Unconsciousness as the main nonfocal symptom of anterior circulation transient ischemic attack: A case report.

RATIONALE: Unconsciousness is a nonfocal symptom of transient ischemic attack (TIA) that is frequently observed in patients with vertebrobasilar artery stenosis or occlusion. Conversely, loss of consciousness due to anterior circulation involvement (e.g., middle cerebral artery [MCA]) is a rare occurrence in TIA. PATIENT CONCERNS: This report describes a rare case in a 59-year-old woman who experienced recurrent episodes of altered consciousness because of the occlusion or stenosis of her MCAs. DIAGNOSES: The diagnosis of the case was updated from TIA to acute cerebral infarction, finally. Following initial loss of consciousness, cranial magnetic resonance imaging (MRI) did not reveal any evidence of acute cerebral infarction. However, following the second and third episodes of unconsciousness, the MRI revealed multiple new acute cerebral infarcts affecting both the cerebral hemispheres. Further evaluation through digital subtraction angiography disclosed complete occlusion of the left MCA and severe stenosis of the right MCA. INTERVENTIONS: Early in her illness, the patient was treated with vasodilators, aspirin and atorvastatin. Finally, 2 stents in her right and left MCAs were placed respectively, followed by treatment with aspirin, clopidogrel, and double-dosed atorvastatin calcium. Meanwhile, the patient focused on avoiding conditions which may lead to dehydration in her daily life routine. OUTCOMES: The episodes of unconsciousness of this patient were completely resolved. During the 1-year postoperative follow-up, the patient remained clinically stable without any symptoms of unconsciousness, limb numbness or weakness, or dizziness. LESSONS: These findings suggested that hypoperfusion in the bilateral cerebral hemispheres played a pivotal role in precipitating the patient episodes of unconsciousness. This case underscores the possibility that occlusion or severe stenosis in both MCAs can contribute to recurrent episodes of unconsciousness due to hypoperfusion. Moreover, it emphasizes the association between these episodes of unconsciousness and an increased risk of subsequent ischemic stroke.

An AIE Controlled "Off-On" Cu2+-Sensitive Probe for Early Detection of Renal Fibrosis.

Early detection of renal fibrosis (RF) is very important given that it is irreversible when it progresses to the terminal stage. A key marker of RF pathogenesis is activation of myomyofibroblasts, and its targeted imaging may be a promising approach for early detection of RF, but no study has directly imaged activation of renal myomyofibroblasts. Cu2+ plays a major role in the fibrotic activity of myofibroblasts. Herein, inspired by that Cu2+ can complex with bovine serum albumin (BSA), BSA-Ag2S quantum dots (QDs) with aggregation-induced emission (AIE) property are synthesized. Then BSA-Ag2S QDs are modified by chitosan (CS) with renal targeting and hyaluronic acid (HA) with myofibroblast targeting to obtain the AIE assay system (QDs@CS@HA). The system is simple to synthesize, and produces a rapid NIR fluorescence signal turn-on response and a low detection limit of 75 × 10-9 m to Cu2+. In addition, cellular and animal experiments have shown that QDs@CS@HA has good biosafety and cell-targeted imaging capability for RF. Based on the successful application of QDs@CS@HA and the mechanism of RF progression in early RF detection, it is expected that QDs@CS@HA may detect RF before the appearance of clinical symptoms.

Light mixed-supervised segmentation for 3D medical image data.

BACKGROUND: Accurate 3D semantic segmentation models are essential for many clinical applications. To train a model for 3D segmentation, voxel-level annotation is necessary, which is expensive to obtain due to laborious work and privacy protection. To accurately annotate 3D medical data, such as MRI, a common practice is to annotate the volumetric data in a slice-by-slice contouring way along principal axes. PURPOSE: In order to reduce the annotation effort in slices, weakly supervised learning with a bounding box (Bbox) was proposed to leverage the discriminating information via a tightness prior assumption. Nevertheless, this method requests accurate and tight Bboxes, which will significantly drop the performance when tightness is not held, that is when a relaxed Bbox is applied. Therefore, there is a need to train a stable model based on relaxed Bbox annotation. METHODS: This paper presents a mixed-supervised training strategy to reduce the annotation effort for 3D segmentation tasks. In the proposed approach, a fully annotated contour is only required for a single slice of the volume. In contrast, the rest of the slices with targets are annotated with relaxed Bboxes. This mixed-supervised method adopts fully supervised learning, relaxed Bbox prior, and contrastive learning during the training, which ensures the network exploits the discriminative information of the training volumes properly. The proposed method was evaluated on two public 3D medical imaging datasets (MRI prostate dataset and Vestibular Schwannoma [VS] dataset). RESULTS: The proposed method obtained a high segmentation Dice score of 85.3% on an MRI prostate dataset and 83.3% on a VS dataset with relaxed Bbox annotation, which are close to a fully supervised model. Moreover, with the same relaxed Bbox annotations, the proposed method outperforms the state-of-the-art methods. More importantly, the model performance is stable when the accuracy of Bbox annotation varies. CONCLUSIONS: The presented study proposes a method based on a mixed-supervised learning method in 3D medical imaging. The benefit will be stable segmentation of the target in 3D images with low accurate annotation requirement, which leads to easier model training on large-scale datasets.

Abnormal mechanical stress induced chondrocyte senescence by YAP loss-mediated METTL3 upregulation.

OBJECTIVES: Abnormal mechanical stress is the pivotal risk factor of temporomandibular joint osteoarthritis (TMJOA). This study investigated the pathogenic mechanism by which abnormal mechanical stress induced chondrocyte senescence. MATERIALS AND METHODS: Cellular senescence was investigated in the rodent model of unilateral anterior crossbite and in the chondrocytes subjected to mechanical overloading in vitro. The effects of Yes-associated protein (YAP) in chondrocyte senescence and its correlation with methyltransferase-like 3 (METTL3) and N6 -methyladenosine (m6 A) modification were evaluated. The role of m6 A modification in chondrocyte senescence was determined. The therapeutic effects of m6 A inhibition in TMJOA were investigated. RESULTS: Senescent chondrocytes were accumulated in the mechanically induced TMJOA lesions in rats and mechanical overloading could trigger chondrocyte senescence in vitro. This mechanical stress-induced cellular senescence was revealed to be mediated by YAP deficiency that promoted METTL3-dependent m6 A modification. Moreover, inhibition of m6 A modification rescued chondrocyte senescence in vitro and in vivo, and suppressed TMJOA progression in rats. CONCLUSIONS: This study uncovered the underlying mechanism of mechanically induced senescence in TMJOA from the perspective of epitranscriptomics and revealed the therapeutic potential of m6 A inhibition in TMJOA.

Perampanel ameliorates nitroglycerin-induced migraine through inhibition of the cAMP/PKA/CREB signaling pathway in the trigeminal ganglion in rats.

Background: Perampanel, a highly selective glutamate AMPA receptor antagonist, is widely used to treat epilepsy. Since the existence of common pathophysiological features between epilepsy and migraine, the aim of this study was to investigate whether perampanel could exert an antimigraine effect. Methods: Nitroglycerin (NTG) was used to induce a migraine model in rats, and the model animals were pretreatment with 50 µg/kg and 100 µg/kg perampanel. The expression of pituitary adenylate-cyclase-activating polypeptide (PACAP) was quantified by western blot and quantitative real-time PCR in the trigeminal ganglion, and rat-specific enzyme-linked immunosorbent assay in serum. Western blot was also conducted to explore the effects of perampanel treatment on the phospholipase C (PLC)/protein kinase C (PKC) and protein kinase A (PKA)/cAMP-responsive-element-binding protein (CREB) signaling pathways. Moreover, the cAMP/PKA/CREB-dependent mechanism was evaluated via in vitro stimulation of hippocampal neurons. The cells were treated with perampanel, antagonists and agonists for 24 hours and cell lysates were prepared for western blot analysis. Results: Perampanel treatment notably increased the mechanical withdrawal threshold and decreased head grooming and light-aversive behaviors in NTG-treated rats. It also decreased PACAP expression and affected cAMP/PKA/CREB signaling pathway. However, PLC/PKC signaling pathway may not be involved in this treatment. In in vitro studies, perampanel notably decreased PACAP expression by inhibiting cAMP/PKA/CREB signaling pathway. Conclusions: This study shows that perampanel inhibits the migraine-like pain response and that this beneficial effect might be attributable to regulation of the cAMP/PKA/CREB signaling pathway.

A nano-delivery system based on preventing degradation and promoting absorption to improve the oral bioavailability of insulin.

Oral insulin delivery can improve patient compliance and simulate the portal-peripheral insulin concentration gradient produced by endogenous insulin, so oral insulin delivery has a broad prospect. However, some characteristics of the gastrointestinal tract, lead to low oral bioavailability. Therefore, a "ternary mutual-assist" nano-delivery system based on poly(lactide-co-glycolide) (PLGA) as the backbone combined with ionic liquids (IL) and vitamin B12-chitosan (VB12-CS) was constructed in this study, the protein protection performance of IL improves the room temperature stability of the loaded insulin during nanocarrier preparation, transportation and storage to a certain extent, and the protein protection function of IL combined with the slow degradation property of PLGA and the pH-responsive function of VB12-CS to prevent the degradation of insulin in the gastrointestinal tract. In addition, the mucosal adhesion function of VB12-CS, VB12 receptor- and clathrin-mediated transcellular transport involving VB12-CS and IL, and paracellular transport mediated by IL and CS can be combined to improve the intestinal epithelial transport efficiency of insulin, thus, the nanocarrier has stronger preventing degradation and promoting absorption effects. Pharmacodynamic studies showed that after oral administration of VB12-CS-PLGA@IL@INS NPs to diabetic mice, the blood glucose level decreased to about 13 mmol/L, below the critical point of 16.7 mmol/L, and the blood glucose reached a normal level, which was 0.4 times of the blood glucose value before administration, its relative pharmacological bioavailability was 31.8 %, higher than the general nanocarriers (10-20 %) and more beneficial to the clinical transformation of oral insulin.

Dumbbell Aptamer Sensor Based on Dual Biomarkers for Early Detection of Alzheimer's Disease.

Finding a timely, sensitive, and noninvasive detection method has become an urgent need for asymptomatic early diagnosis of Alzheimer's disease (AD). MicroRNA-193b (miR-193b) and Aß42 oligomers (AßO42) in neurogenic exosomes were confirmed to reflect pathological changes in the AD early stage. The combination of two biomarkers is promising for the earlier detection of AD. In this study, a detection system based on the principle of the entropy-driven strand displacement reaction (ESDR) was developed, including a dumbbell detection probe (H), an indicator probe (R), and graphene oxide (GO). In the detection system, the two hairpins of H were opened by the interaction of miR-193b (T1) and AßO42 (T2) with the aptamer. Then R hybridized with H and began to displace T, initiating the next round of ESDR to achieve sensitive detection of T. GO specifically adsorbed free R and quenched the fluorescence, further reducing the intensity of the background signal. Both of these points provided the system with a more sensitive analytical performance. The detection limit of miR-193b was 77 pM and the detection limit of AßO42 was 53 pM. This sensor detected the change of "one increase (AßO42) and one decrease (miR-193b)" in the exosome sample. Additionally, results showed that this detection system could distinguish the model of early AD from the non-AD control, which was sufficient for earlier and more sensitive detection of AD. This strategy has strong specificity, high sensitivity, and easy operation, which provides broad prospects for the early diagnosis of AD.

Association of Diet-Related Systemic Inflammation with Periodontitis and Tooth Loss: The Interaction Effect of Diabetes.

Diet is an important factor that can affect inflammatory processes. Diet-related systemic inflammation is closely linked to periodontitis and tooth loss. However, the role that systemic conditions play in influencing this association remains unclear. A cross-sectional analysis was conducted using the National Health and Nutrition Examination Survey (NHANES) from 2009 to 2014. Diet-related systemic inflammation was assessed by the Dietary Inflammatory Index (DII). Multivariate Cox regression models were used to investigate the association between DII and periodontal results, including total periodontitis, tooth loss, severe tooth loss, and the number of teeth lost. The interaction effects between DII and established covariates were tested. Higher DII scores, corresponding to a higher pro-inflammatory potential of the diet, were associated with an increased risk of periodontitis and tooth loss among the 10,096 eligible participants. There was an interaction between diabetes and DII on total periodontitis (p = 0.0136). No significant interaction effect was detected between DII and other established covariates. Participants who consumed an anti-inflammatory diet, and did not have diabetes, experienced the lowest risks of periodontitis and tooth loss. However, in the context of diabetes, the efficacy of such a diet may be weakened or even eliminated. Dietary interventions to manage oral health problems may need to take the individual's metabolic condition into account.

Inhibition of osteoclastogenesis by interleukin-33 administration in the periodontal ligament under mechanical loading.

BACKGROUND AND OBJECTIVES: The molecular mechanisms mediating external root resorption are poorly understood. Interleukin-33 (IL-33) expression increased remarkably in the periodontal ligament (PDL) under orthodontic loading. The IL-33-driven responses are delicately cell type- and tissue context-dependent. It is unknown how IL-33 act on osteoclastogenesis in the context of root surface. This study aimed to investigate the effect of IL-33 on osteoclastogenesis in the PDL under mechanical loading. MATERIALS AND METHODS: C57BL/6J mice were treated with injections of phosphate buffer saline (PBS) or recombinant mouse IL-33 (rmIL-33, 6 µl, 30 µg/ml), and subjected to models of orthodontic tooth movement. Tartrated resistant acid phosphates (TRAP)-positive cells and IL-33 expressions were examined in the PDL. IL-33 release from human PDL cells (hPDLCs) was detected by ELISA. Cementoblast-like (OCCM-30) cells were cultured in the presence of rmIL-33 to examine the release of osteoclast-regulatory proteins. The effects of rmIL-33 on osteoclastogenesis were examined in vitro in cultures of bone marrow macrophages (BMMs) and in BMMs-OCCM-30 cocultures. Expressions of osteoclast-specific or -related genes and proteins were investigated in BMMs-OCCM-30 cocultures treated with or without rmIL-33, in the presence or absence of granulocyte-macrophage colony-stimulating factor (GM-CSF) neutralizing antibody. RESULTS: Interleukin-33 expressions were upregulated in the PDL under orthodontic loading. Static compressive force enhanced expression and release of IL-33 from hPDLCs. Administration of rmIL-33 resulted in reduced number of TRAP-positive cells in the PDL, and inhibited osteoclast differentiation from BMMs in vitro. OCCM-30 cells had varied osteoprotegerin (OPG) / receptor activator for nuclear factor-κB ligand (RANKL) secretion and increased release of GM-CSF under rmIL-33 stimulation. Treatment with rmIL-33 in BMMs-OCCM-30 cocultures resulted in inhibited differentiation and decreased activity of osteoclasts, and these effects were partially reversed by GM-CSF neutralizing antibody. CONCLUSIONS: Interleukin-33 inhibits osteoclastogenesis in the PDL under orthodontic loading. The anti-osteoclastogenic effects were mediated partly by directly affecting osteoclast precursors and partly by cementoblast-mediated release of GM-CSF.

How did COVID-19 impact driving behaviors and crash Severity? A multigroup structural equation modeling.

Risky driving behaviors such as speeding and failing to signal have been witnessed more frequently during the COVID-19 pandemic, resulting in higher rates of severe crashes. This study aims to investigate how the COVID-19 pandemic impacts the likelihood of severe crashes via changing driving behaviors. Multigroup structural equation modeling (SEM) is used to capture the complex interrelationships between crash injury severity, the context of COVID-19, driving behaviors, and other risk factors for two different groups, i.e., highways and non-highways. The SEM constructs two latent variables, namely aggressiveness and inattentiveness, which are indicated by risk driving behaviors such as speeding, drunk driving, and distraction. One great advantage of SEM is that the measurement of latent variables and interrelationship modeling can be achieved simultaneously in one statistical estimation procedure. Group differences between highways and non-highways are tested using different equality constraints and multigroup SEM with equal regressions can deliver the augmented performance. The smaller severity threshold for the highway group indicates that it is more likely that a crash could involve severe injuries on highways as compared to those on non-highways. Results suggest that aggressiveness and inattentiveness of drivers increased significantly after the outbreak of COVID-19, leading to a higher likelihood of severe crashes. Failing to account for the indirect effect of COVID-19 via changing driving behaviors, the conventional probit model suggests an insignificant impact of COVID-19 on crash severity. Findings of this study provide insights into the effect of changing driving behaviors on safety during disruptive events like COVID-19.

Short-term dynamics of circulating tumor DNA predicting efficacy of sintilimab plus docetaxel in second-line treatment of advanced NSCLC: biomarker analysis from a single-arm, phase 2 trial.

OBJECTIVE: Robust biomarker predicting efficacy of immunotherapy is limited. Circulating tumor DNA (ctDNA) sought to effectively monitor therapeutic response as well as disease progression. This study aims to investigate predictive role of ctDNA short-term dynamic change (6 weeks postimmunotherapy) in a single-arm, phase 2 trial of sintilimab plus docetaxel for previously treated advanced non-small cell lung cancer (NSCLC) patients. METHODS: A total of 33 patients with advanced NSCLC with disease progression during or after any first-line treatment were prospectively enrolled between 2019 and 2020. Patients received sintilimab (200 mg, day 1, every 3 weeks) plus docetaxel (75 mg/m2, day 3, every 3 weeks) for 4-6 cycles, followed by maintenance therapy with sintilimab (200 mg, day 1, every 3 weeks) until disease progression or unacceptable toxic effects. Blood samples were prospectively collected at baseline, and after 2 cycles of treatment (6 weeks post-treatment). All samples were subjected to targeted next-generation sequencing with a panel of 448 cancer-related genes. The landscape of high-frequency genomic profile of baseline and 6th week was described. Major molecular characteristics in preselected genes of interest associated with response to second-line chemoimmunotherapy were analyzed. The curative effects and prognosis of patients were evaluated. RESULTS: Patients with ctDNA clearance at 6th week had decreased tumor volume, while most patients with positive ctDNA at 6th-week experienced an increase in tumor volume. Positive 6th-week ctDNA was associated with significantly shorter progression-free survival (PFS) (91 vs NR days; p<0.0001) and overall survival (47 vs 467 days; p =0.0039). Clearance of clonal mutations and none new clonal formation at 6th week were associated with longer PFS (mPFS 89 vs 266 days, p =0.003). ctDNA clearance at 6th week was an independent risk factor for progression or death (HR=100 (95% CI 4.10 to 2503.00), p=0.005). CONCLUSION: ctDNA status and ctDNA mutation clearance putatively serve as predictive biomarkers for sintilimab combined with docetaxel chemotherapy in pretreated advanced NSCLC patients.

Home Coping Strategies for Fatigue Used by Patients With Lung Cancer Receiving Chemotherapy in Rural China: A Qualitative Study.

BACKGROUND: Cancer-related fatigue, a distressing symptom, is frequently reported by patients with lung cancer as increasing in severity with the number of rounds of chemotherapy. Yet, patients and healthcare providers are challenged to control this fatigue. Thus, healthcare providers must have interventions to effectively enhance coping engagement in patients with lung cancer. PURPOSE: The aims of this study were to explore how patients with lung cancer in a rural area of China undergoing chemotherapy cope with the fatigue at home and to summarize their strategies. METHODS: A descriptive qualitative research approach was used, and data were collected using semistructured interviews. Sixteen patients with lung cancer with chemotherapy-related fatigue living in rural communities were recruited from a large, tertiary teaching hospital in Huzhou in eastern China. The transcripts of the interviews were analyzed using content analysis. RESULTS: Coping strategies for cancer-related fatigue were delineated into the three themes of (a) psychological adjustment, (b) efforts to change lifestyles and act as a Chinese health practitioner, and (c) relying on social support. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: The participants in this study provided information on a variety of approaches to reducing/alleviating cancer-related fatigue that were influenced by Chinese culture. Healthcare providers and patients may work together in clinical settings to identify appropriate, effective coping solutions and then to incorporate these into the regular care regimen to help patients transition between hospital and home.

Subarachnoid hemorrhage secondary to Brucella-induced cerebral aneurysm: a case report.

BACKGROUND: Brucellosis is a common zoonotic disease that is prevalent in many areas worldwide. This infectious disease can occasionally affect the central nervous system but intracranial arteries are rarely involved. CASE PRESENTATION: A 17-year-old female who had a history of recurrent fever for 1 month was admitted for subarachnoid hemorrhage due to cerebral aneurysm rupture. Surgery was performed to fix the aneurysm, but the patient had persistent fever after the surgery. Cerebrospinal fluid testing showed a high white blood cell count and elevated protein level but no pathogen was identified in the first two tests. Brucella melitensis was identified in the third cerebrospinal fluid culture, and a diagnosis of brucellosis was finally rendered. The patient was subsequently treated with anti-Brucella medications and her symptoms improved significantly at the last follow-up. CONCLUSION: Although extremely rare, Brucella-induced cerebral aneurysms can occur and this should be considered in the differential diagnosis of cerebrovascular accidents, especially in Brucella epidemic areas.

A two-transcript biomarker of host classifier genes for discrimination of bacterial from viral infection in acute febrile illness: a multicentre discovery and validation study.

BACKGROUND: Acute febrile illness is one of the main reasons for outpatient hospital visits worldwide. However, differential diagnosis between bacterial and viral causes is challenging and misdiagnosis can result in antimicrobial overuse and hinder prompt treatment. We aimed to build and validate a diagnostic model to discriminate bacterial from viral infection in acute febrile illness by evaluating the expression of potential classifier host genes. METHODS: In this multicentre discovery and validation study, we included patients aged 14-85 years with acute febrile illness (fever for ≤14 days, axillary temperature of ≥38°C, and confirmed bacterial infection, viral infection, or non-infectious inflammatory disease), and healthy control participants (no significant medical history and no fever within the past 90 days) from four hospitals in Shandong province, China. Patients from the first hospital were divided into the screening, discovery, and internal validation groups, and patients from the three other hospitals comprised the external validation group. We measured expression of candidate genes in peripheral blood by RT-PCR, and patients for whom a successful RT-PCT result was recorded were included in the next-step analysis. For patients from the first hospital, those enrolled during the early phase of the study were assigned to the screening group, which was used to identify the optimal transcripts (IFI44L and PI3) for discrimination between bacterial and viral infections by screening four candidate genes (FAM89A, IFI44L, PI3, and ITGB2) by RT-PCR. The remaining patients were then randomly assigned (1:1) to discovery and internal validation groups by time of admission and blood drawing via the equidistant random sampling method. A logistic regression model integrating the mRNA levels of IFI44L and PI3 was built by use of the discovery group, and the diagnostic performance of the model was evaluated in the internal and external validation groups using area under the receiver operating curve (AUC), sensitivity, and specificity. FINDINGS: Between March 1, 2018, and Aug 31, 2019, we assessed 1658 individuals for inclusion in the study. After exclusion of ineligible participants, 458 participants were enrolled (178 patients with acute febrile illness caused by bacterial infection, 212 with acute febrile illness caused by viral infection, 38 with non-infectious inflammatory diseases, and 30 healthy controls). The 390 patients with bacterial or viral infections were assigned to one of four groups: screening (n=64, 33 with bacterial infections and 31 with viral infections), discovery (n=124, 55 with bacterial infections and 69 with viral infections), internal validation (n=124, 55 with bacterial infections and 69 with viral infections), and external validation (n=78, 35 with bacterial infections and 43 with viral infections). Of the four candidate host genes (FAM89A, IFI44L, PI3, and ITGB2), IFI44L and PI3 showed the most discriminative expression pattern and were used to build the logistic regression model. We established the optimal cutoff of the bacterial infection likelihood score to be 0·547598. With the diagnostic result from the gold standard tests (culture and PCR) as the reference, the two-transcript classifier model had an AUC of 0·969 (95% CI 0·937-1·000), sensitivity of 0·891 (0·782-0·949), and specificity of 0·971 (0·900-0·992) to discriminate bacterial and viral infections in the internal validation group. The model showed similar results in the external validation group (AUC 0·986, 95% CI 0·968-1·000; sensitivity 0·857, 0·706-0·937; and specificity 0·954, 0·845-0·987). INTERPRETATION: IFI44L and PI3 transcripts, measured by RT-PCR, are robust classifiers to discriminate bacterial from viral infection in acute febrile illness. This two-transcript biomarker has the potential to be transformed into a commercial panel and applied universally. FUNDING: None.

Irrational beliefs surrounding the diagnosis of breast cancer in young Chinese women: An observational study.

ABSTRACT: An irrational belief is the direct cause of negative emotions and behavioral disorders in patients with breast cancer. Thus, this article examines these patients' irrational beliefs, which helps improve the emotions and behavioral disorders of breast cancer patients. Chinese breast cancer patients have unique irrational beliefs due to the influence of Chinese traditional culture. To understand the irrational beliefs surrounding breast cancer diagnosis in young Chinese patients, we conducted an interpretative phenomenological study.Semi-structured interviews were conducted in young Chinese breast cancer patients. According to Colaizzi method modified by Edward and Welsh, transcribed interviews were analyzed to understand patients' irrational beliefs. Based on the theoretical framework, this study adopted interpretative phenomenology. Interpretive description was used to construct participants' experiences of irrational beliefs. Thematic sufficiency was confirmed after 17 interviews.Owing to the lack of knowledge about breast cancer, all participants were more susceptible to traditional Chinese culture, empiric theory, family reassurance, and healthcare providers' behaviors, leading to patients' irrational beliefs, negative emotions, and behavioral disorders.This research confirms that irrational beliefs in young Chinese breast cancer patients are profoundly influenced by traditional Chinese culture. Chinese healthcare providers can use this information to provide targeted nursing, supportive services, and research, and help women identify their beliefs and understand how these beliefs affect their health.

Improved Early Detection of Focal Brucellosis Complications with Anti-Brucella IgG.

To evaluate the associations of inflammatory factors and serological test results with complicated brucellosis, we recruited 285 patients with a diagnosis of brucellosis between May 2016 and September 2019. The patients were subsequently classified into two groups according to the presence of complications. We collected demographic and clinical information and routine laboratory test results in addition to anti-Brucella IgG and IgM levels. Anti-Brucella IgG and IgM were uniformly tested using enzyme-linked immunosorbent assays (ELISAs) in this study. Among the 285 patients with brucellosis, 111 (38.95%) had complicated brucellosis. Osteoarthritis occurred more often in the subacute and chronic stages than in the acute stage (P = 0.002). Genital infection occurred more frequently in the acute stage than in the other stages (P = 0.023). Fever was not frequently observed in complicated cases (P < 0.001). The erythrocyte sedimentation rate (ESR) and the C-reactive protein (CRP) and anti-Brucella IgM and IgG levels were higher in complicated-brucellosis patients than in uncomplicated-brucellosis patients (P < 0.001). Anti-Brucella IgG, with an area under the curve of 0.885 (95% confidence interval [CI], 0.847 to 0.924), was the most robust indicator of complicated brucellosis. Positive culture, anti-Brucella IgM, the ESR, and CRP could be considered indicators, but their efficacy was weaker than that of IgG. In conclusion, a high ESR, high CRP, high anti-Brucella IgM and IgG levels, and positive culture were indicators of complicated brucellosis; among these, anti-Brucella IgG was the most robust biomarker.

The Efficacy and Safety of High-dose Daptomycin in the Treatment of Complicated Skin and Soft Tissue Infections in Asians.

OBJECTIVE: To compare the efficacy and safety of standard-dose (SD) daptomycin with those of high-dose (HD) daptomycin in complicated skin and soft tissue infections (cSSTIs) in an Asian population. MATERIALS AND METHODS: Patients from three medical centers diagnosed with cSSTIs were screened in the clinical information system. Patients included in the analysis were divided into two groups: those who received daptomycin at doses ≥ 6 mg/kg (HD group) and those receiving 4 mg/kg (SD group). The demographics and clinical treatment information were analyzed. RESULTS: Overall, 155 patients were recruited, including 108 patients in the SD group and 47 patients in the HD group. The rate of healthcare-associated infections was higher in the HD group (61.70% vs. 37.04%), demonstrating a statistically significant difference (P = 0.005). Compared with the SD group, the HD group had statistically significant early clinical stabilization (72.34% vs 52.78%, P = 0.023). The results of the multivariate analysis indicated that HD daptomycin was an independent effector for early clinical stabilization (HR=0.394, P < 0.001). The rate of drug-related adverse events was equally distributed in the HD and SD groups (36.17% vs. 26.85%, P = 0.243). CONCLUSION: Compared with SD daptomycin, HD daptomycin increased the rate of early clinical stabilization in Asian patients with cSSTIs, whereas the incidence of adverse events did not increase.

Effect of interleukin-33 on cementoblast-mediated cementum repair during orthodontic tooth movement.

OBJECTIVE: This study aims to uncover the role of interleukin-33 on cementoblast-mediated cementum repair. METHODS: 6-8-week-old C57BL/6 mice were used to establish the model of orthodontic tooth movement. Interleukin-33 and suppression of tumorigenicity2 (ST2) expressions were immunohistochemically detected in the periodontal tissue. In vitro, cementoblast-like (OCCM-30) cells were cultured in the presence of recombinant mouse interleukin-33 protein (rmIL-33) at a 1-14 d time frame. ST2 expressions were immunofluorescently labeled and quantitatively examined. The effects of interleukin-33 on cementoblast differentiation, mineralization and proliferation were examined by alkaline phosphatase, alizarin red staining and cell counting kit-8, respectively. To further clarify the effect of interleukin-33 on cementogenesis-related protein expressions, runt-related transcription factor 2 (RUNX2), osterix, osteopontin, bone sialoprotein(BSP), osteocalcin, osteoprotegerin (OPG) and receptor activator of NF-КB ligand (RANKL) expressions were examined by western blot. RESULTS: Orthodontic load of high magnitude induces external apical root resorption, and increases interleukin-33 expression in the periodontal tissue of mice. Cells in the cementum express ST2. Interleukin-33 initially down-regulates but later recovers ST2 mRNA and protein levels in OCCM-30 cells. Interleukin-33 abates cementoblast differentiation and mineralization, and suppresses RUNX2, osterix, BSP and osteopontin expressions in OCCM-30 cells at the later stage of the culture period. Interleukin-33 enhances RANKL expression, and reduces the ratio of OPG/RANKL in OCCM-30 cells. CONCLUSION: Orthodontic load of high magnitude induces interleukin-33 expression in the periodontal tissue. Interleukin-33 has a negative effect on cementogenesis via suppressing cementoblast differentiation, mineralization and cementogenesis-related protein expressions.

Genetic alteration profile of EGFR-mutant resected IIB-IIIA stage NSCLC and correlation to clinical outcomes.

BACKGROUND: Genetic alteration profile of epidermal growth factor receptor (EGFR) mutant resected non-small cell lung cancer (NSCLC) and its relationship with clinical outcomes remains to be illustrated and genetic biomarkers that can predict recurrence need to be figured out. METHODS: Clinicopathological and follow-up information were collected for 99 EGFR-mutant resected NSCLC. Tumor sections were collected for genetic alteration detection. Targeted next-generation sequencing (NGS) was performed to detect somatic mutations within each sample using a 285-gene panel on the Ion Torrent platform. RESULTS: Concurrent driver gene mutations were detected in 86 participants. Adjuvant therapy was a positive factor in disease-free survival (DFS) period, and patients receiving tyrosine kinase inhibitors (TKIs) gained the longest DFS. A total of 34 concurrent mutant driver genes were found. The median number of mutated driver genes for each sample was 2 (range, 0-12). TP53 and NOTCH1 were the most frequent concurrent mutant driver genes with rates of 53.54% and 25.25% respectively. The number of concurrent mutant genes did not have a significant effect on recurrence. Multivariable analysis found that mutations of ATM (P=0.021), KIT (P=0.002), FGFR2 (P<0.001), MET (P=0.015), PDGFRA (P=0.042), RB1 (P=0.006), and wildtype NOTCH1 (P=0.032), ERBB4 (P=0.012), FGFR3 (P=0.035) were independent risk factors for the recurrence of resected EGFR mutant NSCLC. CONCLUSIONS: TP53 and NOTCH1 was the most common concurrent mutant driver gene. Mutations of ATM, KIT, FGFR2, MET, PDGFRA, RB1, and wildtype NOTCH1, ERBB4, FGFR3 were independent risk factors for the recurrence of resected EGFR mutant NSCLC.

Sulbactam enhances the in vitro activity of sitafloxacin against extensively-drug resistant Acinetobacter baumannii.

The present study aimed to determine the in vitro activities of sulbactam and sitafloxacin against extensively-drug resistant Acinetobacter baumannii (XDR-A. baumannii). A total of 50 strains of XDR-A. baumannii were isolated from clinical specimens. Broth microdilution assay was applied to determine the minimum inhibitory concentration (MIC) for sulbactam and sitafloxacin. Microdilution checkerboard method was used to determine the in vitro activity of this antimicrobial combination. Accordingly, the fractional inhibitory concentration (FIC) and FIC index (FICI) were calculated. Time-kill study was also carried out for four strains with different susceptibilities to determine the bactericidal activities of individual or combined use of sitafloxacin and sulbactam. Isolates with MICs of sitafloxacin ≤2 mg/l were considered to be susceptible to sitafloxacin. The susceptibility rate for sitafloxacin was 92% originally. When combined with sulbactam, this rate increased to 96%. Microdilution checkerboard results indicated that, when tested in combination, sulbactam/sitafloxacin exhibited marked synergistic and partial synergistic effects on 16 and 50% of the 50 strains, respectively. Time-kill assay suggested that sulbactam enhanced the bactericidal activity of sitafloxacin and the combination induced a synergistic effect. For strains that were not susceptible to sitafloxacin, the bactericidal activities of the combination of sitafloxacin and sulbactam at a sub-MIC concentration were impaired. However, this impairment could be overcome with the increase of the concentration to 1X MIC. The present study demonstrated that sulbactam enhanced the in vitro antimicrobial activity of sitafloxacin against XDR-A. baumannii.