Refractory lupus hepatitis successfully treated with telitacicept who failed to belimumab: A case report and literature review.

Background: Systemic lupus erythematosus (SLE)-associated hepatitis ("lupus hepatitis") was one of the most frequent causes of liver function abnormalities in patients with SLE. Lupus hepatitis (LH) is commonly treated with conventional treatment, including non-steroidal anti-inflammatory drugs, corticosteroids, and immunomodulators. However, in refractory cases, other treatment options may be required.Methodology: We report the case of a patient with lupus hepatitis refractory to both conventional therapy and belimumab who was successfully treated with telitacicept, a new dual B lymphocyte stimulator (BLyS)/APRIL (a proliferation-inducing ligand) inhibitor.Literature review was performed on PubMed search forum.Result: The specific search term was "telitacicept", 23 papers were searched, among them 10 case reports/series articles reporting telitacicept treatment were elected.Apart from our literature reporting the effectiveness of telitacicept in treating LH, there is no report on it in treating LH.Conclusion: This case suggests that telitacicept should be an effective and safe treatment for LH refractory, even to those who failed to belimumab based on the standard treatment, and can reduce the dosage of glucocorticoids.However, further investigations, particularly prospective randomized controlled trials, are warranted to verify our findings and ensure patient safety.

Safety and efficacy of telitacicept in refractory systemic lupus erythematosus patients who failed treatment with belimumab : A case series.

OBJECTIVE: This study aimed to determine the effect and safety of telitacicept, an antagonist of BLyS/APRIL-mediated B cell activation, in patients with systemic lupus erythematosus (SLE) who failed treatment with belimumab and in whom telitacicept was administered combined with conventional therapy. A review of published reports on telitacicept for SLE was also performed. METHODS: A retrospective review was performed of the records of patients seen in the Department of Rheumatology at the Wuhan Hospital of Chinese and Western Medicine, Wuhan, China, with refractory SLE who had failed treatment with belimumab. The terms "systemic lupus erythematosus" and "telitacicept" were used to identify patients reported in the English medical literature. RESULTS: Identified were 14 refractory SLE patients, 3 males (21%) and 11 females (79%). The median age was 32.9 years. The median disease duration was 8.9 years. Patients in this cohort received telitacicept for an average of 34.1 weeks (17-62 weeks) and the total SLE responder index 4 (SRI-4) response rate was 78.9% (n = 11). The mean SLE Disease Activity Index (SLEDAI) score declined from 8.6 at baseline (95% confidence interval [CI] 7.87-9.28) to 4.29 at the endpoint (95% CI 3.4-5.16). All cases (100%) had hypocomplementemia at baseline, and 7 cases (50%) reported normal C3 and C4 levels at the follow-up endpoint. At the observation endpoint, the 24­h urinary protein value of the 13 cases with proteinuria (baseline 24­h urinary protein > 0.5 g/d) displayed a reduction, and 3 values turned negative. Although some patients had low serum total immunoglobulin (Ig) levels, subnormal IgG levels, and absolute counts of peripheral blood lymphocytes after treatment, no serious infection was reported. One case was refractory lupus hepatitis confirmed by liver pathology, and upon change to change to telitacicept treatment, liver function returned to normal. CONCLUSION: This is the first case series in SLE patients who accepted telitacicept treatment after failed treatment with belimumab. Our case series and review of the literature show that telitacicept combined with the original standard treatment may significantly improve disease activity while reducing prednisone use. No major safety issues were seen in this group of patients. Telitacicept may be a promising drug for the treatment of refractory lupus hepatitis.

Clinical efficacy of belimumab in central nervous system demyelinating syndromes with systemic lupus erythematosus: A case series.

RATIONALE: Systemic lupus erythematosus (SLE) is a complex autoimmune disease involving multiple systems. Central nervous system (CNS) demyelinating syndromes are one of the rare neurological manifestations of SLE, whose diagnosis, treatment, and prognosis are rarely reported. Belimumab, an anti-BAFF monoclonal antibody, has been approved by the FDA for the treatment of SLE. We aimed to assess the effects of belimumab on demyelinating syndromes in patients with SLE. PATIENT CONCERNS: Six patients with demyelination in SLE who were managed at Traditional Chinese and Western Medicine Hospital of Wuhan from March 2021 to March 2023, who received belimumab ≥ 5 times, were enrolled. Ten age- and sex-matched SLE patients with noutneuropsychiatric systemic lupus erythematosus (NPSLE) and normal controls were recruited to analyze potential biomarkers. DIAGNOSES: All patients were diagnosed with SLE based on the 2012 Systemic Lupus International Collaborating Clinics (SLICC) SLE classification criteria or the 2019 EULAR/ACR classification criteria. All SLE patients with CNS demyelinating syndromes were diagnosed by rheumatologists, neurologists, and radiologists. INTERVENTIONS: These patients were administered belimumab combined with standard treatment (glucocorticoids and/or antimalarials and/or immunosuppressants [cyclophosphamide, mycophenolate, methotrexate, etc.]). OUTCOMES: Six patients were included in the study (100% female, mean [range] age at first demyelinating episode 42.8 [24-66] years). The most common extra-CNS features in these patients were rash, arthritis, alopecia, leukopenia, and hypocomplementemia. After Belimumab treatment, 3 of 6 (50%) patients achieved complete remission with decreased prednisone, 2 improvements, and 1 relapsed with uterine surgery. Compared with the baseline, 3.5 months post belimumab treatment, the disease activity score SLEDAI (21.5-5.5, P < .001), C3 and C4 increased, and extra-CNS symptoms improved rapidly. Moreover, The expression of lupus susceptibility gene PBX1 in CD19+ B cells was lowest in demyelinating syndromes with lupus patients compared with healthy volunteers and lupus patients without demyelination, and its relative expression negatively correlated with SLE disease activity. CONCLUSION: Belimumab could be an effective and safe option for the treatment of SLE demyelination. In addition, PBX1 might be a potential biomarker for the clinical diagnosis of lupus in patients with demyelinating syndrome.

Shape-controlled synthesis of Ni-based metal-organic frameworks with albizia flower-like spheres@nanosheets structure for high performance supercapacitors.

Metal organic frameworks (MOFs) are considered as very promising positive electrode materials for supercapacitors. To achieve good electrochemical performance, in this work, we report a mixed-ligand approach to prepare modified Ni-MOF by using trimesic acid (BTC) as the modulator to partially replace the terephthalic acid (PTA) ligands. The introduction of BTC can induce the formation of nanosheets with inserted albizia flower-like spheres, where the nanowires on the albizia flower-like spheres can provide rich redox reaction sites and the "spacer" spheres between the layers can hinder the aggregation of the 2D nanosheets to provide fast transport pathways. Moreover, adsorption simulation shows that the adsorption energy of OH- on the mixed organic ligands is increased after introducing the BTC ligands, which may improve the reversible redox reaction kinetics in the electrode materials. The as-obtained albizia flower-like spheres@nanosheets structured Ni-MOF with the optimized amount of BTC exhibits a high capacitance of 920 F g-1 at 1 A g-1, good rate capability of 61% at 20 A g-1, and an excellent cycling stability in 6 M KOH electrolyte. This work may provide helpful guidance for controlling the structure and surface property of MOFs to improve the electrochemical performance for supercapacitors.

Association of UCP1 polymorphisms with type 2 diabetes mellitus and their interaction with physical activity and sedentary behavior.

BACKGROUND: Uncoupling protein 1 (UCP1) has been reported to be associated with type 2 diabetes mellitus (T2DM) in different populations, however, little is reported in Chinese population. The present study aimed to explore the association between some polymorphisms of UCP1 with T2DM and the interactions between UCP1 and physical activity/sedentary behavior (PA/SB) lifestyle in Chinese population. METHODS: Three polymorphisms (rs1472268, rs3811790 and rs3811791) were genotyped in 929 T2DM patients and 1044 nondiabetic controls. The data of PA and SB were acquired. Logistic regression and linear regression were conducted to assess the association of UCP1 and T2DM and related traits. RESULTS: The CC genotype of rs3811791 was significantly associated with an increased risk of T2DM [odds ratio (OR) = 1.42, P = 0.042] and a higher level of triglyceride (TG) (ß = 0.048, P = 0.034). This association still existed in the group of SB ≥ 3 h/d (OR = 1.66, P = 0.009) and the group of PA ≥ 150 min/week and SB ≥ 3 h/d (OR = 1.60, P = 0.034). In the group of PA < 150 min/week and SB < 3h/d, CC genotype was associated with a higher level of homeostatic model assessment of insulin resistance (HOMA-IR) index, and in the group of PA < 150 min/week and SB ≥ 3 h/d, CC genotype was associated with increased level of TG and decreased high-density lipoprotein cholesterol (HDL-C). CONCLUSION: This study suggests that rs3811791 of UCP1 may be associated with T2DM and TG. Moreover, we demonstrate that SB interacted with rs3811791 of UCP1 was associated with T2DM, and PA interacted with rs3811791 of UCP1 was associated with the level of HOMA-IR, HDL-C, and TG.

Exploring the mechanism of clear cell renal cell carcinoma metastasis and key genes based on multi-tool joint analysis.

Clear cell renal cell carcinoma (ccRCC) is a highly invasive urological malignant tumor that results in shorter patient survival. At present, the mechanism of ccRCC metastasis is not clear. We explored the possible mechanisms of ccRCC metastasis by analyzing the transcriptome of ccRCC patients from the Cancer Genome Atlas (TCGA) database. Comparing the differences in transcriptome in patients with and without metastasis, we found 323 differential genes (|log2FoldChange| > 1 and P < 0.001). KEGG and GO enrichment analyses of differentially expressed genes (DEGs) suggest that the transfer mechanism of ccRCC may be related to complement and coagulation cascades and cholesterol metabolism. To explore the key genes affecting tumor metastasis, we analyzed the association of these genes with patient survival time and found that 16 genes were significantly associated (P < 0.05). We compared the differences in expression of these 16 genes between ccRCC patients and the normal population, and the results showed that TF and B4GALNT1 were overexpressed in patients. Co-expression gene analysis indicated that TF may participate in the metastasis of cancer through the complement system and mucopolysaccharide biosynthesis. B4GALNT1 may affect metastasis through focal adhesion, calcium signaling pathways, and Hippo signaling pathways. Our studies suggest that the complement system and the coagulation cascade, cholesterol metabolism, calcium pathway and iron transport may be associated in the mechanism of metastasis. TF and B4GALNT1 may be the key genes for metastasis, and they may be potential diagnostic markers and therapeutic targets for ccRCC.

Ultrathin 2D nitrogen-doped carbon nanosheets for high performance supercapacitors: insight into the effects of graphene oxides.

Ultrathin 2D nitrogen-doped carbon nanosheets with a thickness of about 5 nm have been facilely synthesized from potato starch by using graphene oxides (GO) as the structure-directing agent. The pore structures and surface properties can be feasibly and rationally tailored by addition of a certain amount of GO in the precursor. The addition of GO to the potato starch can increase the surface areas and the pyridinic-N and pyrrolic-N ratios of the as-prepared 2D carbon nanosheets. The as-obtained ultrathin nitrogen-doped carbon nanosheets with the optimized amount of GO in potato starch (3 wt%) possess a unique 2D structure, a high N content, and high ratios of pyridinic-N and pyrrolic-N, exhibiting a high capacitance of 301 F g-1 at 0.5 A g-1, superior rate capability of 81% at 50 A g-1, and good cycling stability in 6 M KOH electrolyte. Experimental and theoretical results show that high pyridinic-N and pyrrolic-N ratios in the NCNSs are beneficial for improving the electrochemical performance. This work may provide helpful guidance for understanding the effect of the addition of GO to biomass precursors on the electrochemical performance of the 2D nitrogen-doped carbon electrodes for supercapacitors.

Association of SERPINE1 rs6092 with type 2 diabetes and related metabolic traits in a Chinese population.

BACKGROUND: Plasminogen activator inhibitor-1 (PAI-I), encoded by SERPINE1 gene, is a member of the serine protease inhibitor superfamily, and polymorphisms in SERPINE1 have been reported to be associated with type 2 diabetes (T2D). This study investigated whether the polymorphism in PAI-I contribute to the risk for T2D. METHODS: A 1:1 case-control study was conducted to investigate the association of rs6092 in SERPINE1 with T2D and diabetes-related metabolic traits, including body mass index, waist circumference (WC), triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol, low density lipoprotein cholesterol, fasting plasma glucose and glycosylated hemoglobin (HbA1c) in a Chinese population, with a total of 1572 subjects (786 T2D patients and 786 healthy controls). The polymorphism was genotyped based on MassARRAY genotyping system. RESULTS: The AA genotype and A allele of rs6092 exerted a protective effect on T2D risk (odds ratio (OR) = 0.431 and 0.630, respectively). In a recessive model, we also observed the protective association of rs6092 with T2D (OR = 0.195). The above associations were only observed in men. In female patients, there was a significant difference in HbA1c level between the AA homozygotes and GG homozygotes, as well as between the AA homozygotes and combined GG and GA genotypes. In male patients, the WC level in the subjects carrying AA genotype was lower than those in the subjects with GG genotype (P = 0.000), and the association was also significant in a recessive model (P = 0.000). Additionally, there was a significant difference in TG level between the AA homozygotes and GG homozygotes (P = 0.017), as well as the AA homozygotes and combined GG and GA genotypes (P = 0.032). CONCLUSIONS: Our study suggests that the A allele and AA genotype of rs6092 may protect against T2D, and have a protective effect on WC, but a negative effect on TG in men, while may contribute to a lower HbA1c level in women.