Efficacy and safety of telitacicept in patients with lupus nephritis: a single-center, real-world retrospective study.

BACKGROUND: Telitacicept, an innovative drug used for the treatment of systemic lupus erythematosus (SLE), can effectively control disease progression and achieve favorable outcomes. While case reports have mentioned the use of Telitacicept in lupus nephritis (LN) treatment, its safety and efficacy in treating patients with LN have not been explored. Therefore, in this study, we aimed to evaluate the safety and efficacy of Telitacicept in managing patients with LN. METHODS: In a single-center, real-world retrospective study, 30 LN patients with poor response or adverse reactions to conventional glucocorticoids at our Hospital were enrolled to receive Telitacicept. Patients were administered 160 mg of Telitacicept subcutaneously once a week for at least 24 weeks in addition to standard treatment. We assessed the SLE responder index-4 (SRI-4) at the beginning and the end of the treatment period, measured laboratory test indicators at 3, 6, and 9 months, and observed the occurrence of adverse events in these patients. RESULTS: The SRI-4 response rate was 86.67% (n = 26), with a significantly lower systemic lupus erythematosus disease activity index (SLEDAI) score compared to the baseline. Post Telitacicept treatment, glucocorticoid intake of patients with LN significantly reduced from 50 (IQR:40, 51.25) at baseline to 10 (IQR:5,10) at the endpoint (Z = - 6.547, p < 0.001). Patients with LN showed significantly improved urine occult blood levels after Telitacicept therapy. While the complement (C3 and C4) contents increased, immunoglobulins (IgG, IgA and IgM) reduced markedly (p < 0.001). The negative rate of dsDNA reached 26.67% and adverse events were alleviated post treatment. Only two cases of LN-related adverse reactions were reported, including herpes and infectious fever, respectively. Telitacicept primarily serves as an agent for the induction of remission therapy, with an attainment of complete remission rate standing at a commendable 73.3%. CONCLUSIONS: Telitacicept treatment reduced disease severity in patients with LN. The initial clinical trial provided supportive evidence for the effectiveness and safety of Telitacicept as a viable treatment option for LN, allowing a reduction in the daily glucocorticoid intake while maintaining a good safety profile, and improving hypocomplementation in LN management.

Evolutionary origin and establishment of a dioecious diploid-tetraploid complex.

Polyploids recurrently emerge in angiosperms, but most polyploids are likely to go extinct before establishment due to minority cytotype exclusion, which may be specifically a constraint for dioecious plants. Here we test the hypothesis that a stable sex-determination system and spatial/ecological isolation facilitate the establishment of dioecious polyploids. We determined the ploidy levels of 351 individuals from 28 populations of the dioecious species Salix polyclona, and resequenced 190 individuals of S. polyclona and related taxa for genomic diversity analyses. The ploidy survey revealed a frequency 52% of tetraploids in S. polyclona, and genomic k-mer spectra analyses suggested an autopolyploid origin for them. Comparisons of diploid male and female genomes identified a female heterogametic sex-determining factor on chromosome 15, which probably also acts in the dioecious tetraploids. Phylogenetic analyses revealed two diploid clades and a separate clade/grade of tetraploids with a distinct geographic distribution confined to western and central China, where complex mountain systems create higher levels of environmental heterogeneity. Fossil-calibrated phylogenies showed that the polyploids emerged during 7.6-2.3 million years ago, and population demographic histories largely matched the geological and climatic history of the region. Our results suggest that inheritance of the sex-determining system from the diploid progenitor as intrinsic factor and spatial isolation as extrinsic factor may have facilitated the preservation and establishment of polyploid dioecious populations.

The association of serum magnesium with infection in new-onset systemic lupus erythematosus patients.

OBJECTIVE: To assess the association of serum magnesium with infection in new-onset systemic lupus erythematosus (SLE) patients. METHODS: We conducted a single-center retrospective cohort study of new-onset SLE patients from 2012 to 2021. The hospitalized SLE patients were divided into infection and noninfection groups. Logistic regression analysis was conducted to examine the association of hypomagnesemia with infection. RESULTS: A total of 476 new-onset SLE patients were included, with 299 cases in the infection group and 177 cases in the noninfection group. The patients were mostly females (81.7%). The average age at diagnosis was 43.7 years. The median duration was 1.0 month. The prevalence of hypomagnesemia (<0.70), normomagnesemia (0.70-1.10), and hypermagnesemia (>1.10) in new-onset SLE patients was 14.3%, 83.4%, and 2.3%, respectively. The prevalence of hypomagnesemia was 18.4% in the infection group and 7.3% in the noninfection group (p = .001). The baseline value of serum magnesium was 0.819 mmol/L, with values of 0.799 mmol/L in the infection group and 0.854 mmol/L in the noninfection group (p = .000). The following clinical variables were significantly different between the two groups (p < .05): age, duration, hospitalization stay, fever, serositis, and SLE Disease Activity Index 2000 (SLEDAI 2K). The laboratory parameters, including hemoglobin, white blood cell count, albumin level, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), procalcitonin, and complement C3 were also significantly different between the two groups (p < .05). The mortality was 4.4% (21/476), with 20 cases occurring in the infection group. Logistic regression analysis showed that hypomagnesemia was associated with an increased risk of infection (p = .001) and poor prognosis (p = .015). CONCLUSION: Hypermagnesemia was rare in new-onset SLE patients. Hypomagnesemia was common and was associated with an increased risk of infection in new-onset SLE patients.

Paper-based immune-affinity arrays for detection of multiple mycotoxins in cereals.

Mycotoxins produced by different species of fungi may coexist in cereals and feedstuffs, and could be highly toxic for humans and animals. For quantification of multiple mycotoxins in cereals, we developed a paper-based mycotoxin immune-affinity array. First, paper-based microzone arrays were fabricated by photolithography. Then, monoclonal mycotoxin antibodies were added in a copolymerization reaction with a cross-linker to form an immune-affinity monolith on the paper-based microzone array. With use of a competitive immune-response format, paper-based mycotoxin immune-affinity arrays were successfully applied to detect mycotoxins in samples. The detection limits for deoxynivalenol, zearalenone, T-2 toxin, and HT-2 toxin were 62.7, 10.8, 0.36, and 0.23 µg·kg-1, respectively, which meet relevant requirements for these compounds in food. The recovery rates were 81-86% for deoxynivalenol, 89-117% for zearalenone, 79-86% for T-2 toxin, and 78-83% for HT-2 toxin, and showed the paper-based immune-affinity arrays had good reproducibility. In summary, the paper-based mycotoxin immune-affinity array provides a sensitive, rapid, accurate, stable, and convenient platform for detection of multiple mycotoxins in agro-foods. Graphical abstract Paper-based immune-affinity monolithic array. DON deoxynivalenol, HT-2 HT-2 toxin, T-2 T-2 toxin, PEGDA polyethylene glycol diacrylate, ZEN zearalenone.

Analysis of risk factors for the progression and prognosis of connective tissue disease-associated interstitial lung disease.

Objectives: This study aimed to investigate the risk factors of lung progression in patients with connective tissue disease-associated interstitial lung disease (ILD). Patients and methods: A total of 91 ILD patients (28 males, 63 females; mean age: 54.9±11.3 years; range, 30 to 77 years) were included in the prospective follow-up study conducted throughout 2020. They were divided into progressors (n=27) and nonprogressors (n=64) according to whether the pulmonary disease progressed during a six-month follow-up period. The clinical data of the two groups were analyzed, and a logistic regression model was constructed to analyze the risk factors of the progression of ILD in all patients. Results: Univariate analysis revealed significant differences (p<0.05) between the two groups in smoking history, serum ferritin, FVC% (the percentage of forced vital capacity), DLCO% (the percentage of diffusion capacity for carbon monoxide), and computed tomography involvement range. Further application of a logistic regression model revealed that increased serum ferritin level was an independent risk factor for ILD progression (odds ratio=1.002, 95% confidence interval: 1.000-1.003, p=0.004). The optimal critical value of serum ferritin was 303.25 ng/mL, the sensitivity and specificity were 81.5% and 54.7%, respectively, and the area under the curve was 0.747. Conclusion: The level of serum ferritin may be an independent predictor for ILD progression.

Pattern of Nailfold Capillaroscopy in Patients With Systemic Lupus Erythematosus.

OBJECTIVES: This study aims to assess the nailfold capillary changes in patients with systemic lupus erythematosus (SLE), particularly among those with Raynaud's phenomenon (RP), and the correlation between nailfold capillary changes and autoantibodies and disease activity. PATIENTS AND METHODS: A total of 85 patients (9 males, 76 females; median age 31 years; range, 15 to 58 years) with newly diagnosed SLE were selected between July 2016 and July 2018 from our hospital. Disease activity was scored by the SLE Disease Activity Index. Nailfold capillaroscopy (NFC) was performed in all patients. RESULTS: Normal pattern, non-specific pattern, and scleroderma pattern were found in 13 (15.3%), 64 (75.3%), and eight (9.4%) patients, respectively. There was no significant difference between anti-double stranded deoxyribonucleic acid, anti-Smith antibodies, and low complements (all p>0.05), while significant differences of NFC pattern were found between low disease activity and high disease activity (p=0.002). RP was present in 31.7% of SLE patients, and the NFC findings in SLE patients with and without RP were significantly different in dilatation (81.5% vs. 14.0%). CONCLUSION: The results of our study showed that capillary changes were very common in patients with SLE, which seem to associate with disease activity and RP condition.

Development and characterization of irradiated-corn-starch films.

The effect of 60Co gamma ray irradiation on the physicochemical and crystalline properties of native corn starch were investigated. Fourier transform infrared spectroscopy and X-ray diffraction showed that irradiation had a slight effect on the molecular structure of corn starch with crystallinity decreasing with increasing irradiation dose. Particle size analysis showed that 59.1% of native corn starch granules had sizes of ≥8 µm, which decreased to only 24.1% after treatment with an irradiation dose of 40 kGy. Irradiated-corn-starch films were prepared by casting gelatinized irradiated-corn-starch solutions. An increased irradiation dose was found to increase the tensile strength of the resultant films, but caused a significant decrease in water vapor permeability. The irradiated-corn-starch films showed potential for the development of biodegradable starch films with improved properties.

Identification of serum miR-34a as a potential biomarker in acute myeloid leukemia.

BACKGROUND: MicroRNA-34a (miR-34a), as a tumor-suppressive miRNA, has been found to induce cell apoptosis in acute myeloid leukemia (AML). However, the diagnostic and prognostic significance of miR-34a in AML remains largely unknown. OBJECTIVE: We aimed to explore its associations with clinical characteristics and prognosis of AML patients. METHODS: This study detected serum miR-34a level in 117 diagnosed AML patients and 60 control subjects by using qRT-PCR, and results were compared to clinical features and patient outcome. Since cytogenetically-normal AML (CN-AML) has a good uniformity of cytogenetics and provides a perfect platform for detection of AML biomarkers, we further analyzed miR-34a expression in 56 CN-AML subjects. RESULTS: We found that miR-34a was significantly downregulated in AML and CN-AML patients. MiR-34a underexpression was commonly observed in AML patients with intermediate/poor risk cytogenetic, and M5 subtype. ROC analysis demonstrated that serum miR-34a could well identify AML/CN-AML patients from healthy individuals. More importantly, miR-34a expression was found negatively correlated with aggressive clinical variable, and served as an independent prognostic indicator. In addition, AML/CN-AML patients with low miR-34a expression displayed shorter overall and recurrence free survival. CONCLUSIONS: Altogether, miR-34a might have an application as a diagnostic and prognostic indicator for AML patients.

[Clinical application of blood matching with hemolytic test in vitro for transfusion treatment of crisis puerpera with acute hemolytic anemia].

This study was aimed to establish the matching method of hemolytic test in vitro, and to guide the transfusion treatment for puerpera with acute hemolytic disease. The donor's erythrocytes were sensibilized by all the antibodies in plasma of patient in vitro and were added with complement, after incubation for 6.5 hours at 38 °C, the hemolysis or no hemolysis were observed. It is safe to transfuse if the hemolysis did not occur. The results showed that when the matching difficulty happened to puerpera with acute hemolytic disease, the compatible donor could be screened by hemolytic test in vitro. There were no untoward effects after transfusion of 6 U leukocyte-depleted erythrocyte suspension. The all hemoglobin, total bilirubins, indirect bilirubin, reticulocyte, D-dimex and so on were rapidly improved in patient after transfusion , showing obvious clinical efficacy of treatment. It is concluded that when the matching results can not judge accurately compatible or incompatible through the routine method of cross matching, the agglutinated and no-hemolytic erythrocytes can be screened by hemolytic test in vitro and can be transfused with good efficacy; the hemoglobin level can be promoted rapidly, and no untoward effects occur.

[Antiproliferative effects of LY294002 on MCL Jeko-1 cell line and its mechanism].

This study was aimed to investigate the effects of LY294002, a specific inhibitor of phosphatidylinositol 3-kinase, on growth and apoptosis of MCL Jeko-1 cell line and its mechanism. The proliferation inhibitory rate of Jeko-1 cells treated by different doses of LY294002 was assayed by MTT method; the level of apoptosis of Jeko-1 cells was detected by flow cytometry; the expression level of apoptosis-related protein Cyclin D1, Bcl-2, procaspase-3 and PI3K/Akt signaling pathway protein phosphorylated-Akt (p-Akt), phosphorylated-TOR (p-mTOR), phosphorylated-P70S6K (p-P70S6K) phosphorylated-Akt (p-Akt) in Jeko-1 cells were determined by Western blot. The results showed that the growth of Jeko-1 cell line was inhibited by LY294002. The apoptosis rates of Jeko-1 cells treated with 0, 5, 10 and 20 µmol/L of LY294002 for 24 hours were (3.25 ± 1.27)%, (11.34 ± 2.35)%, (22.81 ± 2.74)%, (43.61 ± 3.48)% respectively, the difference between them was statistically significant (P < 0.01). Phosphorylation levels of PI3K/Akt signaling pathway protein p-Akt, p-mTOR, p-P70S6K decreased, the expression of apoptosis-related protein cyclin D1, Bcl-2, procaspase-3 was down-regulated.It is concluded that the LY294002 can inhibit Jeko-1 cell proliferation, which may be realized through down-regulating the phosphorylation level of p-Akt, p-mTOR, p-P70S6K, inhibiting the P13k/Akt signaling pathway, and promoting the cell apoptosis.