Neuroprotective effects of ulinastatin on Escherichia coli meningitis rats through inhibiting PKCα phosphorylation and reducing zonula occludens-1 degradation.

Ulinastatin, a broad-spectrum inflammatory inhibitor widely employed in the management of severe pancreatitis and sepsis, has not been extensively investigated for its therapeutic potential in bacterial meningitis. This study aims to assess the neuroprotective effects of ulinastatin on bacterial meningitis and elucidate its underlying mechanism. The rat model of bacterial meningitis was established by intracerebral injection of Escherichia coli. 3-week-old SD rats were randomly divided into 5 groups with 8 rats in each group, including control group, E.coli group, E.coli + UTI group (ulinastatin 50000IU/kg), E.coli + UTI + PMA group (ulinastatin 50000IU/kg + PMA 200 ug/kg), and E.coli + PMA group(PMA 200 ug/kg). Behavioral changes were assessed by Loeffler neurobehavioral score. Histomorphologic changes and apoptosis were assessed by hematoxylin and eosin staining, Nissl staining and TUNEL staining. Immunohistochemistry and immunofluorescence and western blotting were used to detect the expression levels of zonula occludens-1 (ZO-1) and phosphorylation protein kinase C (PKCα).It was found that ulinastatin treatment in Escherichia coli meningitis rats improved neurological function, alleviated meningeal inflammatory infiltration, reduced neuronal death, promoted the integrity of the blood-brain barrier structure. Moreover, phorbol myristate acetate (PMA, a protein kinase C activator), blocked the effective action of ulinastatin. These findings suggest that ulinastatin had neuroprotective effects on bacterial meningitis by inhibiting PKCα phosphorylation and reducing ZO-1 degradation, demonstrating that ulinastatin may be a promising strategy in the treatment of bacterial meningitis.

Effect of combined Zhuang medicine treatment on tricuspid annular displacement and heart rate variability in rheumatoid arthritis patients.

Objectives To assess the benefits of Zhuang medicine in treating rheumatoid arthritis (RA), with a focus on cardiac tricuspid annulus displacement and heart rate variability (HRV), thereby providing evidence supporting Zhuang medicine theories. METHODS: This retrospective study analyzed echocardiographic data and HRV of 30 healthy subjects and 60 RA patients. RA patients were divided into two groups for a 6-month treatment: 30 received iguratimod (control group), and 30 underwent combined Zhuang medicine and needle-pricking therapy (test group). Echocardiographic assessments and HRV measures were recorded both before and after treatment. RESULTS: Compared to the healthy group, RA patients showed increased late diastolic tricuspid annular velocity. However, early diastolic tricuspid annular velocity to late diastolic tricuspid annular velocity ratios, tricuspid annular plane systolic excursion (TAPSE), and the standard deviation of average normal RR intervals (SDANN) were significantly lower (all P<0.05). After treatment, the test group exhibited higher clinical efficacy (90% vs. 56.67% in the control group). Significant improvements were observed in TAPSE and HRV indices [SDANN, standard deviation of the RR intervals (SDNN), root mean square of successive RR interval differences (RMSSD), and the percentage of adjacent RR interval differences greater than 50 milliseconds (PNN50)] in the test group (all P<0.05). Additionally, a positive correlation was noted among these measurments. CONCLUSION: Zhuang medicine significantly enhances right ventricular function and autonomic balance in RA patients, thus affirming its therapeutic potential.

[Gene mutations in unexplained infantile epileptic encephalopathy: an analysis of 47 cases].

OBJECTIVE: To investigate the characteristics of gene mutations in unexplained infantile epileptic encephalopathy (EE). METHODS: A total of 47 infants with unexplained infantile EE were enrolled, and next-generation sequencing was used to analyze gene mutations in these infants and their parents. RESULTS: Of all 47 infants, 23 were found to have gene mutations, among whom 13 had de novo mutations and 10 had heterozygous mutations inherited from their father or mother. Among the 23 infants with gene mutations, 17 were found to have the gene mutations related to EE (among whom 14 had ion channel gene mutations), 2 had the gene mutations related to congenital inherited metabolic diseases, 2 had the gene mutations related to brain structural abnormality, and 2 had the gene mutations related to mental retardation. CONCLUSIONS: Unexplained infantile EE may have gene mutations, mainly ion channel gene mutations.