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BACKGROUND: Infectious diarrhea (ID) is a highly prevalent disease worldwide that poses a substantial risk to human well-being. In China, numerous clinical studies have investigated the efficacy of Gegen Qinlian Decoction (GGQLD) in treating ID. However, there is a need for additional rigorous and evidence-based medical research to enhance physicians' confidence in their prescribing practices. METHODS: Seven Chinese and English databases were systematically searched. The Cochrane Risk of Bias tool was used to assess the quality of the included studies. Meta-analysis was conducted using RevMan 5.3, and Stata 16.0 was used for the sensitivity analysis. Trial sequential analysis was performed using TSA v0.9, and GRADEprofiler was utilized to evaluate the quality of evidence. RESULTS: A total of 12 randomized controlled trials (RCTs) involving 1240 patients were included. The meta-analysis demonstrated that the combination of GGQLD with conventional Western medicine had better effects on clinical efficacy (RR=1.15, 95% CI [1.10, 1.20]), duration of diarrhea symptoms (WMD=-10.96, 95% CI [-11.97, -9.96]), duration of abdominal pain symptoms (WMD=-12.01, 95% CI [-14.12, -9.90]), duration of fever symptoms (WMD=-11.91, 95% CI [-13.39, -10.43]), interleukin-6 (IL-6) levels (WMD=-113.59, 95% CI [-113.03, -108.14]), and tumor necrosis factor-α (TNF-α) levels (WMD=-62.18, 95% CI[-65.25, -59.11]) and that no significant adverse reactions occurred (RR = 0.45, 95% CI [0.10, 1.97]). The sample size of the included studies reached the expected size. The quality of evidence for outcome indicators was rated as low or very low. CONCLUSIONS: The combination of GGQLD with conventional Western medicine demonstrates promising efficacy and safety in treating ID. Nonetheless, more high-quality RCTs are required to confirm this conclusion.
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Spalling, a common failure mechanism of gear systems, greatly affects the dynamics of gears operation, which is reflected in the time-varying mesh stiffness (TVMS). Current TVMS models often overestimate the asymmetric spalling phenomenon and may lead to inaccuracy in identifying and predicting the spalling failure. To address this problem, in this paper, a new stiffness, namely torsional stiffness, is introduced to quantify the effect of asymmetric spalling defects, and an equivalent stiffness calculation method for different asymmetric shapes is proposed. Based on this, a shape-independent TVMS model is constructed, which can realize the fast calculation of TVMS for spalling defects with different shapes at arbitrary asymmetric locations. Furthermore, a FEM-based validation method is developed by considering diverse loading states and improving the current result extraction method. Case studies are presented to illustrate the proposed model and to analyze the effects of different types of asymmetric spalling defects on gear dynamics. The FEM validation has shown that the proposed model has a good effectiveness.
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BACKGROUND: This study was designed to evaluate the effect of progesterone receptor (PR) status on the prognosis of advanced estrogen receptor (ER)-high human epidermal growth factor receptor 2 (HER2)-negative breast cancer patients receiving CDK4/6 inhibitor combined with endocrine as first-line therapy. METHODS: Advanced ER-high HER2-negative breast cancer patients who were admitted to Harbin Medical University Cancer Hospital and received cyclin-dependent kinase (CDK)4/6 inhibitor combined with endocrine as first-line therapy were included for analysis. Patients were divided into PR-high group (11-100%), PR-low group (1-10%), and PR-negative group (< 1%) according to the expression of PR. Chi-square test was used to analyze the correlation of variables between groups. COX regression analysis were used to analyze the risk factors of survival. Kaplan-Meier survival curve was used to analyze the differences of progression-free survival (PFS) and overall survival (OS) between groups. RESULTS: Among the 152 patients, 72 were PR-high, 32 were PR-low, and 48 were PR-negative. Compared with PR-negative group, the proportions of disease-free survival (DFS) ≥ 5 years and Ki-67 index ≤ 30% in PR-low group and PR-high group were significant higher. PR-negative patients were more likely to occur first-line progression of disease within 24 months (POD24) than PR-high(P = 0.026). Univariate and multivariate analysis showed that PR-negative and first-line POD24 occurrence were risk factors for survival. Survival curve analysis showed that compared with PR-high group, the PFS and OS were significantly lower in PR-negative group (P = 0.001, P = 0.036, respectively). Patients with first-line POD24 had shorter OS in the overall population as well as in subgroups stratified by PR status. CONCLUSIONS: PR-negative and first-line POD24 occurrence were risk factors of advanced ER-high HER2-negative breast cancer patients receiving CDK4/6 inhibitor combined with endocrine as first-line therapy. PR-negative patients had shortest PFS and OS. Regardless of PR status, first-line POD24 occurrence predicted shorter OS.
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Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias da Mama , Quinase 4 Dependente de Ciclina , Quinase 6 Dependente de Ciclina , Receptor ErbB-2 , Receptores de Estrogênio , Receptores de Progesterona , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/mortalidade , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Receptor ErbB-2/metabolismo , Receptores de Progesterona/metabolismo , Pessoa de Meia-Idade , Receptores de Estrogênio/metabolismo , Quinase 4 Dependente de Ciclina/antagonistas & inibidores , Prognóstico , Quinase 6 Dependente de Ciclina/antagonistas & inibidores , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Idoso , Inibidores de Proteínas Quinases/uso terapêutico , Estimativa de Kaplan-Meier , Estudos Retrospectivos , Antineoplásicos Hormonais/uso terapêuticoRESUMO
This study aims to analyze the current situation of outcome indicators in randomized controlled trial(RCT) of traditional Chinese medicine(TCM) treatment for Alzheimer's disease(AD), so as to provide a reference for establishing a core indicator set in this field. The researchers systematically searched CNKI, Wanfang, VIP, Sino Med, EMbase, PubMed, Medline, and Cochrane Library. Independent screening of literature and extraction of information was conducted according to the inclusion and exclusion criteria. In addition, the Ro B 2. 0 tool was used for bias risk assessment. A total of 78 RCTs were included, involving 6 379 patients,with 122 kinds of outcome indicators. According to functional attributes, the outcome indicators could be categorized into seven groups:TCM diseases(3 kinds, 13 times), symptoms and signs(26 kinds, 196 times), physical and chemical tests(68 kinds, 149 times),qua-lity of life(1 kind, 2 times), long-term prognosis(2 kinds, 2 times), economic evaluation(0 kind), safety events(21 kinds,194 times), and other indicators(1 kind, 1 time). The results show that the literature evaluation of RCTs of TCM treatment for AD is generally risky, and there are some problems in the selection of outcome indicators, such as lack of TCM characteristics, insignificant distinction between primary and secondary outcome indicators, lack of long-term prognosis and economic evaluation indicators, and non-standard safety event reports. It is suggested that future researchers should establish a core indicator set for AD that highlights the characteristics of TCM and then work to improve the quality of clinical trials.
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Doença de Alzheimer , Medicamentos de Ervas Chinesas , Medicina Tradicional Chinesa , Ensaios Clínicos Controlados Aleatórios como Assunto , Doença de Alzheimer/tratamento farmacológico , Humanos , Medicamentos de Ervas Chinesas/uso terapêutico , Resultado do Tratamento , IdosoRESUMO
Despite breakthroughs of immunotherapy synergistically combined with blockade of vascular endothelial growth factor receptor, several patients with advanced non-small cell lung cancer (NSCLC) experience non-response or followed relapse. Organized lymphoid aggregates, termed tertiary lymphoid structures (TLSs), are found to be associated with improved response to immunotherapy. Here, we explore the landscapes of TLSs in tumour tissues from a real-world retrospective study. Our investigation showed that with a median follow-up of 11.2 months, the ORR was 28.6% (18/63, 95% CI 17.9-41.3) and the median PFS was 6.1 (95% CI 5.5-6.6) months in NSCLC patients treated with PD-1 blockade combined with anlotinib. By multiplex immunofluorescence (mIF) analysis, spatially, more TLSs and high CD20+ B-cell ratio in TLSs were associated with higher ORR. High density of intratumoral CD8+ T cells showed better ORR and PFS. The numbers of CD8+ T cells with a distance within 20 µm and 20-50 µm between tumour cells were higher in responders than non-responders. But responders had significantly higher TLSs within 20 µm rather than within 20-50 µm of tumour cells than non-responders. The inflamed immunophenotyping occupied higher proportions in responders and was associated with better PFS. Besides, tumour cells in non-responders were found more temporal cell-in-cell structures than responders, which could protect inner cells from T-cell attacks. Taken together, landscape of TLSs and proximity architecture may imply superior responses to PD-1 blockade combined with anlotinib for patients with advanced non-small cell lung cancer.
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BACKGROUND: Disitamab vedotin (DV; RC48-ADC) is an antibody-drug conjugate comprising a human epidermal growth factor receptor 2 (HER2)-directed antibody, linker and monomethyl auristatin E. Preclinical studies have shown that DV demonstrated potent antitumor activity in preclinical models of breast, gastric, and ovarian cancers with different levels of HER2 expression. In this pooled analysis, we report the safety and efficacy of DV in patients with HER2-overexpression and HER2-low advanced breast cancer (ABC). METHODS: In the phase I dose-escalation study (C001 CANCER), HER2-overexpression ABC patients received DV at doses of 0.5-2.5 mg/kg once every two weeks (Q2W) until unacceptable toxicity or progressive disease. The dose range, safety, and pharmacokinetics (PK) were determined. The phase Ib dose-range and expansion study (C003 CANCER) enrolled two cohorts: HER2-overexpression ABC patients receiving DV at doses of 1.5-2.5 mg/kg Q2W, with the recommended phase 2 dose (RP2D) determined, and HER2-low ABC patients receiving DV at doses of 2.0 mg/kg Q2W to explore the efficacy and safety of DV in HER2-low ABC. RESULTS: Twenty-four patients with HER2-overexpression ABC in C001 CANCER, 46 patients with HER2-overexpression ABC and 66 patients with HER2-low ABC in C003 CANCER were enrolled. At 2.0 mg/kg RP2D Q2W, the confirmed objective response rates were 42.9% (9/21; 95% confidence interval [CI]: 21.8%-66.0%) and 33.3% (22/66; 95% CI: 22.2%-46.0%), with median progression-free survival (PFS) of 5.7 months (95% CI: 5.3-8.4 months) and 5.1 months (95% CI: 4.1-6.6 months) for HER2-overexpression and HER2-low ABC, respectively. Common (≥5%) grade 3 or higher treatment-emergent adverse events included neutrophil count decreased (17.6%), gamma-glutamyl transferase increased (13.2%), asthenia (11.0%), white blood cell count decreased (9.6%), peripheral neuropathy such as hypoesthesia (5.9%) and neurotoxicity (0.7%), and pain (5.9%). CONCLUSION: DV demonstrated promising efficacy in HER2-overexpression and HER2-low ABC, with a favorable safety profile at 2.0 mg/kg Q2W.
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Neoplasias da Mama , Imunoconjugados , Receptor ErbB-2 , Humanos , Feminino , Receptor ErbB-2/metabolismo , Pessoa de Meia-Idade , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Imunoconjugados/administração & dosagem , Imunoconjugados/uso terapêutico , Imunoconjugados/farmacocinética , Imunoconjugados/efeitos adversos , Idoso , Adulto , Idoso de 80 Anos ou maisRESUMO
Immunotherapy combined with chemotherapy regimen has been shown to be effective in recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). However, due to the small number of patients, its efficacy remains controversial in Asian populations, particularly in mainland China. Here a randomized, double-blind phase 3 trial evaluated the efficacy and safety of finotonlimab (SCT-I10A), a programmed cell death 1 (PD-1) monoclonal antibody, combined with cisplatin plus 5-fluorouracil (C5F) for the first-line treatment of R/M HNSCC. Eligible patients (n = 370) were randomly 2:1 assigned to receive finotonlimab plus C5F (n = 247) or placebo plus C5F (n = 123). The primary endpoint was overall survival (OS). In the finotonlimab plus C5F group, OS was 14.1 months (95% confidence interval (CI) 11.1-16.4), compared with 10.5 months (95% CI 8.1-11.8) in the placebo plus C5F group. The hazard ratio was 0.73 (95% CI 0.57-0.95, P = 0.0165), meeting the predefined superiority criteria for the primary endpoint. Finotonlimab plus C5F showed significant OS superiority compared with C5F alone and acceptable safety profile with R/M HNSCC, supporting its use as a first-line treatment option for R/M HNSCC. These results validate the efficacy and safety of the combination of finotonlimab and C5F in Asian patients with R/M HNSCC. ClinicalTrials.gov identifier: NCT04146402 .
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Regressing the accelerated degradation of skeletal muscle protein is a significant goal for cancer cachexia management. Here, we show that genetic deletion of Pgam5 ameliorates skeletal muscle atrophy in various tumor-bearing mice. pgam5 ablation represses excessive myoblast mitophagy and effectively suppresses mitochondria meltdown and muscle wastage. Next, we define BNIP3 as a mitophagy receptor constitutively associating with PGAM5. bnip3 deletion restricts body weight loss and enhances the gastrocnemius mass index in the age- and tumor size-matched experiments. The NH2-terminal region of PGAM5 binds to the PEST motif-containing region of BNIP3 to dampen the ubiquitination and degradation of BNIP3 to maintain continuous mitophagy. Finally, we identify S100A9 as a pro-cachectic chemokine via activating AGER/RAGE. AGER deficiency or S100A9 inhibition restrains skeletal muscle loss by weakening the interaction between PGAM5 and BNIP3. In conclusion, the AGER-PGAM5-BNIP3 axis is a novel but common pathway in cancer-associated muscle wasting that can be targetable. Abbreviation: AGER/RAGE: advanced glycation end-product specific receptor; BA1: bafilomycin A1; BNIP3: BCL2 interacting protein 3; BNIP3L: BCL2 interacting protein 3 like; Ckm-Cre: creatinine kinase, muscle-specific Cre; CM: conditioned medium; CON/CTRL: control; CRC: colorectal cancer; FUNDC1: FUN14 domain containing 1; MAP1LC3A/LC3A: microtubule associated protein 1 light chain 3 alpha; PGAM5: PGAM family member 5, mitochondrial serine/threonine protein phosphatase; S100A9: S100 calcium binding protein A9; SQSTM1/p62: sequestosome 1; TOMM20: translocase of outer mitochondrial membrane 20; TIMM23: translocase of inner mitochondrial membrane 23; TSKO: tissue-specific knockout; VDAC1: voltage dependent anion channel 1.
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OBJECTIVE: To explore the rules of acupoint selection and pattern-acupoint relationship in treatment with acupuncture and moxibustion for endometriosis (EMs) based on complex network analysis technology. METHODS: The articles for clinical trial of EMs treated with acupuncture and moxibustion were searched from CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase and Cochrane Library from the inception of the databases to December 14, 2022. Using Microsoft Excel 2019 software, the database was established to collect the use frequency of acupoint, meridian tropism, location and pattern-acupoint relationship. SPSS Modeler 18.0 Apriori algorithm was adopted to conduct the association rule analysis, Cytoscape3.7.2 software was used to plot the complex co-occurrence network map; and SPSS Statistics 26.0 was adopted to perform hierarchical cluster analysis on high-frequency acupoints and a tree diagram was drawn. RESULTS: A total of 163 articles were included, and 167 core acupoint prescriptions and 74 pattern-associated acupoint prescriptions were extracted, involving 92 acupoints, with a cumulative frequency of 1 223 times. The top five acupoints with the highest use frequency were Guanyuan (CV 4), Sanyinjiao (SP 6), Zhongji (CV 3), Zigong (EX-CA 1) and Qihai (CV 6). The selected acupoints were mostly distributed in the chest, abdomen and lower limbs; and the involved meridians included the conception vessel, the spleen meridian of foot-taiyin and the stomach meridian of foot-yangming. The acupoint compatibility of high frequency referred to Guanyuan (CV 4) - Sanyinjiao (SP 6), Guanyuan (CV 4) - Zhongji (CV 3), and Guanyuan (CV 4) - Zigong (EX-CA 1). The close association was presented among Guanyuan (CV 4), Sanyinjiao (SP 6), Qihai (CV 6) and Zhongji (CV 3), which had the strongest connection with the other acupoints; among the top 25 acupoints with the highest use frequency, 5 acupoint prescriptions with high frequency were obtained by the cluster analysis. Guanyuan (CV 4), Qihai (CV 6), Sanyinjiao (SP 6), Zigong (EX-CA 1) and Zhongji (CV 3) were selected for cold and blood stagnation; Guanyuan (CV 4), Sanyinjiao (SP 6), Zhongji (CV 3), Dahe (KI 12) and Taixi (KI 3) for kidney deficiency and blood stagnation; Zhongji (CV 3), Guanyuan (CV 4), Sanyinjiao (SP 6), Xuehai (SP 10) and Diji (SP 8) for qi and blood stagnation; Qihai (CV 6), Guanyuan (CV 4), Zusanli (ST 36), Xuehai (SP 10), and Zigong (EX-CA 1) for qi deficiency and blood stagnation; Sanyinjiao (SP 6), Fenglong (ST 40), Zhongliao (BL 33), Ciliao (BL 32) and Xialiao (BL 34) for interaction of phlegm and stasis; and Daheng (SP 15), Guanyuan (CV 4), Zhongji (CV 3), Qihai (CV 6) and Zhongwan (CV 12) for retention of damp and heat. CONCLUSION: The core acupoints are Guanyuan (CV 4), Sanyinjiao (SP 6), Zhongji (CV 3), Qihai (CV 6) and Zigong (EX-CA 1) in treatment of endometriosis with acupuncture and moxibustion. Six patterns/syndromes are involved in clinical practice. In terms of the properties, functions and indications, the supplementary acupoints are selected on the basis of the core acupoints for different patterns/sydnromes of the disease.
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Pontos de Acupuntura , Terapia por Acupuntura , Endometriose , Moxibustão , Humanos , Feminino , Moxibustão/métodos , Endometriose/terapiaRESUMO
Metaplastic breast cancer is a rare, aggressive, and chemotherapy-resistant subtype of breast cancers, accounting for less than 1% of invasive breast cancers, characterized by adenocarcinoma with spindle cells, squamous epithelium, and/or mesenchymal tissue differentiation. The majority of metaplastic breast cancers exhibit the characteristics of triple-negative breast cancer and have unfavorable prognoses with a lower survival rate. This subtype often displays gene alterations in the PI3K/AKT pathway, Wnt/ß-catenin pathway, and cell cycle dysregulation and demonstrates epithelial-mesenchymal transition, immune response changes, TP53 mutation, EGFR amplification, and so on. Currently, the optimal treatment of metaplastic breast cancer remains uncertain. This article provides a comprehensive review on the clinical features, molecular characteristics, invasion and metastasis patterns, and prognosis of metaplastic breast cancer, as well as recent advancements in treatment strategies.
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Neoplasias da Mama , Transição Epitelial-Mesenquimal , Humanos , Feminino , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Neoplasias da Mama/genética , Prognóstico , Metaplasia/patologia , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/terapia , Resistencia a Medicamentos Antineoplásicos , MutaçãoRESUMO
Objective: To systematically evaluate and explore the factors influencing depressive symptoms in female breast cancer patients in China through meta-analysis. Methods: Relevant data were retrieved from cross-sectional studies or cohort studies on depressive symptoms of Chinese breast cancer within the following databases: PubMed, Embase, Cohrane Library, Web of 105 Science, Database of Medical Literature (CBM), Wan Fang Data, CNKI, and VIP databases. The literature screening, data extraction and literature quality evaluation were performed by two researchers by carefully reading the title, abstract and full text, and meta-analysis was performed using Stata 1.5 software after extracting relevant data. Results: Fourteen papers were finally included, with a cumulative total of 3,071 people surveyed, and a total of 1,298 breast cancer patients were detected with depression, with a detection rate of depressive symptoms of 42.26%; meta analysis showed that age less than 40 years old, unmarried, less than undergraduate education, monthly income <5,000 yuan, advanced breast cancer, radical breast cancer surgery, family history, living in rural areas, underlying disease stage and chemotherapy were associated with an increased incidence of depression in breast cancer patients. Conclusion: The detection rate of depressive symptoms in female breast cancer patients is high, and there is a need to strengthen depression-related psychological screening of breast cancer patients and provide them with individualized interventions to reduce the incidence of depression in breast cancer patients and to lower the level of depression already present in the patients.
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Passive radiative cooling (PRC) has been acknowledged to be an environmentally friendly cooling technique, and especially artificial photonic materials with manipulating light-matter interaction ability are more favorable for PRC. However, scalable production of radiative cooling materials with advanced biologically inspired structures, fascinating properties, and high throughput is still challenging. Herein, we reported a bioinspired design combining surface ordered pyramid arrays and internal three-dimensional hierarchical pores for highly efficient PRC based on mimicking natural photonic structures of the white beetle Cyphochilus' wings. The biological photonic film consisting of surface ordered pyramid arrays with a bottom side length of 4 µm together with amounts of internal nano- and micropores was fabricated by using scalable phase separation and a quick hot-pressing process. Optimization of pore structures and surface-enhanced photonic arrays enables the bioinspired film to possess an average solar reflectance of â¼98% and a high infrared emissivity of â¼96%. A temperature drop of â¼8.8 °C below the ambient temperature is recorded in the daytime. Besides the notable PRC capability, the bioinspired film exhibits excellent flexibility, strong mechanical strength, and hydrophobicity; therefore, it can be applied in many complex outdoor scenarios. This work provides a highly efficient and mold replication-like route to develop highly efficient passive cooling devices.
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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.
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Neoplasias , Trombocitopenia , Humanos , China , Estudos Transversais , Interleucina-11/uso terapêutico , Neoplasias/tratamento farmacológico , Proteínas Recombinantes/uso terapêutico , Estudos Retrospectivos , Trombocitopenia/induzido quimicamente , Trombocitopenia/tratamento farmacológico , Trombopoetina/uso terapêutico , Adulto Jovem , AdultoRESUMO
PURPOSE: To compare giredestrant and physician's choice of endocrine monotherapy (PCET) for estrogen receptor-positive, HER2-negative, advanced breast cancer (BC) in the phase II acelERA BC study (ClinicalTrials.gov identifier: NCT04576455). METHODS: Post-/pre-/perimenopausal women, or men, age 18 years or older with measurable disease/evaluable bone lesions, whose disease progressed after 1-2 lines of systemic therapy (≤1 targeted, ≤1 chemotherapy regimen, prior fulvestrant allowed) were randomly assigned 1:1 to giredestrant (30 mg oral once daily) or fulvestrant/aromatase inhibitor per local guidelines (+luteinizing hormone-releasing hormone agonist in pre-/perimenopausal women, and men) until disease progression/unacceptable toxicity. Stratification was by visceral versus nonvisceral disease, prior cyclin-dependent kinase 4/6 inhibitor, and prior fulvestrant. The primary end point was investigator-assessed progression-free survival (INV-PFS). RESULTS: At clinical cutoff (February 18, 2022; median follow-up: 7.9 months; N = 303), the INV-PFS hazard ratio (HR) was 0.81 (95% CI, 0.60 to 1.10; P = .1757). In the prespecified secondary end point analysis of INV-PFS by ESR1 mutation (m) status in circulating tumor DNA-evaluable patients (n = 232), the HR in patients with a detectable ESR1m (n = 90) was 0.60 (95% CI, 0.35 to 1.03) versus 0.88 (95% CI, 0.54 to 1.42) in patients with no ESR1m detected (n = 142). Related grade 3-4 adverse events (AEs), serious AEs, and discontinuations due to AEs were balanced across arms. CONCLUSION: Although the acelERA BC study did not reach statistical significance for its primary INV-PFS end point, there was a consistent treatment effect with giredestrant across most key subgroups and a trend toward favorable benefit among patients with ESR1-mutated tumors. Giredestrant was well tolerated, with a safety profile comparable to PCET and consistent with known endocrine therapy risks. Overall, these data support the continued investigation of giredestrant in other studies.
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Neoplasias da Mama , Fulvestranto , Receptor ErbB-2 , Receptores de Estrogênio , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Neoplasias da Mama/mortalidade , Pessoa de Meia-Idade , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Estrogênio/análise , Idoso , Adulto , Fulvestranto/uso terapêutico , Masculino , Inibidores da Aromatase/uso terapêutico , Inibidores da Aromatase/efeitos adversos , Antineoplásicos Hormonais/uso terapêutico , Intervalo Livre de Progressão , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversosRESUMO
Background: As a therapy to prevent and treat essential hypertension (EH), traditional Chinese exercises (TCEs) were widely used in clinical practice. However, there is a lack of strictly comparison of the antihypertensive efficacy of different TCEs, which not conducive to the selection of the best and most optimal treatment. This study aimed to perform a network meta-analysis to objectively evaluate which TCE has the best effects in assisting with lowering blood pressure. Methods: PubMed, Embase, the Cochrane Library, Chinese National Knowledge Infrastructure (CNKI), VIP, SinoMed and Wanfang Data were searched for all randomized controlled trials (RCTs) on TCEs for the treatment of EH published up to July 10, 2023. RoB2.0 tool was utilized to evaluate the quality of the RCTs. The network meta-analysis was performed by R 4.1.2 and Stata 17.0. Weighted mean difference (WMD) was calculated for continuous outcomes. Results: A total of 29 studies, including 2,268 patients were included to analyze 6 different interventions. The network meta-analysis results presented that in comparison with control group, Tai Chi + antihypertensive medication [WMD = -10.18, 95% CI, (-14.94, -5.44)] is the most effective intervention for lowering systolic blood pressure (SBP), and Wuqinxi + antihypertensive medication [WMD = -10.36, 95% CI (-18.98, -1.66)] is the most effective intervention for lowering diastolic blood pressure (DBP). Conclusion: TCEs combined with antihypertensive medication may be able to achieve more prominent antihypertensive effects with Tai Chi and Wuqinxi potentially being the higher-priority options. However, well-designed randomized studies are warranted to further verify currently conclusion.
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Importance: The bioequivalence of denosumab biosimilar has yet to be studied in a 53-week, multicenter, large-scale, and head-to-head trial. A clinically effective biosimilar may help increase access to denosumab in patients with solid tumor-related bone metastases. Objectives: To establish the biosimilarity of MW032 to denosumab in patients with solid tumor-related bone metastases based on a large-scale head-to-head study. Design, Setting, and Participants: In this 53-week, randomized, double-blind, phase 3 equivalence trial, patients with solid tumors with bone metastasis were recruited from 46 clinical sites in China. Overall, 856 patients were screened and 708 eligible patients were randomly allocated to receive either MW032 or denosumab. Interventions: Patients were randomly assigned (1:1) to receive MW032 or reference denosumab subcutaneously every 4 weeks until week 49. Main Outcomes and Measures: The primary end point was percentage change from baseline to week 13 of natural logarithmic transformed urinary N-telopeptide/creatinine ratio (uNTx/uCr). Results: Among the 701 evaluable patients (350 in the MW032 group and 351 in the denosumab group), the mean (range) age was 56.1 (22.0-86.0) years and 460 patients were women (65.6%). The mean change of uNTx/uCr from baseline to week 13 was -72.0% (95% CI, -73.5% to -70.4%) in the MW032 group and -72.7% (95% CI, -74.2% to -71.2%) in the denosumab group. These percent changes corresponded to mean logarithmic ratios of -1.27 and -1.30, or a difference of 0.02. The 90% CI for the difference (-0.04 to 0.09) was within the equivalence margin (-0.13 to 0.13); the mean changes of uNTx/uCr and bone-specific alkaline phosphatase (s-BALP) at each time point were also similar during 53 weeks. The differences of uNTx/uCr change were 0.015 (95% CI, -0.06 to 0.09), -0.02 (95% CI, -0.09 to 0.06), -0.05 (95% CI, -0.13 to 0.03) and 0.001 (95% CI, -0.10 to 0.10) at weeks 5, 25, 37, and 53, respectively. The differences of s-BALP change were -0.006 (95% CI, 0.06 to 0.05), 0.00 (95% CI, -0.07 to 0.07), -0.085 (95% CI, -0.18 to 0.01), -0.09 (95% CI, -0.20 to 0.02), and -0.13 (95% CI, -0.27 to 0.004) at weeks 5, 13, 25, 37 and 53, respectively. No significant differences were observed in the incidence of skeletal-related events (-1.4%; 95% CI, -5.8% to 3.0%) or time to first on-study skeletal-related events (unadjusted HR, 0.86; P = .53; multiplicity adjusted HR, 0.87; P = .55) in the 2 groups. Conclusions and Relevance: MW032 and denosumab were biosimilar in efficacy, population pharmacokinetics, and safety profile. Availability of denosumab biosimilars may broaden the access to denosumab and reduce the drug burden for patients with advanced tumors. Trial Registration: ClinicalTrials.gov Identifier: NCT04812509.
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Medicamentos Biossimilares , Neoplasias Ósseas , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Masculino , Denosumab , Anticorpos Monoclonais Humanizados , Neoplasias Ósseas/secundário , Creatinina , Método Duplo-CegoRESUMO
This multicenter, phase II study (NCT03872791) aims to evaluate the efficacy and safety of the anti-PD-L1/CTLA-4 bispecific antibody KN046 combined with nab-paclitaxel in the first-line treatment of patients with metastatic triple-negative breast cancer (TNBC). The primary endpoints included objective response rate (ORR) and duration of response (DoR), and secondary endpoints included progression-free survival (PFS), overall survival (OS) rate, safety, and the correlation of PD-L1 status with clinical efficacy. This trial met pre-specified endpoints. 27 female patients were enrolled sequentially to receive KN046 in two dose levels (3 mg/kg or 5 mg/kg). Among the 25 evaluable patients, the ORR achieved 44.0% (95% CI, 24.4% - 65.1%), and the median DoR was not mature. The median PFS reached 7.33 months (95%CI, 3.68 - 11.07 months), and the median OS was 30.92 months (95%CI, 14.75 - NE months). In PD-L1 positive patients, PFS was 8.61 months (versus 4.73 months) and the 2-year OS rate was 62.5% (versus 57.1%) compared to PD-L1 negative patients. Patients tolerated well the combination therapy. In general, KN046 combined with nab-paclitaxel showed favorable efficacy and survival benefits with tolerable toxicity in the first-line treatment of metastatic TNBC, especially PD-L1 positive, which is worth further investigation.
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Antineoplásicos , Neoplasias de Mama Triplo Negativas , Feminino , Humanos , Albuminas , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Antígeno B7-H1 , Antígeno CTLA-4 , Paclitaxel/efeitos adversos , Paclitaxel/uso terapêutico , Neoplasias de Mama Triplo Negativas/patologiaRESUMO
Tamoxifen (TAM) resistance poses a significant clinical challenge in human breast cancer and exhibits high heterogeneity among different patients. Rg3, an original ginsenoside known to inhibit tumor growth, has shown potential for enhancing TAM sensitivity in breast cancer cells. However, the specific role and underlying mechanisms of Rg3 in this context remain unclear. Aerobic glycolysis, a metabolic process, has been implicated in chemotherapeutic resistance. In this study, we demonstrate that elevated glycolysis plays a central role in TAM resistance and can be effectively targeted and overcome by Rg3. Mechanistically, we observed upregulation of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3), a key mediator of glycolysis, in TAM-resistant MCF-7/TamR and T-47D/TamR cells. Crucially, PFKFB3 is indispensable for the synergistic effect of TAM and Rg3 combination therapy, which suppresses cell proliferation and glycolysis in MCF-7/TamR and T-47D/TamR cells, both in vitro and in vivo. Moreover, overexpression of PFKFB3 in MCF-7 cells mimicked the TAM resistance phenotype. Importantly, combination treatment significantly reduced TAM-resistant MCF-7 cell proliferation in an in vivo model. In conclusion, this study highlights the contribution of Rg3 in enhancing the therapeutic efficacy of TAM in breast cancer, and suggests that targeting TAM-resistant PFKFB3 overexpression may represent a promising strategy to improve the response to combination therapy in breast cancer.
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Neoplasias da Mama , Ginsenosídeos , Humanos , Feminino , Tamoxifeno/farmacologia , Neoplasias da Mama/patologia , Ginsenosídeos/farmacologia , Ginsenosídeos/uso terapêutico , Antineoplásicos Hormonais/farmacologia , Antineoplásicos Hormonais/uso terapêutico , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos , Células MCF-7 , Glicólise , Regulação Neoplásica da Expressão GênicaRESUMO
AIM: The number of breast cancer patients is increasing, but there are insufficient sources of information for their family caregivers. The purpose of this systematic review was to elaborate the psychologically realistic experiences and corresponding needs of family members of patients with breast cancer in the course of their experience in the disease which may provide them with effective, targeted intervention strategies to improve their quality of life. DESIGN: Protocol for a meta-synthesis. METHODS: We will search the Chinese databases (i.e., China National Knowledge Infrastructure, VIP Database and Wanfang Database) and the English databases (i.e., PubMed, Embase, Web of Science, the Cochrane Library, CINAHL and PsycINFO). Qualitative studies from the above databases, studying the psychological experiences of family members of patients with breast cancer, will be searched comprehensively. The quality of the study will be evaluated by two reviewers independently using the Joanna Briggs Institute (JBI) critical appraisal tools for qualitative study, and any disagreements will be discussed and judged by the third reviewer. Data will be extracted using JBI standardized data extraction tool. Then, the literature will be compared and analysed, and the raw results summarized using the JBI meta-aggregation tool. The reliability and credibility of the overall quality of the included studies will be assessed by using the JBI ConQual approach. RESULTS: N/A. No Patient or Public Contribution. PROSPERO REGISTRATION NUMBER: REDACTED.
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Neoplasias da Mama , Cuidadores , Feminino , Humanos , Qualidade de Vida , Revisões Sistemáticas como AssuntoRESUMO
BACKGROUND AND OBJECTIVE: As a chronic inflammatory disease, periodontitis threatens oral health and is a risk factor for Alzheimer's disease (AD). There is growing evidence that these two diseases are closely related. However, current research is still incomplete in understanding the common genes and common mechanisms between periodontitis and AD. In this study, we aimed to identify common genes in periodontitis and AD and analyze the relationship between crucial genes and immune cells to provide new therapeutic targets for clinical treatment. MATERIALS AND METHODS: We evaluated differentially expressed genes (DEGs) specific to periodontitis and AD. Co-expressed genes were identified by obtaining gene expression profile data from the Gene Expression Omnibus (GEO) database. Using the STRING database, protein-protein interaction (PPI) networks were constructed, and essential genes were identified. We also used four algorithms to identify critical genes and constructed regulatory networks. The association of crucial genes with immune cells and potential therapeutic effects was also assessed. RESULTS: PDGFRB, VCAN, TIMP1, CHL1, EFEMP2, and IGFBP5 were obtained as crucial common genes. Immune infiltration analysis showed that Natural killer cells and Myeloid-derived suppressor cells were significantly differentially expressed in patients with PD and AD compared with the normal group. FOXC1 and GATA2 are important TFs for PD and AD. MiR-23a, miR-23b, miR-23a, and miR-23b were associated with AD and PD. Finally, the hub genes retrieved from the DSigDB database indicate multiple drug molecule and drug-target interactions. CONCLUSION: This study reveals commonalities in common hub genes and immune infiltration between periodontitis and AD, and the analysis of six hub genes and immune cells may provide new insights into potential therapeutic directions for the pathogenesis of periodontitis complicated by AD.