Shikonin alleviates doxorubicin-induced cardiotoxicity via Mst1/Nrf2 pathway in mice.

Doxorubicin (DOX) is a popular and potent anticancer drug, but its cardiotoxicity limits its clinical application. Shikonin has a wide range of biological functions, including antioxidant and anti-inflammatory effects. The aim of this study was to investigate the effects of shikonin on DOX-induced cardiac injury and to identify the underlying mechanisms. Mice receiving shikonin showed reduced cardiac injury response and enhanced cardiac function after DOX administration. Shikonin significantly attenuated DOX-induced oxidative damage, inflammation accumulation and cardiomyocyte apoptosis. Shikonin protects against DOX-induced cardiac injury by inhibiting Mammalian sterile 20-like kinase 1 (Mst1) and oxidative stress and activating the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. In conclusion, shikonin alleviates DOX-induced cardiotoxicity by inhibiting Mst1 and activating Nrf2. Shikonin may be used to treat DOX-induced cardiac injury.

The diagnosis and treatment of pediatric clinical myocarditis in China: a multicenter retrospective study.

This study aims to examine the clinical characteristics and outcomes of clinical myocarditis in pediatric patients in China. This is a multicenter retrospective study. Children diagnosed with clinical myocarditis from 20 hospitals in China and admitted between January 1, 2015, and December 30, 2021, were enrolled. The clinical myocarditis was diagnosed based on the "Diagnostic Recommendation for Myocarditis in Children (Version 2018)". The clinical data were collected from their medical records. A total of 1210 patients were finally enrolled in this study. Among them, 45.6% had a history of respiratory tract infection. An abnormal electrocardiogram was observed in 74.2% of patients. Echocardiography revealed that 32.3% of patients had a left ventricular ejection fraction of less than 50%. Cardiac MRI was performed in 4.9% of children with clinical myocarditis, of which 61% showed localized or diffuse hypersignal on T2-weighted images. Serum levels of cardiac troponin I (cTnI), creatine kinase-MB (CK-MB), and N-terminal B-type natriuretic peptide (NT-proBNP) were higher in patients with fulminant myocarditis than in patients with myocarditis, making them potential risk factors for fulminant myocarditis. Following active treatment, 12.1% of patients were cured, and 79.1% were discharged with improvement. CONCLUSION: Clinical myocarditis in children often presents with symptoms outside the cardiovascular system. CK-MB, cTnI, and NT-proBNP are important indicators for assessing clinical myocarditis. The electrocardiogram and echocardiogram findings in children with clinical myocarditis exhibit significant variability but lack specificity. Cardiac MRI can be a useful tool for screening clinical myocarditis. Most children with clinical myocarditis have a favorable prognosis. WHAT IS KNOWN: • Pediatric myocarditis presents complex clinical manifestations and exhibits varying degrees of severity. Children with mild myocarditis generally have a favorable prognosis, while a small number of children with critically ill myocarditis experience sudden onset, hemodynamic disorders, and fatal arrhythmias. Therefore, early diagnosis and timely treatment of myocarditis are imperative. WHAT IS NEW: • To the best of our knowledge, this multicenter retrospective study is the largest ever reported in China, aiming to reveal the clinical characteristics and outcomes of pediatric clinical myocarditis in China. We provided an extensive analysis of the clinical characteristics, diagnosis, treatment, prognosis, and factors impacting disease severity in pediatric clinical myocarditis in China, which provides insights into the epidemiological characteristics of pediatric clinical myocarditis.

Arc and Homer1 are involved in comorbid epilepsy and depression: A microarray data analysis.

BACKGROUND: Depression is one of the most common comorbid psychiatric condition associated with epilepsy. It has a negative impact on the patient's quality of life. However, the underlying molecular mechanisms leading to depression are currently unclear. The aim of this study was to determine the hub genes associated with epilepsy and depression. METHODS: Gene expression profiles (GSE47752 and GSE20388) were downloaded from the gene expression omnibus (GEO) database. Differentially expressed genes (DEGs) for epilepsy and depression groups were separately searched. Subsequently, network analyses methods were employed to establish protein-protein interaction (PPI) networks, and to perform Gene Ontology (GO) terms and pathway enrichment analyses for co-expressed DEGs. RESULTS: A total of 772 genes were upregulated in patients with epilepsy whereas 91 genes were up-regulated in patients with depression. In addition, 1304 genes were down-regulated in epilepsy whereas 141 genes were down-regulated in patients with depression. Among co-expressed DEGs, 5 DEGs were up-regulated and 19 were down-regulated. Further analysis revealed that the co-expressed DEGs were involved in regulation of vasculature development, regulation of angiogenesis, glutamate receptor signaling pathway, cellular response to interleukin-1 and positive regulation of protein kinase B signaling. The Arc and Homer1 genes were identified as the common candidate genes involved in the pathogenesis of epilepsy and depression. CONCLUSIONS: Arc and Homer1 may contribute to the comorbidity of epilepsy and depression.

Neuraminidase 1 deficiency attenuates cardiac dysfunction, oxidative stress, fibrosis, inflammatory via AMPK-SIRT3 pathway in diabetic cardiomyopathy mice.

Diabetic cardiomyopathy (DCM) is associated with oxidative stress and augmented inflammation in the heart. Neuraminidases (NEU) 1 has initially been described as a lysosomal protein which plays a role in the catabolism of glycosylated proteins. We investigated the role of NEU1 in the myocardium in diabetic heart. Streptozotocin (STZ) was injected intraperitoneally to induce diabetes in mice. Neonatal rat ventricular myocytes (NRVMs) were used to verify the effect of shNEU1 in vitro. NEU1 is up-regulated in cardiomyocytes under diabetic conditions. NEU1 inhibition alleviated oxidative stress, inflammation and apoptosis, and improved cardiac function in STZ-induced diabetic mice. Furthermore, NEU1 inhibition also attenuated the high glucose-induced increased reactive oxygen species generation, inflammation and, cell death in vitro. ShNEU1 activated Sirtuin 3 (SIRT3) signaling pathway, and SIRT3 deficiency blocked shNEU1-mediated cardioprotective effects in vitro. More importantly, we found AMPKα was responsible for the elevation of SIRT3 expression via AMPKα-deficiency studies in vitro and in vivo. Knockdown of LKB1 reversed the effect elicited by shNEU1 in vitro. In conclusion, NEU1 inhibition activates AMPKα via LKB1, and subsequently activates sirt3, thereby regulating fibrosis, inflammation, apoptosis and oxidative stress in diabetic myocardial tissue.

Cardiac Biomarker Abnormalities Are Closely Related to Prognosis in Patients with COVID-19.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is erupting and spreading globally. Cardiovascular complications secondary to the infection have caught notice. This study aims to delineate the relationship of cardiac biomarkers and outcomes in severe cases of corona virus disease 2019 (COVID-19). One hundred forty-eight critically ill adult patients with COVID-19 were enrolled. From these patients, the demographic data, symptoms, cardiac biomarkers, treatments, and clinical outcomes were collected. Data were compared between survivors and non-survivors. Four patients in the non-survivor group were selected, and their cardiac biomarkers were collected and analyzed. Among the 148 patients, the incidence of cardiovascular complications was 19 (12.8%). Five of them were survivors (5.2%), and 14 of them were non-survivors (26.9%). Compared with the survivors, the non-survivors had higher levels of high-sensitivity cardiac troponin I, creatine kinase isoenzyme-MB, myoglobin, and N-terminal pro-brain natriuretic peptide (P < 0.05). The occurrence of cardiovascular events began at 11-15 days after the onset of the disease and reached a peak at 14-20 days. COVID-19 not only is a respiratory disease but also causes damage to the cardiovascular system. Cardiac biomarkers have the potential for early warning and prognostic evaluation in patients with COVID-19. It is recommended that cardiac biomarker monitoring in patients with COVID-19 should be initiated at least from the 11th day of the disease course.

The metabolic and immunological characteristics of pregnant women with COVID-19 and their neonates.

Our aim was to investigate whether SARS-CoV-2 infection raised high risks of late pregnancy complications, and posed health problems in fetuses and neonates. We analyzed the data of COVID-19 pregnant women with COVID-19 during late pregnancy and their neonates. Eleven out of 16 (69%) pregnant women with COVID-19 had ++ or +++ of ketone body in urine. The blood uric acid of pregnant patients was 334 µmol/L (IQR, 269-452). D-dimer and FDP in pregnant patients were 3.32 mg/L (IQR, 2.18-4.21) and 9.6 mg/L (IQR, 5.9-12.4). Results of blood samples collected at birth showed that 16 neonates had leukocytes (15.7 × 109/L (IQR, 13.7-17.2)), neutrophils (11.1 × 109/L (IQR, 9.2-13.2)), CK (401 U/L (IQR, 382-647)), and LDH (445 U/L (IQR, 417-559)). Twenty-four hours after birth, a neonate from COVID-19 woman had fever and positive of SARS-CoV-2 gene. Another woman had strongly positive for SARS-CoV-2 gene (+++) for 4 weeks, and delivered one neonate who had SARS-CoV-2 IgM (46 AU/mL) and IgG (140 AU/mL) on day 1 after birth. In the third trimester, COVID-19 infection in pregnant patients raised high risks of ketonuria, hypercoagulable state, and hyperfibrinolysis, which may lead to severe complications. COVID-19 increased the inflammatory responses of placenta, and fetuses and neonates had potential organ dysregulation and coagulation disorders. There was a potential intrauterine transmission while pregnant women had high titer of SARS-CoV-2, but it is necessary to detect SARS-CoV-2 in the blood cord, placenta, and amniotic fluid to further confirm intrauterine infection of fetuses.

Risk factor analysis of incisional infection in Crohn's disease patients after bowel resection / 中华消化外科杂志

Objective To analyze the risk factors affecting postoperative incisional infection in Crohn's disease (CD) patients after bowel resection.Methods The retrospective case-control study was conducted.The clinicopathologieal data of 239 CD patients who underwent bowel resection in the Sixth Affiliated Hospital of Sun Yat-sen University between January 2007 and December 2016 were collected.All patients underwent bowel resection.Observation indicators:(1) surgical situations;(2) follow-up;(3) risk factors analysis affecting postoperative incisional infection;(4) clinical factors affecting preoperative anemia.The follow-up using outpatient examination or ward diagnosis was performed to detect incisional infection within 30 days postoperatively up to January 2017.The normality test was done by Shapiro-Wilk.Measurement data with normal distribution were represented as x-±s,and comparison between groups was evaluated with the t test.Measurement data with skewed distribution were described as M (range),and comparison between groups was analyzed using the Wilcoxon ranksum test.The univariate analysis and multivariate analysis were done using the Logistic regression model.The P＜ 0.05 in univariate analysis was incorporated into multivariate analysis for analysis in the forward wald.Results (1) Surgical situations:of 239 patients,11 underwent emergency surgery and 228 underwent elective surgery;65 and 174 underwent respectively laparoscopic surgery and open surgery;179 received digestive tract reconstruction and anastomosis and 81 received enterostomy (21 combined with anastomosis and enterostomy).Among 239 patients,137,113,101,58,54 and 11 were complicated respectively with fiber stenosis,intestinal fistula,obstruction of small intestine,abscess,cellulitis and enterobrosis (some patients combined with multiple signs).(2) Follow-up:239 patients were followed up at 30 days postoperatively.During the follow-up,48 with incisional infection were improved by symptomatic treatment.(3) Risk factors analysis affecting postoperative incisional infection:① Results of univariate analysis showed that illness behavior,sedimentation rate of RBC ＞ 20 mm/h,preoperative anemia,preoperative chronic intestinal fistula,open surgery,intraoperative fiber stenosis and intraoperative intestinal fistula were risk factors affecting occurrence of postoperative incisional infection [odds ratio (0R)=2.530,2.579,4.233,2.988,2.554,0.503,3.052,95％ confidence interval (CI):1.218-2.259,1.141-5.833,1.598-11.210,1.522-5.864,1.082-6.029,0.265-0.954,1.555-5.993,P＜0.05].② Results of multivariate analysis showed that preoperative anemia and intraoperative intestinal fistula were independent risk factors affecting occurrence of postoperative incisional infection (OR =3.881,2.837,95％ CI:1.449-10.396,1.429-5.634,P＜0.05).(4) Clinical factors affecting preoperative anemia:cases (male) with preoperative anemia,body mass index (BMI),cases with sedimentation rate of RBC ＞ 20 mm/h,platelet (PLT) ＞ 300x109/L,elevated C-reactive protein,albumin (Alb) ＜35 g/L were respectively 120,(17.4±2.9)kg/m2,130,75,139,65 in patients with preoperative anemia and 65,(18.3±2.9)kg/m2,36,12,39,10 in patients without preoperative anemia,with statistically significant differences (x2 =17.966,t =2.210,x2 =12.219,14.440,14.661,12.272,P＜0.05).Conclusion The preoperative anemia and intraoperative intestinal fistula are independent risk factors affecting occurrence of postoperative incisional infection,and preoperative anemia is associated with perioperative inflammatory conditions.

Influence of CCL21 on the invasion and metastasis of colorectal cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the influence of CCL21 on the invasion and metastasis of colorectal cancer (CRC).</p><p><b>METHODS</b>CCL21 over-expressing CRC cell line was constructed by lentivirus infection and CCL21 low-expressing CRC cell line was constructed by lipofection. The effects of CCL21 on the invasion and metastasis of CRC cells and the stem cell-like phenotype were investigated by Transwell migration, invasion assay, wound healing assay and sphere formation assay.</p><p><b>RESULTS</b>Real-time quantitative PCR and western blot confirmed that the expression of CCL21 was up-regulated by lentiviral transfection and down-regulated by siRNA liposome transfection. In vitro, Transwell assays showed that the invasion and migration in CCL21 over-expressing CRC cells decreased significantly as compared to those of CCL21 low-expressing cells. In wound healing assay, the CCL21 over-expressing CRC cells showed a significantly lower rate of migration. In addition, the sphere formation rate and density of CCL21 over-expressing CRC cells were lower than those with low-expression of CCL21.</p><p><b>CONCLUSION</b>CCL21 can suppress the migration and invasion of CRC cells and weaken their stem cell-like phenotype.</p>

A report of 136 cases of upper eyelid fold formation together with medial canthoplasty / 中华整形外科杂志

<p><b>OBJECTIVE</b>To find a new method to perform medial canthoplasty and upper eyelid fold formation at one stage.</p><p><b>METHODS</b>Based on the principle to release the skin tension and minimize incision scarring around the medial canthus, an operation was designed for medial canthoplasty together with upper eyelid fold formation. 136 patients with mild or moderate epicanthus underwent this procedure. Postoperative follow-up was as long as 34 months.</p><p><b>RESULTS</b>Based on the follow-up of 67 cases, the appearances of the upper eyelid fold and medial canthus were evaluated. The upper eyelid fold was the parallel type. The epicanthus was corrected completely or mostly.</p><p><b>CONCLUSION</b>This new method for medial canthoplasty together with upper eyelid fold formation is suitable to all the simple epicanthus except the reverse epicanthus. The operative results were effective and satisfactory.</p>