OBJECTIVE: To analyze the clinical characteristics, treatment effect and prognosis of patients with non-Hodgkin lymphoma (NHL) complicated by hypercalcemia. METHODS: The clinical features, treatment and prognosis of 47 patients with NHL complicated by hypercalcemia in Ningde Municipal Hospital of Ningde Normal University and Affiliated Hospital of Nantong University from January 2018 to January 2023 were retrospectively analyzed. RESULTS: Among the 47 lymphoma patients, 33 cases were T-cell NHL, 14 cases were B-cell NHL. The median serum calcium level of the 47 patients was 3.10 (2.77-4.86) mmol/L, with 27 cases (57.4%) experiencing mild hypercalcemia (2.75-3.00 mmol/L), 8 cases (17.0%) experiencing moderate hypercalcemia (3.00-3.50 mmol/L), and 12 cases (25.5%) experiencing severe hypercalcemia (>3.50 mmol/L). All 47 patients were treated with hydration, alkalization, diuresis, etc. 32 cases (68.1%) received combination chemotherapy, 21 cases (44.7%) received salmon calcitonin treatment, and 3 cases were treated with denosumab in 5 patients with renal insufficiency. After treatment, 38 patients' serum calcium gradually returned to normal, with a median recovery time of 6 (1-18) days, while 9 patients still failed to recover their serum calcium after treatment and all died within 1 month. 32 patients undergoing combination chemotherapy were evaluated for efficacy after 2-4 courses of chemotherapy. Among them, 8 cases (25.0%) achieved complete response (CR), 11 cases (34.4%) achieved partial response (PR), 7 cases (21.9%) showed stable disease (SD), and 6 cases (18.8%) showed progressive disease (PD). The median follow-up time was 10 months. There were 13 cases of disease progression after combination chemotherapy and a total of 28 deaths. The survival time ranged from 0.8 to 23.7 months, and the median progression time was 4.9 months. Multivariate Cox regression analysis showed that the T-cell NHL, blood calcium >3.5 mmol/L, and no decrease in blood calcium after treatment were independent risk factors for the OS, and the T-cell NHL was independent risk factors for the PFS. CONCLUSION NHL complicated by hypercalcemia has a poor prognosis, and hypercalcemia can be used as one of the indicators reflecting the tumor burden. Patients with NHL complicated by hypercalcemia should be given more clinical attention and treated actively.
Humans ; Hypercalcemia/complications* ; Lymphoma, Non-Hodgkin/diagnosis* ; Prognosis ; Retrospective Studies ; Female ; Male ; Middle Aged ; Adult ; Aged ; Calcium/blood*

Cardiac fibrosis is characterized by an elevated amount of extracellular matrix (ECM) within the heart. However, the persistence of cardiac fibrosis ultimately diminishes contractility and precipitates cardiac dysfunction. Circular RNAs (circRNAs) are emerging as important regulators of cardiac fibrosis. Here, we elucidate the functional role of a specific circular RNA CELF1 in cardiac fibrosis and delineate a novel feedback loop mechanism. Functionally, circ-CELF1 was involved in enhancing fibrosis-related markers' expression and promoting the proliferation of cardiac fibroblasts (CFs), thereby exacerbating cardiac fibrosis. Mechanistically, circ-CELF1 reduced the ubiquitination-degradation rate of BRPF3, leading to an elevation of BRPF3 protein levels. Additionally, BRPF3 acted as a modular scaffold for the recruitment of histone acetyltransferase KAT7 to facilitate the induction of H3K14 acetylation within the promoters of the Celf1 gene. Thus, the transcription of Celf1 was dramatically activated, thereby inhibiting the subsequent response of their downstream target gene Smad7 expression to promote cardiac fibrosis. Moreover, Celf1 further promoted Celf1 pre-mRNA transcription and back-splicing, thereby establishing a feedback loop for circ-CELF1 production. Consequently, a novel feedback loop involving CELF1/circ-CELF1/BRPF3/KAT7 was established, suggesting that circ-CELF1 may serve as a potential novel therapeutic target for cardiac fibrosis.

Objective To investigate the potential mechanism of miR-21-5p in alleviating cerebral ischemia-reperfusion injury by targeting STAT3.Methods The HT22 cells were induced by OGD/R to construct a cell model of cerebral ischemia reperfusion injury.The expression of miR-21-5p was detected by RT-qPCR.The CCK-8 assay,TUNEL staining and flow cytometry were respectively used to detect the cell viability and apoptosis.ELISA assay was used to determine the contents of inflammatory factors IL-6,IL-10 and TNF-α in the cell supernatant.Western blot was used to detect the expression levels of p-STAT3/STAT3,Cleaved-Caspase-3,Bax and Bcl-2 proteins.The TargetScan database was used to predict the binding sites of miR-21-5p and STAT3.The dual-luciferase reporter gene assay was used to verify the targeting relationship between miR-21-5p and STAT3.Results The relative expression level of miR-21-5p was down-regulated in HT22 cells which induced by OGD/R(P<0.001).The cell viability(P<0.0001)was decreased and the apoptosis rate(P<0.001)was increased in OGD/R induced-HT22 cells.The contents of pro-inflammatory factors IL-6(P<0.001)and TNF-α(P<0.001)was increased,while the content of anti-inflammatory factor IL-10(P<0.001)decreased.After transfection with miR-21-5p mimic,cell viability was enhanced,apoptosis rate was reduced and neuroinflammation was inhibited.MiR-21-5p could target and bind to STAT3.After miR-21-5p inhibitor transfection,cell viability decreased,apoptosis was promoted,and neuroinflammation occurred;STAT3 inhibitor Stattic could reverse the effect of miR-21-5p inhibitor.Conclusion MiR-21-5p could specifically bind to STAT3 and reduce the neuroinflammation and apoptosis of OGD/R induced-HT22 cells.

Objective To study the in vitro expression of three phenylalanine hydroxylase(PAH)mutants(p.R243Q,p.R241C,and p.Y356X)and determine their pathogenicity.Methods Bioinformatics techniques were used to predict the impact of PAH mutants on the structure and function of PAH protein.Corresponding mutant plasmids of PAH were constructed and expressed in HEK293T cells.Quantitative reverse transcription polymerase chain reaction was used to measure the mRNA expression levels of the three PAH mutants,and their protein levels were assessed using Western blot and enzyme-linked immunosorbent assay.Results Bioinformatics analysis predicted that all three mutants were pathogenic.The mRNA expression levels of the p.R243Q and p.R241C mutants in HEK293T cells were similar to the mRNA expression level of the wild-type control(P>0.05),while the mRNA expression level of the p.Y356X mutant significantly decreased(P<0.05).The PAH protein expression levels of all three mutants were significantly reduced compared to the wild-type control(P<0.05).The extracellular concentration of PAH protein was reduced in the p.R241C and p.Y356X mutants compared to the wild-type control(P<0.05),while there was no significant difference between the p.R243Q mutant and the wild type control(P>0.05).Conclusions p.R243Q,p.R241C and p.Y356X mutants lead to reduced expression levels of PAH protein in eukaryotic cells,with p.R241C and p.Y356X mutants also affecting the function of PAH protein.These three PAH mutants are to be pathogenic.[Chinese Journal of Contemporary Pediatrics,2024,26(2):188-193]

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective To monitor the antifungal resistance of clinical isolates of Candida spp.in the East China region.Methods MALDI-TOF MS or molecular methods were used to re-identify the strains collected from January 2018 to December 2022.Antifungal susceptibility testing was performed using the broth microdilution method.The susceptibility test results were interpreted according to the breakpoints of 2022 Clinical and Laboratory Standards Institute(CLSI)documents M27 M44s-Ed3 and M57s-Ed4.Results A total of 3 026 strains of Candida were collected,65.33％of which were isolated from sterile body sites,mainly from blood(38.86％)and pleural effusion/ascites(10.21％).The predominant species of Candida were Candida albicans(44.51％),followed by Candida parapsilosis complex(19.46％),Candida tropicalis(13.98％),Candida glabrata(10.34％),and other Candida species(0.79％).Candida albicans showed overall high susceptibility rates to the 10 antifungal drugs tested(the lowest rate being 93.62％).Only 2.97％of the strains showed dose-dependent susceptibility(SDD)to fluconazole.Candida parapsilosis complex had a SDD rate of 2.61％and a resistance rate of 9.42％to fluconazole,and susceptibility rates above 90％to other drugs.Candida glabrata had a SDD rate of 92.01％and a resistance rate of 7.99％to fluconazole,resistance rates of 32.27％and 48.24％to posaconazole and voriconazole non-wild-type strains(NWT),respectively,and susceptibility rates above 90％to other drugs.Candida tropicalis had resistance rates of 29.55％and 26.24％to fluconazole and voriconazole,respectively,resistance rates of 76.60％and 21.99％to posaconazole and echinocandins non-wild-type strains(NWT),and a resistance rate of 2.36％to echinocandins.Conclusions The prevalence and species distribution of Candida spp.in the East China region are consistent with previous domestic and international reports.Candida glabrata exhibits certain degree of resistance to fluconazole,while Candida tropicalis demonstrates higher resistance to triazole drugs.Additionally,echinocandins resistance has emerged in Candida albicans,Candida glabrata,Candida tropicalis,and Candida parapsilosis.

Objective To investigate the expression of spalt like transcription factor 4(Sall4)in pancreatic cancer tissues and its clinical significance,as well as the impact of inhibiting its gene expression on the migration and invasion of pancreatic cancer cells.Methods This study involved 64 patients with pancreatic cancer treated at the 2nd Affiliated Hospital of Kunming Medical University from January 2014 to January 2018.Immunohistochemical staining was used to detect the expression of Sall4 protein in adjacent non-tumor tissues and pancreatic cancer tissues,respectively.Real-time quantitative PCR was used to measure the mRNA expression levels of Sall4 in the cancerous and adjacent non-tumor tissues,respectively.The relationship between the clinicopathological data of these patients and the expression of Sall4 protein was also analyzed.The cells of high Sall4 expression were screened from the human pancreatic cancer cell lines PANC-1,Capan-1,SW 1990,HPAC,and HPAF-Ⅱ.The pancreatic cancer cells of high Sall4 expression were divided into three groups:control group,shRNA-1 group,and shRNA-2 group.The shRNA-1 and shRNA-2 groups were transfected with the corresponding Sall4 lentiviral inhibitory gene sequences,while the control group was transfected with the reagent without an interference sequence.Western blotting was used to measure the expression of Sall4,and cells with significantly reduced expression were selected for subsequent experiments.The transfected cells were then assessed for their invasive and migratory abilities.Results Among the 64 samples of pancreatic cancer tissues,28 cases(43.8％)were positive for Sall4 expression,a rate significantly higher than 5 cases(7.8％)in adjacent non-tumor tissues.Furthermore,16 cases exhibited strong positivity,while 12 cases showed moderate or weak positivity.Recurrence occurred in 11 pancreatic cancer patients.The difference was statistically significant.The expression of Sall4 was correlated with tumor differentiation,staging,and lymph node metastasis,suggesting that Sall4 positivity might be an independent risk factor affecting the prognosis of pancreatic cancer.Among the five cell lines,PANC-1 had the highest relative expression of Sall4 and was selected for further experiments.The shRNA-1 and shRNA-2 groups successfully suppressed the expression of Sall4,with the shRNA-1 group showing a more pronounced effect.Compared to the control group,the invasive and migratory abilities of SW480 cells were significantly reduced in the shRNA-1 group(P＜0.05).Conclusion Sall4 is highly expressed in pancreatic cancer tissues,and higher expression is associated with a greater likelihood of postoperative recurrence.Inhibiting the expression of Sall4 can significantly suppress the invasion and migration abilities of human pancreatic cancer cells.

Objective: To investigate the timing of pericardial drainage catheter removal and restart of the anticoagulation in patients with atrial fibrillation (AF) suffered from perioperative pericardial tamponade during atrial fibrillation catheter ablation and uninterrupted dabigatran. Methods: A total of 20 patients with pericardial tamponade, who underwent AF catheter ablation with uninterrupted dabigatran in Beijing Anzhen Hospital from January 2019 to August 2021, were included in this retrospective analysis. The clinical characteristics of enrolled patients, information of catheter ablation procedures, pericardial tamponade management, perioperative complications, the timing of pericardial drainage catheter removal and restart of anticoagulation were analyzed. Results: All patients underwent pericardiocentesis and pericardial effusion drainage was successful in all patients. The average drainage volume was (427.8±527.4) ml. Seven cases were treated with idarucizumab, of which 1 patient received surgical repair. The average timing of pericardial drainage catheter removal and restart of anticoagulation in 19 patients without surgical repair was (1.4±0.7) and (0.8±0.4) days, respectively. No new bleeding, embolism and death were reported during hospitalization and within 30 days following hospital discharge. Time of removal of pericardial drainage catheter, restart of anticoagulation and hospital stay were similar between patients treated with idarucizumab or not. Conclusion: It is safe and reasonable to remove pericardial drainage catheter and restart anticoagulation as soon as possible during catheter ablation of atrial fibrillation with uninterrupted dabigatran independent of the idarucizumab use or not in case of confirmed hemostasis.
Humans ; Atrial Fibrillation/drug therapy* ; Dabigatran/therapeutic use* ; Cardiac Tamponade/complications* ; Anticoagulants/therapeutic use* ; Retrospective Studies ; Treatment Outcome ; Drainage/adverse effects* ; Catheter Ablation ; Catheters/adverse effects*

The extracellular domain (p75ECD) of p75 neurotrophin receptor (p75NTR) antagonizes Aβ neurotoxicity and promotes Aβ clearance in Alzheimer's disease (AD). The impaired shedding of p75ECD is a key pathological process in AD, but its regulatory mechanism is largely unknown. This study was designed to investigate the presence and alterations of naturally-occurring autoantibodies against p75ECD (p75ECD-NAbs) in AD patients and their effects on AD pathology. We found that the cerebrospinal fluid (CSF) level of p75ECD-NAbs was increased in AD, and negatively associated with the CSF levels of p75ECD. Transgenic AD mice actively immunized with p75ECD showed a lower level of p75ECD and more severe AD pathology in the brain, as well as worse cognitive functions than the control groups, which were immunized with Re-p75ECD (the reverse sequence of p75ECD) and phosphate-buffered saline, respectively. These findings demonstrate the impact of p75ECD-NAbs on p75NTR/p75ECD imbalance, providing a novel insight into the role of autoimmunity and p75NTR in AD.
Mice ; Animals ; Alzheimer Disease/pathology* ; Receptor, Nerve Growth Factor ; Amyloid beta-Peptides ; Autoantibodies ; Mice, Transgenic

OBJECTIVE: To compare the efficacy of eltrombopag combined with cyclosporine A (CsA) and CsA alone in patients with transfusion-dependent non-severe aplastic anemia (TD-NSAA). METHODS: The clinical data of 76 patients with treatment-naive TD-NSAA in Ningde Municipal Hospital of Ningde Normal University and Affiliated Hospital of Nantong University from December 2017 to June 2021 were retrospectively analyzed. Among them, 45 cases were treated with eltrombopag combined with CsA, and 31 patients with compatible baseline characters were treated with CsA alone. The efficacy of patients between the two groups was compared, and the factors affecting the curative effects were also analyzed. RESULTS: There were significant differences in hematological response (HR) and complete response(CR) rates between the two groups at 3, 6, 12 months, and follow-up endpoint of treatment (P<0.05). With the prolongation of eltrombopag treatment time, the curative effect increased gradually, and the patients achieved more CR and HR rates by the end of the follow-up period. Simultaneously, with the increase in the maximum stable dose of eltrombopag, the HR rate increased gradually. The megakaryocyte count in eltrombopag group was higher than that in control at 6 and 12 months (P<0.05). Compared with the control group, the median time of platelet transfusion independence in eltrombopag group was more shorter (P=0.018), and the median platelets transfusion volume was lower (P=0.009). At 3, 6, 12 months after eltrombopag, the change of platelet in eltrombopag group was higher than that in the control group (P<0.05). Analysis of related factors affecting the efficacy showed that sex, age, iron overload, platelet count before treatment had no effect on the efficacy, and the median maximum stable dosage and the administration period for eltrombopag were related to the curative effect. The patients of eltrombopag group experienced adverse events of varying degrees, but the reactions were mild and mostly tolerated. CONCLUSION Eltrombopag can effectively improve the hematopoietic response and promote platelet recovery for TD-NSAA patients with relatively more residual hematopoietic cells, and it is safe and well tolerated.
Humans ; Anemia, Aplastic/therapy* ; Retrospective Studies ; Treatment Outcome ; Cyclosporine/therapeutic use* ; Immunosuppression Therapy ; Immunosuppressive Agents/therapeutic use*