Epimedin B(EB)is one of the main flavonoid ingredients present in Epimedium brevicornum Maxim.,a traditional herb widely used in China.Our previous study showed that EB was a stronger inducer of melanogenesis and an activator of tyrosinase(TYR).However,the role of EB in melanogenesis and the mechanism underlying the regulation remain unclear.Herein,as an extension to our previous investi-gation,we provide comprehensive evidence of EB-induced pigmentation in vivo and in vitro and eluci-date the melanogenesis mechanism by assessing its effects on the TYR family of proteins(TYRs)in terms of expression,activity,and stability.The results showed that EB increased TYRs expression through microphthalmia-associated transcription factor-mediated p-Akt(referred to as protein kinase B(PKB))/glycogen synthase kinase 3β(GSK3β)/β-catenin,p-p70 S6 kinase cascades,and protein 38(p38)/mitogen-activated protein(MAP)kinase(MAPK)and extracellular regulated protein kinases(ERK)/MAPK pathways,after which EB increased the number of melanosomes and promoted their maturation for melanogenesis in melanoma cells and human primary melanocytes/skin tissues.Furthermore,EB exerted repigmentation by stimulating TYR activity in hydroquinone-and N-phenylthiourea-induced TYR inhibitive models,including melanoma cells,zebrafish,and mice.Finally,EB ameliorated monobenzone-induced depigmentation in vitro and in vivo through the enhancement of TYRs stability by inhibiting TYR misfolding,TYR-related protein 1 formation,and retention in the endoplasmic reticulum and then by downregulating the ubiquitination and proteolysis processes.These data conclude that EB can target TYRs and alter their expression,activity,and stability,thus stimulating their pigmentation function,which might provide a novel rational strategy for hypopigmentation treatment in the pharmaceutical and cosmetic industries.

For the treatment of atrial fibrillation,Professor WU Wei innovatively put forward the theory of heart-blood-vessels trinity and the theory of stasis-toxin causing palpitation.It is believed that atrial fibrillation is caused by stasis and toxin,and affects the heart,blood and vessels.The core pathogenesis of atrial fibrillation is due to qi stagnation,blood stasis and toxin.The treatment for atrial fibrillation should be closely based on the pathogenesis,the therapeutic principles of treating from the perspective of stasis and together by removing toxin gradually is advocated.And the therapy of regulating qi,activating blood and removing stasis is also the way to remove toxin.The medication is based on the modified Taoren Honghua Decoction,which is mainly composed of Persicae Semen,Carthami Flos,Chuanxiong Rhizoma,Corydalis Rhizoma,Rehmanniae Radix,Paeoniae Radix Rubra,Salviae Miltiorrhizae Radix et Rhizoma,Jujubae Fructus,Puerariae Lobatae Radix,Nardostachyos Radix et Rhizoma,Ostreae Concha,Poria,and Polygonati Odorati Rhizoma.According to the characteristics of Lingnan climate and atrial fibrillation mostly being easy to affect the emotions,the pungent drugs in the prescription are usually removed,and the specific herbal pair of Puerariae Lobatae Radix-Nardostachyos Radix et Rhizoma is added to remove toxin according to the differentiation of disease.Moreover,for the treatment of atrial fibrillation,Professor WU Wei also adopts traditional Chinese medicine(TCM)external treatment such as foot bath,acupuncture and moxibustion,and physical-breathing exercise as well as health-care methods for comprehensive regulation,relieving the toxin and restoring the original qi.During the treatment atrial fibrillation,Professor WU Wei follows the principle of precise intervention and comprehensive regulation with Chinese medicine,so as to achieve the purpose of eliminating symptoms,restoring sinus rhythm and improving physical constitution.The thoughts of Professor WU Wei for the syndrome differentiation and treatment of atrial fibrillation will provide reference for the treatment of atrial fibrillation with TCM.

Objective: To examine the short-term curative effect with minimally invasive right infra-axillary thoracotomy for transaortic modified Morrow procedure. Methods: The clinical data of 60 patients who underwent video-assisted thoracoscopic transaortic modified Morrow procedure from August 2021 to August 2022 at Department of Cardiovascular Surgery, Zhejiang Provincial People's Hospital were retrospectively analyzed. There were 31 males and 29 females, with the age (M (IQR)) of 54.0(22.3) years (range: 15 to 71 years). The echocardiography confirmed the diagnosis of moderate mitral regurgitation in 30 patients, and severe mitral regurgitation in 13 patients. Systolic anterior motion (SAM) was present preoperatively in 54 patients. All 60 patients underwent transaortic modified Morrow procedure through a right infra-axillary thoracotomy using femorofemoral cardiopulmonary bypass. Surgical procedures mainly included transverse aortic incision, exposure of left ventricular outflow tract (LVOT), septal myectomy, and correction of the abnormal mitral valve and subvalvular structures. Results: All 60 patients underwent the programmatic procedures successfully without conversion to full sternotomy. The cardiopulmonary bypass time was (142.0±32.1) minutes (range: 89 to 240 minutes), while the cross-clamp time was (95.0±23.5) minutes (range: 50 to 162 minutes). The patients had a postoperative peak LVOT gradient of 7.0 (5.0) mmHg (range: 0 to 38 mmHg) (1 mmHg=0.133 kPa). A total of 57 patients were extubated on the operating table. The drainage volume in the first 24 h was (175.9±57.0) ml (range: 60 to 327 ml). The length of intensive care unit stay was 21.0 (5.8)h (range: 8 to 120 h) and postoperative hospital stay was 8 (5) days (range: 5 to 19 days). The postoperative septal thickness was 11 (2) mm (range: 8 to 14 mm). All patients had no iatrogenic ventricular septal perforation or postoperative residual SAM. The patients were followed up for 4 (9) months (range: 1 to 15 months), and none of them needed cardiac surgery again due to valve dysfunction or increased peak LVOT gradient during follow-up. Conclusion: Using a video-assisted thoracoscopic transaortic modified Morrow procedure through a right infra-axillary minithoracotomy can provide good visualization of the LVOT and hypertrophic ventricular septum, ensure optimal exposure of the mitral valve in the presence of complex mitral subvalvular structures, so that allows satisfactory short-term surgical results.
Male ; Female ; Humans ; Mitral Valve Insufficiency/surgery* ; Thoracotomy ; Retrospective Studies ; Cardiomyopathy, Hypertrophic/surgery* ; Ventricular Septum/surgery* ; Treatment Outcome ; Minimally Invasive Surgical Procedures/methods*

Objective: To grasp the epidemiological characteristics of influenza outbreaks in Guangdong Province by analyzing the outbreaks of influenza-like cases reported in Guangdong Province from January 2015 to the end of August 2022. Methods: In response to the outbreak of epidemics in Guangdong Province from 2015 to 2022, information on on-site epidemic control was collected, and epidemiological analysis was conducted to describe the characteristics of the epidemics. The factors that influence the intensity and duration of the outbreak were determined through a logistic regression model. Results: A total of 1 901 influenza outbreaks were reported in Guangdong Province, with an overall incidence of 2.05%. Most outbreak reports occurred from November to January of the following year (50.24%, 955/1 901) and from April to June (29.88%, 568/1 901). A total of 59.23% (1 126/1 901) of the outbreaks were reported in the Pearl River Delta region, and primary and secondary schools were the main places where outbreaks occurred (88.01%, 1 673/1 901). Outbreaks with 10-29 cases were the most common (66.18%, 1 258/1 901), and most outbreaks lasted less than seven days (50.93%,906/1 779). The size of the outbreak was related to the nursery school (aOR=0.38, 95%CI:0.15-0.93), the Pearl River Delta region (aOR=0.60, 95%CI:0.44-0.83), the time interval between the onset of the first case and the time of report (>7 days compared with ≤3 days: aOR=3.01, 95%CI:1.84-4.90), the influenza A(H1N1) (aOR=2.02, 95%CI:1.15-3.55) and the influenza B (Yamagata) (aOR=2.94, 95%CI: 1.50-5.76). The duration of outbreaks was related to school closures (aOR=0.65, 95%CI: 0.47-0.89), the Pearl River Delta region (aOR=0.65, 95%CI: 0.50-0.83) and the time interval between the onset of the first case and the time of report (>7 days compared with ≤3 days: aOR=13.33, 95%CI: 8.80-20.19; 4-7 days compared with ≤3 days: aOR=2.56, 95%CI: 1.81-3.61). Conclusions: An influenza outbreak in Guangdong Province exhibits two peaks, one in the winter and spring seasons and the other in the summer. Primary and secondary schools are high-risk areas, and early reporting of outbreaks is critical for controlling influenza outbreaks in schools. Furthermore, comprehensive measures should be taken to prevent the spread of the epidemic.
Humans ; Influenza A Virus, H1N1 Subtype ; Influenza, Human/epidemiology* ; Disease Outbreaks ; Epidemics ; China/epidemiology*

BACKGROUND: The molecular mechanisms of heart failure (HF) are still poorly understood. Circular RNA (circRNA) has been discovered in the heart in increasing numbers of studies. The goal of this research is to learn more about the potential roles of circRNAs in HF. METHODS & RESULTS: We used RNA sequencing data to identify the characteristics of circRNAs expressed in the heart and discovered that the majority of circRNAs screened were less than 2000 nt. Additionally, chromosomes One and Y had the most and least number of circRNAs, respectively. After excluding duplicate host genes and intergenic circRNAs, a total of 238 differentially expressed circRNAs (DECs) and 203 host genes were discovered. However, only four of the 203 host genes of DECs were examined in HF differentially expressed genes. Another study used Gene Oncology analysis of DECs host genes to elucidate the underlying pathogenesis of HF, and it found that binding and catalytic activity accounted for a large portion of DECs. Immune system, metabolism, and signal transduction pathways were significantly enriched. Furthermore, 1052 potentially regulated miRNAs from the top 40 DECs were collected to build a circRNA-miRNA network, and it was discovered that 470 miRNAs can be regulated by multiple circRNAs, while others are regulated by a single circRNA. In addition, a comparison of the top 10 mRNAs in HF and their targeted miRNAs revealed that DDX3Y and UTY were regulated by the most and least circRNA, respectively. CONCLUSION These findings demonstrated circRNAs have species and tissue specific expression patterns; while circRNA expression is independent on host genes, the same types of genes in DECs and DEGs worked in HF. Our findings would contribute to a better understanding of the critical roles of circRNAs and lay the groundwork for future studies of HF molecular functions.

Clustered Regularly Interspaced Short Palindromic Repeats/genetics* ; CRISPR-Cas Systems/genetics* ; Gene Editing

Humans ; Blast Crisis/genetics* ; Leukemia, Promyelocytic, Acute/genetics* ; Oncogene Proteins, Fusion/genetics* ; Tretinoin

Objective: To analyze the clinical epidemiological characteristics including composition of pathogens , clinical characteristics, and disease prognosis acute bacterial meningitis (ABM) in Chinese children. Methods: A retrospective analysis was performed on the clinical and laboratory data of 1 610 children <15 years of age with ABM in 33 tertiary hospitals in China from January 2019 to December 2020. Patients were divided into different groups according to age,<28 days group, 28 days to <3 months group, 3 months to <1 year group, 1-<5 years of age group, 5-<15 years of age group; etiology confirmed group and clinically diagnosed group according to etiology diagnosis. Non-numeric variables were analyzed with the Chi-square test or Fisher's exact test, while non-normal distrituction numeric variables were compared with nonparametric test. Results: Among 1 610 children with ABM, 955 were male and 650 were female (5 cases were not provided with gender information), and the age of onset was 1.5 (0.5, 5.5) months. There were 588 cases age from <28 days, 462 cases age from 28 days to <3 months, 302 cases age from 3 months to <1 year of age group, 156 cases in the 1-<5 years of age and 101 cases in the 5-<15 years of age. The detection rates were 38.8% (95/245) and 31.5% (70/222) of Escherichia coli and 27.8% (68/245) and 35.1% (78/222) of Streptococcus agalactiae in infants younger than 28 days of age and 28 days to 3 months of age; the detection rates of Streptococcus pneumonia, Escherichia coli, and Streptococcus agalactiae were 34.3% (61/178), 14.0% (25/178) and 13.5% (24/178) in the 3 months of age to <1 year of age group; the dominant pathogens were Streptococcus pneumoniae and the detection rate were 67.9% (74/109) and 44.4% (16/36) in the 1-<5 years of age and 5-<15 years of age . There were 9.7% (19/195) strains of Escherichia coli producing ultra-broad-spectrum β-lactamases. The positive rates of cerebrospinal fluid (CSF) culture and blood culture were 32.2% (515/1 598) and 25.0% (400/1 598), while 38.2% (126/330)and 25.3% (21/83) in CSF metagenomics next generation sequencing and Streptococcus pneumoniae antigen detection. There were 4.3% (32/790) cases of which CSF white blood cell counts were normal in etiology confirmed group. Among 1 610 children with ABM, main intracranial imaging complications were subdural effusion and (or) empyema in 349 cases (21.7%), hydrocephalus in 233 cases (14.5%), brain abscess in 178 cases (11.1%), and other cerebrovascular diseases, including encephalomalacia, cerebral infarction, and encephalatrophy, in 174 cases (10.8%). Among the 166 cases (10.3%) with unfavorable outcome, 32 cases (2.0%) died among whom 24 cases died before 1 year of age, and 37 cases (2.3%) had recurrence among whom 25 cases had recurrence within 3 weeks. The incidences of subdural effusion and (or) empyema, brain abscess and ependymitis in the etiology confirmed group were significantly higher than those in the clinically diagnosed group (26.2% (207/790) vs. 17.3% (142/820), 13.0% (103/790) vs. 9.1% (75/820), 4.6% (36/790) vs. 2.7% (22/820), χ²=18.71, 6.20, 4.07, all P<0.05), but there was no significant difference in the unfavorable outcomes, mortility, and recurrence between these 2 groups (all P>0.05). Conclusions: The onset age of ABM in children is usually within 1 year of age, especially <3 months. The common pathogens in infants <3 months of age are Escherichia coli and Streptococcus agalactiae, and the dominant pathogen in infant ≥3 months is Streptococcus pneumoniae. Subdural effusion and (or) empyema and hydrocephalus are common complications. ABM should not be excluded even if CSF white blood cell counts is within normal range. Standardized bacteriological examination should be paid more attention to increase the pathogenic detection rate. Non-culture CSF detection methods may facilitate the pathogenic diagnosis.
Adolescent ; Brain Abscess ; Child ; Child, Preschool ; Escherichia coli ; Female ; Humans ; Hydrocephalus ; Infant ; Infant, Newborn ; Male ; Meningitis, Bacterial/epidemiology* ; Retrospective Studies ; Streptococcus agalactiae ; Streptococcus pneumoniae ; Subdural Effusion ; beta-Lactamases

Taking the Chinese city of Xiamen as an example, simulation and quantitative analysis were performed on the transmissions of the Coronavirus Disease 2019 (COVID-19) and the influence of intervention combinations to assist policymakers in the preparation of targeted response measures. A machine learning model was built to estimate the effectiveness of interventions and simulate transmission in different scenarios. The comparison was conducted between simulated and real cases in Xiamen. A web interface with adjustable parameters, including choice of intervention measures, intervention weights, vaccination, and viral variants, was designed for users to run the simulation. The total case number was set as the outcome. The cumulative number was 4,614,641 without restrictions and 78 under the strictest intervention set. Simulation with the parameters closest to the real situation of the Xiamen outbreak was performed to verify the accuracy and reliability of the model. The simulation model generated a duration of 52 days before the daily cases dropped to zero and the final cumulative case number of 200, which were 25 more days and 36 fewer cases than the real situation, respectively. Targeted interventions could benefit the prevention and control of COVID-19 outbreak while safeguarding public health and mitigating impacts on people's livelihood.
COVID-19/prevention & control* ; China/epidemiology* ; Humans ; Machine Learning ; Pandemics/prevention & control* ; Policy ; Reproducibility of Results ; SARS-CoV-2

OBJECTIVES: To investigate the clinical treatment outcomes and the changes of the outcomes over time in extremely preterm twins in Guangdong Province, China. METHODS: A retrospective analysis was performed for 269 pairs of extremely preterm twins with a gestational age of <28 weeks who were admitted to the department of neonatology in 26 grade A tertiary hospitals in Guangdong Province from January 2008 to December 2017. According to the admission time, they were divided into two groups: 2008-2012 and 2013-2017. Besides, each pair of twins was divided into the heavier infant and the lighter infant subgroups according to birth weight. The perinatal data of mothers and hospitalization data of neonates were collected. The survival rate of twins and the incidence rate of complications were compared between the 2008-2012 and 2013-2017 groups. RESULTS: Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of severe asphyxia and smaller head circumference at birth (P<0.05). The mortality rates of both of the twins, the heavier infant of the twins, and the lighter infant of the twins were lower in the 2013-2017 group compared with the 2008-2012 group (P<0.05). Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of pulmonary hemorrhage, patent ductus arteriosus (PDA), periventricular-intraventricular hemorrhage (P-IVH), and neonatal respiratory distress syndrome (NRDS) and a higher incidence rate of bronchopulmonary dysplasia (P<0.05). CONCLUSIONS There is a significant increase in the survival rate over time in extremely preterm twins with a gestational age of <28 weeks in the 26 grade A tertiary hospitals in Guangdong Province. The incidences of severe asphyxia, pulmonary hemorrhage, PDA, P-IVH, and NRDS decrease in both the heavier and lighter infants of the twins, but the incidence of bronchopulmonary dysplasia increases. With the improvement of diagnosis and treatment, the multidisciplinary collaboration between different fields of fetal medicine including prenatal diagnosis, obstetrics, and neonatology is needed in the future to jointly develop management strategies for twin pregnancy.
Bronchopulmonary Dysplasia/epidemiology* ; Female ; Gestational Age ; Humans ; Infant ; Infant, Extremely Premature ; Infant, Newborn ; Pregnancy ; Respiratory Distress Syndrome, Newborn/epidemiology* ; Retrospective Studies ; Treatment Outcome