Microvascular rarefaction caused by the NOTCH signaling pathway is a key cause of TKI-apatinib-induced hypertension and cardiac damage.

With the advancement of tumour-targeted therapy technology, the survival of cancer patients has continued to increase, and cardiovascular events have gradually become an important cause of death in cancer patients. This phenomenon occurs due to adverse cardiovascular reactions caused by the cardiovascular toxicity of antitumour therapy. Moreover, the increase in the proportion of elderly patients with cancer and cardiovascular diseases is due to the extension of life expectancy. Hypertension is the most common cardiovascular side effect of small molecule tyrosine kinase inhibitors (TKIs). The increase in blood pressure induced by TKIs and subsequent cardiovascular complications and events affect the survival and quality of life of patients and partly offset the benefits of antitumour therapy. Many studies have confirmed that in the pathogenesis of hypertension, arterioles and capillary thinness are involved in its occurrence and development. Our previous findings showing that apatinib causes microcirculation rarefaction of the superior mesenteric artery and impaired microvascular growth may inspire new therapeutic strategies for treating hypertension. Thus, by restoring microvascular development and branching patterns, total peripheral resistance and blood pressure are reduced. Therefore, exploring the key molecular targets of TKIs that inhibit the expression of angiogenic factors and elucidating the specific molecular mechanism involved are key scientific avenues for effectively promoting endothelial cell angiogenesis and achieving accurate repair of microcirculation injury in hypertension patients.

Sevoflurane Inhalation Anesthesia for Uncooperative Pediatric Outpatients in the Treatment of Ankyloglossia: A Retrospective Study of 137 Cases.

Background: To retrospectively assess the efficacy and safety of sevoflurane inhalation anesthesia for the treatment of ankyloglossia on uncooperative pediatric outpatients. Methods: Pediatric patients with ankyloglossia (Degree 3 to Degree 5, coarse or thick) were enrolled in this retrospective analysis. The treatment of ankyloglossia was conducted with sevoflurane induction (8%) and maintenance (2%-3%) continuously with nasal cannula. Heart rate, respiratory rate, electrocardiogram, blood pressure, and peripheral blood oxygen saturation were monitored continuously during operations. Onset time, recovery time, adverse complications were recorded until Aldrete score was ≥ 9. Patients were followed up 24 h, 1 and 2 weeks after operation. Results: One hundred and thirty-seven children completed surgeries with ideal anesthesia status. The operation duration were 10-20 minutes (15.15 ± 2.04), and the children woke up in 10-30 minutes (18.95 ± 3.91). The average intra-operative blood oxygen saturation were lower than preoperative ones (p = .005). Adverse effects were 13.1%, including 3 (2.2%) respiratory depression (SpO2 < 90%), 11 (8.0%) dysphoria and crying during recovery, 2 (1.5%) transient fever symptom. Conclusions: Sevoflurane inhalation anesthesia in the treatment of ankyloglossia resulted in rapid onset and recovery, with few adverse reactions and significant clinical efficacy, and was suited to uncooperative pediatric outpatients.

Analysis of survival and factors associated with failure of primary tooth pulpectomies performed under general anaesthesia in children from South China.

BACKGROUND: Pulpectomy is a technique recommended for treatment of irreversible pulp inflammation or necrosis. Treatment-related variables and patient factors may affect the prognosis of pulpectomy. AIM: To investigate the survival and related predictors associated with failure of pulpectomies performed under general anaesthesia for early childhood caries. DESIGN: Dental records of 124 patients, who underwent pulpectomy as part of comprehensive dental treatment under general anaesthesia, were reviewed and assessed. Relapse of pulpitis and periodontal periodontitis were evaluated by clinical examination and periapical film assessment at each follow-up appointment after original treatment. RESULTS: A total of 389 teeth of 124 children were evaluated. By the end of the fourth year, 45% of teeth with pulpitis and 46% of teeth with periapical periodontitis were estimated to relapse; the median (interquartile range) number of years to relapse was 3.5 (3.4-3.8) and 3.0 (1.8-3.0) years, respectively. The follow-up frequency, number of teeth extracted, plaque index, tooth position, type of restoration, pulp status, and quality of root canal filling were observed to have independent effects on relapse. CONCLUSION: Recurrence came earlier in teeth diagnosed with periapical periodontitis than those with pulpitis. Both treatment-related variables and patient factors could affect the prognosis of pulpectomy.

Protoporphyrin IX catalyzed hydrogen peroxide to generate singlet oxygen.

AIM: To study the role of protoporphyrin IX (pPIX) in mitochondrial metabolism of hydrogen peroxide (H2O2). METHODS: O2 (-) specific fluorescent markers DMA (9,10-dimerthylanthracence) and SOSG (Singlet Oxygen Sensor Green reagent) were used for measurement of singlet oxygen ((1)O2). Catalyzing conversion of H2O2 into (1)O2 by pPIX was monitored in vitro under varied H2O2 content, temperature, and PH value in the reaction. Ex vivo mitochondrial model was used to analyze effects of ferrochelatase (FECH) and high energy X-rays on this catalytic reaction. RESULTS: In complete dark, measurable (1)O2 was generated when 1.5 mM of H2O2 was incubated with 24 µM of pPIX H2O2 at 37°C for 3 hours. Mitochondrial yield of H2O2 was 0.11±0.03 nmole/mg/min. Mitochondrial FECH significantly improve the catalytic ability of pPIX converting H2O2 into (1)O2. At presence of high-energy X-ray, incubation of 14.4 µM of pPIX with 0.54 µM of H2O2 also generated (1)O2, during which the fluorescence density of 1.05 µM of DMA decreased by 41.5% (P < 0.05). This conversion was not observed when pPIX was replaced with structurally similar hematoporphyrin. CONCLUSION: pPIX can catalyze conversion of H2O2 into (1)O2.

Polygenic determinants of Parkinson's disease in a Chinese population.

It has been reported that some single-nucleotide polymorphisms (SNPs) are associated with the risk of Parkinson's disease (PD), but whether a combination of these SNPs would have a stronger association with PD than any individual SNP is unknown. Sixteen SNPs located in the 8 genes and/or loci (SNCA, LRRK2, MAPT, GBA, HLA-DR, BST1, PARK16, and PARK17) were analyzed in a Chinese cohort consisting of 1061 well-characterized PD patients and 1066 control subjects from Central South of Mainland China. We found that Rep1, rs356165, and rs11931074 in SNCA gene; G2385R in LRRK2 gene; rs4698412 in BST1 gene; rs1564282 in PARK17; and L444P in GBA gene were associated with PD with adjustment of sex and age (p < 0.05) in the analysis of 16 variants. PD risk increased when Rep1 and rs11931074, G2385R, rs1564282, rs4698412; rs11931074 and G2385R, rs1564282, rs4698412; G2385R and rs1564282, rs4698412; and rs1564282 and rs4698412 were combined for the association analysis. In addition, PD risk increased cumulatively with the increasing number of variants (odds ratio for carrying 3 variants, 3.494). In summary, we confirmed that Rep1, rs356165, and rs11931074 in SNCA gene, G2385R in LRRK2 gene, rs4698412 in BST1 gene, rs1564282 in PARK17, and L444P in GBA gene have an independent and combined significant association with PD. SNPs in these 4 genes have a cumulative effect with PD.