ABSTRACT
Animal models have highlighted the importance of innate lymphoid cells (ILCs) in multiple immune responses. However, technical limitations have hampered adequate characterization of ILCs in humans. Here, we used mass cytometry including a broad range of surface markers and transcription factors to accurately identify and profile ILCs across healthy and inflamed tissue types. High dimensional analysis allowed for clear phenotypic delineation of ILC2 and ILC3 subsets. We were not able to detect ILC1 cells in any of the tissues assessed, however, we identified intra-epithelial (ie)ILC1-like cells that represent a broader category of NK cells in mucosal and non-mucosal pathological tissues. In addition, we have revealed the expression of phenotypic molecules that have not been previously described for ILCs. Our analysis shows that human ILCs are highly heterogeneous cell types between individuals and tissues. It also provides a global, comprehensive, and detailed description of ILC heterogeneity in humans across patients and tissues.
Subject(s)
Flow Cytometry/methods , Lymphocyte Subsets/immunology , Lymphocytes/immunology , Humans , Immunity, Innate , PhenotypeABSTRACT
Articular cartilage injury is one of the most common diseases in orthopedic clinics. Following an articular cartilage injury, an inability to resist vascular invasion can result in cartilage calcification by newly formed blood vessels. This process ultimately leads to the loss of joint function, significantly impacting the patient's quality of life. As a result, developing anti-angiogenic methods to repair damaged cartilage has become a popular research topic. Despite this, tissue engineering, as an anti-angiogenic strategy in cartilage injury repair, has not yet been adequately investigated. This exhaustive literature review mainly focused on the process and mechanism of vascular invasion in articular cartilage injury repair and summarized the major regulatory factors and signaling pathways affecting angiogenesis in the process of cartilage injury. We aimed to discuss several potential methods for engineering cartilage repair with anti-angiogenic strategies. Three anti-angiogenic tissue engineering methods were identified, including administering angiogenesis inhibitors, applying scaffolds to manage angiogenesis, and utilizing in vitro bioreactors to enhance the therapeutic properties of cultured chondrocytes. The advantages and disadvantages of each strategy were also analyzed. By exploring these anti-angiogenic tissue engineering methods, we hope to provide guidance for researchers in related fields for future research and development in cartilage repair.
Subject(s)
Cartilage, Articular , Quality of Life , Humans , Immunotherapy , Angiogenesis Inhibitors , Calcification, PhysiologicABSTRACT
OBJECTIVES: The emergence and expansion of carbapenem-resistant Klebsiella pneumoniae infections is a concern due to the lack of 'first-line' antibiotic treatment options. The ceftazidime/avibactam is an important clinical treatment for carbapenem-resistant K. pneumoniae infections but there is an increasing number of cases of treatment failure and drug resistance. Therefore, a potential solution is combination therapies that result in synergistic activity against K. pneumoniae carbapenemase: producing K. pneumoniae (KPC-Kp) isolates and preventing the emergence of KPC mutants resistant to ceftazidime/avibactam are needed in lieu of novel antibiotics. METHODS: To evaluate their synergistic activity, antibiotic combinations were tested against 26 KPC-Kp strains. Antibiotic resistance profiles, molecular characteristics and virulence genes were investigated by susceptibility testing and whole-genome sequencing. Antibiotic synergy was evaluated by in vitro chequerboard experiments, time-killing curves and dose-response assays. The mouse thigh model was used to confirm antibiotic combination activities in vivo. Additionally, antibiotic combinations were evaluated for their ability to prevent the emergence of ceftazidime/avibactam resistant mutations of blaKPC. RESULTS: The combination of ceftazidime/avibactam plus meropenem showed remarkable synergistic activity against 26 strains and restored susceptibility to both the partnering antibiotics. The significant therapeutic effect of ceftazidime/avibactam combined with meropenem was also confirmed in the mouse model and bacterial loads in the thigh muscle of the combination groups were significantly reduced. Furthermore, ceftazidime/avibactam plus meropenem showed significant activity in preventing the occurrence of resistance mutations. CONCLUSIONS: Our results indicated that the combination of ceftazidime/avibactam plus meropenem offers viable therapeutic alternatives in treating serious infections due to KPC-Kp.
Subject(s)
Anti-Bacterial Agents , Azabicyclo Compounds , Bacterial Proteins , Ceftazidime , Disease Models, Animal , Drug Combinations , Drug Synergism , Klebsiella Infections , Klebsiella pneumoniae , Meropenem , Microbial Sensitivity Tests , beta-Lactamases , Animals , Ceftazidime/pharmacology , Ceftazidime/therapeutic use , Klebsiella pneumoniae/drug effects , Klebsiella pneumoniae/genetics , Azabicyclo Compounds/pharmacology , Azabicyclo Compounds/therapeutic use , Meropenem/pharmacology , Meropenem/administration & dosage , Klebsiella Infections/drug therapy , Klebsiella Infections/microbiology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Mice , beta-Lactamases/genetics , Bacterial Proteins/genetics , Female , Whole Genome Sequencing , Drug Therapy, Combination , Carbapenem-Resistant Enterobacteriaceae/drug effects , Carbapenem-Resistant Enterobacteriaceae/geneticsABSTRACT
BACKGROUND: Radiotherapy (RT) is an effective and available local treatment for patients with refractory or relapsed (R/R) aggressive B-cell lymphomas. However, the value of hypofractionated RT in this setting has not been confirmed. METHODS: We retrospectively analyzed patients with R/R aggressive B-cell lymphoma who received hypofractionated RT between January 2020 and August 2022 at a single institution. The objective response rate (ORR), overall survival (OS), progression-free survival (PFS) and acute side effects were analyzed. RESULTS: A total of 30 patients were included. The median dose for residual disease was 36 Gy, at a dose per fraction of 2.3-5 Gy. After RT, the ORR and complete response (CR) rates were 90% and 80%, respectively. With a median follow-up of 10 months (range, 2-27 months), 10 patients (33.3%) experienced disease progression and three died. The 1-year OS and PFS rates for all patients were 81.8% and 66.3%, respectively. The majority (8/10) of post-RT progressions involved out-of-field relapses. Patients with relapsed diseases, no response to systemic therapy, multiple lesions at the time of RT, and no response to RT were associated with out-of-field relapses. PFS was associated with response to RT (P = 0.001) and numbers of residual sites (P < 0.001). No serious non-hematological adverse effects (≥ grade 3) associated with RT were reported. CONCLUSION: These data suggest that hypofractionated RT was effective and tolerable for patients with R/R aggressive B-cell lymphoma, especially for those that exhibited localized residual disease.
Subject(s)
Lymphoma, B-Cell , Lymphoma, Large B-Cell, Diffuse , Humans , Rituximab/therapeutic use , Retrospective Studies , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/radiotherapy , Lymphoma, B-Cell/drug therapy , Lymphoma, B-Cell/radiotherapy , Recurrence , Lymphoma, Large B-Cell, Diffuse/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Treatment OutcomeABSTRACT
Various forms of immunotherapy, such as checkpoint blockade immunotherapy, are proving to be effective at restoring T cell-mediated immune responses that can lead to marked and sustained clinical responses, but only in some patients and cancer types1-4. Patients and tumours may respond unpredictably to immunotherapy partly owing to heterogeneity of the immune composition and phenotypic profiles of tumour-infiltrating lymphocytes (TILs) within individual tumours and between patients5,6. Although there is evidence that tumour-mutation-derived neoantigen-specific T cells play a role in tumour control2,4,7-10, in most cases the antigen specificities of phenotypically diverse tumour-infiltrating T cells are largely unknown. Here we show that human lung and colorectal cancer CD8+ TILs can not only be specific for tumour antigens (for example, neoantigens), but also recognize a wide range of epitopes unrelated to cancer (such as those from Epstein-Barr virus, human cytomegalovirus or influenza virus). We found that these bystander CD8+ TILs have diverse phenotypes that overlap with tumour-specific cells, but lack CD39 expression. In colorectal and lung tumours, the absence of CD39 in CD8+ TILs defines populations that lack hallmarks of chronic antigen stimulation at the tumour site, supporting their classification as bystanders. Expression of CD39 varied markedly between patients, with some patients having predominantly CD39- CD8+ TILs. Furthermore, frequencies of CD39 expression among CD8+ TILs correlated with several important clinical parameters, such as the mutation status of lung tumour epidermal growth factor receptors. Our results demonstrate that not all tumour-infiltrating T cells are specific for tumour antigens, and suggest that measuring CD39 expression could be a straightforward way to quantify or isolate bystander T cells.
Subject(s)
Bystander Effect/immunology , CD8-Positive T-Lymphocytes/cytology , CD8-Positive T-Lymphocytes/immunology , Colorectal Neoplasms/immunology , Lung Neoplasms/immunology , Lymphocytes, Tumor-Infiltrating/cytology , Lymphocytes, Tumor-Infiltrating/immunology , Antigens, Neoplasm/immunology , Antigens, Viral/immunology , Apyrase/analysis , Apyrase/deficiency , Apyrase/metabolism , CD8-Positive T-Lymphocytes/metabolism , Cell Separation , Colorectal Neoplasms/genetics , ErbB Receptors/genetics , Humans , Lung Neoplasms/genetics , Lymphocytes, Tumor-Infiltrating/metabolism , PhenotypeABSTRACT
Disaster plant pathology addresses how natural and human-driven disasters impact plant diseases and the requirements for smart management solutions. Local to global drivers of plant disease change in response to disasters, often creating environments more conducive to plant disease. Most disasters have indirect effects on plant health through factors such as disrupted supply chains and damaged infrastructure. There is also the potential for direct effects from disasters, such as pathogen or vector dispersal due to floods, hurricanes, and human migration driven by war. Pulse stressors such as hurricanes and war require rapid responses, whereas press stressors such as climate change leave more time for management adaptation but may ultimately cause broader challenges. Smart solutions for the effects of disasters can be deployed through digital agriculture and decision support systems supporting disaster preparedness and optimized humanitarian aid across scales. Here, we use the disaster plant pathology framework to synthesize the effects of disasters in plant pathology and outline solutions to maintain food security and plant health in catastrophic scenarios. We recommend actions for improving food security before and following disasters, including (i) strengthening regional and global cooperation, (ii) capacity building for rapid implementation of new technologies, (iii) effective clean seed systems that can act quickly to replace seed lost in disasters, (iv) resilient biosecurity infrastructure and risk assessment ready for rapid implementation, and (v) decision support systems that can adapt rapidly to unexpected scenarios. [Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY 4.0 International license.
Subject(s)
Plant Diseases , Plant Diseases/prevention & control , Humans , Plant Pathology , Disasters , Climate Change , Food SecurityABSTRACT
Ulcerative colitis is a chronic, recurrent, and nonspecific intestinal inflammatory disease, which is difficult to cure and has the risk of deterioration into related tumors. Long-term chronic inflammatory stimulation can increase the risk of cancerization. With the signaling pathway as a key link in the regulation of tumor microenvironments, nuclear factor-kappa B(NF-κB) is an important regulator of intestinal inflammation. It can also be co-regulated as downstream factors of other signaling pathways, such as TLR4, MAPK, STAT, PI3K, and so on. At present, a large number of animal experiments have proved that traditional Chinese medicine(TCM) can reduce inflammation by interfering with NF-κB-related signaling pathways, improve intestinal inflammation, and inhibit the progression of inflammation to tumors. This article reviewed the relationship between NF-κB-related signaling pathways and the intervention mechanism of TCM, so as to provide a reference for the clinical treatment of ulcerative colitis and the optimization of related cancer prevention strategies.
Subject(s)
Colitis, Ulcerative , Colorectal Neoplasms , Animals , Colitis, Ulcerative/complications , Colitis, Ulcerative/drug therapy , Colitis, Ulcerative/genetics , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/genetics , Disease Models, Animal , Inflammation , Medicine, Chinese Traditional , NF-kappa B/genetics , NF-kappa B/metabolism , Signal Transduction , Tumor MicroenvironmentABSTRACT
A search for interactions from solar ^{8}B neutrinos elastically scattering off xenon nuclei using PandaX-4T commissioning data is reported. The energy threshold of this search is further lowered compared with the previous search for dark matter, with various techniques utilized to suppress the background that emerges from data with the lowered threshold. A blind analysis is performed on the data with an effective exposure of 0.48 tonne year, and no significant excess of events is observed. Among the results obtained using the neutrino-nucleus coherent scattering, our results give the best constraint on the solar ^{8}B neutrino flux. We further provide a more stringent limit on the cross section between dark matter and nucleon in the mass range from 3 to 9 GeV/c^{2}.
ABSTRACT
We report the search results of light dark matter through its interactions with shell electrons and nuclei, using the commissioning data from the PandaX-4T liquid xenon detector. Low energy events are selected to have an ionization-only signal between 60 to 200 photoelectrons, corresponding to a mean nuclear recoil energy from 0.77 to 2.54 keV and electronic recoil energy from 0.07 to 0.23 keV. With an effective exposure of 0.55 tonne·year, we set the most stringent limits within a mass range from 40 MeV/c^{2} to 10 GeV/c^{2} for pointlike dark matter-electron interaction, 100 MeV/c^{2} to 10 GeV/c^{2} for dark matter-electron interaction via a light mediator, and 3.2 to 4 GeV/c^{2} for dark matter-nucleon spin-independent interaction. For DM interaction with electrons, our limits are closing in on the parameter space predicted by the freeze-in and freeze-out mechanisms in the early Universe.
Subject(s)
Cell Nucleus , ElectronsABSTRACT
BACKGROUND: The existing ex vivo models of endoscopic submucosal dissection (ESD) cannot simulate intraoperative hemorrhage well. We aimed to establish an ESD training method by applying an ex vivo training model with continuous perfusion (ETM-CP). METHODS: Four training sessions were conducted for 25 novices under the guidance of 2 experts. Eventually, 10 novices completed ESD operations on a total of 89 patients after the training. The resection effectiveness, resection speed, complication rate, and novice performance before and after the training were compared. The data regarding the effects of the training and the model were gathered through a questionnaire survey. RESULTS: In terms of the simulation effect of the model, ETM-CP was evaluated as similar to the live pig in all aspects (P > 0.05). The questionnaire analysis revealed that the ESD theoretical knowledge, skill operation, and self-confidence of novices were improved after the training (P < 0.05). The resection time per unit area had a correlation with the number of training periods (rs = - 0.232). For novice performance, the resection time per unit area was shortened (P < 0.05). There was no difference in patient performance between the novice group and the expert group after the training in terms of en bloc resection, R0 resection, complication rate, endoscopic resection bleeding (ERB) score, muscularis propria injury (MPI) score, and resection time per unit area (P > 0.05). CONCLUSION: The ETM-CP is effective for ESD training.
Subject(s)
Endoscopic Mucosal Resection , Swine , Animals , Endoscopic Mucosal Resection/methods , Blood Loss, Surgical , China , PerfusionABSTRACT
OBJECTIVE: This study was conducted to investigate key long noncoding RNAs (lncRNAs) involved in competitive endogenous RNA (ceRNA) network associated with laryngeal squamous cell carcinoma (LSCC). MATERIALS AND METHODS: Three mRNA datasets, two miRNA datasets, and one lncRNA dataset of LSCC were downloaded from GEO database. Following the identification of differentially expressed mRNAs (DEmRNAs), (microRNAs) miRNAs (DEmiRNAs), and lncRNAs (DElncRNAs) in LSCC compared with adjacent tissues, functional enrichment of DEmRNAs was performed. Then, construction of the ceRNA (DElncRNA-DEmiRNA-DEmRNA) regulatory network and functional analyses of all DEmRNAs in ceRNA regulatory network were conducted. Quantitative real-time polymerase chain reactions (qRT-PCR) were used to detect the expression levels of selected DEmRNAs, DEmiRNAs, and DElncRNAs. RESULTS: A total of 3449 DEmRNAs, 40 DEmiRNAs, and 100 DElncRNAs were identified in LSCC. The ceRNA networks, which contained 132 DElncRNA-DEmiRNA pairs and 287 DEmiRNA-DEmRNA pairs, involving 44 lncRNAs, 3 miRNAs, and 271 mRNAs, were obtained. DEmRNAs in ceRNA regulatory networks were significantly enriched in pathways in cancer, prostate cancer, and aldosterone-regulated sodium reabsorption. Except for HCG22 and hsa-miR-1246, expressions of the others in the qRT-PCR results played the same pattern with that in our integrated analysis, generally. CONCLUSIONS: We concluded that HCG22/EGOT-hsa-miR-1275-FAM107A and HCG22/EGOT-hsa-miR-1246-Glycerol-3-phosphate dehydrogenase 1 like interaction pairs may play a central role in LSCC.
Subject(s)
Head and Neck Neoplasms , MicroRNAs , RNA, Long Noncoding , Male , Humans , Squamous Cell Carcinoma of Head and Neck/genetics , RNA, Long Noncoding/genetics , Gene Regulatory Networks , MicroRNAs/genetics , MicroRNAs/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Head and Neck Neoplasms/genetics , Gene Expression Regulation, Neoplastic/geneticsABSTRACT
BACKGROUND: Breathing exercise has been utilized as a promising approach to pain management in cancer survivors. However, the development process of the breathing exercise intervention protocol was rarely reported. AIM: To develop an evidence-based breathing exercise intervention protocol for chronic pain management in breast cancer survivors and to provide a detailed account of the intervention development process. METHODS: The study design was guided by the Medical Research Council Framework for Developing and Evaluating Complex Intervention. The breathing exercise intervention development process adopted phase one of the Medical Research Council Framework for Developing and Evaluating Complex Intervention framework. The content validity index was applied to determine the consensus of the appropriateness of the breathing exercise intervention protocol among the panel experts. RESULTS: The preliminary breathing exercise intervention protocol was developed based on fight-or-flight theory and vagus nerve theory, and the best available research evidence identified from seven systematic reviews, three clinical trials, and four practice recommendations. The breathing exercise intervention was designed as slow deep pursed-lip breathing with a time ratio of inspiration to expiration 1:2-3. The intensity of the breathing exercise was determined as 3 to 5 sessions a day, 5 minutes per session, for 4 weeks. The content validity of the breathing exercise intervention protocol was excellent as consensus was achieved among all panel experts with both the item-level and scale-level CVIs reaching 1.0. CONCLUSIONS: This study developed an evidence-based breathing exercise intervention protocol for chronic pain management in breast cancer survivors. The protocol is well-supported by the relevant theories, research evidence, practice recommendations, and experts' consensus.
Subject(s)
Breast Neoplasms , Cancer Survivors , Humans , Female , Pain Management , Breast Neoplasms/complications , Breathing Exercises , Exercise Therapy/methodsABSTRACT
OBJECTIVES: To evaluate the clinical effectiveness of integrated management during the perinatal period for fetuses diagnosed with total anomalous pulmonary venous connection (TAPVC) by prenatal echocardiography. METHODS: Clinical data of 64 cases of TAPVC fetuses diagnosed by prenatal echocardiography and managed with integrated perinatal care in Qingdao Women and Children's Hospital from January 2017 to December 2021 were retrospectively analyzed. Integrated perinatal care included multidisciplinary collaboration among obstetrics, fetal medicine, ultrasound, pediatric cardiology, pediatric anesthesia, and neonatology. RESULTS: Among the 64 TAPVC fetuses, there were 29 cases of supracardiac type, 27 cases of intracardiac type, 2 cases of infracardiac type, and 6 cases of mixed type. Chromosomal analysis was performed in 42 cases, and no obvious abnormalities were found. Among the 64 TAPVC fetuses, 37 were induced labor, and 27 were followed up until term birth. Among the 27 TAPVC cases, 2 cases accepted palliative care, 2 cases were referred to another hospital for treatment and lost to follow-up, while the remaining 23 cases underwent primary repair surgery. One case died within 6 months after the operation due to low cardiac output syndrome, while the other 22 cases were followed up for (2.1±0.3) years with good outcomes (2 cases underwent a second surgery within 1 year after the first operation due to anastomotic stenosis or pulmonary vein stenosis). CONCLUSIONS: TAPVC fetuses can achieve good outcomes with integrated management during the perinatal period.
Subject(s)
Heart Defects, Congenital , Pulmonary Veins , Scimitar Syndrome , Female , Humans , Pregnancy , Echocardiography , Heart Defects, Congenital/surgery , Pulmonary Veins/diagnostic imaging , Pulmonary Veins/abnormalities , Pulmonary Veins/surgery , Retrospective Studies , Scimitar Syndrome/diagnostic imaging , Scimitar Syndrome/surgery , Infant, NewbornABSTRACT
OBJECTIVES: To explore the role and potential mechanisms of chitinase-3-like protein 1 (CHI3L1) in coronary artery lesions in a mouse model of Kawasaki disease (KD)-like vasculitis. METHODS: Four-week-old male SPF-grade C57BL/6 mice were randomly divided into a control group and a model group, with 10 mice in each group. The model group mice were intraperitoneally injected with 0.5 mL of lactobacillus casei cell wall extract (LCWE) to establish a mouse model of KD-like vasculitis, while the control group mice were injected with an equal volume of normal saline. The general conditions of the mice were observed on the 3rd, 7th, and 14th day after injection. Changes in coronary artery tissue pathology were observed using hematoxylin-eosin staining. The level of CHI3L1 in mouse serum was measured by enzyme-linked immunosorbent assay. Immunofluorescence staining was used to detect the expression and localization of CHI3L1, von Willebrand factor (vWF), and α-smooth muscle actin (α-SMA) in coronary artery tissue. Western blot analysis was used to detect the expression of CHI3L1, vWF, vascular endothelial cadherin (VE cadherin), Caspase-3, B cell lymphoma-2 (Bcl-2), Bcl-2 associated X protein (Bax), nuclear factor κB (NF-κB), and phosphorylated NF-κB (p-NF-κB) in coronary artery tissue. RESULTS: The serum level of CHI3L1 in the model group was significantly higher than that in the control group (P<0.05). Compared to the control group, the expression of CHI3L1 in the coronary artery tissue was higher, while the expression of vWF was lower in the model group. The relative expression levels of CHI3L1, Bax, Caspase-3, NF-κB, and p-NF-κB were significantly higher in the model group than in the control group (P<0.05). The relative expression levels of vWF, VE cadherin, and Bcl-2 were lower in the model group than in the control group (P<0.05). CONCLUSIONS: In the LCWE-induced mouse model of KD-like vasculitis, the expression levels of CHI3L1 in serum and coronary arteries increase, and it may play a role in coronary artery lesions through endothelial cell apoptosis mediated by inflammatory reactions.
Subject(s)
Mucocutaneous Lymph Node Syndrome , Male , Animals , Mice , Mucocutaneous Lymph Node Syndrome/pathology , Coronary Vessels/pathology , NF-kappa B , Caspase 3/metabolism , bcl-2-Associated X Protein/metabolism , Chitinase-3-Like Protein 1 , von Willebrand Factor/metabolism , Mice, Inbred C57BL , CadherinsABSTRACT
Compared with the signature of dark matter elastic scattering off nuclei, the absorption of fermionic dark matter by nuclei opens up a new searching channel for light dark matter with a characteristic monoenergetic signal. In this Letter, we explore the 95.0-day data from the PandaX-4T commissioning run and report the first dedicated searching results of the fermionic dark matter absorption signal through a neutral current process. No significant signal was found, and the lowest limit on the dark matter-nucleon interaction cross section is set to be 1.5×10^{-50} cm^{2} for a fermionic dark matter mass of 40 MeV/c^{2} with 90% confidence level.
ABSTRACT
We report a search on sub-MeV fermionic dark matter absorbed by electrons with an outgoing active neutrino using the 0.63 tonne year exposure collected by the PandaX-4T liquid xenon experiment. No significant signals are observed over the expected background. The data are interpreted into limits to the effective couplings between such dark matter and the electron. For axial-vector or vector interactions, our sensitivity is competitive in comparison to existing astrophysical bounds on the decay of such a dark matter candidate into photon final states. In particular, we present the first direct detection limits for a vector (axial-vector) interaction which are the strongest in the mass range from 35 to 55 (25 to 45) keV/c^{2} in comparison to other astrophysical and cosmological constraints.
ABSTRACT
We report a novel search for the cosmic-ray boosted dark matter using the 100 tonne·day full dataset of the PandaX-II detector located at the China Jinping Underground Laboratory. With the extra energy gained from the cosmic rays, sub-GeV dark matter particles can produce visible recoil signals in the detector. The diurnal modulations in rate and energy spectrum are utilized to further enhance the signal sensitivity. Our result excludes the dark matter-nucleon elastic scattering cross section between 10^{-31} and 10^{-28} cm^{2} for dark matter masses from 0.1 MeV/c^{2} to 0.1 GeV/c^{2}, with a large parameter space previously unexplored by experimental collaborations.
ABSTRACT
The efficient construction of cyclopropyl spiroindoline skeletons and the exploration of related follow-up synthetic transformations have elicited considerable interest amongst members of the chemistry community. Here, we describe a formal (2 + 1) annulation and three-component (1 + 1 + 1) cascade cyclisation via sulphur ylide cyclopropanation under mild conditions. The spiro-cyclopropyl iminoindoline moiety can be readily transformed into another medicinally interesting pyrrolo[3,4-c]quinoline framework through a novel rearrangement process.
Subject(s)
Sulfur , CyclizationABSTRACT
BACKGROUND: Aromatase inhibitor (AI)-induced joint pain is a common toxicity of AI treatment. Although many studies have been conducted to examine the occurrence and severity of AI-induced joint pain in breast cancer survivors, none of the studies focused on the Chinese population with breast cancer. Given that the differences in cultural background and the genetic structure between Asians and Caucasians may contribute to different phenotypes of joint pain, this cross-sectional study was therefore conducted to examine the prevalence of AI-induced joint pain among Chinese breast cancer survivors receiving AI treatment and the correlates of pain. METHODS: This cross-sectional study was conducted in a tertiary hospital in China. Breast cancer survivors undergoing AI treatment were recruited to complete the following questionnaires: a self-designed baseline data form, the Nordic Musculoskeletal Questionnaire (NMQ), the Brief Pain Inventory (BPI), the 36-Item Short Form Health Survey (SF-36), and the Functional Assessment of Cancer Therapy-Breast (FACT-B). Based on the assessment results of NMQ (if the participant indicated pain in specific body parts), participants were then invited to complete other questionnaires to specifically assess the joint symptoms, including the Oxford Knee Score (OKS), the Oxford Hip Score (OHS), the Michigan Hand Outcomes Questionnaire (MHQ), and the Manchester Foot Pain Disability Questionnaire (MFPDQ). Descriptive analysis was used to analyse participants' baseline data and the prevalence of pain. Stepwise multiple regression was used to identify the correlates of pain. RESULTS: Four hundred and ten participants were analysed. According to the NMQ, 71.7% of the participants experienced joint symptoms in at least one joint, and the most frequently mentioned joint was knee (39.0%). The diagram in BPI indicated that 28.0% of the participants had the worst pain around knees. In patients with knee pain, the mean OKS score was 40.46 ± 6.19. The sub-scores of BPI for pain intensity and pain interference were 1.30 ± 1.63 and 1.24 ± 1.79, respectively. Patients' poorer physical well-being/functioning, previous use of AI treatment, presence of osteoarthritis, and receiving of physiotherapy were identified as four common correlates of greater severity of pain and pain interference (p < 0.05). CONCLUSIONS: Chinese breast cancer survivors can experience joint pain at various locations, particularly knees. In addition to increasing the use of interventions for pain alleviation, a comprehensive assessment of survivors' conditions such as physical functioning, history of AI treatment, and presence of osteoarthritis should be emphasized to identify survivors who need more attention and tailored interventions.