INTRODUCTION: Rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (ACPA) are used in the diagnosis and prognostication of rheumatoid arthritis (RA). We wanted to determine the specific contributions of RF and ACPA to the biological nature of RA and whether they act synergistically. METHODS: We identified 731 patients from our prospective multi-ethnic RA cohort and categorised them into four groups: ACPA-positive, RF-positive, doubly positive and doubly negative. We compared the demographics, Disease Activity Score-28, Health Assessment Questionnaire score, quality of life using Short Form 36 and the use of prednisolone and disease-modifying antirheumatic drugs (DMARDs) of these patient groups. RESULTS: Four hundred and ninety-one patients (67.2%) were ACPA+RF+, 54 (7.4%) were ACPA+RF-, 82 (11.2%) were ACPA-RF+ and 104 (14.2%) were ACPA-RF-. Mean disease duration before the study entry was not different in the four groups. Patients with older age of onset were less likely to be positive for RF and ACPA. Fewer ACPA+RF+ patients were in remission compared to those in the other groups ( P < 0.05). Erythrocyte sedimentation rate (ESR) was higher at study entry in the ACPA+RF+ group (40.4 mm/h vs. 30.6-30.9 mm/h, P < 0.05). Prednisolone and number of DMARDs used were higher in the ACPA+RF+ group compared to the doubly negative group. There were no differences in the functional status and quality of life. CONCLUSIONS RA patients who were positive for both ACPA and RF had lower remission rate, higher baseline ESR and required more corticosteroid and DMARD treatment compared to those who were singly positive or doubly negative. Being doubly positive confers a worse outcome to RA patients.
Humans ; Arthritis, Rheumatoid/diagnosis* ; Male ; Female ; Middle Aged ; Rheumatoid Factor/blood* ; Anti-Citrullinated Protein Antibodies/blood* ; Adult ; Quality of Life ; Prospective Studies ; Antirheumatic Agents/therapeutic use* ; Aged ; Peptides, Cyclic/immunology* ; Prednisolone/therapeutic use* ; Surveys and Questionnaires ; Severity of Illness Index ; Prognosis

INTRODUCTION: Rheumatoid arthritis (RA) is associated with heightened cardiovascular disease and increased susceptibility to osteoporosis, with shared underlying mechanisms. This study aimed to investigate the association between vascular function and bone mineral density (BMD). METHODS: We conducted a cross-sectional study of 49 patients with RA at Tan Tock Seng Hospital, Singapore. Endothelial function was measured as reactive hyperaemia index (RHI)-endothelial peripheral arterial tonometry and aortic stiffness as carotid-femoral pulse wave velocity (cf-PWV) using SphygmoCor. Univariable and multivariable linear regression analyses were performed to evaluate the associations between BMD and vascular function. We used natural logarithm RHI (lnRHI) and cf-PWV as response variables, and each BMD as covariate, adjusting for body mass index, positive anti-cyclic citrullinated peptide, cumulative prednisolone dose, hydroxychloroquine use and Systematic COronary Risk Evaluation 2. RESULTS: We recruited 49 patients (mean age 61.08 ± 8.20 years), of whom 44 (89.80%) were women and 39 (81.25%) were Chinese. Significant associations were found between lnRHI and BMD at the lumbar spine (β = 0.4289, P = 0.037) and total hip (β = 0.7544, P = 0.014) in univariable analyses. Multivariable analyses confirmed these associations, showing that lower BMD at the lumbar spine (β = 0.7303, P = 0.001), femoral neck (β = 0.8694, P = 0.030) and total hip (β = 0.8909, P = 0.010) were significantly associated with worse lnRHI. No significant associations were found between BMD and cf-PWV. CONCLUSION Lower BMD is associated with endothelial dysfunction, but not aortic stiffness in patients with RA. Further longitudinal studies are needed to confirm these associations and understand the underlying mechanisms.
Humans ; Arthritis, Rheumatoid/complications* ; Female ; Male ; Bone Density ; Middle Aged ; Cross-Sectional Studies ; Vascular Stiffness ; Aged ; Singapore ; Pulse Wave Analysis ; Osteoporosis/complications* ; Endothelium, Vascular/physiopathology* ; Cardiovascular Diseases/complications* ; Carotid-Femoral Pulse Wave Velocity ; Hyperemia

Stem cell treatment may enhance erectile dysfunction (ED) in individuals with cavernous nerve injury (CNI). Nevertheless, no investigations have directly ascertained the implications of varying amounts of human umbilical cord-derived mesenchymal stem cells (HUC-MSCs) on ED. We compare the efficacy of three various doses of HUC-MSCs as a therapeutic strategy for ED. Sprague-Dawley rats (total = 175) were randomly allocated into five groups. A total of 35 rats underwent sham surgery and 140 rats endured bilateral CNI and were treated with vehicles or doses of HUC-MSCs (1 × 10 6 cells, 5 × 10 6 cells, and 1 × 10 7 cells in 0.1 ml, respectively). Penile tissues were harvested for histological analysis on 1 day, 3 days, 7 days, 14 days, 28 days, 60 days, and 90 days postsurgery. It was found that varying dosages of HUC-MSCs enhanced the erectile function of rats with bilateral CNI and ED. Moreover, there was no significant disparity in the effectiveness of various dosages of HUC-MSCs. However, the expression of endothelial markers (rat endothelial cell antigen-1 [RECA-1] and endothelial nitric oxide synthase [eNOS]), smooth muscle markers (alpha smooth muscle actin [α-SMA] and desmin), and neural markers (neurofilament [RECA-1] and neurogenic nitric oxide synthase [nNOS]) increased significantly with prolonged treatment time. Masson's staining demonstrated an increased in the smooth muscle cell (SMC)/collagen ratio. Significant changes were detected in the microstructures of various types of cells. In vivo imaging system (IVIS) analysis showed that at the 1 st day, the HUC-MSCs implanted moved to the site of damage. Additionally, the oxidative stress levels were dramatically reduced in the penises of rats administered with HUC-MSCs.
Male ; Animals ; Erectile Dysfunction/metabolism* ; Rats, Sprague-Dawley ; Mesenchymal Stem Cell Transplantation/methods* ; Rats ; Penis/pathology* ; Humans ; Disease Models, Animal ; Umbilical Cord/cytology* ; Peripheral Nerve Injuries/complications* ; Mesenchymal Stem Cells ; Nitric Oxide Synthase Type III/metabolism* ; Actins/metabolism* ; Nitric Oxide Synthase Type I/metabolism*

ObjectiveTo investigate the levels of neutralizing antibodies against the novel coronavirus in the serum of elderly individuals aged 60 years and above in Shanghai’s Changning District， following natural infection and mixed immunity， in order to provide a basis for strengthening immunity in the elderly. MethodsElderly people who participated in free health check-ups at 10 community health service centers in Changning District from May to June 2023 were selected as the subjects. Information such as gender， age， COVID-19 infection history， COVID-19 vaccine immunization history， and chronic disease history were collected. Serum samples of the subjects were collected and quantitative detection of SARS-CoV-2 neutralizing antibodies was performed by magnetic particle chemiluminescence method. The antibody levels of different populations were analyzed. ResultsA total of 620 subjects were included， 586 of whom （241 males and 345 females） met the study conditions. There were 90 people in the full vaccination + infection group， 224 people in the intensive vaccination + infection group， and 272 people in the unvaccinated + infection group. The positive rates of COVID-19 antibody in the three groups were 94.44% （95%CI： 87.51%‒98.17%）， 95.98% （95%CI：92.51%‒98.15%） and 22.06% （95%CI： 17.28%‒27.46%）， respectively. The positive rates in full vaccination + infection group and intensive vaccination + infection group was significantly higher than that in unvaccinated + infection group （χ²=147.561，P<0.01；χ²=271.729，P<0.01）. The antibody level in full vaccination + infection group （640.74 AU·mL^-1） and intensive vaccination + infection group （1 200.88 AU·mL^-1） was significantly higher than that in unvaccinated + infection group （4.51 AU·mL^-1） （all P<0.01）.The antibody level in the intensive vaccination + infection group was also significantly higher than that in the whole vaccination + infection group （P < 0.05）. ConclusionAfter 5‒6 months of infection， the neutralizing antibody positive rate and antibody level were significantly higher in the elderly who received the full vaccination and infection or intensive vaccination and infection. It is recommended that elderly individuals， who have been infected for more than 5‒6 months but have not been vaccinated， should consider getting vaccinated to enhance their levels of neutralizing antibodies.

Objective To investigate the effect of chemokine CXC ligand 9(CXCL9)on cognitive function impairment in patients with breast cancer brain metastases undergoing whole-brain radiotherapy(WBRT)using bioinformatics methods.Methods The mRNA of breast cancer brain metastases datasets GSE43837 and GSE12276 and Alzheimer's disease(AD)dataset GSE161199 were screened and downloaded from GEO database.Limma method and Venn diagrams were used to identify common differentially expressed genes(DEGs),and protein-protein interaction and functional prediction through GeneMANIA website assays were performed.A total of 42 patients with breast cancer brain metastases who first visited the Department of Radiotherapy at the First Affiliated Hospital of Hebei North University from January 2021 to January 2023 were selected.Patients were divided into normal cognitive function group and cognitive function impairment group based on cognitive status.Enzyme-linked immunosorbent assay(ELISA)was employed to detect serum CXCL9 levels one week before and three months after radiotherapy.The mini-mental state examination(MMSE)was used to assess patients'cognitive function.Results The DEGs from datasets GSE43837 and GSE12276 included PKP1,POLDIP2,SPAG5,ALDOC,PTPRZ1,PKIA,TLCD1,CPE,PMP22 and CXCL9.The DEGs from GSE161199 included RPS16,CD79A,LYPD3,RPL28,HBG2,RPL23AP7,TRNR,CXCL9.Venn diagram showed that CXCL9 was a common DEG between breast cancer brain metastasis and AD.Functional enrichment analysis indicated that CXCL9 was involved in cellular responses to chemokines,negative regulation of immune system processes,negative regulation of vascular morphogenesis,Toll-like receptor signaling pathway,nucleotide oligomerization domain(NOD)-like receptor signaling pathway,and JAK-STAT signaling pathway.Before radiotherapy,patients with cognitive function impairment and normal cognitive function accounted for 61.9%and 38.1%,respectively,with a statistically significant difference in MMSE scores[(24.53±2.19)vs.(28.89±1.36),P＜0.01].Compared with normal cognitive function group,patients with cognitive function impairment had a significantly increased number of brain metastases and significantly lower Karnofsky performance status(KPS)scores and serum CXCL9 levels(P＜0.05).Three months after radiotherapy,patients with cognitive function impairment and normal cognitive function accounted for 47.6%and 52.4%,respectively,with a statistically significant difference in MMSE scores[(25.16±1.98)vs.(28.18±1.08),P＜0.01].Compared with normal cognitive function group,patients with cognitive function impairment had significantly lower CXCL9 levels(P=0.003).In patients with normal cognitive function,CXCL9 levels were remarkably lower after radiotherapy compared to those before radiotherapy(P=0.009).Conclusions Patients with cognitive function impairment had significantly lower CXCL9 levels than those with normal cognitive function,and whole-brain radiotherapy may be related to a certain degree of reduction in CXCL9 levels.

Objective To investigating the microbial communities and physicochemical properties of soil and distribution of Oncomelania hupensis snails in marshlands along the Yangtze River basin at different types of land use, and to examine the effects of soil microorganisms and physicochemical properties on snail distribution, so as to provide insights into snail control and schistosomiasis prevention in marshland along the Yangtze River basin. Methods Marshlands with four types of land use were selected along the Yangtze River basin on April 2021, including poplar forest-crops integrated planting, reed areas, agricultural cultivation lands and ditches. The distribution of snails and physicochemical properties of soil were investigated in marshlands with different types of land use, and the V3 to V4 regions of the bacterial 16S ribosomal RNA (16S rRNA) gene, fungal internal transcribed spacer-1 (ITS1) gene and algal ribulose-bisphosphate carboxylase (rbcL) gene in soils were subjected to high-throughput sequencing. The occurrence of frames with living snails and density of living snails were compared in marshland with different types of land use. The associations of soil microorganisms and physicochemical properties with the density of living snails were examined using Pearson correlation analysis, and the contributions of soil microorganisms and physicochemical properties to the density of living snails were evaluated using variance partitioning analysis. Results In marshlands with four types of land use, the greatest occurrence of frames with living snails [(4.94 ± 2.14)%] and density of living snails [(0.070 ± 0.026) snails/0.1 m²] were seen in ditches, and the lowest were found in [(1.23 ± 1.23)%] agricultural cultivation lands [(0.016 ± 0.019) snails/0.1 m²]. A total of 2 phyla, 5 classes, 8 orders, 9 families and 11 genera of algae were detected in soils at four types of land use, with Chlorophyta as the dominant phylum and Pseudoneochloris as the dominant genus. A total of 44 phyla, 134 classes, 281 orders, 338 families and 516 genera of bacteria were detected in soils at four types of land use, with Proteobacteria and Acidobacteriota as the dominant phyla and uncultured Acidobacterium, MND1, Mitrospira, Haliangium and Sphingomonas as dominant genera. A total of 11 phyla, 41 classes, 108 orders, 223 families and 408 genera of fungi were detected in soils at four types of land use, with phyla Ascomycota, Basidiomycota and Mortierellomycota presenting high relative abundances and genera Cladorrhinum, Mortierella and Humicola presenting high relative abundances. Pearson correlation analysis revealed that the density of living snails correlated negatively with the relative abundance of Proteobacteria (r = −0.965, P < 0.05) and soil electronic conductivity (r = −0.962, P < 0.05) and positively with soil moisture (r = 0.951, P < 0.05). Variance partitioning analysis demonstrated that the physicochemical properties and microorganisms of soil contributed 69% and 10% to the density of living snails, respectively. Conclusion The diversity of microbial communities varies in soils at different types of land use in marshland along the Yangtze River basin, and the physicochemical properties and microorganisms of soils may affect the distribution of O. hupensis snails.

ObjectiveTo observe the effect of transcranial direct current stimulation (tDCS) on motor function of upper limbs of stroke patients with hemiplegia. MethodsFrom October, 2020 to October, 2021, 65 patients from Wuhan No.1 Hospital were randomly divided into control group (n = 32) and observation group (n = 33). All the patients received routine rehabilitation and mirror therapy, and the observation group received tDCS in addition, for four weeks. They were assessed with Fugl-Meyer Assessment-Upper Extremities (FMA-UE), Action Research Arm Test (ARAT) and modified Barthel index (MBI) before and after treatment. ResultsThe scores of FMA-UE, ARAT and MBI improved in the both groups after treatment (|t| > 10.455, Z = -2.793, P < 0.001), and all the scores were better in the observation group than in the control group (|t| > 4.152, Z = -2.045, P < 0.05). ConclusionThe combination of tDCS can effectively promote the recovery of upper limb motor function of stroke patients.

OBJECTIVE To observe the toxic effects of single administration and repeated administration of Qingzi granules for 13 weeks on rats, and to evaluate their preclinical safety. METHODS For the single dose toxicity experiment, SD rats were randomly divided into two groups, vehicle control group(deionized water) and Qingzi group(18 g·kg-1), which were given in a volume of 30 mL·kg-1 per time, twice in 24 h(interval more than 4 h), and observation was performed for 14 d after administration. The toxicity reaction was evaluated through observation of body weight change and pathological anatomy. For the repeated dose toxicity experiment, juvenile SD rats(postnatal day, PND 4) were randomly divided into vehicle control group (deionized water) and low, medium and high dose of Qingzi groups(1, 2 and 4 g·kg-1). The rats were orally administered twice daily with vehicle or Qingzi for 13 weeks in a volume of 10 mL·kg-1 per time. A recovery period of 4 weeks was followed. Test items included clinical observations, body weight measurement, food intake measurement, hematology test, biochemical test, urinalysis, sex hormone level determination, cellular immune function assay, growth indexes and histopathology test. RESULTS For the single dose toxicity experiment, Qingzi granules were orally administered to SD rats without significant toxicity, and the maximum-tolerated dose was greater than 18 g·kg-1. In the repeated dose toxicity test, juvenile SD rats were given Qingzi granules by gavage and repeated administration for 13 weeks, the no observed adverse effect level was 2 g·kg-1. The target organ of toxicity was the liver and the main toxic effect was inflammatory necrosis of hepatocytes, no dose-dependent relationship. CONCLUSION No overt toxicity of Qingzi granules was observed on the tested animals within the intended clinical dosage range.

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

To summarize the nursing experience of a patient undergoing laryngeal transplantation due to laryngeal cancer.The case involved the development of a critical care management plan by a multidisciplinary team.By implementing nursing measures such as refined airway care,professional neck wound complication management,precise administration of immunosuppressants,ultrasound monitoring for nutritional management assurance,individualized psychological care,early rehabilitation of swallowing,speech and body function,thyroid function and hyperglycemia monitoring and other measures,the patient stayed in ICU for 23 days post-surgery and discharged after 40 days from admission.