Anti-neutrophil cytoplasmic antibody associated vasculitis in patients with rheumatoid arthritis.

BACKGROUND: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) may coexist with rheumatoid arthritis (RA). However, it is unclear whether the manifestations of AAV with and without coexisting RA are similar. This observational study aimed to investigate the clinicopathological manifestations of AAV with coexisting RA and to explore potential predictors for identifying AAV superimposed on RA. METHODS: Patients with both AAV and RA were identified by searching our hospital database and the literature. Data including age, sex, clinical manifestation, laboratory tests, renal pathology, and therapeutic regimens were retrieved. To assess the difference in clinical features and renal pathology between AAV patients with and without RA, we conducted 1:4 matched case-control studies. RESULTS: A total of 47 patients were identified, 15 from our hospital and 32 from the literature, and 33 (70.2%) were women. AAV was diagnosed later than RA in 83.0% of the patients and manifested as microscopic polyangiitis (MPA) in 78.7% of the patients. The kidney was the most frequently involved extra-articular organ (74.5%), followed by the lung (51.1%), and skin (8.5%). Patients with both AAV and RA were more likely to be asymptomatic (26.7% vs 3.3%, p = 0.013) than those with isolated AAV. However, they did not differ in other clinicopathological features. In RA patients, those with ANCA associated glomerulonephritis, were more likely to have decreased renal function at renal biopsy as opposed to those with primary glomerulonephritis. CONCLUSIONS: AAV can coexist with RA. In this coexistence, AAV usually develops after RA, is more likely to be asymptomatic, and manifests predominately as MPA with renal involvement. Thus, we should remain vigilant to superimposed AAV on RA.

[Study on origin and authentication of medicinal materials of Dalbergiae Lignum in crude drug's market].

The study is aimed to distinguish morphological characteristics of Dalbergiae Lignum collected from crude drug's markets and establish a identification methods and the quality standard for Dalbergiae Lignum. The macroscopic and microscopic features of Dalbergiae Lignum from crude drug's market were observed, analyzed and compared according to Hongmu specification issued by the People's Republic of China in 2000, and by the characteristics recorded in domestic monograph of Mucai Shibie (wood identification). The redwood of Dalbergiae Lignum cut into small pieces as medicinal material are dry heart wood of mahogany (trees from Dalbergia sp.), which characteristics of the small pieces as crude drug are different. There are differences in macroscopic and microscopic features about texture of wood and color, odor, taste, transverse section, radial section, tangential section. The results can provide basis for identification, application and improment of the quality standard of Dalbergiae Lignum as medicinal material.

Gut Dysbiosis Drives Inflammatory Bowel Disease Through the CCL4L2-VSIR Axis in Glycogen Storage Disease.

Patients with glycogen storage disease type Ib (GSD-Ib) frequently have inflammatory bowel disease (IBD). however, the underlying etiology remains unclear. Herein, this study finds that digestive symptoms are commonly observed in patients with GSD-Ib, presenting as single or multiple scattered deep round ulcers, inflammatory pseudo-polyps, obstructions, and strictures, which differ substantially from those in typical IBD. Distinct microbiota profiling and single-cell clustering of colonic mucosae in patients with GSD are conducted. Heterogeneous oral pathogenic enteric outgrowth induced by GSD is a potent inducer of gut microbiota immaturity and colonic macrophage accumulation. Specifically, a unique population of macrophages with high CCL4L2 expression is identified in response to pathogenic bacteria in the intestine. Hyper-activation of the CCL4L2-VSIR axis leads to increased expression of AGR2 and ZG16 in epithelial cells, which mediates the unique progression of IBD in GSD-Ib. Collectively, the microbiota-driven pathomechanism of IBD is demonstrated in GSD-Ib and revealed the active role of the CCL4L2-VSIR axis in the interaction between the microbiota and colonic mucosal immunity. Thus, targeting gut dysbiosis and/or the CCL4L2-VISR axis may represent a potential therapy for GSD-associated IBD.

Effects of Low-Impact Development Facilities (Water Systems of the Park) on Stormwater Runoff in Shallow Mountainous Areas Based on Dual-Model (SWMM and MIKE21) Simulations.

Rapid urbanization has triggered more serious urban flood risks. Many studies have focused on intra-urban flooding, but less attention has been paid to rainfall and flood risks at the urban fringe. Nowadays, China is vigorously promoting the construction of sponge cities in the whole area. It is important to study the construction of sponge cities in shallow mountainous areas, which are an important barrier between cities and mountains. The purpose of this paper is to investigate the performance of Low-Impact Development (LID) facilities under different rainfall scenarios in developed shallow mountainous areas. The second garden and flower exposition ("the Expo Park") in Hebei Province is used as an example. The SWMM and MIKE21 models were used to simulate the hydrological processes before and after the construction of "the Expo Park", and the models were calibrated with the measured data. Peak flow rate, outflow volume, rainfall-outflow ratio, runoff velocity, and water feature area of the water system were used as indicators to evaluate their effectiveness. The results showed that the placement of LID facilities had a positive impact on the construction of the shallow mountain area. Specifically, (1) LID facilities can reduce the peak flow rate, delayed peak flow time, outflow volume, and rainfall outflow ratio of stormwater runoff in mountainous areas; and (2) they can effectively collect rainwater and become a supplement to the landscape water system of the site. These findings provide a scientific basis for the construction of LID facilities in shallow mountainous areas, which is important for the development and flood management of shallow mountainous areas.

Clinical Features and Factors Associated With Sepsis-Associated Encephalopathy in Children: Retrospective Single-Center Clinical Study.

Background: Sepsis-associated encephalopathy (SAE) is a common complication in septic patients with a higher ICU and hospital mortality in adults and poorer long-term outcomes. Clinical presentation may range from mild confusion to convulsions and deep coma; however, little is known about SAE in children. We aimed to retrospectively analyze the data for children with sepsis, to illustrate the epidemiology, performance, and adverse outcome, and to evaluate the association between risk factors and SAE in children. Methods: All children with sepsis who were admitted to the Department of Pediatrics, Guangdong Provincial People's Hospital, Guangzhou, Guangdong, China from January 2010 to December 2020 were retrospectively analyzed. Results: A total of 210 patients with sepsis were retrospectively assigned to the SAE and non-SAE groups, of which 91 (43.33%) were diagnosed with SAE with a mortality of 6.70% (14/210). Significant differences were observed in the level of white blood platelet, platelets, international normalized ratio, prothrombin time, activated partial thromboplastin time, total protein, Ccr, UREA, blood urea nitrogen, alanine transaminase, aspartate transaminase, creatine kinase, creatine kinase isoenzymes, lactate dehydrogenase, procalcitonin, and lactic acid (p < 0.05). In the risk assessment scales, significant differences were observed in the modified Glasgow Coma score, PCIS, Pediatric Logistic Organ Dysfunction Score 2 (PELOD-2), Pediatric Sequential Organ Failure Assessment Score, and Pediatric Risk of Mortality III (p < 0.05). The incidence of septic shock, acute kidney disease, liver dysfunction, and coagulation disorder were higher in the SAE group (p < 0.05). The mechanical ventilation time ([6.57 d ± 16.86 d] vs. [2.05 d ± 5.79 d]; p < 0.001), CRRT time ([1.74 d ± 6.77 d] vs. [0.11 d ± 0.63 d]; p < 0.001), ICU stay time ([299.90 h ± 449.50 h] vs. [177.67 h ± 245.36 h]); p < 0.001 was longer than that of non-SAE. Both the PCT, Ca2+, septic shock, PELOD-2, and midazolam were identified as independent risk factors, and fentanyl was a protective factor for SAE in pediatric patients (p < 0.05). The main clinical neurological symptoms consisted of agitation, hypnosia, hypnosis alternates agitated, anterior fontanelle full/bulging/high tension, coma, muscle hypertonia, muscle hypotonia, hyperreflexia, focal seizure, and generalized seizure. Conclusions: The incidence of SAE in children was found high and the prognosis poor. In this retrospective study, the identified patients were more susceptible to SAE, with an inflammatory storm with hypocalcemia or septic shock. The use of midazolam will increase the occurrence of SAE, whereas fentanyl will reduce the incidence of SAE, and PELOD-2 may predict the occurrence of SAE.

Psychometric properties of the Chinese version of the Pediatric Quality of Life Inventory 4.0 generic core scales.

PURPOSE: The aim of this study was to evaluate the psychometric properties of the Chinese version of the Pediatric Quality of Life Inventory 4.0 (PedsQL 4.0) generic core scales. METHODS: The standard procedure of cross-culture adaptation was used to develop the Chinese version PedsQL4.0. We enrolled 1583 healthy children and 1335 pediatric patients (aged from 5 to 18 years) and 325 proxies. The psychometric properties of the measure were evaluated. RESULTS: The subscales of physical functioning, social functioning and psychosocial showed alpha coefficients above 0.7 for self-report in healthy children and the total pediatric patients, and all coefficients were higher than 0.7 for proxy report for all subscales. There were higher correlations between items and hypothesized subscales than with other subscales. Healthy children reported higher scores than pediatric patients in all subscales. Confirmatory factor analysis showed that some of the indices of goodness of fit did not reach the standard of acceptable construct validity. Moderate to high correlations were found between self-reported and proxy-reported scores. CONCLUSION: The Chinese version PedsQL4.0 has acceptable psychometric properties except the construct validity tested by confirmatory factor analysis and the internal reliability for self-report in pediatric patients with migraine or Gilles and Tourette's syndrome.

[Effect of recombinant human tumor necrosis factor receptor type II-Fc fusion protein antibody on cytokines and bone metabolism in patients with juvenile idiopathic arthritis].

OBJECTIVE: To evaluate the influence of the recombinant human type II tumor necrosis factor receptor-antibody Fc fusion protein (rhTNFR:Fc) on cytokines and bone metabolism in patients with juvenile idiopathic arthritis (JIA). METHODS: This was a prospective, non-randomized, controlled and open-label study. Thirty-one patients with JIA in active state were enrolled at our hospital from December 2006 to June 2009. The mean age was 12.7 ± 2.3 years. Exclusive criteria included infection with tuberculosis and hepatitis B etc., abnormal renal or hepatic function. Study consists of two phases. During the first phase (0-3 months), according to the economic status, all JIA patients were divided into treatment and control groups. The treatment group consisted of 18 patients (enthesitis-related arthritis, n = 15; polyarticular-onset arthritis, n = 2; systemic-onset type, n = 1) on a regimen of rhTNFR:Fc 0.4 mg/kg, subcutaneously injected twice weekly. The control group contained 13 patients (enthesitis-related arthritis, n = 9; polyarticular-onset arthritis, n = 2; systemic-onset type, n = 2) on a regimen of MTX 10 mg × m(-2) × w(-1). Two intolerance patients were given sulfasalazine (SASP) 30-50 mg × kg(-1) × d(-1). During the second phase (3-6 months), the responding patients continued the original therapy. The rhTNFR:Fc group received a reduced dosage of 0.4 mg × kg(-1) × w(-1). All patients of both groups who became complicated with peripheral arthritis or were non-responding had the addition of SASP. Follow-up was conducted at baseline, 1 month, 3 months and 6 months. And TNF-α, MMP-3, IL-1ß, osteocalcin (BGP), ß-collagen fragment (ß-CTx), alkaline phosphatase, erythrocyte sedimentation rate (ESR), c-reactive protein (CRP) and bone mineral density dynamic changes were examined respectively in the treatment process. RESULTS: Alkaline phosphatase and lumbar spine bone mineral density increased while TNF-α, IL-1ß, ESR and CRP decreased significantly in two groups (P < 0.05). ESR were 16 ± 8.0 mm/h vs 60 ± 38 mm/h, CRP 10 ± 7 mg/L vs 47 ± 37 mg/L and ß-CTx 2.1 ± 0.8 vs 1.1 ± 0.9 µg/L at 1 month in two groups respectively with statistic difference (P < 0.05). BGP increased and MMP-3 decreased in both groups with no statistic difference. Femur Ward's triangular area and forearm bone mineral density had no statistic difference between two groups. Interestingly, one case with bone fracture for two years has healed after a 6-month therapy of rhTNFR:Fc as proved by X-ray. CONCLUSION: Both rhTNFR:Fc and traditional DMARDs both can reduce the levels of TNF-α, IL-1ß, ESR and CRP and increase lumbar spine bone mineral density and ALP significantly. RhTNFR: Fc improves the acute phase index and bone metabolism index earlier than the traditional therapy. Thus disease and bone destruction are controlled more earlier.

Varinostat Alters Gene Expression Profiles in Aortic Tissues from ApoE-/- Mice.

Atherosclerosis (AS) is a complex, chronic inflammatory disease that is characterized by plaque buildup within arterial vessel walls. Preclinical trials have suggested that vorinostat, a pan-histone deacetylase inhibitor (HDACi), reduces vascular inflammation and AS, but the underlying protective mechanism has not been fully elucidated. The present study aimed to identify altered gene expression profiles in aortic tissues from ApoE-/- mice after vorinostat treatment. Male ApoE-/- mice fed a high-fat diet were treated with either vorinostat or vehicle, and the aortic plaque area was quantified 8 weeks after treatment. Aortic tissues were collected from both the vorinostat group (n = 3) and vehicle group (n = 3) for deep sequencing of the cDNA to construct sRNA libraries. Oral administration of vorinostat significantly reduced plaque size in the ApoE-/- mice (p < 0.05). In total, 1,550 differentially expressed mRNAs, 56 differentially expressed miRNAs, and 381 differentially expressed lncRNAs were identified in the vorinostat group compared to the vehicle group. Subsequently, a global lncRNA-miRNA-mRNA triple network was constructed based on the competitive endogenous RNA (ceRNA) theory. The hepatitis C signaling pathway was significantly enriched among the differentially expressed mRNAs from the ceRNA network, which suggests that vorinostat has anti-inflammatory properties. Importantly, the identified target pair of mmu-miR-3075-5p/lncRNA-A330023F24Rik/Ldlr may regulate drug response. Upregulation of low-density lipid receptor (Ldlr) and lncRNA-A330023F24Rik and downregulation of mmu-miR-3075-5p were further verified by quantitative real-time polymerase chain reaction. To conclude, vorinostat reduced AS in ApoE-/- mice. Differentially expressed mRNA, lncRNAs, and miRNAs, as well as their interactions and pathways, were identified, which partially explain vorinostat's anti-atherosclerotic effects.

Bio-inspired cisplatin nanocarriers for osteosarcoma treatment.

In this study, cisplatin (cis-diaminedichloroplatinum, CDDP) nanocarriers with phosphorylcholine surface tailoring were developed to enhance the anti-tumor potential of CDDP for the treatment of osteosarcoma. Poly(2-methacryloyloxyethyl phosphorylcholine)-b-poly(methacrylic acid) (PMPC-b-PMAA) was synthesized for the preparation of CDDP/PMPC-b-PMAA micelles. The synthesis, self-assembly, and in vitro drug release were well characterized. In vitro cytotoxicity showed that CDDP/PMPC-b-PMAA micelles can strongly inhibit the proliferation of Saos-2 cells. In vivo experiments indicated that CDDP/PMPC-b-PMAA micelles showed prolonged circulation time, reduced renal accumulation, and enhanced tumor accumulation compared to free CDDP. Overall, the CDDP/PMPC-b-PMAA micelles exhibited optimal anti-tumor activity with minimal side effects in the treatment of osteosarcoma.