β2-adrenergic receptor （β2-AR） agonists are widely used as first-line drugs in the treatment of bronchial asthma （hereinafter referred to as “asthma”）， but long-term use can lead to β2-AR desensitization and reduce its clinical efficacy， resulting in poor symptom control of some asthma patients. The mechanism of β2-AR desensitization induced by β2-AR agonists mainly includes slow hyposensitization （related to the decrease of β2-AR density in airway mucosa） and rapid hyposensitization （related to the mechanism of stimulatory G protein decoupling）. Cyclic adenosine monophosphate（cAMP）-protein kinase A and cAMP- exchange protein activated by cAMP signaling pathways are closely related to β2-AR desensitization. Glucocorticoids， peroxisome proliferator-activated receptor-gamma agonists， ASM-024， Chinese medicine monotherapies and formulations， when combined with β2-AR agonists， can improve the sensitivity of β2-AR， so as to better control asthma symptoms.

Objective: To examine the causal relationship between body mass index (BMI) and 25 types of autoimmune diseases (ADs) using Mendelian randomization (MR) study method. Methods: The genome-wide association study (GWAS) data for BMI and 25 types of ADs were obtained from IEU OPEN GWAS database. Single nucleotide polymorphisms (SNPs) related to BMI were used as instrumental variables, 25 types of ADs were used as study outcomes, and MR analysis was performed using inverse variance weighted (IVW) method. Heterogeneity was evaluated using Cochran's Q test, horizontal pleiotropy was tested using MR-Egger regression and MR-PRESSO, and results robustness was verified with leave-one-out method. Results: Cochran's Q test showed heterogeneity of MR analysis results (P<0.05), and a random effect model was employed. The results of MR analysis showed that elevated BMI increased the incidence risks of type 1 diabetes mellitus (OR=1.519, 95%CI: 1.281-1.801), IgA nephropathy (OR=1.227, 95%CI: 1.134-1.327), adult Still disease (OR=1.002, 95%CI: 1.001-1.003), multiple sclerosis (OR=1.303, 95%CI: 1.115-1.523), narcolepsy (OR=1.029, 95%CI: 1.017-1.040), Hashimoto thyroiditis (OR=1.561, 95%CI: 1.391-1.751), autoimmune hepatitis (OR=1.481, 95%CI: 1.076-2.038), rheumatoid arthritis (OR=1.209, 95%CI: 1.054-1.386), psoriasis vulgaris (OR=1.719, 95%CI: 1.427-2.070) and pernicious anemia (OR=1.001, 95%CI: 1.000-1.002). No causal relationship was found with other ADs (all P>0.05). MR-Egger regression identified no horizontal pleiotropy of instrumental variables (all P>0.05), while MR-PRESSO test identified partial horizontal pleiotropy (all P<0.05), which remained consistent with the original results after adjustment (P>0.05). Leave-one-out analysis showed results robustness. Conclusion There are causal relationship among BMI and type 1 diabetes mellitus, IgA nephropathy, adult Still disease, multiple sclerosis, narcolepsy, Hashimoto thyroiditis, autoimmune hepatitis, rheumatoid arthritis, psoriasis vulgaris and pernicious anemia.

Objective:To evaluate the influence of different teaching modes in the creativity of nursing students in China.Methods:A systematic search of PubMed, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Wanfang Database, Chinese Biomedical Literature Database and VIP Database were carried out. Randomized control trials (RCTs) examining the influence of different teaching modes in the creativity of nursing students were included from inception to March 5, 2023. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies according to the Cochrane Handbook for Systematic Reviews of Interventions and combined with the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE), then network Meta-analysis with random effects was performed by using WinBugs 1.4.3 and Stata 17.0 software.Results:A total of 63 studies involving 22 teaching modes were included. The network Meta-analysis showed that Case-based Learning Mode, Evidence-based Nursing Teaching Mode, 3D Printing Model Teaching Mode, Hands-on Inquiry Based Learning, Quality Control Circle Teaching Mode, Six Thinking Hats Teaching Mode, Theory, Drill, Practice, Combine (TDPC, T:theory; D:drill; P:practice; C:combine) Teaching Mode were more effective than Lecture-based Learning Mode ( SMD values were 4.61-22.51, all P<0.05). Sensitivity analysis showed the effectiveness of TDPC Teaching Mode was the greatest in nursing theoretical teaching[surface under the cumulative ranking (SUCRA)=98.08%], the Quality Control Circle Teching Mode was the second most effective (SUCRA=83.13%). The effectiveness of Six Thinking Hats Teaching Mode was the greatest in nursing practical teaching (SUCRA=95.73%), followed by the 3D Printing Model Teching Mode (SUCRA=86.97%). Conclusions:TDPC Teaching Mode, Six Thinking Hats Teaching Mode, 3D Printing Model, Quality Control Circle Teaching Mode were superior to other teaching modes in improving creativity of nursing students.

Objective To investigate the effect of body mass index(BMI)on the clinicopathological characteristics of patients with idiopathic membranous nephropathy(IMN).Methods A total of 261 patients with IMN were divided into the normal group(66 cases),the overweight group(105 cases)and the obese group(90 cases)according to BMI.Clinical and renal pathological data of patients were compared between the three groups.The correlation between BMI and clinicopathological indexes was analyzed by Pearson or Spearman's correlation.The influencing factors of estimated glomerular filtration rate(eGFR)were analyzed by multiple linear regression,and the influencing factors of interstitial fibrosis(IF),tubular atrophy(TA),glomerulosclerosis(GS)and mesangial cell proliferation(MCP)were analyzed by binary Logistic regression.Results Compared with the normal group,the prevalence of diabetes mellitus,triglycerides(TG)and low-density lipoprotein cholesterol(LDL-C)were elevated in the overweight group.The prevalence of hypertension,hemoglobin(HGB),uric acid(UA),LDL-C,TG,24-h urinary protein(UTP)and serum complement 3(C3)were elevated,and high-density lipoprotein cholesterol(HDL-C)was decreased in the obese group(P＜0.05).The prevalence of hypertension,UA,TG and serum C3 were elevated in the obese group compared to the overweight group(P＜0.05).The glomerular basement membrane(GBM)thickness was higher in the obese group and the overweight group than that in the normal group,and the proportion of GS and IF was higher in the obese group than that in the normal group(P＜0.05).BMI was positively correlated with hypertension,TG,LDL-C,serum C3,UTP,GS,IF,MCP and deposition in the mesangial region of C3,and negatively correlated with HDL-C(P＜0.05).Multiple linear regression analysis showed that age,blood urea nitrogen(BUN),anti-phospholipase A2 receptor antibody(anti-PLA2R),UTP and TA were independent risk factors of eGFR.Binary Logistic regression analysis showed that elevated BMI,age,UTP and serum creatinine(Scr)were independent risk factors for IF.Age,Scr and elevated UA were independent risk factors for TA.Elevated BMI and decreased eGFR were independent risk factors for GS.Elevated BMI was an independent risk factor for MCP.There was no significant difference in the treatment protocol of IMN patients between the three groups.Conclusion Obesity can exacerbate multiple clinical and pathological outcomes in IMN patients.

Humans ; Gastrointestinal Microbiome ; Constipation/therapy* ; Probiotics/therapeutic use* ; Patients

The Death Cafe has promoted globally, breaking the silence and taboo surrounding death, allowing the public to freely discuss topics related to death and end-of-life, raising public awareness of death, and promoting public thinking and understanding of death. This paper reviews the overview of Death Cafe and its application in palliative care, in order to provide reference for the research and practice of palliative care in China.

The global incidence rate of cancer continues to rise,and shows an obvious trend of youth.Implementing digital health interventions can improve the accessibility and quality of palliative care for adolescent cancer patients.At present,there is a gradual increase in related research,but foreign research is the main focus,and domestic research is relatively small,which has not yet attracted the attention of medical staff.Starting from the needs of palliative care for adolescent cancer patients,this article reviews the forms of digital health interventions and their applications in health education,symptom assessment,psychological support and grief counseling,and the development of advance care planning.It analyzes existing problems and proposes nursing strategies,aiming to provide references for clinical nursing practice.

Rituximab is currently used as a first-line therapy for phospholipase A 2 receptor-associated membranous nephropathy due to its good efficacy and safety. Although the remission rate after rituximab treatment is more than 60%, nearly 40% patients still do not respond to treatment. We used obinutuzumab to treat 3 cases of rituximab resistant PLA 2R-associated membranous nephropathy. After the first dose of 1 000 mg with or without additional dose, the amount of anti-PLA 2R antibody and urinary protein decreased significantly and the adverse reactions were mild. The results show that obinutuzumab has a certain therapeutic effect on rituximab resistant PLA 2R-associated membranous nephropathy, but the time of follow-up observation is short and can only be used as individual cases, which needs to be confirmed by a large sample and high-quality prospective cohort study.

The paper reports a rare case of alkaptonuria (AKU) with IgA nephropathy, and analyzes its clinical manifestations, imaging findings, pathological features, gene diagnosis and treatment process, so as to provide reference for the diagnosis and treatment of the disease. The clinical symptoms of the patient were mainly black urine, microscopic hematuria and proteinuria. Renal pathology showed mild mesangial hyperplasia IgA nephropathy, and renal tubular epithelial cytochrome deposition. Genetic analysis indicated that a pathogenic mutation was detected on the AKU-related homogentisate 1, 2-dioxygenase gene possibly associated with the phenotype of the patient. Genetic testing and renal pathology were effective methods to make a definite diagnosis for the case.

Objective:To calculate the single-event dose-averaged specific energy of particles delivered in spherical domains based on the track structure model and using triple integration, and to investigate the influence of the domain shape on the key model parameters of microdosimetric kinetic model (MKM) and its corresponding physical significance.Methods:The domains are assumed to be cylinders and spheres, respectively. With α 0, domain radius, rd, and nucleus radius, Rn, as undetermined coefficients, the nuclear charge numbers, kinetic energies and their corresponding LETs of three kinds of charged particles ( 3He, 12C, 20Ne) as independent variables, D10 as dependent variable, the mean value of squared residuals, J2, between the D10 calculated values and D10 experimental values as the optimization objective, the final fitting values of the above undetermined coefficients of human salivary gland (HSG) cells and Chinese hamster lung (V79) cells obtained after iteration by the robust least square method are the optimal model parameter values of MKM. Results:For HSG cells, cylindrical domain: α 0=0.073/Gy, rd=0.29 μm, Rn=4.1 μm, J2=0.039 7 Gy 2; spherical domain: α 0=0.023/Gy, rd=0.29 μm, Rn=4.4 μm, J2=0.039 3 Gy 2; For V79 cells, cylindrical domain: α 0=0.114/Gy, rd=0.25 μm, Rn=3.8 μm, J2=0.097 4 Gy 2; spherical domain: α 0=0.095/Gy, rd=0.26 μm, Rn=4.1 μm, J2=0.096 9 Gy 2. Conclusions:For the same type of cells, cylindrical and spherical domains were selected respectively, and there are significant differences in MKM parameters obtained by fitting. The fitting values of the domain radius, rd of the two shapes of domains show no significant difference, while the fitting values of α0 of spherical domains are smaller than those of cylindrical domains, the fitting values of nucleus radius, Rn, of spherical domain are larger than those of cylindrical domains, closer to the nucleus radius observed by fluorescence microscopy. In the low LET (<20 keV/μm) region, D10 calculated according to the parameters of the two different shapes of domains are different, so the selection of the domain shape will cause differences in the relative biological effectiveness(RBE) calculation of proton in the region near Bragg peak.