OBJECTIVE: To investigate the serum level of lumican (LUM) and its clinical correlation with disease and immune activities in patients with rheumatoid arthritis (RA). METHODS: The serum LUM levels in both RA patients and health controls (HCs) were detected by enzyme-linked immunosorbent assay (ELISA). The clinical and laboratory data of the patients were collected. The LUM levels in the patients with different clinical features were analyzed. The correlation between the clinical data, laboratory parameters, and serum LUM levels were also analyzed. Independent samples t test, Spearman correlation were used for statistical analysis. Analysis of variance and Kruskal-Wallis test, the least significant difference (LSD)-t test and Bonferroni correction were used for statistical analysis. The Pearson Chi-square test was used for comparison of the rates between the groups. Statistical significance was set at P < 0.05. RESULTS: The levels of LUM were elevated in the RA patients than in the HCs (P < 0.000 1). Serum LUM levels were correlated with the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), immunoglobulin A (IgA), titers of platelet (PLT) and 28-joint disease activity score (DAS28, all P < 0.05). Next, we compared the serum LUM levels in the RA patients with different characteristics, and no difference was found in serum LUM levels between early-RA and RA, the same to RA with different gender (P>0.05). The levels of serum LUM were elevated in the RF positive patients (P < 0.000 1), and in the RF and anti-CCP positive patients (P < 0.05) than in the RA patients with negative RF whether the anti-CCP was positive. In addition, no differences were found between the RA patients with negative RF whether the anti-CCP was positive (P>0.05). All the levels of serum LUM were elevated in the RA patients with different CRP or ESR than in the HCs (P < 0.05), and the serum LUM levels in the RA patients with elevated ESR and CRP were significantly elevated in those with normal ESR and CRP (P < 0.05). Additionally, the results demonstrated that serum LUM levels were positively associated with RA disease activity, and they were declined in RA sustained remission than those in middle or high disease activity (P < 0.05). Furthermore, no difference was found between the RA patients in remission and HCs (P>0.05). No differences were found in the RA patients with and without complications including interstitial pneumonia disease, Sjögren's syndrome, thyroid gland diseases and osteoporosis (P>0.05). The LUM positivity rates were significantly elevated in the RF positive patients than the RF negative patients in RA (P < 0.05). CONCLUSION LUM, a cyclocitrullinated protein, might be a promising biomarker which could reflect both disease activity and immune activity in RA.
Humans ; Arthritis, Rheumatoid/immunology* ; Lumican/blood* ; C-Reactive Protein/metabolism* ; Female ; Male ; Rheumatoid Factor/blood* ; Middle Aged ; Adult ; Chondroitin Sulfate Proteoglycans/blood* ; Blood Sedimentation ; Keratan Sulfate/blood* ; Enzyme-Linked Immunosorbent Assay ; Aged

ObjectiveTo establish an ultra-high performance liquid chromatography-tandem triple quadrupole mass spectrometry（UHPLC-QqQ-MS） for determination of the active ingredients in Erdongtang， and to predict the targets and pathways of anti-insulin resistance action of this formula. MethodThe analysis was performed on an ACQUITY UPLC BEH C₁₈ column（2.1 mm×100 mm， 1.7 μm） with the mobile phase of 0.1% formic acid aqueous solution（A）-acetonitrile（B） for gradient elution（0-3 min， 90%-87%A； 3-6 min， 87%-86%A； 6-9 min， 86%-83%A； 9-11 min， 83%-75%A； 11-18 min， 75%-70%A； 18-19 min， 70%-52%A； 19-22 min， 52%A； 22-25 min， 52%-5%A； 25-27 min， 5%-90%A； 27-30 min， 90%A）. The contents of active ingredients in Erdongtang was detected by electrospray ionization（ESI） and multiple reaction monitoring（MRM） mode under positive and negative ion modes. On this basis， network pharmacology was applied to predict the targets and pathways of Erdongtang exerting anti-insulin resistance effect. ResultThe 20 active ingredients in Erdongtang showed good linear relationships within a certain mass concentration range， and the precision， stability， repeatability and recovery rate were good. The results of determination showed that the ingredients with high content in 15 batches of samples were baicalein（1 259.39-1 635.78 mg·L^-1）， baicalin（1 078.37-1 411.52 mg·L^-1）， the ingredients with medium content were mangiferin（148.59-217.04 mg·L^-1）， timosaponin BⅡ（245.10-604.89 mg·L^-1）， quercetin-3-O-glucuronide（89.30-423.26 mg·L^-1）， rutin（46.91-1 553.61 mg·L^-1）， glycyrrhizic acid（55.97-391.47 mg·L^-1）， neomangiferin（37.45-127.03 mg·L^-1）， nuciferine（0.89-63.48 mg·L^-1）， hyperoside（6.96-136.78 mg·L^-1）， liquiritin（30.89-122.78 mg·L^-1）， liquiritigenin（26.64-110.67 mg·L^-1）， protodioscin（58.57-284.26 mg·L^-1）， the ingredients with low content were wogonin（7.16-20.74 mg·L^-1）， pseudoprotodioscin（5.49-22.96 mg·L^-1）， ginsenoside Rb₁（7.31-23.87 mg·L^-1）， ginsenoside Rg₁（10.78-28.33 mg·L^-1）， ginsenoside Re（7.78-24.76 mg·L^-1）， ophiopogonin D（2.08-4.29 mg·L^-1）， methylophiopogonanone A（0.74-1.67 mg·L^-1）. The results of network pharmacology indicated that the mechanism of anti-insulin resistance exerted by Erdongtang might be related to the phosphatidylinositol 3-kinase/protein kinase B（PI3K/Akt） signaling pathway. ConclusionThe established UHPLC-QqQ-MS has the advantages of simple sample processing， strong exclusivity and high sensitivity， and can simultaneously determine the contents of the main ingredients from seven herbs in Erdongtang， which can lay the foundation for the development of Erdongtang compound preparations. The results of the network pharmacology can provide a reference for the mechanism study of Erdongtang in the treatment of type 2 diabetes mellitus.

Monoclonal gammopathy of undetermined significance combined with renal damage is named monoclonal gammopathy of renal significance. There are few reports about IgA vasculitis in patients with monoclonal gammopathy of undetermined significance. Here, we report a case of monoclonal gammopathy of renal significance, who had manifestations of IgA vasculitis, including purpura, gastrointestinal bleeding and joint pain. The patient had elevated serum creatinine levels, prompting further investigation through immunofixation electrophoresis and bone marrow aspiration biopsy. Immunofixation electrophoresis showed IgA-λ-type monoclonal immunoglobulin, while the bone marrow aspiration biopsy suggested plasmacytosis. Kidney biopsy indicated membranous hyperplastic glomerulonephritis, light and heavy chain deposition, IgA-λ. The patient was diagnosed with monoclonal gammopathy of renal significance. In light of the elevated serum creatinine, the patient was treated with chemotherapy regimen (bortezomib +cyclophosphamide +dexamethasone). After chemotherapy, there was no significant improvement in the patient's renal function. Subsequently, the patient experienced abdominal pain, skin purpura, joint pain and severe gastrointestinal bleeding. Gastroenteroscopy did not find the exact bleeding position. Angiography revealed hyperplasia of left jejunal artery. Surgical operation found that the bleeding site was located between the jejunum and ileum, where scattered hemorrhagic spots and multiple ulcers were present on the surface of the small intestine, with the deepest ulcers reaching the serosal layer. And the damaged intestine was removed during the operation. Intestinal pathology showed multiple intestinal submucosal arteritis, rusulting in intestinal wall necrosis and multiple ulcers. Considering intestinal lesions as gastrointestinal involvement of IgA vasculitis, methylprednisolone was used continually after the operation, and the patient's condition was improved. However, after half a year, the patient suffered a severe respiratory infection and experienced a recurrence of serious gastrointestinal bleeding. It was considered that the infection triggered the activity of IgA vasculitis, accompanied by gastrointestinal involvement. Finally, the patient died from gastrointestinal bleeding. The present case represented a patient with monoclonal gammopathy of renal significance and IgA vasculitis, prominently presenting with renal insufficiency and severe gastrointestinal bleeding, making the diagnosis and treatment process complex. Patients with IgA monoclonal gammopathy who presented with abdominal pain, purpura, and arthralgia should be vigilant for the possibility of concomitant IgA vasculitis. The treatment of cases with IgA vasculitis combined with monoclonal gammopathy of renal significance was rather challenging. Plasma cell targeting therapy might be an effective regimen for IgA vasculitis with monoclonal gammopathy. However, patients with poor renal response to the treatment indicated poor prognosis.
Humans ; Cyclophosphamide/administration & dosage* ; Gastrointestinal Hemorrhage/etiology* ; IgA Vasculitis/complications* ; Immunoglobulin A ; Intestine, Small/pathology* ; Kidney/pathology* ; Kidney Diseases/pathology* ; Monoclonal Gammopathy of Undetermined Significance/complications* ; Necrosis ; Paraproteinemias/complications* ; Vasculitis/etiology*

Rheumatoid arthritis (RA) and myasthenia gravis (MG) are two distinct autoimmune diseases. Compared with the general population, the incidence of RA is notably higher among patients with MG. Similarly, the rate of MG in patients diagnosed with RA is also significantly increased. In this report, we presented an elderly female patient with a history usage of long-term glucocorticoid and conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), whose RA symptoms remained inadequately controlled. She later exhibited drooping of the right eyelid and double vision, leading to a diagnosis of ocular myasthenia gravis (OMG). Then, we made a literature review and found that the RA patients with co-existing MG were relatively more common in middle-aged and elderly women, and most of them did not have thymoma. Thymoma wasn ' t found in our patient, which was consistent with the cli-nical characteristics of RA complicated with MG reported in previous reports. In addition, there was li-mited treatment experience in patients with both RA and MG. The treatment stratergies for RA or MG included glucocorticoids and immunosuppressants. Among the 18 patients we analyzed, 8 patients expe-rienced relief after csDMARDs, while other 8 patients received biologics or targeted DMARDs, including tumor necrosis factor inhibitors (TNFi) in 5 cases, JAK inhibitors in 2 cases, and B-cell depletion therapy (rituximab) in 2 cases. What called for special attention was that one RA patient was diagnosed with MG after using 23 months of methotrexate and 6 weeks of etanercept (TNFi), with rituximab 1 000 mg for the first time, followed by 500 mg every 6 months, and finally both RA and MG were well controlled. For the patient in this study, MG symptoms improved with increased dosage of prednisone. In order to tapper the dose of glucocorticoid, it was necessary for more potent immunosuppressant for both RA and MG. Given her history of cardiac conditions, JAK inhibitors were not considered, and due to the uncertain efficacy of TNFi, we chose to administer low-dose rituximab (100 mg). Subsequent follow-up revealed stable conditions for both RA and MG, allowing for discontinuance of glucocorticoid after 5 months. It reflected the potential efficacy and cost-effectiveness of low-dose, long-interval rituximab in treating RA patients combined with MG, while it also minimized infection risks. However, the duration for subsequent infusions remained uncertain and required further observation. In conclusion, RA combined with MG is rare. For patients exhibiting poor responses to csDMARDs, low-dose, long-interval rituximab might be a promising treatment option.
Humans ; Arthritis, Rheumatoid/drug therapy* ; Rituximab/administration & dosage* ; Myasthenia Gravis/drug therapy* ; Female ; Antirheumatic Agents/administration & dosage* ; Aged ; Glucocorticoids/therapeutic use*

BACKGROUND: Type 2 diabetes mellitus (T2DM) is an independent risk factor for colorectal cancer (CRC), and the patients with CRC and T2DM have worse survival. The human gut microbiota (GM) is linked to the development of CRC and T2DM, respectively. However, the GM characteristics in patients with CRC and T2DM remain unclear. METHODS: We performed fecal metagenomic and targeted metabolomics studies on 36 samples from CRC patients with T2DM (DCRC group, n = 12), CRC patients without diabetes (CRC group, n = 12), and healthy controls (Health group, n = 12). We analyzed the fecal microbiomes, characterized the composition and function based on the metagenomics of DCRC patients, and detected the short-chain fatty acids (SCFAs) and bile acids (BAs) levels in all fecal samples. Finally, we performed a correlation analysis of the differential bacteria and metabolites between different groups. RESULTS: Compared with the CRC group, LefSe analysis showed that there is a specific GM community in DCRC group, including an increased abundance of Eggerthella , Hungatella , Peptostreptococcus , and Parvimonas , and decreased Butyricicoccus , Lactobacillus , and Paraprevotella . The metabolomics analysis results revealed that the butyric acid level was lower but the deoxycholic acid and 12-keto-lithocholic acid levels were higher in the DCRC group than other groups ( P < 0.05). The correlation analysis showed that the dominant bacterial abundance in the DCRC group ( Parvimonas , Desulfurispora , Sebaldella , and Veillonellales , among others) was negatively correlated with butyric acid, hyodeoxycholic acid, ursodeoxycholic acid, glycochenodeoxycholic acid, chenodeoxycholic acid, cholic acid and glycocholate. However, the abundance of mostly inferior bacteria was positively correlated with these metabolic acid levels, including Faecalibacterium , Thermococci , and Cellulophaga . CONCLUSIONS Unique fecal microbiome signatures exist in CRC patients with T2DM compared to those with non-diabetic CRC. Alterations in GM composition and SCFAs and secondary BAs levels may promote CRC development.
Humans ; Gastrointestinal Microbiome/genetics* ; Diabetes Mellitus, Type 2 ; Microbiota ; Bacteria/genetics* ; Fatty Acids, Volatile ; Colorectal Neoplasms/metabolism* ; Butyrates ; Feces/microbiology*

Sjögren's syndrome(SS)is a chronic autoimmune disease that affects exocrine glands, especially salivary and lacrimal glands. The main clinical manifestations are dry mouth and dry eyes, but also multi-organ and multi-system can be involved. Cold agglutinin disease(CAD)is an autoimmune disease characterized by red blood cell agglutination in the blood vessels of extremities caused by cold agglutinin at low temperature, resulting in skin microcirculation disturbance, or hemolytic anemia. Cold agglutinin disease is divided into two categories, primary cold agglutinin disease and secondary cold agglutinin disease. Primary cold agglutinin disease is characterized with cold agglutinin titer of 1 ∶4 000 or more and positive Coomb's test. However, the Coomb's test is not necessarily positive and the cold agglutinin titer is between 1 ∶32 and 1 ∶4 000 in secondary cold agglutinin disease. Here, we reported an elderly patient admitted to hospital due to fever. He was diagnosed with respiratory infection, but he showed incompletely response to the anti-infection treatment. Further laboratory tests showed the patient with positive ANA and anti-SSA antibodies. Additionally, the patient complained that he had dry mouth and dry eyes for 1 year. Schirmer test and salivate gland imaging finally confirmed the diagnosis Sjogren's syndrome. During the hospital stay, the blood clots were found in the anticoagulant tubes. Hemolytic anemia was considered as the patient had anemia with elevated reticulocytes and indirect bilirubin. In addition, further examination showed positive cold agglutination test with a titer of 1 ∶1 024, and cold agglutinin disease was an important type of cold-resistant autoimmune hemolytic anemia. Furthermore, the patient developed cyanosis after ice incubating at the tip of the nose. Hence, the patient was diagnosed as CAD and he was successfully treated with glucocorticoids instead of anti-infection treatments. Hence, the patient was diagnosed with SS combined with secondary CAD. SS combined CAD are rarely reported, and they are both autoimmune diseases. The abnormal function of B lymphocytes and the production of autoantibodies might be the common pathogenesis of them. Cold agglutinin disease can lead to severe hemolytic anemia, even life-threatening. In clinical practice, timely recognizing and dealing with CAD might promote the prognosis of the patient.
Male ; Humans ; Aged ; Anemia, Hemolytic, Autoimmune/diagnosis* ; Sjogren's Syndrome/diagnosis* ; Anemia, Hemolytic/complications* ; Dry Eye Syndromes/complications* ; Autoantibodies

A common clinical problem encountered by colorectal surgeons is the secondary tumors of the ovary (STO), particularly in young female patients. Most STO are from the digestive tract, and the known possible metastatic mechanisms include lymphatic, hematogenous, and intraperitoneal spreading. The molecular and histopathological characteristics of STO from different sites are diverse. It is particularly important to correctly identify the origin and feature of STO, which should be clarified by combining medical history, histopathology, immunohistochemistry, molecular biology, imaging and other means. The prognosis of patients with STO is poor in general. Comprehensive therapies based on surgical resection can benefit some patients. There is no specific treatment for STO at present, but not giving up easily on these patients is the right choice that every surgeon should understand.
Colorectal Neoplasms/therapy* ; Female ; Humans ; Krukenberg Tumor ; Ovarian Neoplasms/surgery* ; Prognosis ; Surgeons

Objective To evaluate the implementation feasibility of the nurse performance appraisal and allocation plan based on the holistic nursing mode, and the clinical effect in mobilizing nursing staff's work enthusiasm and ensuring the quality of nursing service. Methods The nurse performance appraisal and allocation plan were further improved based on the previous research of this index system construction. The model were implemented in 32 clinical departments of Yidu Center Hospital of Weifang City. Four aspects data were collected for analysis six months later to evaluate the effect. They were nurses on merit pay distribution satisfaction, patients′satisfaction, doctors′satisfaction with nursing job, different clinical departments′nursing quality scores. Results Six months later, four factor scores of nurses to the satisfaction of merit pay distribution were significantly improved. The scores of fairness and impartiality evaluation of the merit pay distribution, incentive effect evaluation, pay and return on equity evaluation and performance pay gap rationality evaluation were higher than before [(3.39 ±0.64) points vs. (1.88 ±0.33) points, (3.28 ±0.74) points vs. (1.84 ±0.49) points , (3.28 ±0.71) points vs. (1.88 ±0.42) points and (3.38 ±0.67) points vs. (2.01±0.53) points, t=19.28, 16.22, 18.08, 16.79, all P<0.05]. Patients′satisfaction, doctors′satisfaction with nursing job and different clinical department' nursing quality scores were significantly increased as well [(99.14±0.82) points vs. (96.78±0.84) points, (96.59±0.91) points vs. (93.59±1.27) points and(97.67±0.41) points vs. (95.70±1.13) points]. Difference had statistical significance (t=11.79, 11.63, 9.60, P<0.05). Conclusions The performance salary allocation plan can effectively improve the hospital nurses on performance salary allocation satisfaction, patients′satisfaction, doctor′s satisfaction with nursing work and the quality of nursing department, and has good incentive in arousing the work enthusiasm of nursing staff and in ensuring the quality of nursing service.

BACKGROUNDVery recent studies revealed that obstructive sleep apnoea (OSA) is a contributor of the increased incidence and mortality of cancer in humans, but mechanisms of how OSA promotes tumorigenesis remains largely unknown. We investigated whether intermittent hypoxia with and without hypercapnia plays a role in tumorigenesis.

METHODSFirst, Sprague-Dawley (SD) male rats (12 weeks old) were subjected to different hypoxia exposures: intermittent hypoxia and intermittent hypoxia with hypercapnia; continuous hypoxia and normal air. The systemic application of chronic fast rate hypoxia with or without hypercapnia mimicked severe OSA patients with apnoea/hypopnea index equivalent to 60 events per hour. Then routine blood tests were performed and the levels of brain derived neurotrophic factor (BDNF) and miR-34a were examined.

RESULTSIn contrast to intermittent hypoxia with hypercapnia, both intermittent hypoxia and continuous hypoxia treatments caused significantly higher levels of haematology parameters than normoxia treatments. Compared to normoxia, intermittent hypoxia with hypercapnia exposure resulted in substantial decrease of serum BDNF and, miR-34a in the lower brainstem, while less pronounced results were found in intermittent hypoxia and continuous hypoxia exposure.

CONCLUSIONSThe exposure of intermittent hypoxia with or without hypercapnia, mimicking the situations in severe OSA patients, was associated with, or even promoted tumorigenesis.

Animals ; Brain Stem ; metabolism ; Brain-Derived Neurotrophic Factor ; blood ; metabolism ; Cell Transformation, Neoplastic ; Hypercapnia ; blood ; complications ; Hypoxia ; blood ; complications ; Male ; MicroRNAs ; metabolism ; Rats ; Rats, Sprague-Dawley ; Real-Time Polymerase Chain Reaction

Objective To estimate dry weight (DW) and prevent dialysis-related hypotension and hypertension with the on-line monitoring of relative blood volume (RBV) and other judgments.Methods One hundred and eight maintenance hemodialysis patients were assigned to three groups according to their blood pressure:normal blood pressure group (A group,n=43),hypotension group (B group,n=35) and hypertension group (C group,n=35).The level of hemoglobin,serum albumin,dialysis adequacy were determined.Systolic blood pressure,diastolic blood pressure,mean arterial pressure,heart rate,ultrafiltration volume,relative blood volume changes and the corresponding clinical symptoms were monitored during hemodialysis in all patients.Each of the patients was continuously monitored of the indicators above for 10-12 times.At the observing period,the inferior vena cava diameter (IVCD),brain natriuretic peptide (BNP) and cardiothoracic ratio(CTR) were measured.Then according to the monitoring results,appropriate clinical interventions were given under on-line blood volume monitoring guidance.Results (1)The shape of RBV curve in group A showed doubleexponential curve early,then down to the final linear decling ended during hemodialysis.(2)The RBV curve in group B was stable in the former two hours,then rapidly linear declined.RBV changes were significantly higher in group B than group A (P ＜ 0.05),but when changes in RBV were plotted against ultrafiltration volume,there was no significant difference in the two groups.The level of RBV reduction at which symptomatic hypotension occurred showed considerable inter-individual variability (P ＜ 0.05,coefficient of variation=0.28).(3)The RBV curve in group C slowly linear declined.At the end of dialysis,RBV changes were significantly lower in group C than group A (P ＜ 0.05).(4)The IVCD values in three groups of patients before dialysis were greater than normal,significantly decreased after the dialysis (P ＜ 0.05),but that in group B and group C were still greater than that in group A (P ＜ 0.05).The BNP values were significantly greater in three groups before and after dialysis (P ＜ 0.05),but after dialysis,the values decreased significantly than that before dialysis (P ＜ 0.05).(5)After appropriate clinical intervention were given under on-line blood volume monitoring in hemodialysis,the patients of group B controlled weight gain,and even cut dry weight,the RBV change significantly decreased at the end of dialysis and significantly reduced the incidence of hypotension events (P ＜ 0.05); When the patients of group C cut dry weight,increased ultrafiltration,the RBV change increased,the mean arterial pressure decreased significantly than before (P＜ 0.05).Conclusions (1)Hemodialysis patients with symptomatic hypotension show larger RBV decline rate in the forth hour and lager total RBV changes,which provides important information for forecasting the symptomatic hypotension in hemodialysis.(2)IVCD and CTR have certain significance to the adjustment of dry weight,but the BNP has guiding significance to volume change.(3)On-line monitoring of RBV can effectively guide the adjustment of dry weight,reduction of symptomatic hypotension occruence,and controlling of refractory hypertension in hemodialysis.