With the rapid development of social economy and the continuous improvement of human living standard, the incidence, fatality and recurrence rates of cardiovascular disease (CVD) are increasing year by year, which seriously affects people's life and health. Conventional therapeutic drugs have limited improvement on the disability rate, so the search for new therapeutic drugs and action targets has become one of the hotspots of current research. In recent years, the therapeutic role of the natural compound rosmarinic acid (RA) in CVD has attracted much attention, which is capable of preventing CVD by modulating multiple signalling pathways and exerting physiological activities such as antioxidant, anti-apoptotic, anti-inflammatory, anti-platelet aggregation, as well as anti-coagulation and endothelial function protection. In this paper, the role of RA in the prevention of CVD is systematically sorted out, and its mechanism of action is summarised and analysed, with a view to providing a scientific basis and important support for the in-depth exploration of the prevention value of RA in CVD and its further development as a prevention drug.

OBJECTIVE: To analyze two families with inherited dysfibrinogenemia, and explore the molecular pathogenic mechanisms. METHODS: The coagulation indexes of the probands and their family members were detected. The FGA, FGB, and FGG exons and their flanking sequences were amplified by PCR, and the mutation sites were identified by sequencing. SIFT, PolyPhen2, LRT, ReVe, MutationTaster, phyloP, and phastCons bioinformatics software were used to predict the functional impact of the mutation sites. Protein structure and amino acid conservation analysis of the variant were conducted using PyMOL and Clustal X software. RESULTS: The thrombin time (TT) of the proband in family 1 was prolonged to 37.00 s, and Fg∶C decreased to 0.52 g/L. The TT of the proband in family 2 was 20.30 s, and Fg∶C was 1.00 g/L, which was lower than the normal range. Genetic analysis revealed that the proband in family 1 had a heterozygous mutation c.80T>C in FGA, resulting in the substitution of phenylalanine 27 with serine (Phe27Ser). The proband in family 2 had a heterozygous mutation c.1007T>A in FGG, resulting in the substitution of methionine 336 with lysine (Met336Lys). Bioinformatics software prediction analysis indicated that both mutations were deleterious variants. PyMOL mutation models revealed that the Aα chain mutation (Phe27Ser) in family 1 and γ chain mutation (Met336Lys) in family 2 resulted in alterations in spatial structure and reduced protein stability. Clustal X results showed that both Aα Phe27 and γMet336 were highly conserved across homologous species. CONCLUSION Heterozygous mutations of FGA gene c.80T>C and FGG gene c.1007T>A are both pathogenic variants, causing inherited dysfibrinogenemia.
Female ; Humans ; Male ; Afibrinogenemia/genetics* ; Fibrinogen/genetics* ; Heterozygote ; Mutation ; Pedigree

OBJECTIVES: To reprogram human placental fibroblasts (HPFs) into chemically induced epithelioid-like cells (ciEP-Ls) using a combination of small-molecule compounds. METHODS: HPFs cultured under normoxic conditions were identified using immunofluorescence assay, PCR and chromosomal karyotyping. Under hypoxic conditions (37 ℃, 5% O₂), HPFs were cultured in a medium containing small-molecule compounds C6TSEDRVAJZ (CHIR99021, 616452, TTNPB, SAG, EPZ5676, DZNep, Ruxolitinib, VTP50469, Afuresertib, JNK-IN-8, and EZM0414), and the cell morphology was observed daily. The expression levels of epithelial cell markers in the induced cells were detected by immunofluorescence, Western blotting and PCR. Chromosomal karyotyping of the induced cells was performed and the induction efficiency was calculated. RESULTS: Before induction, HPFs showed positive expressions of fibroblast surface markers CD34 and vimentin and were negative for epithelial surface markers. PCR results showed high expressions of fibroblast-specific genes S100A4 and COL1A1 in HPFs with a normal human diploid karyotype. After one day of induction, the HPFs underwent morphological changes from a multinodular spindle shape to a round or polygonal shape, which was morphologically characteristic of ciEP-Ls. On day 4 of induction, the cells exhibited high expressions of the epithelial cell markers E-cadherin and Lin28A. RT-qPCR results also showed that the cells expressed the epithelial markers Smad3, GLi3, PAX8, WT1, KRT19, and KRT18 with significantly down-regulated expressions of all the fibroblast surface markers and a normal human diploid karyotype. The reprogramming efficiency of HPFs into ciEP-Ls ranged from (64.53±2.8)% to (68.10±3.6)%. CONCLUSIONS The small-molecule compound combination C6TSEDRVAJZ is capable of inducing HPFs into ciEP-Ls under hypoxic conditions with a high induction efficiency.
Humans ; Fibroblasts/drug effects* ; Pregnancy ; Female ; Cell Differentiation/drug effects* ; Pyrimidines/pharmacology* ; Placenta/cytology* ; Cells, Cultured ; Pyridines/pharmacology* ; Pyrazoles/pharmacology* ; Epithelial Cells/cytology*

The rol genes on pRiA4 plasmid of Agrobacterium rhizogenes are potent genes that promote secondary metabolism. Molecular breeding of Atropa belladonna can be conducted by introducing rol genes to increase tropane alkaloids (TAs) content in A. belladonna. In this study, the rolB gene was overexpressed in A. belladonna plants to study the effect of rolB gene on the biosynthesis of TAs. The phenotype, TAs content and expression levels of key enzyme genes in the pathway of TAs biosynthesis of transgenic A. belladonna were analyzed. The results showed that transgenic A. belladonna had developed root system, enlarged leaves, increased leaf fresh weight, deepened leaf color, enlarged flowers, changed flower shape, reduced pistil height and decreased pollen vitality. The content of TAs in the stems of transgenic A. belladonna was significantly higher than that of the control, and the contents of scopolamine, anisodamine, hyoscyamine can reach 2.11-2.91, 1.23-2.37 and 4.88-5.20 times of the control, respectively. Compared with the control group, the expressions of key enzymes putrescine N-methyltransferase (PMT), type III polyketide synthase (PYKS), tropinone reductase I (TRI), aromatic amino acid aminotransferase 4 (ArAT4), UDP-glycosyltransferase 1 (UGT1) and hyoscyamine 6-β-hydroxylase (H6H) in the TAs biosynthesis pathway were up-regulated, and the expression of tropinone reductase II (TRII) as a metabolic shunting gene was down-regulated. The results indicated that rolB gene enhanced TAs synthesis ability in roots and accumulation in stems of A. belladonna by enhancing metabolic flow of TAs synthesis pathway and weakening the metabolic shunt of competing pathway. This study laid a foundation for molecular breeding of A. belladonna with high-yield TAs content using rolB gene.

Objective:To explore the feasibility and clinical outcomes of punch excision combined with superficial X-ray and intralesional drug injection in the treatment of chest multiple keloids.Methods:Patients with chest multiple keloids in Dermatology Hospital of Southern Medical University from March 2020 to June 2021 were selected and randomly divided into observation group and control group according to random number table. In the observation group, punch excision was performed first, superficial X-ray was irradiated once within 24 h after surgery, and then once a week, for a total of 4 sessions. One week after radiotherapy, intralesional injection was performed with 5 ml mixture of 1 ml triamcinolone acetate injection, 0.6 ml fluorouracil injection and 3.4 ml 2% lidocaine hydrochloride injection, once a month, for a total of 4 times. Single injection endpoint reaction was keloid whiteness. The control group did not receive punch excision, and other treatments were the same as those in the observation group. Vancouver scar scale (VSS) score and efficacy evaluation (cure, excellent, improvement, ineffective) were performed before treatment and 3, 6, 12 months after treatment. Total keloids volume, intralesional injection volume and adverse reactions before and after treatment were recorded. SPSS 26.0 software was used for data analysis, and the measurement data were expressed as Mean±SD. Independent sample t-test was used for comparison between two groups, and repeated measurement data analysis of variance was used for comparison before and after treatment in the same group. Statistical data were expressed as % and χ2 test was used for comparison between groups. P<0.05 was considered statistically significant. Results:A total of 58 patients were included, 29 in each group. There were 36 males and 22 females. The age ranged from 18 to 59 years old, with an average age of 29. The number of chest keloids in each patient was 5-12. Before treatment, the VSS scores of observation group and control group was 13.21±1.24 and 12.90±1.21 respectively. There was no significant difference in VSS scores between the two groups before treatment ( t=0.97, P=0.337). After 3, 6 and 12 months of follow-up, the VSS scores of the observation group were 4.21±1.26, 4.34±1.40 and 4.55±1.33 respectively, while those of the control group were 5.66±1.32, 6.07±1.44 and 6.62±1.40 respectively. The differences between the two groups were statistically significant ( t=-4.27, -4.63, -5.78, all P<0.001). Intra-group comparison showed that there were no statistically significant differences in VSS scores at 3, 6 and 12 months after treatment in the observation group ( F=2.50, P=0.111), while VSS scores at 3, 6 and 12 months after treatment in the control group showed a gradually increasing trend, with statistically significant difference ( F=30.75, P<0.001). In the observation group, 22 cases showed excellent effect, 7 cases improved, and the excellent rate was 75.86%(22/29). In the control group, there were 6 cases of excellent effect and 23 cases of improvement, the excellent rate was 20.69%(6/29), and the difference between the two groups was statistically significant ( χ2=17.68, P<0.001). Before treatment, the total keloids volume of the observation group was (7.76±1.71) cm 3, which was (8.27±1.26) cm 3 of the control group, and there was no significant difference between the two groups before treatment ( t=-1.28, P=0.207). In the follow-up of 12 months after treatment, the total keloids volume of the observation group[(2.57±0.59) cm 3] was significantly smaller than that of the control group[(5.51±1.39) cm 3], and the difference was statistically significant ( t=-10.47, P<0.001). The total amount of intralesional injection in the observation group[(6.45±1.25) ml] was less than that in the control group[(11.00±1.73) ml], and the difference was statistically significant ( t=-11.48, P<0.001). Transient hyperpigmentation appeared in the irradiation area 3-5 days after superficial X-ray, which subsided naturally within 6 months in both groups. In addition, there were 5 adverse reactions in the observation group, including delayed healing (2 cases), telangiectasia (2 cases) and abnormal menstrual cycle (1 case). There were 13 cases of adverse reactions in the control group, including telangiectasia (7 cases), abnormal menstrual cycle (2 cases), and atrophic and sunken skin (4 cases). The incidence of adverse reactions in the observation group was significantly lower than that in the control group, and the difference was statistically significant [17.24%(5/29) vs. 44.83%(13/29), χ2=5.16, P<0.001]. Conclusion:Punch excision combined with superficial X-ray and intralesional drug injection for the treatment of chest multiple keloids has the advantages of simple operation, good therapeutic effect and less adverse reactions.

Objective:To explore the feasibility and clinical outcomes of punch excision combined with superficial X-ray and intralesional drug injection in the treatment of chest multiple keloids.Methods:Patients with chest multiple keloids in Dermatology Hospital of Southern Medical University from March 2020 to June 2021 were selected and randomly divided into observation group and control group according to random number table. In the observation group, punch excision was performed first, superficial X-ray was irradiated once within 24 h after surgery, and then once a week, for a total of 4 sessions. One week after radiotherapy, intralesional injection was performed with 5 ml mixture of 1 ml triamcinolone acetate injection, 0.6 ml fluorouracil injection and 3.4 ml 2% lidocaine hydrochloride injection, once a month, for a total of 4 times. Single injection endpoint reaction was keloid whiteness. The control group did not receive punch excision, and other treatments were the same as those in the observation group. Vancouver scar scale (VSS) score and efficacy evaluation (cure, excellent, improvement, ineffective) were performed before treatment and 3, 6, 12 months after treatment. Total keloids volume, intralesional injection volume and adverse reactions before and after treatment were recorded. SPSS 26.0 software was used for data analysis, and the measurement data were expressed as Mean±SD. Independent sample t-test was used for comparison between two groups, and repeated measurement data analysis of variance was used for comparison before and after treatment in the same group. Statistical data were expressed as % and χ2 test was used for comparison between groups. P<0.05 was considered statistically significant. Results:A total of 58 patients were included, 29 in each group. There were 36 males and 22 females. The age ranged from 18 to 59 years old, with an average age of 29. The number of chest keloids in each patient was 5-12. Before treatment, the VSS scores of observation group and control group was 13.21±1.24 and 12.90±1.21 respectively. There was no significant difference in VSS scores between the two groups before treatment ( t=0.97, P=0.337). After 3, 6 and 12 months of follow-up, the VSS scores of the observation group were 4.21±1.26, 4.34±1.40 and 4.55±1.33 respectively, while those of the control group were 5.66±1.32, 6.07±1.44 and 6.62±1.40 respectively. The differences between the two groups were statistically significant ( t=-4.27, -4.63, -5.78, all P<0.001). Intra-group comparison showed that there were no statistically significant differences in VSS scores at 3, 6 and 12 months after treatment in the observation group ( F=2.50, P=0.111), while VSS scores at 3, 6 and 12 months after treatment in the control group showed a gradually increasing trend, with statistically significant difference ( F=30.75, P<0.001). In the observation group, 22 cases showed excellent effect, 7 cases improved, and the excellent rate was 75.86%(22/29). In the control group, there were 6 cases of excellent effect and 23 cases of improvement, the excellent rate was 20.69%(6/29), and the difference between the two groups was statistically significant ( χ2=17.68, P<0.001). Before treatment, the total keloids volume of the observation group was (7.76±1.71) cm 3, which was (8.27±1.26) cm 3 of the control group, and there was no significant difference between the two groups before treatment ( t=-1.28, P=0.207). In the follow-up of 12 months after treatment, the total keloids volume of the observation group[(2.57±0.59) cm 3] was significantly smaller than that of the control group[(5.51±1.39) cm 3], and the difference was statistically significant ( t=-10.47, P<0.001). The total amount of intralesional injection in the observation group[(6.45±1.25) ml] was less than that in the control group[(11.00±1.73) ml], and the difference was statistically significant ( t=-11.48, P<0.001). Transient hyperpigmentation appeared in the irradiation area 3-5 days after superficial X-ray, which subsided naturally within 6 months in both groups. In addition, there were 5 adverse reactions in the observation group, including delayed healing (2 cases), telangiectasia (2 cases) and abnormal menstrual cycle (1 case). There were 13 cases of adverse reactions in the control group, including telangiectasia (7 cases), abnormal menstrual cycle (2 cases), and atrophic and sunken skin (4 cases). The incidence of adverse reactions in the observation group was significantly lower than that in the control group, and the difference was statistically significant [17.24%(5/29) vs. 44.83%(13/29), χ2=5.16, P<0.001]. Conclusion:Punch excision combined with superficial X-ray and intralesional drug injection for the treatment of chest multiple keloids has the advantages of simple operation, good therapeutic effect and less adverse reactions.

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

Neuroscientists have emphasized visceral influences on consciousness and attention, but the potential neurophysiological pathways remain under exploration. Here, we found two neurophysiological pathways of heart-brain interaction based on the relationship between oxygen-transport by red blood cells (RBCs) and consciousness/attention. To this end, we collected a dataset based on the routine physical examination, the breaking continuous flash suppression (b-CFS) paradigm, and an attention network test (ANT) in 140 immigrants under the hypoxic Tibetan environment. We combined electroencephalography and multilevel mediation analysis to investigate the relationship between RBC properties and consciousness/attention. The results showed that RBC function, via two independent neurophysiological pathways, not only triggered interoceptive re-representations in the insula and awareness connected to orienting attention but also induced an immune response corresponding to consciousness and executive control. Importantly, consciousness played a fundamental role in executive function which might be associated with the level of perceived stress. These results indicated the important role of oxygen-transport in heart-brain interactions, in which the related stress response affected consciousness and executive control. The findings provide new insights into the neurophysiological schema of heart-brain interactions.
Awareness ; Brain ; Consciousness ; Humans ; Oxygen ; Visual Perception

Hair roots induced by Agrobacterium rhizogene produce higher levels of secondary metabolites than non-induced plants, and the enhanced metabolic capacity is driven by the rol gene. We hypothesized that rol genes can be utilized to improve the biosynthesis of tropane alkaloids (TAs) in Atropa belladonna. In this study, the rolC gene from Agrobacterium rhizogene pRiA4 plasmid, driven by a CaMV35S promoter, was overexpressed in A. belladonna. The phenotypes, TAs content and transcriptional expression of key genes in TAs biosynthesis were analyzed in transgenic A. belladonna plants. Results show that transgenic A. belladonna exhibited a well-developed root system, male sterility, higher stamen column length than pistil, early flowering, internode shortening, smaller but more flowers, increased axillary buds and lateral buds, decreased apical dominance, and long and narrow leaves as compared to wild-type plants. Transgenic A. belladonna produced more TAs than wild-type plants, with the content of hyoscyamine, anisodamine and scopolamine reaching 2.58, 3.59 and 15.77-fold that of the control group, respectively. The gene expression of putrescine N-methyltransferase (PMT), tropinone reductase I (TRⅠ) and hyoscyamine 6-β-hydroxylase (H6H), key enzymes in TAs biosynthesis, were up-regulated compared with the control group. The above results indicate that the rolC gene enhances TAs biosynthesis in A. belladonna by up-regulating the expression of key enzymes in the TAs biosynthesis pathway, laying a foundation for genetic manipulation of A. belladonna to increase TAs content by increasing rolC gene expression.