Vonoprazan-amoxicillin dual therapy for Helicobacter pylori eradication in Chinese population: A prospective, multicenter, randomized, two-stage study.

BACKGROUND: The efficacy of Vonoprazan-amoxicillin dual therapy (VAT) in the treatment of Helicobacter pylori (H. pylori) is controversial. AIM: To evaluate the efficacy of VAT in the Chinese population. METHODS: This prospective, multicenter, randomized, open-label, and two-stage study was conducted at 23 centers in Fujian, China (May 2021-April 2022). H. pylori-infected patients were randomized to bismuth quadruple therapy (BQT), BQT-Vonoprazan (BQT-V), seven-day VAT (VAT-7), ten-day VAT (VAT-10), and fourteen-day VAT (VAT-14) groups. The primary endpoint was the H. pylori eradication rate. The secondary endpoint was the frequency of adverse events. This study was registered with the Chinese Clinical Trial Registry, ChiCTR2100045778. RESULTS: In the first stage, VAT-7 and BQT-V groups were selected for early termination because less than 23 among 28 cases were eradicated. In the second stage, the eradication rates for BQT, VAT-10, and VA-14 were 80.2% [95% confidence interval (95%CI): 71.4%-86.8%], 93.2% (86.6%-96.7%), 92.2% (85.3%-96.0%) in the intention-to-treat (ITT) analysis, and 80.9% (95%CI: 71.7%-87.5%), 94.0% (87.5%-97.2%), and 93.9% (87.4%-97.2%) in the per-protocol analysis. The ITT analysis showed a higher eradication rate in the VAT-10 and VAT-14 groups than in the BQT group (P = 0.022 and P = 0.046, respectively). The incidence of adverse events in the VAT-10 and VAT-14 groups was lower than in the BQT group (25.27% and 13.73% vs 37.62%, respectively; P < 0.001). CONCLUSION: VAT with a duration of 10 or 14 days achieves a higher eradication rate than the BQT, with a more tolerable safety profile in H. pylori-infected patients in Fujian.

Integrin ß3 enhances glycolysis and increases lactate production in endometriosis.

BACKGROUND: Endometriosis (EMs) is a chronic disease characterized by endometrial-like tissue present outside of the uterus. Macrophages have been confirmed to participate in the development of EMs. Integrin ß3 (ITGB3), a ß-subunit of the integrin family, is crucial in tumor progression. In this study, we investigated the pivotal role of ITGB3 in endometrial stromal cells (ESCs) and its influence on the development of EMs, particularly focusing on the regulatory impact of macrophages. METHODS: In this study, we used western blot, Real-time qPCR, Immunohistochemistry to detected the high expression of ITGB3 in ESCs. ITGB3-overexpression ESCs (ITGB3-OE) was constructed and detected by RNA-seq with normal ESCs. ATP and lactate expression assay, transwell migration assay, wound healing, cell adhesion assay and other molecular biology techniques were used to explore the potential mechanisms. In vivo, we constructed the EMs mouse model and injected with cilengitite to inhibit ITGB3. RESULTS: Here, we found ITGB3 highly expressed in ectopic lesions in EMs. The increasing ITGB3 resulted in activating the glycolysis, which produced more ATP and lactate in ITGB3-OE. After culturing with lactate, the migration, proliferation and invasion ability of ESCs were enhanced, while the result in 2-DG was reversed. In vivo, the results showed that after antagonizing ITGB3, the number of ectopic lesions was decrease. CONCLUSIONS: Our findings indicate that ITGB3 up-regulated by macrophages are able to regulate the glycolysis to promote the development of EMs and lactate enhances the ability of proliferation, migration, invasion and adhesion of EMs iv vivo and in vitro.

Multi-Sensor-Assisted Low-Cost Indoor Non-Visual Semantic Map Construction and Localization for Modern Vehicles.

With the transformation and development of the automotive industry, low-cost and seamless indoor and outdoor positioning has become a research hotspot for modern vehicles equipped with in-vehicle infotainment systems, Internet of Vehicles, or other intelligent systems (such as Telematics Box, Autopilot, etc.). This paper analyzes modern vehicles in different configurations and proposes a low-cost, versatile indoor non-visual semantic mapping and localization solution based on low-cost sensors. Firstly, the sliding window-based semantic landmark detection method is designed to identify non-visual semantic landmarks (e.g., entrance/exit, ramp entrance/exit, road node). Then, we construct an indoor non-visual semantic map that includes the vehicle trajectory waypoints, non-visual semantic landmarks, and Wi-Fi fingerprints of RSS features. Furthermore, to estimate the position of modern vehicles in the constructed semantic maps, we proposed a graph-optimized localization method based on landmark matching that exploits the correlation between non-visual semantic landmarks. Finally, field experiments are conducted in two shopping mall scenes with different underground parking layouts to verify the proposed non-visual semantic mapping and localization method. The results show that the proposed method achieves a high accuracy of 98.1% in non-visual semantic landmark detection and a low localization error of 1.31 m.

Utilizing Raman spectroscopy for urinalysis to diagnose acute kidney injury stages in cardiac surgery patients.

BACKGROUND: The successful treatment and improvement of acute kidney injury (AKI) depend on early-stage diagnosis. However, no study has differentiated between the three stages of AKI and non-AKI patients following heart surgery. This study will fill this gap in the literature and help to improve kidney disease management in the future. METHODS: In this study, we applied Raman spectroscopy (RS) to uncover unique urine biomarkers distinguishing heart surgery patients with and without AKI. Given the amplified risk of renal complications post-cardiac surgery, this approach is of paramount importance. Further, we employed the partial least squares-support vector machine (PLS-SVM) model to distinguish between all three stages of AKI and non-AKI patients. RESULTS: We noted significant metabolic disparities among the groups. Each AKI stage presented a distinct metabolic profile: stage 1 had elevated uric acid and reduced creatinine levels; stage 2 demonstrated increased tryptophan and nitrogenous compounds with diminished uric acid; stage 3 displayed the highest neopterin and the lowest creatinine levels. We utilized the PLS-SVM model for discriminant analysis, achieving over 90% identification rate in distinguishing AKI patients, encompassing all stages, from non-AKI subjects. CONCLUSIONS: This study characterizes the incidence and risk factors for AKI after cardiac surgery. The unique spectral information garnered from this study can also pave the way for developing an in vivo RS method to detect and monitor AKI effectively.

ATP6V0A1-dependent cholesterol absorption in colorectal cancer cells triggers immunosuppressive signaling to inactivate memory CD8+ T cells.

Obesity shapes anti-tumor immunity through lipid metabolism; however, the mechanisms underlying how colorectal cancer (CRC) cells utilize lipids to suppress anti-tumor immunity remain unclear. Here, we show that tumor cell-intrinsic ATP6V0A1 drives exogenous cholesterol-induced immunosuppression in CRC. ATP6V0A1 facilitates cholesterol absorption in CRC cells through RAB guanine nucleotide exchange factor 1 (RABGEF1)-dependent endosome maturation, leading to cholesterol accumulation within the endoplasmic reticulum and elevated production of 24-hydroxycholesterol (24-OHC). ATP6V0A1-induced 24-OHC upregulates TGF-ß1 by activating the liver X receptor (LXR) signaling. Subsequently, the release of TGF-ß1 into the tumor microenvironment by CRC cells activates the SMAD3 pathway in memory CD8+ T cells, ultimately suppressing their anti-tumor activities. Moreover, we identify daclatasvir, a clinically used anti-hepatitis C virus (HCV) drug, as an ATP6V0A1 inhibitor that can effectively enhance the memory CD8+ T cell activity and suppress tumor growth in CRC. These findings shed light on the potential for ATP6V0A1-targeted immunotherapy in CRC.

Prospective study of urinary incontinence recovery following endoscopic enucleation of the prostate.

OBJECTIVE: To investigate the clinical trajectories and identify risk factors linked to post-enucleation urinary incontinence (UI). PATIENTS AND METHODS: In this prospective study (April 2020 to March 2022) at a single institution, 316 consecutive patients receiving endoscopic enucleation due to benign prostatic enlargement were included. Patient information and perioperative details were collected. Follow-ups, from 1 to 6 months, assessed postoperative UI using International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form and a four-item pad questionnaire, classified per International Continence Society definitions. Logistic regression analysed predictors at 1 week, while generalised estimating equation assessed risk factors from 1 to 3 months postoperatively. RESULTS: Patients with a median prostate volume of 57 mL underwent enucleation, with 22.5% experiencing postoperative UI at 1 week, 5.6% at 3 months, decreasing to 1.9% at 6 months. Multivariable analysis identified age (>80 years), specimen weight (>70 g), en bloc with anteroposterior dissection, and anal tone (Digital Rectal Examination Scoring System score <3) as potential factors influencing UI. Subgroup analysis revealed that specimen weight was associated with both continuous and stress UI. Anal tone was related to both other types and stress UI, while overactive bladder symptoms were associated with urge UI. CONCLUSION: In summary, our study elucidates transient risk factors contributing to temporary post-enucleation UI after prostatectomy. Informed decisions and personalised interventions can effectively alleviate concerns regarding postoperative UI.

UiO-66/PIM-1 Mixed-Matrix Membrane for Hexane Isomer Separation.

The separation of high-octane dibranched alkanes from naphtha is critical in the refining of gasoline. To date, research on the membrane-based separation of alkane isomers has been limited, with a particular paucity of investigations into mixed-matrix membranes. Herein, the continuous and dense UiO-66/PIM-1 mixed-matrix membrane, which was prepared through precise control of the interfacial structure, was first applied to the differentiation of C6 alkane isomers. Due to the synergistic combination of UiO-66 with differential adsorption capabilities for alkanes and PIM-1 that possesses a cross-linkable structure, the resulting UiO-66/PIM-1-(20) membrane demonstrated remarkable separation performance and high stability. Pervaporation measurements showed that the mass fraction of 2,2-dimethylbutane in the feed side was increased from 50.0 to 75.8 wt % while an excellent flux of 1700 g m-2 h-1 was maintained over a continuous 40 h period. The UiO-66/PIM-1-(20) membrane, characterized by its facile replication and processing, shows potential for large-scale fabrication. This study offers a new approach to the membrane separation of alkane isomers.

Use of fluoroquinolones and the risk of aortic and mitral regurgitation: A nationwide case-crossover study.

BACKGROUND: Recently, there have been conflicting results reporting an increased risk of AR or MR associated with oral fluoroquinolones (FQs).This study investigated whether the use of FQs increases the risk of mitral regurgitation (MR) or aortic regurgitation (AR). METHODS: A retrospective cohort study was conducted by using the Taiwan National Health Insurance research database. A unidirectional case-crossover design without selecting controls from an external population was adopted in this study. A total of 26,650 adult patients with new onset of AR or MR between January 1, 2000, and December 31, 2012, were identified. The risk of outcomes was compared between the hazard period and one of the randomly selected referent periods of the same individuals. RESULTS: Before exclusion of pneumonia diagnosed within 2 months before the index date, patients who took FQs had a significantly greater risk of AR or MR (adjusted odds ratio [aOR] 1.51, 95% confidence interval [CI] 1.30-1.77), any AR (combined AR and MR) (aOR 1.50, 95% CI 1.10-2.04), and any MR (combined AR and MR) (aOR 1.37, 95% CI 1.16-1.62). After exclusion of pneumonia, FQs exposure remained significantly associated with a greater risk of MR (aOR 1.38, 95% CI 1.17-1.62) and any MR (aOR 1.25, 95% CI 1.05-1.48). CONCLUSIONS: The findings suggested that patients treated with FQs could be warned about the potential risk for MR even after considering the possibility of protopathic bias. Reducing unnecessary FQs prescriptions may be considered to reduce the risk of valvular heart disease.

Potential and application of abortive transcripts as a novel molecular marker of cancers.

Abortive transcript (AT) is a 2-19 nt long non-coding RNA that is produced in the abortive initiation stage. Abortive initiation was found to be closely related to RNA polymerase through in vitro experiments. Therefore, the distribution of AT length and the scale of abortive initiation are correlated to the promoter, discriminator, and transcription initiation sequence, and can be affected by transcription elongation factors. AT plays an important role in the occurrence and development of various diseases. Here we summarize the discovery of AT, the factors responsible for AT formation, the detection methods and biological functions of AT, to provide new clues for finding potential targets in the early diagnosis and treatment of cancers.

Early reduction in albuminuria is associated with a steeper 'dip' in initial estimated glomerular filtration rate but favourable long-term kidney outcomes in people with diabetes receiving sodium-glucose cotransporter-2 inhibitors.

AIM: To assess if early change in albuminuria was linked to an initial change in estimated glomerular filtration rate (eGFR) and long-term kidney outcomes in people with type 2 diabetes (T2D) receiving sodium-glucose cotransporter-2 (SGLT2) inhibitors. METHODS: Using a medical database from a multicentre healthcare institute in Taiwan, we retrospectively enrolled 8310 people receiving SGLT2 inhibitors from 1 June 2016 to 31 December 2021. We compared the risks of initial eGFR decline, major adverse renal events (MARE; >50% eGFR reduction or development of end-stage kidney disease), major adverse cardiovascular events (MACE), or hospitalization for heart failure (HHF) using a Cox proportional hazards model. RESULTS: In all, 36.8% (n = 3062) experienced a >30% decrease, 21.0% (n = 1743) experienced a 0%-30% decrease, 14.4% (n = 1199) experienced a 0%-30% increase, and 27.7% (n = 2306) experienced a >30% increase in urine albumin-to-creatine ratio (UACR) after 3 months of SGLT2 inhibitor treatment. Greater acute eGFR decline at 3 months correlated with greater UACR reduction: -3.6 ± 10.9, -2.0 ± 9.5, -1.1 ± 8.6, and -0.3 ± 9.7 mL/min/1.73 m2 for the respective UACR change groups (p < 0.001). Over a median of 29.0 months, >30% UACR decline was associated with a higher risk of >30% initial eGFR decline (hazard ratio [HR] 2.68, 95% confidence interval [CI] 1.61-4.47]), a lower risk of MARE (HR 0.66, 95% CI 0.48-0.89), and a comparable risk of MACE or HHF after multivariate adjustment (p < 0.05). The nonlinear analysis showed early UACR decline was linked to a lower risk of MARE but a higher risk of initial steep eGFR decline of >30%. CONCLUSION: Physicians should be vigilant for the potential adverse effects of abrupt eGFR dipping associated with a profound reduction in UACR, despite the favourable long-term kidney outcomes in the population with T2D receiving SGLT2 inhibitor treatment.

Validation of the NULL-EASE Score for Predicting Survival in a Multiethnic Asian Cohort of Out-of-Hospital Cardiac Arrest.

BACKGROUND: NULL-PLEASE is a simple and accurate clinical scoring system developed in a Western cohort of patients with out-of-hospital cardiac arrest (OHCA). The need for blood test results limits its use in early stages of care. We adapted and validated the NULL-EASE score (without laboratory tests) in an independent, multiethnic Asian cohort of patients with out-of-hospital cardiac arrest. METHODS AND RESULTS: Using the Singapore OHCA registry, we included consecutive adult patients with out-of-hospital cardiac arrest who survived to hospital admission between April 2010 to December 2020. In-hospital mortality was the primary outcome. Logistic regression analyses were performed with STATA MP v18. Of 3274 patients (median age 64, interquartile range 54-75; 67.9% male) included in the study, 2476 (75.6%) had in-hospital mortality. NULL-EASE score was significantly lower in survivors compared with nonsurvivors (median [inter quartile range] 3 [1-4] versus 6 [4-7]; P<0.001) and strongly predictive of mortality (area under receiver operating characteristic, 0.81 [95% CI, 0.79-0.83]). Patients with a score of ≥3 had higher odds of mortality (adjusted odds ratio, 8.11 [95% CI, 6.57-10.00]) when compared with those with lower scores, after adjusting for sex, residential arrest, diabetes, respiratory disease, and stroke. A cutoff value of ≥3 predicted mortality with 92.2% sensitivity, 84.1% positive predictive value, 46.1% specificity, and 65.5% negative predictive value. NULL-EASE score performed better in younger compared with older patients (area under receiver operating characteristic, 0.82 versus 0.77, P=0.008). CONCLUSIONS: The NULL-EASE score has good discriminative performance (sensitivity and accuracy) in our multiethnic Asian cohort, but the cutoff of ≥3 falls short of the desired level of specificity for therapeutic decision-making.

MAS-CL: An End-to-End Multi-Atlas Supervised Contrastive Learning Framework for Brain ROI Segmentation.

Brain region-of-interest (ROI) segmentation with magnetic resonance (MR) images is a basic prerequisite step for brain analysis. The main problem with using deep learning for brain ROI segmentation is the lack of sufficient annotated data. To address this issue, in this paper, we propose a simple multi-atlas supervised contrastive learning framework (MAS-CL) for brain ROI segmentation with MR images in an end-to-end manner. Specifically, our MAS-CL framework mainly consists of two steps, including 1) a multi-atlas supervised contrastive learning method to learn the latent representation using a limited amount of voxel-level labeling brain MR images, and 2) brain ROI segmentation based on the pre-trained backbone using our MSA-CL method. Specifically, different from traditional contrastive learning, in our proposed method, we use multi-atlas supervised information to pre-train the backbone for learning the latent representation of input MR image, i.e., the correlation of each sample pair is defined by using the label maps of input MR image and atlas images. Then, we extend the pre-trained backbone to segment brain ROI with MR images. We perform our proposed MAS-CL framework with five segmentation methods on LONI-LPBA40, IXI, OASIS, ADNI, and CC359 datasets for brain ROI segmentation with MR images. Various experimental results suggested that our proposed MAS-CL framework can significantly improve the segmentation performance on these five datasets.

Inter-reader Agreement for Prostate Cancer Detection Using Micro-ultrasound: A Multi-institutional Study.

Background and objective: Micro-ultrasound (MUS) uses a high-frequency transducer with superior resolution to conventional ultrasound, which may differentiate prostate cancer from normal tissue and thereby allow targeted biopsy. Preliminary evidence has shown comparable sensitivity to magnetic resonance imaging (MRI), but consistency between users has yet to be described. Our objective was to assess agreement of MUS interpretation across multiple readers. Methods: After institutional review board approval, we prospectively collected MUS images for 57 patients referred for prostate biopsy after multiparametric MRI from 2022 to 2023. MUS images were interpreted by six urologists at four institutions with varying experience (range 2-6 yr). Readers were blinded to MRI results and clinical data. The primary outcome was reader agreement on the locations of suspicious lesions, measured in terms of Light's κ and positive percent agreement (PPA). Reader sensitivity for identification of grade group (GG) ≥2 prostate cancer was a secondary outcome. Key findings and limitations: Analysis revealed a κ value of 0.30 (95% confidence interval [CI] 0.21-0.39). PPA was 33% (95% CI 25-42%). The mean patient-level sensitivity for GG ≥2 cancer was 0.66 ± 0.05 overall and 0.87 ± 0.09 when cases with anterior lesions were excluded. Readers were 12 times more likely to detect higher-grade cancers (GG ≥3), with higher levels of agreement for this subgroup (κ 0.41, PPA 45%). Key limitations include the inability to prospectively biopsy reader-delineated targets and the inability of readers to perform live transducer maneuvers. Conclusions and clinical implications: Inter-reader agreement on the location of suspicious lesions on MUS is lower than rates previously reported for MRI. MUS sensitivity for cancer in the anterior gland is lacking. Patient summary: The ability to find cancer on imaging scans can vary between doctors. We found that there was frequent disagreement on the location of prostate cancer when doctors were using a new high-resolution scan method called micro-ultrasound. This suggests that the performance of micro-ultrasound is not yet consistent enough to replace MRI (magnetic resonance imaging) for diagnosis of prostate cancer.

POEMS syndrome with undetectable M-protein: a case report and literature review.

BACKGROUND: Polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes (POEMS) syndrome is a rare plasma cell (PC) neoplasm with associated paraneoplastic syndrome. According to the current diagnostic criteria, peripheral polyneuropathy and monoclonal PC proliferative disorder represent two mandatory criteria. CASE PRESENTATION: We report a 54-year-old male with peripheral neuropathy of bilateral lower limbs, sclerotic bone lesions, elevated vascular endothelial growth factor (VEGF) levels, splenomegaly, extravascular volume overload, endocrinopathy, and skin hemangiomas. Of note, serum and urine protein electrophoresis (PEP) and immunofixation electrophoresis (IFE) of this patient indicated undetectable M-protein and the normal ratio of free light chains κ and λ (FLC-R (κ/λ)). No monoclonal PCs were found in bone marrow examinations or biopsy of diseased bones. However, his clinical manifestations matched most of the diagnostic criteria. After excluding other diseases that are easily confused with POEMS syndrome, the diagnosis of variant POEMS syndrome with undetectable M-protein was proposed. The patient obtained clinically significant improvement and elevated VEGF returned to normal after 6 months of treatment with lenalidomide plus dexamethasone. CONCLUSIONS: Monoclonal PC dyscrasia (M-protein) while being a mandatory criterion for POEMS syndrome is undetectable in a considerable amount of patients that otherwise demonstrate typical symptoms. Here, we reported a case of variant POEMS syndrome with featured clinical manifestations, elevated VEGF levels, and good response to therapies targeting PCs but no evidence of M-protein. Therefore, negative results in M-protein and monoclonal PCs aren't enough to reject the diagnosis of POEMS syndrome. It is imperative to recognize the variant form of POEMS syndrome.

[Application of modified Frosch approach for Schatzker typeâ ¡tibial plateau fractures with posterolateral column].

OBJECTIVE: To explore clnical efficacy of modified Frosch approach for Schatzker typeⅡtibial plateau fracture with posterolateral column. METHODS: From January 2019 to September 2020, totally 11 patients with Schatzker typeⅡtibial plateau fractures with posterolateral column were treated, including 7 males and 4 females, aged from 21 to 49 years old. Modified Frosch approach was adopted for lateral decubitus position, and posterolateral fractures were fixed with support plates or posterolateral screws. Anterolateral fixation with conventional tibial plateau lateral locking plate. Tibial plateau varus angle and posterior inclination angle were measured by X-ray immediately and 12 months after operation, as well as knee motion at 12 months after operation. Knee function at 12 months after operation was evaluated by knee score of Hospital for Special Surgery(HSS). RESULTS: Eleven patients were followed up for 12 to 15 months. Varus angle and inclination angle at immediately after operation ranged from 76° to 86° and 6° to 10°, respectively, and 79° to 88° and 6° to 10°, respectively at 12 months after operation. The range of extension of knee ranged from 0° to 5°, and flexion was 106° to 137° at 12 months after operation. Postoperative HSS knee score at 12 months ranged from 74 to 94 scores, 8 patients were excellent and 3 good. CONCLUSION: Modified Frosch approach is an effective surgical method for Schatzker typeⅡtibial plateau fracture with posterolateral column. A single incision is used to complete fracture exposure and fixation at two sites, avoiding use of combined incisions, and could obtain good postoperative knee joint function. During operation, popliteal fossa structure should be familiar, and the common peroneal nerve should be protected to avoid injury.

Pancreatic islet transplantation: current advances and challenges.

Diabetes is a prevalent chronic disease that traditionally requires severe reliance on medication for treatment. Oral medication and exogenous insulin can only temporarily maintain blood glucose levels and do not cure the disease. Most patients need life-long injections of exogenous insulin. In recent years, advances in islet transplantation have significantly advanced the treatment of diabetes, allowing patients to discontinue exogenous insulin and avoid complications.Long-term follow-up results from recent reports on islet transplantation suggest that they provide significant therapeutic benefit although patients still require immunotherapy, suggesting the importance of future transplantation strategies. Although organ shortage remains the primary obstacle for the development of islet transplantation, new sources of islet cells, such as stem cells and porcine islet cells, have been proposed, and are gradually being incorporated into clinical research. Further research on new transplantation sites, such as the subcutaneous space and mesenteric fat, may eventually replace the traditional portal vein intra-islet cell infusion. Additionally, the immunological rejection reaction in islet transplantation will be resolved through the combined application of immunosuppressant agents, islet encapsulation technology, and the most promising mesenchymal stem cells/regulatory T cell and islet cell combined transplantation cell therapy. This review summarizes the progress achieved in islet transplantation, and discusses the research progress and potential solutions to the challenges faced.

Qualitative study on the perception of good death in patients with end-stage cancer in oncology nurses.

OBJECTIVE: To explore the perception of good death of patients with end-stage cancer by nurses in the oncology department. METHOD: In the study we used a phenomenological approach and semi-structured interviews. A total of 11 nurses from the oncology department of a Grade A hospital in Taizhou were interviewed on the cognition of good death from July 1 to September 30, 2022. Colaizzi's analysis method was used to analyse the interview data. This study followed the consolidated criteria for reporting qualitative research (COREQ). RESULT: Four themes were identified: a strong sense of responsibility and mission; To sustain hope and faith; The important role of family members; Improve patients' quality of life. CONCLUSION: The nurses in the department of oncology have a low level of knowledge about the "good death", and the correct understanding and view of the "good death" is the premise of the realization of " good death". The ability of nursing staff to improve the "good death", attention, and meet the needs and wishes of individuals and families, is the guarantee of the realization of "good death".

Creatine and L-carnitine attenuate muscular laminopathy in the LMNA mutation transgenic zebrafish.

Lamin A/C gene (LMNA) mutations contribute to severe striated muscle laminopathies, affecting cardiac and skeletal muscles, with limited treatment options. In this study, we delve into the investigations of five distinct LMNA mutations, including three novel variants and two pathogenic variants identified in patients with muscular laminopathy. Our approach employs zebrafish models to comprehensively study these variants. Transgenic zebrafish expressing wild-type LMNA and each mutation undergo extensive morphological profiling, swimming behavior assessments, muscle endurance evaluations, heartbeat measurement, and histopathological analysis of skeletal muscles. Additionally, these models serve as platform for focused drug screening. We explore the transcriptomic landscape through qPCR and RNAseq to unveil altered gene expression profiles in muscle tissues. Larvae of LMNA(L35P), LMNA(E358K), and LMNA(R453W) transgenic fish exhibit reduced swim speed compared to LMNA(WT) measured by DanioVision. All LMNA transgenic adult fish exhibit reduced swim speed compared to LMNA(WT) in T-maze. Moreover, all LMNA transgenic adult fish, except LMNA(E358K), display weaker muscle endurance than LMNA(WT) measured by swimming tunnel. Histochemical staining reveals decreased fiber size in all LMNA mutations transgenic fish, excluding LMNA(WT) fish. Interestingly, LMNA(A539V) and LMNA(E358K) exhibited elevated heartbeats. We recognize potential limitations with transgene overexpression and conducted association calculations to explore its effects on zebrafish phenotypes. Our results suggest lamin A/C overexpression may not directly impact mutant phenotypes, such as impaired swim speed, increased heart rates, or decreased muscle fiber diameter. Utilizing LMNA zebrafish models for drug screening, we identify L-carnitine treatment rescuing muscle endurance in LMNA(L35P) and creatine treatment reversing muscle endurance in LMNA(R453W) zebrafish models. Creatine activates AMPK and mTOR pathways, improving muscle endurance and swim speed in LMNA(R453W) fish. Transcriptomic profiling reveals upstream regulators and affected genes contributing to motor dysfunction, cardiac anomalies, and ion flux dysregulation in LMNA mutant transgenic fish. These findings faithfully mimic clinical manifestations of muscular laminopathies, including dysmorphism, early mortality, decreased fiber size, and muscle dysfunction in zebrafish. Furthermore, our drug screening results suggest L-carnitine and creatine treatments as potential rescuers of muscle endurance in LMNA(L35P) and LMNA(R453W) zebrafish models. Our study offers valuable insights into the future development of potential treatments for LMNA-related muscular laminopathy.

New-onset Fibromyalgia After Total Knee Replacement in Patients With Osteoarthritis: A Propensity-score-matched Cohort Study in the United States.

BACKGROUND/AIM: The risk of new-onset fibromyalgia after total knee replacement (TKR) in osteoarthritis patients is not well-established. This study aimed to assess the risk of developing fibromyalgia post-TKR, considering potential variations across age and sex. PATIENTS AND METHODS: Utilizing a multicenter retrospective cohort design and data from the TriNetX research network, electronic health records of osteoarthritis patients who underwent TKR and the same number of matched controls were analyzed. Propensity-score matching was performed by matching critical confounders. Hazard ratios were evaluated to assess fibromyalgia risk in the TKR cohort compared to non-TKR controls. RESULTS: The hazard ratio of future fibromyalgia for the TKR cohort was 2.08 (95% confidence interval=1.74-2.49) for 1 year after the index date, 1.81 (95% confidence interval=1.62-2.02) for 3 years, and 1.69 (95% confidence interval=1.54-1.86) for 5 years compared with non-TKR controls. The significant association remained in sensitivity models and stratification analyses in different age and sex subgroups. CONCLUSION: Clinicians should be vigilant about the potential for fibromyalgia development post-TKR and consider tailored interventions; our findings emphasize the need for further research to elucidate underlying mechanisms and identify modifiable risk factors.