The patient was a girl aged 10 years and 10 months, with weakness, pale complexion, and rash as the initial presentation. She had the manifestations of anemia, thrombocytopenia, hematuria-proteinuria with renal insufficiency, hypocomplementemia, polyserositis, and positive anti-nuclear antibody and anti-dsDNA antibody. The girl was initially diagnosed with systemic lupus erythematosus and lupus nephritis. She demonstrated a suboptimal response to methylprednisolone pulse therapy, intravenous immunoglobulin administration, and therapeutic plasma exchange. She had persistent anemia, thrombocytopenia, abnormal renal function, elevated lactate dehydrogenase, decreased complement factors H and I, increased antibodies to C3 converting enzyme, and normal ADAMTS13 activity. She was diagnosed with complement-mediated hemolytic thrombotic microangiopathy secondary to systemic lupus erythematosus. The patient's condition improved after treatment with two doses of eculizumab (600 mg per dose). Patients with systemic lupus erythematosus complicated by thrombotic microangiopathy often have a severe disease course and poor prognosis; therefore, early recognition and aggressive intervention are crucial for improving outcomes.
Humans ; Female ; Lupus Erythematosus, Systemic/drug therapy* ; Thrombotic Microangiopathies/etiology* ; Antibodies, Monoclonal, Humanized/therapeutic use* ; Child

Aim To investigate the therapeutic effects of a newly developed Tadalafil tablet on pulmonary fi-brosis induced by paraquat(PQ)in rats,as well as its impact on histone acetylation levels in epithelial cells.Methods SD rats were randomly divided into four groups:the control group(control),the model group(PQ),the Tadalafil new tablet treatment group(N-Tad,1 mg·kg-1),and the positive control drug treatment group(Cialis,5 mg·kg-1).The model group and treatment group rats were intraperitoneally injected with PQ(30 mg·kg-1).Two hours after the initial treatment,the rats in the treatment group re-ceived N-Tad or Cialis via gavage,while the control and model groups were administered an equal volume of physiological saline by gavage once daily for 28 days.The weight gain rate and lung tissue index for each group of rats were calculated.Additionally,the effects of N-Tad treatment on lung tissue structural damage and collagen deposition in rats with PQ-in-duced pulmonary fibrosis were observed using HE stai-ning,Masson trichrome staining,and immunohisto-chemical techniques.By employing the Western blot technique,the effects of Tadalafil intervention on the expression of the epithelial marker E-cadherin(E-Cad),the stromal marker fibronectin(Fn),and the histone acetylation marker acetylated histones(Ac-his-tones)in A549 cells were observed.Results Com-pared to the control group,rats with PQ-induced pul-monary fibrosis exhibited a significant decrease in the rate of body weight growth,an increase in lung tissue index(P＜0.05),and a notable increase in the expression and distribution of the fibrosis marker alpha-smooth muscle actin(α-SMA)in lung tissue.The structure of the lung tissue was disrupted,accompanied by the deposition of interstitial collagen fibers.Both N-Tad and Cialis treatments could significantly enhance the rate of weight gain,decrease the lung tissue index,inhibit the expression of α-SMA,and reduce the depo-sition of interstitial collagen in the lung tissue of rats with pulmonary fibrosis.Notably,low-dose N-Tad treatment was comparable to high-dose Cialis treat-ment.At the cellular level,Tadalafil significantly in-hibited the high expression of Fn induced by transfor-ming growth factor beta 1(TGF-β1)in A549 cells.It also upregulated the expression of E-cadherin and sig-nificantly increased the levels of acetylated histones(P＜0.05).Conclusions N-Tad promotes histone acetylation in alveolar epithelial cells,significantly in-hibits epithelial-mesenchymal transition,increases E-cadherin expression,and improves lung tissue structur-al damage and collagen deposition caused by PQ.Ad-ditionally,it offers the advantage of a lower effective dose compared to Cialis,providing a new option for the treatment of pulmonary fibrosis.

Objective To predict and preliminarily validate potential shared key genes involved in cardiac complications caused by influenza A virus(IAV)and severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infections.Methods Differentially expressed genes(DEGs)associated with cardiac complications were obtained from the Gene Expression Omnibus(GEO)database.A hierarchical intersection strategy was applied.First,cardiac complication related DEGs were overlapped with 2 independent virus related gene sets:3 454 human genes linked to IAV infection in GeneCards and 333 human protein-coding genes interacting with SARS-CoV-2 in the Human Protein Atlas.The 2 overlap results were then intersected to yield 22 hub genes.Lasso regression,random forest(RF)and support vector machine algorithms(SVM)were employed to refine this list.Predicted genes were validated in vitro in H1N1-infected human cardiomyocyte AC16 cells and in vivo in IFITM3 knockout mice challenged with H1N1,assessing transcriptional changes.Results A total of 22 hub genes were identified through integrative bioinformatics analysis.Application of the 3 machine learning algorithms resulted in 5 common key genes:ACE2,TBK1,NUP210,PUSL1,and MEPCE.In vitro infection of AC16 cells with H1N1 revealed dynamic transcriptional changes in all 5 genes post-infection(P<0.05).In vivo experiments using H1N1-infected IFITM3 knockout mice confirmed the dynamic mRNA expression changes of these 5 genes,consistent with the in vitro results(P<0.05).Conclusion By combining multilayered bioinformatics analysis with 3 machine learning approaches,5 common key genes are identified:ACE2,TBK1,NUP210,PUSL1 and MEPCE.Validation in H1N1 infection models confirms their relevance to IAV-induced cardiac complications.

Objective:To observe the efficacy of eculizumab in children with atypical hemolytic uremic syndrome.Methods:It was a single-center observational study. The clinical data of children diagnosed with atypical hemolytic uremic syndrome and treated with eculizumab in Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology from January 2023 to May 2024 were retrospectively collected. Eculizumab was used at the conventional dose based on the children 's weight. Event-free survival (no death or end-stage renal disease) rate, complete remission rate and recurrence rate of thrombotic microangiopathy in children with atypical hemolytic uremic syndrome after eculizumab treatment were analyzed. The complete remission time of estimated glomerular filtration rate, hemoglobin, platelet, lactic dehydrogenase, urine routine and the adverse reactions during the treatment were observed. Whole exome sequencing was used to conduct genetic testing based on blood samples of the children and their parents.Results:There were 4 children enrolled in the study. Four children were all Han Chinese, including 3 males and 1 female. The median age of onset was 8 years (ranging from 7 to 10 years). Two patients had complement gene abnormalities, both of which were homozygous deletions of complement factor H-related 1 and complement factor H-related 3. All the patients were free of plasma exchange or perfusion after treatment with eculizumab, and the 6-month event-free survival rate and thrombotic microangiopathy complete remission rate were both 4/4. The complete remission time was 19 (14-28) days. The time for the complete recovery of platelets, lactate dehydrogenase, estimated glomerular filtration rate and hemoglobin in 4 children was 4 (1-5), 19 (14-28), 10 (5-14) and 29 (20-42) days, respectively. Except for 1 patient whose urine routine fluctuated between negative and weakly positive expression, the other 3 patients had normal urine routine. All the patients discontinued eculizumab. Two patients without gene mutations discontinued eculizumab after 7 doses, and there was no recurrence during the 1-year follow-up after drug withdrawal. Two patients with genetic abnormalities discontinued eculizumab after 26 weeks of treatment, and no recurrence was found during the 3-month follow-up after drug withdrawal. One patient developed rash approximately 7 days after receiving the third dose of eculizumab. The rash was relieved after anti-allergic treatment, and there was no recurrence after the continued use of eculizumab.Conclusion:Eculizumab is effective and safe in the treatment of children with atypical hemolytic uremic syndrome. Discontinuation of eculizumab can be considered in patients without gene mutations when their condition is stable, but close monitoring and follow-up are needed after drug withdrawal.

Aim To investigate the therapeutic effects of a newly developed Tadalafil tablet on pulmonary fi-brosis induced by paraquat(PQ)in rats,as well as its impact on histone acetylation levels in epithelial cells.Methods SD rats were randomly divided into four groups:the control group(control),the model group(PQ),the Tadalafil new tablet treatment group(N-Tad,1 mg·kg-1),and the positive control drug treatment group(Cialis,5 mg·kg-1).The model group and treatment group rats were intraperitoneally injected with PQ(30 mg·kg-1).Two hours after the initial treatment,the rats in the treatment group re-ceived N-Tad or Cialis via gavage,while the control and model groups were administered an equal volume of physiological saline by gavage once daily for 28 days.The weight gain rate and lung tissue index for each group of rats were calculated.Additionally,the effects of N-Tad treatment on lung tissue structural damage and collagen deposition in rats with PQ-in-duced pulmonary fibrosis were observed using HE stai-ning,Masson trichrome staining,and immunohisto-chemical techniques.By employing the Western blot technique,the effects of Tadalafil intervention on the expression of the epithelial marker E-cadherin(E-Cad),the stromal marker fibronectin(Fn),and the histone acetylation marker acetylated histones(Ac-his-tones)in A549 cells were observed.Results Com-pared to the control group,rats with PQ-induced pul-monary fibrosis exhibited a significant decrease in the rate of body weight growth,an increase in lung tissue index(P＜0.05),and a notable increase in the expression and distribution of the fibrosis marker alpha-smooth muscle actin(α-SMA)in lung tissue.The structure of the lung tissue was disrupted,accompanied by the deposition of interstitial collagen fibers.Both N-Tad and Cialis treatments could significantly enhance the rate of weight gain,decrease the lung tissue index,inhibit the expression of α-SMA,and reduce the depo-sition of interstitial collagen in the lung tissue of rats with pulmonary fibrosis.Notably,low-dose N-Tad treatment was comparable to high-dose Cialis treat-ment.At the cellular level,Tadalafil significantly in-hibited the high expression of Fn induced by transfor-ming growth factor beta 1(TGF-β1)in A549 cells.It also upregulated the expression of E-cadherin and sig-nificantly increased the levels of acetylated histones(P＜0.05).Conclusions N-Tad promotes histone acetylation in alveolar epithelial cells,significantly in-hibits epithelial-mesenchymal transition,increases E-cadherin expression,and improves lung tissue structur-al damage and collagen deposition caused by PQ.Ad-ditionally,it offers the advantage of a lower effective dose compared to Cialis,providing a new option for the treatment of pulmonary fibrosis.

Objective:To observe the efficacy of eculizumab in children with atypical hemolytic uremic syndrome.Methods:It was a single-center observational study. The clinical data of children diagnosed with atypical hemolytic uremic syndrome and treated with eculizumab in Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology from January 2023 to May 2024 were retrospectively collected. Eculizumab was used at the conventional dose based on the children 's weight. Event-free survival (no death or end-stage renal disease) rate, complete remission rate and recurrence rate of thrombotic microangiopathy in children with atypical hemolytic uremic syndrome after eculizumab treatment were analyzed. The complete remission time of estimated glomerular filtration rate, hemoglobin, platelet, lactic dehydrogenase, urine routine and the adverse reactions during the treatment were observed. Whole exome sequencing was used to conduct genetic testing based on blood samples of the children and their parents.Results:There were 4 children enrolled in the study. Four children were all Han Chinese, including 3 males and 1 female. The median age of onset was 8 years (ranging from 7 to 10 years). Two patients had complement gene abnormalities, both of which were homozygous deletions of complement factor H-related 1 and complement factor H-related 3. All the patients were free of plasma exchange or perfusion after treatment with eculizumab, and the 6-month event-free survival rate and thrombotic microangiopathy complete remission rate were both 4/4. The complete remission time was 19 (14-28) days. The time for the complete recovery of platelets, lactate dehydrogenase, estimated glomerular filtration rate and hemoglobin in 4 children was 4 (1-5), 19 (14-28), 10 (5-14) and 29 (20-42) days, respectively. Except for 1 patient whose urine routine fluctuated between negative and weakly positive expression, the other 3 patients had normal urine routine. All the patients discontinued eculizumab. Two patients without gene mutations discontinued eculizumab after 7 doses, and there was no recurrence during the 1-year follow-up after drug withdrawal. Two patients with genetic abnormalities discontinued eculizumab after 26 weeks of treatment, and no recurrence was found during the 3-month follow-up after drug withdrawal. One patient developed rash approximately 7 days after receiving the third dose of eculizumab. The rash was relieved after anti-allergic treatment, and there was no recurrence after the continued use of eculizumab.Conclusion:Eculizumab is effective and safe in the treatment of children with atypical hemolytic uremic syndrome. Discontinuation of eculizumab can be considered in patients without gene mutations when their condition is stable, but close monitoring and follow-up are needed after drug withdrawal.

Background: In the field of neuroscience research, executive functions (EFs) are of great significance. Patients with Parkinson’s disease (PD) often encounter the problem of EFs impairment, which severely affects their lives and health.However, currently, the methods for evaluating EFs in experimental mice are limited, and there is a lack of effective evaluation indicators for touchscreen behavioral tests in different disease model mice. This study aims to establish a paradigm process and an evaluation baseline for touchscreen behavioral analysis in PD model mice, deeply explore the mechanisms of EFs impairment in PD, and provide a crucial foundation for subsequent research and treatment. Methods: Thirty clean - grade SNCA*A53T transgenic mice and forty clean - grade C57BL/6J wild - type mice were selected. For A53T mice, genetic identification was carried out. Molecular biology techniques such as PCR were used to determine their genetic characteristics. Protein detection was conducted through methods like Western blot to clarify the expression of relevant proteins. In terms of behavioral tests, the five - choice serial reaction time task (5 - CSRT) was adopted, and various behavioral data of mice in this task were recorded. Four groups were set up: the control group, the MPTP group. Different groups of mice were given specific treatments. For example, the MPTP group of mice was injected with MPTP to construct a drug - induced PD model. Principal component analysis (PCA) and receiver operating characteristic (ROC) curves were used to analyze the obtained touchscreen behavioral baseline indicators of mice, and key indicators were screened and evaluated. Results: In the 5 - CSRT, the optimal stage for wild - type C57 mice to achieve an accuracy rate of ≥ 80% was from the 11th to the 13th cycle, while for A53T mice, it was the 11th cycle. The EFs of A53T mice were impaired, with abnormalities in the accuracy rate, trace number, and number of punished times in the 5 - CSRT. When identifying drug - induced PD models, the 13th cycle of the 5 - CSRT was more effective; when identifying transgenic PD models, the 11th cycle was more suitable. Interventions could be carried out after the baseline accuracy rate reached 80%. Through the “genetic - environmental” dual - axis drive, the “chronic - acute” time - dimension complementarity, and the “mechanism - transformation” multi - level verification, the A53T and MPTP dual models were used to comprehensively cover the pathological cycle of PD EFs impairment. Conclusions This study has successfully established a paradigm process and an evaluation baseline for touchscreen behavioral analysis in PD model mice. This provides an important basis for a deep understanding of the mechanisms of EFs impairment in PD patients, has potential guiding significance for the development of intervention strategies and treatment methods for EFs impairment in PD patients, and is expected to promote new progress in PD research in the field of neuroscience.

BackgroundPrevious studies have found that patients with generalized anxiety disorder （GAD） have impaired performance in executive function， and group cognitive behavioral therapy （CBT） has been shown to be effective in alleviating negative affect in patients with GAD， while its efficacy on executive function remains unclear. ObjectiveTo explore the efficacy of group CBT on anxiety symptom and executive function in GAD patients， so as to provide references for the rehabilitation program for GAD. MethodsA total of 80 consecutive patients with GAD who were hospitalized in Sleep and Psychosomatic Medical Center of Shiyan Taihe Hospital from March 2021 to August 2022 and met the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5） diagnostic criteria for GAD were enrolled， and they were assigned into study group （n=40） and control group （n=40） using random number table methods. All patients were subjected to routine medication treatment and regular health education， based on this， study group received group CBT once a week （6 weeks， 60 to 90 minutes per session）. At the enrollment and after 6 weeks of treatment， patients were assessed using Hamilton Anxiety Scale （HAMA） and Frontal Assessment Battery （FAB）. ResultsANOVA with repeated measures on HAMA score revealed a significant time effect （F=1 870.320， P<0.01）， no significant group effect and no significant time×group interaction effect （F=1.254， 0.293， P>0.05）. Significant time effect， group effect and time×group interaction effect were reported on FAB scores （F=311.190， 4.399， 7.021， P<0.05 or 0.01）. Further analysis indicated that FAB scores of both groups after treatment were higher than those at baseline （t=200.569， 115.401， P<0.01）.And the FAB score of study group was higher than that of control group after treatment （t=-3.211， P<0.01）. ConclusionGroup CBT combined with medication treatment for GAD may alleviate the anxiety symptoms and improve executive function in GAD patients. ［Funded by Shiyan Science and Technology Bureau Pilot Scientific Research Project （number， 21Y21）］

Background: The initiation of sodium-glucose cotransporter-2 inhibitors (SGLT2i) typically leads to a reversible initial dip in estimated glomerular filtration rate (eGFR). The implications of this phenomenon on clinical outcomes are not well-defined. Methods: We searched MEDLINE, Embase, and Cochrane Library from inception to March 23, 2023 to identify randomized controlled trials and cohort studies comparing kidney and cardiovascular outcomes in patients with and without initial eGFR dip after initiating SGLT2i. Pooled estimates were calculated using random-effect meta-analysis. Results: We included seven studies in our analysis, which revealed that an initial eGFR dip following the initiation of SGLT2i was associated with less annual eGFR decline (mean difference, 0.64; 95% confidence interval [CI], 0.437 to 0.843) regardless of baseline eGFR. The risk of major adverse kidney events was similar between the non-dipping and dipping groups but reduced in patients with a ≤10% eGFR dip (hazard ratio [HR], 0.915; 95% CI, 0.865 to 0.967). No significant differences were observed in the composite of hospitalized heart failure and cardiovascular death (HR, 0.824; 95% CI, 0.633 to 1.074), hospitalized heart failure (HR, 1.059; 95% CI, 0.574 to 1.952), or all-cause mortality (HR, 0.83; 95% CI, 0.589 to 1.170). The risk of serious adverse events (AEs), discontinuation of SGLT2i due to AEs, kidney-related AEs, and volume depletion were similar between the two groups. Patients with >10% eGFR dip had increased risk of hyperkalemia compared to the non-dipping group. Conclusion Initial eGFR dip after initiating SGLT2i might be associated with less annual eGFR decline. There were no significant disparities in the risks of adverse cardiovascular outcomes between the dipping and non-dipping groups.

Objective The leptin receptor,encoded by the LEPR gene,is involved in tumorigenesis.A potential functional variant of LEPR,rs1137101(Gln223Arg),has been extensively investigated for its contribution to the risk of digestive system(DS)cancers,but results remain conflicting rather than conclusive.Here,we performed a case-control study and subsequent meta-analysis to examine the association between rs1137101 and DS cancer risk. Methods A total of 1,727 patients with cancer(gastric/liver/colorectal:460/480/787)and 800 healthy controls were recruited.Genotyping of rs1137101 was conducted using a polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP)assay and confirmed using Sanger sequencing.Twenty-four eligible studies were included in the meta-analysis. Results After Bonferroni correction,the case-control study revealed that rs1137101 was significantly associated with the risk of liver cancer in the Hubei Chinese population.The meta-analysis suggested that rs1137101 is significantly associated with the risk of overall DS,gastric,and liver cancer in the Chinese population. Conclusion The LEPR rs1137101 variant may be a genetic biomarker for susceptibility to DS cancers(especially liver and gastric cancer)in the Chinese population.