Elevated serum FGF21 is an independent predictor for adverse events in hemodialysis patients from two large centers: a prospective cohort study.

Introduction: We explored the relationship and the predictive value of serum fibroblast growth factor 21 (FGF21) with all-cause mortality, major adverse cardiovascular events (MACEs) and pneumonia in hemodialysis (HD) patients.Methods: A total of 388 Chinese HD patients from two HD centers were finally enrolled in this prospective cohort study (registration number: ChiCTR 1900028249) between January 2018 and December 2018. Serum FGF21 was detected. Patients were followed up with a median period of 47 months to record the MACEs and pneumonia until death or 31 December 2022.Results: The incidence of all-cause mortality, MACEs and pneumonia in HD patients were 20.6%, 29.6%, and 34.8%, respectively. The optimal cutoffs for FGF21 to predict all-cause mortality, MACEs and pneumonia were 437.57 pg/mL, 216.99 pg/mL and 112.79 pg/mL. Multivariate Cox regression analyses showed that FGF21, as a categorical variable, was an independent predictor for all-cause mortality, MACEs and pneumonia (HR, 3.357, 95% CI, 2.128-5.295, p < 0.001; HR, 1.575, 95% CI, 1.046-2.371, p = 0.029; HR, 1.784; 95% CI, 1.124-2.830; p = 0.014, respectively). The survival nomogram, MACEs-free survival nomogram and pneumonia-free survival nomogram based on FGF21 constructed for individualized assessment of HD patients had a high C-index with 0.841, 0.706 and 0.734.Conclusion: Higher serum FGF21 is an independent predictor of all-cause mortality, MACEs and pneumonia in HD patients.

 Carexmalipoensis (Cyperaceae), a new species from southeast Yunnan, China.

Carexmalipoensis, a new species from southeast Yunnan, China, is here described and illustrated. It is morphologically similar to C.trichophylla in sect. Euprepes, but differs from it by its longer inflorescences and peduncles, pendulous spikes, hispidulous female glumes, densely hispidulous utricles, and longer nutlets.

Rare mutation in MKRN3 in two twin sisters with central precocious puberty: Two case reports.

BACKGROUND: Caused by premature activation of the hypothalamic-pituitary-gonadal axis, there is increasing incidence of central precocious puberty (CPP), especially in girls. Makorin ring finger protein 3 (MKRN3), a maternal imprinted gene with a highly conserved sequence, is the most common genetic etiology associated with CPP. Approximately 50 different mutations in MKRN3 have been found in CPP. CASE SUMMARY: This case report involves identical twin sisters presenting with premature thelarche at the age of 6 years. The left hand bone age of both patients revealed advanced age (9 years). Pelvic B ultrasound indicated enlargement of the ovaries. Luteinizing hormone (LH) releasing hormone testing confirmed CPP. Whole-exome sequencing detected the c.841C>T mutation in MKRN3, leading to a single base substitution, in the twins. This mutation was inherited from the father and paternal grandmother. After 3 mo of treatment with a gonadotropin-releasing hormone analog, levels of LH, follicle-stimulating hormone, and estradiol in the proband's sister returned to normal levels. CONCLUSION: Here, we report a rare mutation (c.841C>T) in MKRN3 in identical twin sisters with CPP.

Effect of minimally invasive surgery on the sleep quality and work ability of patients with obstructive sleep apnea-hypopnea syndrome.

OBJECTIVE: To explore the effect of minimally invasive surgical treatment on the sleep quality and work ability of patients with obstructive sleep apnea-hypopnea syndrome (OSAHS). METHODS: Fifty-one patients who underwent minimally invasive surgery in the Sleep Respiratory Disease Diagnostic and Treatment Center of the West China Fourth Hospital of Sichuan University from January 2017 to January 2019 were selected as study subjects. All subjects completed polysomnography monitoring (PSG), an Epworth sleepiness scale (ESS), and a work ability index (WAI) before and 1 year after the minimally invasive surgery so that the changes could be compared. RESULTS: (1) The apnea-hypopnea index (AHI), microarousal index (MAI), ESS, longest duration of apnea, and longest duration of hypoventilation in OSAHS patients decreased, while the lowest blood oxygen saturation (LsaO2) increased after minimally invasive surgery. The differences were statistically significant (p < 0.05). (2) The WAI questionnaire score increased from (37.76 ± 4.46) to (40.00 ± 4.53) after minimally invasive surgery (P < 0.05). (3) The change in the WAI questionnaire score after minimally invasive surgery was influenced by the occupational category and the change in ESS. CONCLUSION: Minimally invasive surgical treatment shows significant benefit in improving the sleep quality and working ability of patients with OSAHS.

Change in Quality of Life of OSAHS Patients with Minimally Invasive Surgery or CPAP Therapy: A 2-year Retrospective, Single-center Parallel-group Study.

BACKGROUND: By including untreated obstructive sleep apnea-hypopnea syndrome (OSAHS) patients as the control group, this study explores the influence of minimally invasive surgical treatment and continuous positive airway pressure (CPAP) therapy on OSAHS patients, with the subjective and objective performance. The study also discusses their relationship, determines the effect factor, and provides a simple and practical method for evaluation of clinical efficacy. METHODS: A total of 90 OSAHS patients, who were diagnosed in the Sleep Disorders Diagnosis and Treatment Center of Sichuan Province from May 2014 to May 2016, were selected for the present study. These patients were divided into three groups: surgery group, CPAP group, and untreated group. These patients were followed up at six months, one year, and two years, respectively. The physiological indicators, clinical symptoms, degree of daytime sleepiness and quality of life were compared among these three groups. The daytime sleepiness and the quality of life before and after minimally invasive surgery and CPAP treatment were evaluated, and the subjective and objective efficacy of surgery and CPAP treatment was explored. RESULTS: Among these 90 patients, 11 (12.2%) patients had hypertension, while two (2.2%) patients had diabetes. The average AHI score was 50.53±23.39 per hour, and the mean minimum oxygen saturation and mean oxygen saturation was 71.25±14.16% and 90.13±5.90%, respectively. There were statistically significant differences in mouth breathing, morning sore throat and daytime sleepiness in the group having received surgery at 0.5 year and one year. In the CPAP group, there were statistically significant differences in mouth breathing, morning sore throat and daytime sleepiness at 0.5 year, one year and two years. Moreover, there were statistically significant differences in memory loss at one year and two years, and there were statistically significant differences in frequent nocturia at one year. The ESS value in the surgery group decreased at 0.5 year and one year, but increased at two years. The situation was the same in terms of the total points and in each dimension of the SF-36 paramter. The delta values of ESS among the three groups had statistical significance at 0.5 year, one year and two years, in which the CPAP group experienced the most changes, followed by the surgery group and the group received health education. CONCLUSION: For minimally invasive surgery, CPAP therapy and health education can improve daytime sleepiness and quality of life. CPAP therapy was found to be the most effective, followed by minimally invasive surgery and provision of health education. However, the treatment of OSAHS should be comprehensive.

The profibrotic effects of MK-8617 on tubulointerstitial fibrosis mediated by the KLF5 regulating pathway.

The discovery of hypoxia-inducible factor (HIF)-prolyl hydroxylase inhibitor (PHI) has revolutionized the treatment strategy for renal anemia. However, the presence of multiple transcription targets of HIF raises safety concerns regarding HIF-PHI. Here, we explored the dose-dependent effect of MK-8617 (MK), a kind of HIF-PHI, on renal fibrosis. MK was administered by oral gavage to mice for 12 wk at doses of 1.5, 5, and 12.5 mg/kg. In vitro, the human proximal tubule epithelial cell line HK-2 was treated with increasing doses of MK administration. Transcriptome profiling was performed, and fibrogenesis was evaluated. The dose-dependent biphasic effects of MK on tubulointerstitial fibrosis (TIF) were observed in chronic kidney disease mice. Accordingly, high-dose MK treatment could significantly enhance TIF. Using RNA-sequencing, combined with in vivo and in vitro experiments, we found that Krüppel-like factor 5 (KLF5) expression level was significantly increased in the proximal tubular cells, which could be transcriptionally regulated by HIF-1α with high-dose MK treatment but not low-dose MK. Furthermore, our study clarified that HIF-1α-KLF5-TGF-ß1 signaling activation is the potential mechanism of high-dose MK-induced TIF, as knockdown of KLF5 reduced TIF in vivo. Collectively, our study demonstrates that high-dose MK treatment initiates TIF by activating HIF-1α-KLF5-TGF-ß1 signaling. These findings provide novel insights into TIF induction by high-dose MK (HIF-PHI), suggesting that the safety dosage window needs to be emphasized in future clinical applications.-Li, Z.-L., Lv, L.-L., Wang, B., Tang, T.-T., Feng, Y., Cao, J.-Y., Jiang, L.-Q., Sun, Y.-B., Liu, H., Zhang, X.-L., Ma, K.-L., Tang, R.-N., Liu, B.-C. The profibrotic effects of MK-8617 on tubulointerstitial fibrosis mediated by the KLF5 regulating pathway.

Risk factors for arterial ischemic and hemorrhagic stroke in childhood.

This study assessed potential etiologies of arterial ischemic stroke and hemorrhagic stroke among children of Mainland China. From January 1996-June 2006, 251 patients with consecutive childhood stroke (aged 1 month through 16 years) were admitted to Beijing Children's Hospital. Arterial ischemic stroke accounted for the majority of cases (62.5%). Idiopathic stroke (32.5%) was more common than cardiac stroke (8.9%), vascular or arteriopathic stroke (21.0%), hematologic disorder-associated stroke (10.8%), and other etiologies (26.8%). Vitamin K deficiency was a major etiology in 72 of 94 hemorrhagic strokes (76.6%), most of which occurred in breastfeeding infants (80.6%) and those who received no vitamin K after birth (73.6%). Arteriovenous malformation (6.4%) was a frequent etiology in the remaining hemorrhagic stroke cases. We found that ischemic stroke in children is more common than hemorrhagic stroke, and many cases of ischemic stroke are idiopathic. Vitamin K deficiency was a major etiology in these young infants who experienced hemorrhagic stroke.

Arterial ischemic stroke: experience in Chinese children.

The aim of this study was to review cases of pediatric arterial ischemic stroke among Chinese subjects and thereby evaluate risk factors, clinical and neuroimaging features, and treatment, to establish a reasonable guideline for assessment and management of the disease. Between 1996 and 2006, 157 children (male:female ratio, 1.4:1) with arterial ischemic stroke were identified at Beijing Children's Hospital. The median age at stroke was 32 months (range, 4-192). Among patients with determined etiology, infections (12.1%), moyamoya disease (12.1%), and trauma (10.8%) were the most common. In 51 patients, there were no obvious risk factors (32.5%). Hemiplegia was the most common presenting feature (81.5%). The region of left middle cerebral artery was most frequently affected (36.3%), followed by the right middle cerebral artery (29.9%). Of the 157 patients, 56 were treated by intravenous thrombolytic agents (35.7%), all but one of them successfully (the one exception involving hemorrhagic complication). Randomized controlled trials are needed to establish primary prevention, acute treatment, and secondary prevention of pediatric ischemic stroke.