced virus shedding period.

Two novel recombinant avian leukosis virus isolates from Luxi gamecock chickens.

Avian leukosis virus (ALV) is associated with immune suppression, neoplasia, and reduced performance in chickens. In this study, two strains of ALV were isolated from Luxi gamecocks by DF-1 cell culture and identified by PCR, immunofluorescence assay, and sequencing of the viral genome. These strains were found to be novel recombinant viruses with nucleotide sequence identity of over 93.0% in the LTR and 94.4% in U3 to ALV-J, over 95.0% in the 5'UTR to ALV-C, over 93.4% in gp85 to ALV-B, and over 96.0% in gp37 to ALV-E. These results indicate that these two isolates are recombinants between ALV-J, ALV-C, ALV-E and ALV-B.

Pretreatment anti-Mullerian hormone-based nomogram predicts menstruation status after chemotherapy for premenopausal women with hormone receptor-positive early breast cancer.

PURPOSE: Ovarian function is important for optimizing endocrine treatment in patients with hormone receptor-positive (HR+) early breast cancer (eBC). The aim of the study was to determine whether patients' pretreatment levels of anti-Mullerian hormone (AMH) were associated with menses status after chemotherapy and to build a predictive nomogram model for amenorrhea in women with HR+ eBC. METHODS: Between August 2013 and December 2014, 120 premenopausal patients with HR+ eBC were included retrospectively. The associations among age, prechemotherapy levels of AMH, follicle-stimulating hormone (FSH),and estradiol (E2) and the 2-year postchemotherapy menses status were analyzed. We determined the cutoff values of hormone levels by using the biostatistical tool (Cutoff Finder). A novel nomogram was established to predict the 2-year amenorrhea status based on the logistic analysis. Concordance index (C-index) was used to validate the capacity. RESULTS: One hundred nine women (90.8%) experienced amenorrhea after chemotherapy. AMH < 0.965 ng/ml predicted amenorrhea at 2 years (AUC 0.84, sensitivity 74% and specificity 81.8%), independent of age. The predictive nomogram based on age and pretreatment AMH and FSH levels was developed to predict the probability of 2-year postchemotherapy amenorrhea with a C-index of 0.88 (95% CI 0.84-0.91). CONCLUSIONS: In premenopausal patients with HR+ eBC, prechemotherapy AMH concentration was associated with the patient's 2-year amenorrhea status, independent of age. The nomogram model based on age and pretreatment AMH and FSH levels accurately predicted the 2-year amenorrhea status.

Detection of viral components in exosomes derived from NDV-infected DF-1 cells and their promoting ability in virus replication.

Exosomes are micro messengers encapsulating RNA, DNA, and proteins for intercellular communication associated with various physiological and pathological reactions. Several viral infection processes have been reported to pertain to exosomal pathways. However, because of the difficulty in obtaining avian-sourced exosomes, avian virus-related exosomes are scarcely investigated. In this study, we developed a protein A/G-correlated method and successfully obtained the Newcastle disease virus-related exosome (NDV Ex). These exosomes promoted NDV propagation, proven by both GW4869-mediated deprivation and exosomal supplementation. Viral structural proteins NP and F were detected in the NDV Ex and further investigation indicated that the NP protein can be transferred to DF-1 cells through exosomes. The intracellular NP protein exhibited viral replication-promoting and cytokine-suppressing abilities. Therefore, NDV infection produces exosomes, which transfer viral NP protein and promote NDV infection, emphasizing the importance of exosomes in an NDV infection.

Olanzapine-Based Triple Regimens Versus Neurokinin-1 Receptor Antagonist-Based Triple Regimens in Preventing Chemotherapy-Induced Nausea and Vomiting Associated with Highly Emetogenic Chemotherapy: A Network Meta-Analysis.

BACKGROUND: The current antiemetic prophylaxis for patients treated with highly emetogenic chemotherapy (HEC) included the olanzapine-based triplet and neurokinin-1 receptor antagonists (NK-1RAs)-based triplet. However, which one shows better antiemetic effect remained unclear. MATERIALS AND METHODS: We systematically reviewed 43 trials, involving 16,609 patients with HEC, which compared the following antiemetics at therapeutic dose range for the treatment of chemotherapy-induced nausea and vomiting: olanzapine, aprepitant, casopitant, fosaprepitant, netupitant, and rolapitant. The main outcomes were the proportion of patients who achieved no nausea, complete response (CR), and drug-related adverse events. A Bayesian network meta-analysis was performed. RESULTS: Olanzapine-based triple regimens showed significantly better no-nausea rate in overall phase and delayed phase than aprepitant-based triplet (odds ratios 3.18, 3.00, respectively), casopitant-based triplet (3.78, 4.12, respectively), fosaprepitant-based triplet (3.08, 4.10, respectively), rolapitant-based triplet (3.45, 3.20, respectively), and conventional duplex regimens (4.66, 4.38, respectively). CRs of olanzapine-based triplet were roughly equal to different NK-1RAs-based triplet but better than the conventional duplet. Moreover, no significant drug-related adverse events were observed in olanzapine-based triple regimens when compared with NK-1RAs-based triple regimens and duplex regimens. Additionally, the costs of olanzapine-based regimens were obviously much lower than the NK-1RA-based regimens. CONCLUSION: Olanzapine-based triplet stood out in terms of nausea control and drug price but represented no significant difference of CRs in comparison with NK-1RAs-based triplet. Olanzapine-based triple regimens should be an optional antiemetic choice for patients with HEC, especially those suffering from delayed phase nausea. IMPLICATIONS FOR PRACTICE: According to the results of this study, olanzapine-based triple antiemetic regimens were superior in both overall and delayed-phase nausea control when compared with various neurokinin-1 receptor antagonists-based triple regimens in patients with highly emetogenic chemotherapy (HEC). Olanzapine-based triplet was outstanding in terms of nausea control and drug price. For cancer patients with HEC, especially those suffering from delayed-phase nausea, olanzapine-based triple regimens should be an optional antiemetic choice.

Newcastle disease virus-like particles induce dendritic cell maturation and enhance viral-specific immune response.

Circulating of genotype VII Newcastle disease virus (NDV) is a great threat to the poultry industry worldwide. Virus-like particles (VLPs) are increasingly being considered as potential viral vaccines due to their safety and efficacy. In this study, we analyzed in vitro the stimulatory effects of VLPs containing the matrix and hemagglutinin-neuraminidase of genotype VII NDV on dendritic cells (DCs) and evaluated their immunogenicity in mice. The results showed that immature bone marrow-derived dendritic cells (BMDCs) responded to stimulation with VLPs by up-regulating expressions of MHC II, CD40, CD80, and CD86 molecules and by increasing the cytokine secretions of TNF-α, IFN-γ, IL-6, and IL-12p70. Besides, VLPs enhanced the immunostimulatory capacity of DCs to stimulate autologous T cell proliferation. Furthermore, VLPs can induce efficient humoral and cellular immune responses, and recruit mature DCs to the spleen in C57BL/6 mice, as shown by an obvious increase in double-positive proliferation of splenic CD11c+CD86+ cells. These data indicate that NDV VLPs can be a valuable candidate for NDV vaccine development.

Genetic diversity of the genotype VII Newcastle disease virus: identification of a novel VIIj sub-genotype.

Newcastle disease (ND) is a highly contagious disease of poultry caused by Newcastle disease virus (NDV). Multiple genotypes of NDV have been circulating worldwide and NDV is continuously evolving, resulting into more diversity. Of multiple viral genotypes, VII is particularly important given that it had been associated with most recent ND outbreaks worldwide. In this study, an epidemiological investigation performed in northeastern China during 2014-2015 showed that 11 genotype VII isolates amounted to 55 percent in a total number of NDV isolates. Therefore, to evaluate the genetic diversity worldwide and epidemiological distribution in China of genotype VII NDV, a phylogenetic analysis based on the 1255 complete F gene sequences showed that VII is the most predominant genotype worldwide. A further detailed characterization on genotype VII was conducted based on the 477 complete F gene sequences from 11 isolates and 466 reference viruses available in GenBank. The results demonstrated that VII can be further divided into 8 sub-genotypes (VIIb, VIId-VIIj), indicating its complex genetic diversity. It is worthy of note that the isolation rate of VIIj is increasing recently. It emphasizes the necessity to pay close attention to the epidemiological dynamic of genotype VII NDV and highlights the importance of vaccination program.

A ratiometric fluorescent probe for sensing hydrogen peroxide based on a hemicyanine-naphthol fluorophore.

The synthesis, properties and applications of a water-soluble boronate-functioned hemicyanine-naphthol hybrid as a novel ratiometric fluorescent sensor for hydrogen peroxide are presented. The dye displayed remarkable a colour change from pale orange (λ(em) = 590 nm) to pink (λ(em) = 690 nm) in the presence of H2O2, which could be rationalized by the chemoselective H2O2-mediated transformation of arylboronate to phenolate with high selectivity and a fast response (within 2 min). A good linear relationship (R(2) = 0.9951) was obtained with the H2O2 concentration ranging from 0 to 25 µM, with a limit of detection of 0.09 µM according to the signal-to-noise ratio (S/N = 3). The advantages of this fluorophore include easy modification, excellent aqueous solubility and superior photostability, and it has been applied to the detection of trace amounts of hydrogen peroxide in water samples.