Correlation between disease activity and patient-reported health-related quality of life in rheumatoid arthritis: a cross-sectional study.

OBJECTIVE: We aimed to provide a comprehensive assessment of health-related quality of life (HRQoL) in patients with rheumatoid arthritis (RA) of different activities and to evaluate the correlation between clinical activity measures and HRQoL instruments. This research also analysed the extent to which different aspects of HRQoL (physical, psychological and social) were affected. DESIGN: Cross-sectional, observational, non-interventional study. SETTING: The study was conducted at the Department of Rheumatology and Immunology, Qilu Hospital, Shandong University. METHODS: From December 2019 to October 2020, a total of 340 RA patients participated in the survey using convenient sampling. Three generic instruments, EQ-5D-5L,SF-12 and the AQoL-4D, as well as an RA-specific instrument,the Stanford Health Assessment Questionnaire Disability Index (HAQ-DI), were administered to assess patients' HRQoL. The Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS28-ESR) was used by doctors to measure patients' clinical activity. Multivariable linear regression was used to compare patients' HRQoL across different levels of activity. Spearman's correlation was used to assess the correlation between doctor-reported clinical activity and HRQoL. RESULTS: A total of 314 patients with RA participated in this study. The mean score of HAQ-DI was 0.87 (SD: 0.91). Using patients in the clinical remission group as a reference, patients in the moderate and high disease activity groups showed significantly reduced health state utility values and HRQoL scores (all p<0.05). On the contrary, there was an increase in HAQ-DI scores, indicating more impairment (p<0.05). All instruments included in the study tended to differentiate disease activity based on multiple criteria, with scores showing a moderate to strong correlation with RA activity (|rs|=0.50 to 0.65). Among them, the disease-specific instrument had the highest correlation. CONCLUSIONS: RA can have considerable impairment on patients' HRQoL, both in terms of physical and psychosocial functioning. Given the strong correlation between clinical activity and HRQoL scores, and the fact that HRQoL can be an important clinical supplement. The EQ-5D-5L is probably the most appropriate generic measurement instrument for measuring HRQoL in RA patients.

Proteomics and ß-hydroxybutyrylation Modification Characterization in the Hearts of Naturally Senescent Mice.

Aging is widely accepted as an independent risk factor for cardiovascular disease (CVD), which contributes to increasing morbidity and mortality in the elderly population. Lysine ß-hydroxybutyrylation (Kbhb) is a novel post-translational modification (PTM), wherein ß-hydroxybutyrate is covalently attached to lysine ε-amino groups. Recent studies have revealed that histone Kbhb contributes to tumor progression, diabetic cardiomyopathy progression, and postnatal heart development. However, no studies have yet reported a global analysis of Kbhb proteins in aging hearts or elucidated the mechanisms underlying this modification in the process. Herein, we conducted quantitative proteomics and Kbhb PTM omics to comprehensively elucidate the alterations of global proteome and Kbhb modification in the hearts of aged mice. The results revealed a decline in grip strength and cardiac diastolic function in 22-month-old aged mice compared to 3-month-old young mice. High-throughput liquid chromatogram-mass spectrometry analysis identified 1710 ß-hydroxybutyrylated lysine sites in 641 proteins in the cardiac tissue of young and aged mice. Additionally, 183 Kbhb sites identified in 134 proteins exhibited significant differential modification in aged hearts (fold change (FC) > 1.5 or <1/1.5, p < 0.05). Notably, the Kbhb-modified proteins were primarily detected in energy metabolism pathways, such as fatty acid elongation, glyoxylate and dicarboxylate metabolism, tricarboxylic acid cycle, and oxidative phosphorylation. Furthermore, these Kbhb-modified proteins were predominantly localized in the mitochondria. The present study, for the first time, provides a global proteomic profile and Kbhb modification landscape of cardiomyocytes in aged hearts. These findings put forth novel possibilities for treating cardiac aging and aging-related CVDs by reversing abnormal Kbhb modifications.

Barriers to prophylactic treatment among patients with haemophilia A in Shandong Province, China: a qualitative study.

BACKGROUND: Haemophilia A is a rare, hereditary haemorrhagic disease that manifests as induced spontaneous bleeding and leads to disability or premature death in severe cases. Prophylactic treatment is optimal for patients to prevent uncontrolled bleeding and reduce the severity of the injury. However, little is known about the use of prophylactic treatment among patients with haemophilia A in China, especially barriers that predispose them to low or non-adherence. In this study, we explore the barriers to the prophylactic treatment of patients with haemophilia A. METHOD: We used personal interviews and focus groups to collect the data and analysed the data through thematic analysis. Purposive sampling was employed to recruit our participants. We continued recruiting participants until data saturation was reached from the thematic analysis. Ultimately, we obtained 37 participants, among whom 19 participated in personal interviews and 18 participated in focus groups (i.e., 3 focus groups with 6 participants each). RESULTS: Three themes and nine subthemes were identified from the thematic analysis. Nine subthemes (i.e., perceived barriers) emerged from the analysis, which were further clustered into three themes: (1) poor primary health care, (2) inadequate financial support, and (3) a lack of patient-centred care. CONCLUSION: The findings presented in this descriptive qualitative study offer a unique view of Chinese patients with haemophilia A and their barriers to prophylactic treatment. Our findings not only provide an in-depth understanding of barriers to prophylactic treatment encountered by Chinese patients with haemophilia A but also address the urgent need to strengthen primary care, provide adequate financial support, and establish patient-centred care for these suffering patients.

Patient-reported outcomes in Gaucher's disease: a systematic review.

BACKGROUND: Gaucher's disease (GD), a rare condition, represents the most common lysosomal storage disorder. The cardinal manifestations of GD are fatigue, hepatosplenomegaly, anemia, thrombocytopenia, bone pain, and bone infarction, thereby culminating in a marked deterioration of patients' quality of life (QoL). Patient-reported outcomes (PROs) offer valuable insights into the impact of GD on patients' QoL and symptoms. This systematic review aimed to identify and analyze PROs and outcome measures in GD patients. METHODS: We systematically searched PubMed, Web of Science Core Collections, EMBASE, SCOPUS, Cochrane Library, PsycINFO, Wan Fang Data, China National Knowledge Infrastructure (CNKI), and the Chinese Biomedical Literature Database (CBM). The methodological quality of the included studies was assessed using a mixed methods assessment tool. RESULTS: A total of 33 studies were identified, encompassing 24 distinct patient-reported outcome instruments, with the most frequently employed instrument being the SF-36. The study designs included eighteen cross-sectional studies, seven pre- and post-intervention investigations, three randomized controlled trials, two cohort studies, two qualitative inquiries, and one validation study. These studies explored diverse domains such as the QoL and cardinal symptoms (e.g., fatigue, pain, bleeding, cognition, social relationships, and psychological functioning) in patients with GD. Furthermore, significant attention was directed towards the appraisal of the therapeutic benefits of various interventions in patients with GD. A novel GD-specific instrument has also been developed, which has two applied versions: a 24-item variant for routine clinical monitoring and a 17-item form for use in clinical trials. CONCLUSION: PROs have garnered increased attention and concern in the realm of GD. Despite this progress, it is noteworthy that the instruments used to measure PROs in GD are still predominantly generic instruments. While researchers have endeavored to develop and validate a disease-specific instrument, currently the use of this instrument is limited. Owing to several challenges, including the small number of patients, heterogeneity of the disease, and cross-regional discrepancies in study findings, GD poses substantial difficulties in the measurement of QoL and development of instruments. Consequently, patients with GD require more dependable measurement instruments that accurately reflect their QoL, efficacy of treatment, and facilitate healthcare decision-making.

Undersampled Fourier ptychography for reflective-based long range imaging.

Fourier ptychography (FP) can be a promising technique for long-range and high-resolution imaging. In this work, we explore reconstructions with undersampled data for meter-scale reflective based Fourier ptychographic imaging. To reconstruct with under-sampling captures, we propose a novel cost function for FP phase retrieval and design a new optimization algorithm based on gradient descent. To verify the proposed methods, we perform the high-fidelity reconstruction of the targets with sampling parameter less than one. Compared to the state-of-the-art alternative-projectionbased FP algorithm, the proposed one can achieve the same performance but with much less data.

Quantification and Proteomic Characterization of ß-Hydroxybutyrylation Modification in the Hearts of AMPKα2 Knockout Mice.

AMP-activated protein kinase alpha 2 (AMPKα2) regulates energy metabolism, protein synthesis, and glucolipid metabolism myocardial cells. Ketone bodies produced by fatty acid ß-oxidation, especially ß-hydroxybutyrate, are fatty energy-supplying substances for the heart, brain, and other organs during fasting and long-term exercise. They also regulate metabolic signaling for multiple cellular functions. Lysine ß-hydroxybutyrylation (Kbhb) is a ß-hydroxybutyrate-mediated protein posttranslational modification. Histone Kbhb has been identified in yeast, mouse, and human cells. However, whether AMPK regulates protein Kbhb is yet unclear. Hence, the present study explored the changes in proteomics and Kbhb modification omics in the hearts of AMPKα2 knockout mice using a comprehensive quantitative proteomic analysis. Based on mass spectrometry (LC-MS/MS) analysis, the number of 1181 Kbhb modified sites in 455 proteins were quantified between AMPKα2 knockout mice and wildtype mice; 244 Kbhb sites in 142 proteins decreased or increased after AMPKα2 knockout (fold change >1.5 or <1/1.5, p < 0.05). The regulation of Kbhb sites in 26 key enzymes of fatty acid degradation and tricarboxylic acid cycle was noted in AMPKα2 knockout mouse cardiomyocytes. These findings, for the first time, identified proteomic features and Kbhb modification of cardiomyocytes after AMPKα2 knockout, suggesting that AMPKα2 regulates energy metabolism by modifying protein Kbhb.

Bacteriolytic therapy with Clostridium ghonii for experimental solid tumors.

Clostridium ghonii (C. ghonii) is a non-pathogenic Clostridium species and a strictly anaerobic, spore-forming bacterium. However, its bacterial oncolytic capabilities and applications have not yet been reported. This study aimed to determining the bacterial oncolytic capability of C. ghonii for the treatment of experimental solid tumors. C. ghonii secreted collagenase IV and phospholipase c and significantly promoted apoptosis and necrosis in cultured A549 cells. C. ghonii spores specially germinated and were distributed in the tumors, and elicited the immune responses after intratumoral injection in tumor-bearing mice. C. ghonii spores decreased tumor volumes and increased tumor necrosis and inhibition rates in tumor-bearing mice. Furthermore, the combination of radiation and C. ghonii exerted additive anti-tumor effects. Taken together, our data indicate that C. ghonii is a bacteriolytic therapeutic agent against solid tumors. Given the proven natural safety of C. ghonii, it is attractive as a potential novel bacteriolytic therapy for solid tumors.

Rare Meningitis and Epileptic Seizure Infected with Brucella melitensis: a Case Report.

BACKGROUND: Although brucellosis is the most common zoonotic disease worldwide, human meningitis infected with Brucella melitensis is rare and difficult to diagnosis. Herein we describe the clinical aspects of a rare case of Brucella melitensis meningitis accompanied by epileptic seizure. METHODS: Bacterial culture of CSF was utilized to find the pathogen. Serum and CSF agglutination tests were used to detect the capacity of Brucella antigen. Bacterial clone was identified by the matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF). Magnetic resonance imaging (MRI) was used to monitor the recovery changes for meningitis. RESULTS: The bacterial culture was positive for Brucella app. Antigen-antibody agglutination test was also positive with a titer more than 1/200. A reliable identification score of 2.8 for Brucella melitensis was obtained by MALDI-TOF. MRI showed obviously improved meningitis after therapy. CONCLUSIONS: The results of this study suggest the treatments for Brucella meningitis must be planned depending on the patient's clinical conditions and the laboratory identification of pathogen infection as early as possible.

Rapid and High-Throughput Detection of Peripheral Blood Chromosome Aberrations in Radiation Workers.

There is a pressing need to establish automated solutions for the rapid, high-throughput, and automatic detection of chromosome aberrations (CAs) in the occupational health surveillance of large-scale radiation workers. Here, we described and verified the accuracy of a new measurement system based on the automatic scanning and analysis of dicentric chromosomes (DICs). The effects of cell number on DIC detection by automatic scanning and analysis were studied, and the distribution of DIC values per cell was calculated. In total, 1088 cases were detected by automatic DIC scanning and analysis in 26 663 radiation workers, and 73 cases were further confirmed by a technician, including 5 cases in which radiation exposure lead to harmful medical consequences. Our approach reduces the workload by 96% and increases the speed of assessment approximately 7-fold. Overall, this study validates the utility of a novel rapid and high-throughput CA detection procedure as a means of occupational health surveillance of large-scale radiation workers.

Successful Rescue of the Victim Exposed to a Super High Dose of Iridium-192 during the Nanjing Radiological Accident in 2014.

Here we report on the interventions taken to treat a patient exposed to high-dose radiation and provide a protocol for treating such patients in the future. The patient, Mr. Wang, was a 58-year-old male janitor who was accidentally exposed to a 192Ir source with an activity of 966.4 GBq or 26.1 Ci. The dose estimated to the lower right limb was 4,100 Gy, whereas the whole-body effective dose was 1.51 Gy. The diagnosis was made according to the results of the patient dose estimation and clinical manifestations. Systemic treatment included stimulating bone marrow hematopoietic cells, enhancing immunity, anti-infection and vitamin supplements. The treatment of radiation-induced skin lesions consisted of several debridements, two skin-flap transplantations and application of mesenchymal stem cells (MSCs). Skin-flap transplantations and MSCs play important roles in the recovery of skin wound. A combination of antibiotics and antimycotic was useful in reducing inflammation. The application of vacuum sealing drainage was effective in removing necrotic tissue and bacteria, ameliorating ischemia and hypoxia of wound tissue, providing a fresh wound bed for wound healing and improving skin or flap graft survival rates. The victim survived the accident without amputation, and function of his highly exposed right leg was partially recovered. These results demonstrate the importance of collaboration among members of a multidisciplinary team in the treatment of this patient.

Multiple Organ Lesions in a Case of Contamination With Multiple Radionuclides After 38 Years.

The patient was contaminated with multiple radionuclides 38 years ago due to an accident. To investigate the effects of radionuclide contamination on humans, he has been followed up by examinations for many years. Long-term effects gradually emerge in these years. Lung cancer was diagnosed by medical examinations. Besides, chronic gastritis with intestinal metaplasia was indicated by gastroscopic biopsies, while colorectal polyps found by colonoscopy. All 13 colorectal polyps were removed, and radical surgery for lung cancer was performed. Fortunately, pathological examinations indicated that it was early lung cancer. The ground glass nodule (GGN) in left lung identified during the follow-up will be resected when needed. It is speculated that multiple manifestations of the patient may be related to radiation, and different lesions in the organs may be related to systemic adaptive response. However, longer follow-up is needed due to a lack of effective and direct evidence. This work is expected to provide experiences for similar patients' treatment and follow-up.

Complete Technical Scheme for Automatic Biological Dose Estimation Platform.

To establish a complete technical solution for the automatic radiation biological dose estimation platform for biological dose estimation and classification of the wounded in large-scale radiation accidents, the "dose-effect curve by dicentric chromosome (DIC) automatic analysis" was established and its accuracy was verified. The effects of analyzed cell number and the special treatment of the culture on dose estimation by DIC automatic analysis were studied. Besides, sample processing capabilities of the special equipments were tested. The fitted "dose-effect curve by DIC automatic analysis" was presented as follows: Y = (0.01806 ± 0.00032) D 2 + (0.01279 ± 0.00084) D + (0.0004891 ± 0.0001358) (R 2 = 0.961). Three-gradient scanning method, culture refrigeration method, and interprofessional collaboration under extreme conditions were proposed to improve the detection speed, prolong the sample processing time window, and reduce the equipment investment. In addition, the optimized device allocation ratio for the automatic biological dose estimation laboratory was proposed to eliminate the efficiency bottleneck. The complete set of technical solutions for the high-throughput automatic biological dose estimation laboratory proposed in this study can meet the requirements of early classification and rapid biological dose assessment of the wounded during the large-scale nuclear radiation events, and it is worthy of further promotion.

[An epidemic outbreak of respiratory infection caused by Chlamydia pneumoniae in medical workers].

OBJECTIVE: To investigate the clinical manifestations and the chest imaging characteristics of an epidemic outbreak of respiratory infection caused by Chlamydia pneumoniae (CP). METHODS: A prospective study for CP infection in 15 patients from September 2003 was carried out. Sputum and throat swab specimen were obtained and CP DNA was detected by polymerase chain reaction (PCR). Serum samples were obtained and immunoglobulin G and M (IgG and IgM) of antibodies to CP. pneumoniae were studied by microimmunofluorescence test. Chest X-ray and computed tomography were retrospectively analyzed. RESULTS: All patients presented fever, headache, sore throat, hoarseness, muscular ache, and dry cough. Acute cough was often associated with chest pain. The sputum blood was present in 3 patients (20%). Moist rales were heard in 4 patients. Chest imaging abnormalities were present in 67% (10 patients). The organism was demonstrated in 87% (13 patients) by PCR. The most common imaging abnormalities were unilateral and (or) bilateral multi-focal or solitary alveolar nodular opacities (9 patients). The patchy shadows were found in 2 patients, and pulmonary consolidation associated with the local pulmonary edema in 1 patient. Hilar or mediastinal lymphadenopathy and pleural effusion was not found. CONCLUSIONS: The colony occurrences and similar clinical and chest imaging manifestations are characteristics of an outbreak of respiratory infection caused by CP in medical workers. An outbreak of respiratory infection caused by CP should be differentiated from severe acute respiratory syndrome (SARS).