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Background Patients with chronic obstructive pulmonary disease (COPD) often have comorbid generalized anxiety disorder (GAD), which requires early screening in respiratory clinics. The Generalized Anxiety Disorder-7 (GAD-7) questionnaire is a brief and commonly used screening tool for GAD but has not been validated among patients with COPD in China. Methods Stable patients with COPD from a cross-sectional observational study were assessed using the GAD-7 questionnaire and then assessed by a senior psychiatrist to confirm a diagnosis of GAD according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Demographic characteristics, spirometry, and patient-reported outcomes were collected. Cronbach’s α coefficient was calculated, and receiver operating curve (ROC) analysis was performed to validate the GAD-7. Results A total of 226 patients with COPD were enrolled, and 50 (22.1%) of these patients were diagnosed with GAD. The Cronbach’s α coefficient for the GAD-7 was 0.869, which indicated good internal consistency. ROC curve analysis showed that the GAD-7 had an area under the curve (AUC) value of 0.829 (95% CI: 0.774–0.876) for identifying GAD. The optimal cut-off score was ≥ 4, with a sensitivity of 66.0% and a specificity of 89.2%. Higher GAD-7 scores were significantly associated with health-related quality of life and the symptom burden of COPD. The discriminatory power of GAD-7 did not differ statistically when stratified by COPD severity. Conclusions The GAD-7 was shown to be a reliable and valid screening tool for patients with COPD in China, and its screening performance for GAD was not influenced by disease severity.

Objective To evaluate the safety and efficacy of intra-articular (IA) injection of allogeneic adipose-derived stem cells (ADSCs) ELIXCYTE® for knee osteoarthritis. Methods This was a patient-blind, randomized, active-control trial consisted of 4 arms including hyaluronic acid (HA) control and 3 ELIXCYTE® doses. A total of 64 subjects were screened, and 57 subjects were randomized. The primary endpoints included the changes from baseline to post-treatment visit of Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score at Week 24 and the incidence of adverse events (AEs) and serious adverse events (SAEs). Results No ELIXCYTE®-related serious adverse events were reported during 96 weeks of follow-up and no suspected unexpected serious adverse reaction (SUSAR) or death was reported. The changes of the primary endpoint, WOMAC pain score at Week 24, showed significant differences in all ELIXCYTE® groups, as well as in HA groups between post-treatment visit and baseline. The ELIXCYTE® groups revealed significant decreases at Week 4 compared to HA group in WOMAC total scores, stiffness scores, functional limitation scores suggested the potential of ELIXCYTE® in earlier onset compared to those from HA. The significant differences of visual analog scale (VAS) pain score and Knee Society Clinical Rating System (KSCRS) functional activities score at Week 48 after ELIXCYTE® administration suggested the potential of ELIXCYTE® in the longer duration of the effectiveness compared to HA group. Conclusions ELIXCYTE® for knee osteoarthritis treatment was effective, safe, and well-tolerated. The efficacy results were showed that ELIXCYTE® conferred the earlier onset of reductions in pain scores and improvements in functional scores than HA group. Trial registration : ClinicalTrials.gov Identifier: NCT02784964. Registered 16 May, 2016—Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02784964

Epithelial-mesenchymal transition drives tumor metastasis and therapeutic resistance, yet few treatments have been developed that target this process. Here, we show that ELMO2 represents a specific vulnerability in mesenchymal-like cells. ELMO2 suppression induces excessive autophagy and cell death via FAK activity inhibition. We identify ELMO3 as a functional paralog that compensates for ELMO2 loss, establishing a synthetic lethal interaction. The epithelial-mesenchymal transition core regulator ZEB1 represses ELMO3 transcription in mesenchymal-like cells, rendering them sensitive to ELMO2 blockade. ELMO3 is significantly downregulated in epithelial-mesenchymal transition-associated EGFR inhibitor-resistant cells. Furthermore, the survival of these resistant, mesenchymal-like cells depends on ELMO2/FAK signaling. Through structure-based screening, we identify C52, a small-molecule ELMO2 inhibitor that effectively kills ELMO3 -low lung cancer cells and EGFR inhibitor-resistant cells. Our study uncovers an ELMO2-ELMO3 synthetic lethal interaction and establishes ELMO2 as a potential therapeutic target for mesenchymal-like cancer and drug-resistant non-small cell lung cancer. Epithelial-mesenchymal transition (EMT) is a common mechanism for acquired resistance to EGFR tyrosine kinase inhibitors (TKIs). Here, the authors discover that ZEB1-mediated repression of ELMO3 creates a synthetic-lethal dependence on ELMO2, and that inhibiting ELMO2 selectively kills mesenchymal-like cells and EGFR TKIs–resistant cancer cells.

Background Patient Health Questionnaire (PHQ-9) and PHQ-2 are commonly used screening tools for depression but have not been validated in Chronic obstructive pulmonary disease (COPD) patients. We aimed to validate PHQ-9 and PHQ-2 among COPD patients in China. Methods Stable COPD patients were assessed using a PHQ-9 questionnaire and then assessed by a senior psychiatrist to confirm the diagnosis of major depressive disorder (MDD) according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Receiver operating characteristic curve analysis was performed to validate the PHQ-9/PHQ-2. Results Out of 265 COPD patients, 11.7% were diagnosed with MDD. The Cronbach’s α-coefficient for PHQ-9 was 0.751. Both PHQ-9 and PHQ-2 showed good correlations with COPD symptoms and quality of life. The AUC values of PHQ-9 and PHQ-2 were 0.848 and 0.736, respectively, for identifying MDD. Based on the highest Youden index, the optimal cut-off scores were PHQ-9 ≥ 7 and PHQ-2 ≥ 2, with a sensitivity of 74.2% and 58.1% and specificity of 89.7% and 89.3%, respectively. Conclusion PHQ-9 score ≥ 7 and PHQ-2 score ≥ 2 should be used as the optimal cut-offs for COPD patients in China. PHQ-9 is a valid tool for detecting MDD in COPD patients, while PHQ-2 (score < 2) is more useful for quickly excluding MDD.

Intratumoral heterogeneity, including epithelial–mesenchymal transition (EMT), is one major cause of therapeutic resistance. The induction of ferroptosis, an iron‐dependent death, has the potential in overcoming this resistance to traditional treatment modalities. However, the roles of distinct EMT phenotypes in ferroptosis remain an enigma. This study reports that 3D soft fibrin microenvironment confers colorectal cancer (CRC) cells hybrid EMT phenotype and high level of resistance to ferroptosis. The activation of histone acetylation and WNT/β‐catenin signaling drives this EMT phenotypic transition, which promotes the defense of 3D CRCs against ferroptosis via glutathione peroxidases/ferritin signaling axis. Unexpectedly, E‐cadherin knockout in 3D but not 2D CRCs mediates an integrin β3 marked‐late hybrid EMT state and further enhances the resistance to ferroptosis via integrin‐mediated tension and mitochondrial reprogramming. The inhibition of integrin αvβ3‐mediated tension and WNT/β‐catenin‐mediated hybrid EMT sensitizes 3D CRCs with and without E‐cadherin deficiency to ferroptosis in vivo, respectively. Further, the EMT phenotype of patient‐derived tumoroids is associated with CRC therapeutic resistance. In summary, this study uncovers previously unappreciated roles of hybrid EMT and cell membrane tension in ferroptosis, which not only predict the treatment efficacy but also potentiate the development of new ferroptosis‐based targeted therapeutic strategies. Colorectal cancer cells (CRCs) cultured in 3D soft fibrin exhibit hybrid epithelial–mesenchymal transition (EMT) mediated ferroptosis resistance via WNT/β‐catenin signaling. Unlike 2D cells, 3D CRCs exhibit reduced E‐cadherin, knockout of which further enhances the defense against ferroptosis via adhesion‐mediated tension. This work reveals the distinct roles of EMT states in CRC ferroptosis and the biomechanical vulnerability of therapeutic resistance.

In this study, a novel oxygenated nanocomposite thin film, TaON-Ag, was investigated in vitro and in vivo to evaluate its biocompatibility and antibacterial ability. The antibacterial ability of TaON-Ag nanocomposite-coated titanium (Ti) was evaluated using the Kirby-Bauer disk diffusion susceptibility test. The effects of TaON-Ag nanocomposite-coated metal on osteogenesis were further evaluated in an in vitro osteogenic culture model with rat marrow-derived mesenchymal stem cells (rMSCs). Furthermore, titanium rods coated with TaON-Ag were implanted into a rat femur fracture model either with or without osteomyelitis to investigate the effects of TaON-Ag in osteogenesis. The TaON-Ag-coated Ti exhibited an effective antibacterial effect against , coagulase-negative , and the Gram-negative strains and . Using an osteogenic culture with rMSCs and a rat femoral fracture model, the TaON-Ag-coated Ti did not interfere with the ossification of rMSCs in vitro or during fracture healing in vivo. Field-emission scanning electron microscopy (FE-SEM) revealed that coating with TaON-Ag could inhibit pathogen adhesion and biofilm formation in both and Using the proposed novel oxygenation process, TaON-Ag nanocomposite-coated Ti yielded robust biocompatibility and antibacterial ability against common microorganisms in orthopedic infections, thereby demonstrating potential for use in clinical applications.

Mobile phones (MPs) have been an essential part of the lives of healthcare professionals and have improved communication, collaboration, and sharing of information. Nonetheless, the widespread use of MPs in hospitals has raised concerns of nosocomial infections, especially in areas requiring the highest hygienic standards such as operating rooms (ORs). This study evaluated the incidence of bacterial contamination of the MPs carried by medical staff working in the OR and determined its association with bacterial colonization of this personnel. This is an observational cohort study. Medical staffs working in the OR were asked to take bacterial cultures from their MPs, anterior nares, and dominant hands. To identify the relation between MP contamination and bacterial colonization of the medical staff, genotyping of Staphylococcus aureus (SA) was done via Staphylococcus protein A gene (spa) typing and pulsed-field gel electrophoresis (PFGE). A total of 216 swab samples taken from 72 medical-staff members were analyzed. The culture-positive rate was 98.1% (212/216). In 59 (27.3%) samples, the bacteria were possible clinical pathogens. The anterior nares were the most common site of colonization by clinical pathogens (58.3%, 42/72), followed by MPs (13.9%, 10/72) and the dominant hand (9.7%, 7/72). SA was the most commonly isolated clinical pathogen and was found in 43 (19.9%) samples. In 66 (94.3%) of the 70 staff members for whom bacteria were detected on their MPs, the same bacteria were detected in nares or hand. Among 31 medical staff who were carriers of SA in the anterior nares or dominant hand, 8 (25.8%) were found to have SA on their MPs, and genotyping confirmed the same SA strain in 7 (87.5%) of them. A high rate of bacterial nasal colonization and MPs contamination were found among the OR medical staff. An MP may be a reservoir for pathogen contamination in the OR.

Purpose The Coronavirus Disease 2019 (COVID-19) pandemic delayed elective procedures such as total joint arthroplasty. As surgical volumes return to prepandemic levels, understanding the implications of COVID-19 becomes imperative. This study explored the effects of COVID-19 on the short-term outcomes of hip arthroplasty. Methods This multicenter, retrospective, case–control study included patients who had undergone hip arthroplasty between 2020 and 2022. Propensity score matching (PSM) was performed to compare demographic characteristics, primary outcomes, and secondary outcomes between patients with a history of COVID-19 (COVID-19 cohort) and those without it (control cohort). The primary outcomes were surgical site infection, periprosthetic joint infection (PJI), dislocation, prosthesis loosening, deep vein thrombosis, and pulmonary embolism. The secondary outcomes were intraoperative blood loss, nerve injury, renal injury, urinary tract infection (UTI), pneumonia, and acute coronary syndrome. Results The COVID-19 and control cohorts comprised 153 and 4925 patients, respectively. After PSM, significant between-cohort differences were observed in the incidence of pneumonia ( p  < 0.001) and UTI ( p  = 0.0424). The odds ratio for PJI was 1.62, which is not significant ( p  = 0.3238) but the culture-negativity rate is higher in the COVID-19 cohort (25%). Conclusion Our findings suggest that COVID-19 only elevated risks of postoperative pneumonia and UTI after hip arthroplasty. This disease significantly increases the risk of postoperative pneumonia but not of 90-day mortality or any major perioperative complication. On the other hand, PJI still remains a concern because its treatment is challenging owing to its culture-negativity, often necessitating the Girdlestone procedure.

The spin Hall effect (SHE), typically emerging in non-magnetic metals with strong spin-orbit couplings, has attracted significant attention for its ability to convert a charge current into a spin current, a key feature in power-efficient spintronic devices. Recently, an enhanced SHE has been detected in the magnetic alloys, where the spin Hall conductivity is strongly modified by the dynamical and thermal spin fluctuations. We find that the spin Hall angle (${\\theta _{{\\text{SH}}}$) in Pt _100− _x Co _x alloys dramatically changes at the Curie temperature, which is positive in the paramagnetic phase akin to Pt, while negative in the ferromagnetic phase. Such intriguing behavior of${\\theta _{{\\text{SH}}}$stemming from individual and collective fluctuations in the magnetic moments is further substantiated with the full-fledged Monte Carlo simulations. Our work broadens insights into the SHE and highlights the importance of spin fluctuations for the spin-current generation near the ferromagnetic instability point of magnetic alloys.

Mycobacterium tuberculosis periprosthetic joint infection (TBPJI) is a rare complication of hip/knee joint arthroplasty. The outcomes of hip/knee TBPJI treatment are still unreported. The objective of this study was to investigate the outcomes of hip/knee TBPJI following treatment with two-stage exchange arthroplasty. From 2003 to 2013, 11 patients with TBPJI (six hips and five knees) were treated with two-stage exchange arthroplasty at our institution. We collected and analyzed variables including demographic data, comorbidities, microbiological data, duration of symptoms, and types of antibiotic used in bone cement. At the most recent follow-up, the success rate of two-stage exchange arthroplasty was 63.3% (7 of 11). All five knee treatments resulted in infection eradication and successful prosthesis reimplantation. However, only two hip TBPJI treatments resulted in successful outcomes; two patients died and two experienced chronic infection. Overall, secondary bacterial infections were common in patients with TBPJI (5 of 11 cases, 45.5%). Streptomycin in bone cement increased the success rate (83.33% vs. 40%). More than one third of the patients treated with two-stage exchange arthroplasty for TBPJI showed infection relapse or uncontrolled infection. Streptomycin-loaded interim cement spacers appeared to help ensure successful treatment. Routine M. tuberculosis culture is recommended when treating TBPJI in areas of high tuberculosis prevalence.