The aim of this study was to investigate the virulence determinants and genetic diversity of foodborne Yersinia enterocolitica from Wenzhou.A total of 71 strains of Yersinia enterocolitica were isolated from food and foodborne diarrhea ca-ses in Wenzhou,and their biotypes,serotypes,and drug resistance were analyzed.On the basis of whole genome sequencing,we assessed virulence gene profiles,and performed multilocus sequence typing(MLST)and core gene multilocus sequence typ-ing(cgMLST).A total of 94.4％(67/71)of isolates belonged to biotype 1A,and the highest proportion had serotype lA/O∶5(29.6％,21/71).The sensitivity rates of the isolates to 14 antibiotics exceeded 95.8％.A total of 16 categories and 126 viru-lence genes were identified,with two strains carrying the pYV plasmid and chromosome-related virulence genes.ST3(31.6％,12/38)was the most widespread MLST type,and cgMLST analysis revealed no dense clusters of genotypes except for strains sharing the same ST.In conclusion,pathogenic strains were identified from foodborne Yersinia enterocolitica in Wenzhou and were found to exhibit high genetic polymorphism.Enhanced regulatory supervision is essential to prevent the outbreak of food-borne diseases caused by Yersinia enterocolitica.

The purpose of this study was to explore the clinical efficacy and safety of Gynostemma pentaphyllum (G. pentaphyllum) in the treatment of hyperlipidemia, and to provide systematic evaluation basis for clinical application. CNKI, Wanfang Data, VIP, Web of science, PubMed, Embase and Cochrane Library were searched for randomized controlled trials (RCTs) about G. pentaphyllum in the treatment of hyperlipidemia. Review Manager 5.4 were used for statistical analysis. Through reading topics, abstracts, and full texts, 27 papers with 2311 cases involved that met the inclusion and exclusion criteria were finally included for the analysis. In terms of curative effect, the effect of G. pentaphyllum alone in increasing high density lipoprotein (HDL) index was better than that of conventional treatment, and the effect of reducing total cholesterol (TC), triglyceride (TG) and low density lipoprotein (LDL) was similar to that of conventional treatment. There was a synergistic effect between G. pentaphyllum and conventional drugs, and the combination of G. pentaphyllum and conventional drugs was superior to conventional treatment in reducing TG and increasing HDL. G. pentaphyllum can also decrease the levels of serum glutamic pyruvic transaminase and glutamic oxaloacetic transaminase in the treatment of hyperlipidemia, indicating a certain protective function of the liver. In terms of safety, there were fewer cases of adverse reactions in the G. pentaphyllum treatment group, and the adverse reaction events reported in the literature was mild. According to the results of meta-analysis, G. pentaphyllum was effective in the treatment of hyperlipidemia, and it has the potential to be combined with traditional drugs, has a certain liver protection function, and was superior to traditional drugs in the treatment of hyperlipidemia.

OBJECTIVE: This study aimed to assess the associations between maternal drug use, cytochrome P450 ( CYP450) genetic polymorphisms, and their interactions with the risk of congenital heart defects (CHDs) in offspring. METHODS: A case-control study involving 569 mothers of CHD cases and 652 controls was conducted from November 2017 to January 2020. RESULTS: After adjusting for potential confounding factors, the results show that mothers who used ovulatory drugs (adjusted odds ratio [a OR] = 2.12; 95% confidence interval [ CI]: 1.08-4.16), antidepressants (a OR = 2.56; 95% CI: 1.36-4.82), antiabortifacients (a OR = 1.55; 95% CI: 1.00-2.40), or traditional Chinese drugs (a OR = 1.97; 95% CI: 1.26-3.09) during pregnancy were at a significantly higher risk of CHDs in offspring. Maternal CYP450 genetic polymorphisms at rs1065852 (A/T vs. A/A: OR = 1.53, 95% CI: 1.10-2.14; T/T vs. A/A: OR = 1.57, 95% CI: 1.07-2.31) and rs16947 (G/G vs. C/C: OR = 3.41, 95% CI: 1.82-6.39) were also significantly associated with the risk of CHDs in offspring. Additionally, significant interactions were observed between the CYP450genetic variants and drug use on the development of CHDs. CONCLUSIONS In those of Chinese descent, ovulatory drugs, antidepressants, antiabortifacients, and traditional Chinese medicines may be associated with the risk of CHDs in offspring. Maternal CYP450 genes may regulate the effects of maternal drug exposure on fetal heart development.
Adult ; Cytochrome P-450 Enzyme System/genetics* ; Female ; Genotype ; Heart Defects, Congenital/genetics* ; Humans ; Infant, Newborn ; Polymorphism, Genetic ; Pregnancy ; Pregnancy Complications/drug therapy*

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

OBJECTIVES: To investigate the incidence of extrauterine growth retardation (EUGR) and its risk factors in very preterm infants (VPIs) during hospitalization in China. METHODS: A prospective multicenter study was performed on the medical data of 2 514 VPIs who were hospitalized in the department of neonatology in 28 hospitals from 7 areas of China between September 2019 and December 2020. According to the presence or absence of EUGR based on the evaluation of body weight at the corrected gestational age of 36 weeks or at discharge, the VPIs were classified to two groups: EUGR group (n=1 189) and non-EUGR (n=1 325). The clinical features were compared between the two groups, and the incidence of EUGR and risk factors for EUGR were examined. RESULTS: The incidence of EUGR was 47.30% (1 189/2 514) evaluated by weight. The multivariate logistic regression analysis showed that higher weight growth velocity after regaining birth weight and higher cumulative calorie intake during the first week of hospitalization were protective factors against EUGR (P<0.05), while small-for-gestational-age birth, prolonged time to the initiation of total enteral feeding, prolonged cumulative fasting time, lower breast milk intake before starting human milk fortifiers, prolonged time to the initiation of full fortified feeding, and moderate-to-severe bronchopulmonary dysplasia were risk factors for EUGR (P<0.05). CONCLUSIONS It is crucial to reduce the incidence of EUGR by achieving total enteral feeding as early as possible, strengthening breastfeeding, increasing calorie intake in the first week after birth, improving the velocity of weight gain, and preventing moderate-severe bronchopulmonary dysplasia in VPIs.
Female ; Fetal Growth Retardation ; Gestational Age ; Hospitalization ; Humans ; Incidence ; Infant ; Infant, Newborn ; Infant, Premature ; Infant, Very Low Birth Weight ; Prospective Studies ; Risk Factors

Cardiovascular disease (CVD) and its complications are the leading cause of morbidity and mortality in the world. Because of the side effects and incomplete recovery from current therapy, stem cell therapy emerges as a potential therapy for CVD treatment, and endothelial progenitor cell (EPC) is one of the key stem cells used for therapeutic applications. The effect of this therapy required the expansion of EPC function. To enhance the EPC activation, proliferation, and angiogenesis using dronedarone hydrochloride (DH) is the purpose of this study. DH received approval for atrial fibrillation treatment and its cardiovascular protective effects were already reported. In this study, DH significantly increased EPC proliferation, tube formation, migration, and maintained EPCs surface marker expression. In addition, DH treatment up-regulated the phosphorylation of AKT and reduced the reactive oxygen species production. In summary, the cell priming by DH considerably improved the functional activity of EPCs, and the use of which might be a novel strategy for CVD treatment.

Acetaminophen (APAP, also known as paracetamol)-induced liver injury is the leading cause of drug-induced liver injury in the world. Wuzhi Tablet (WZ, an ethanol extract of Schisandra sphenanthera) is widely used in clinical practice to protect liver function. Our previous studies have shown that pretreatment with WZ for 3 days can significantly protect against APAP-induced liver injury; however, the effect of different intervals between APAP and WZ treatment on APAP-induced liver injury remains unclear. In this study, the change in liver injury indexes, APAP metabolites, and the activity of cytochrome P450 (CYP450) enzymes after treatment with WZ and APAP at different intervals were determined. The animal experiment was reviewed and approved by the Animal Ethics Committee of Sun Yat-sen University. The results show that 0 h, 0.5 h, and 2 h pretreatment with WZ significantly protected against APAP-induced liver injury in mice, as evidenced by a significant decrease in biochemical parameters such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), and malonaldehyde (MDA). WZ inhibited the metabolic activation of APAP mediated by CYP450 enzymes and reduced the formation of APAP metabolites. This study further demonstrates that pretreatment with WZ at different intervals (0 h, 0.5 h, and 2 h before APAP dosing) exerts a significant hepatoprotective effect against APAP-induced liver injury, and a single-dose of WZ inhibits the activity of CYP450 enzymes related to APAP metabolic activation, thereby protecting against APAP-induced hepatotoxicity.

High mobility group protein B1 (HMGB1), a highly conversed non-histone nucleoproteins with strong pro-inflammatory property, is one of the inflammatory mediator of the acute respiratory distress syndrome (ARDS). Numerous studies have confirmed that HMGB1 regulates ARDS by binding to receptor for advanced glycation end product (RAGE), Toll-like receptor (TLR) and etc. And it can significantly increase the mortality of ARDS. But the mechanism of HMGB1 release is still unclear. This study focuses on the HMGB1 release progress, which connected with Janus kinases/signal transducer and activator of transcription (JAK/STAT), nuclear factor-κB (NF-κB), Notch, inflammasome, tumor necrosis factor (TNF), mitogen-activated protein kinase (MAPK), reactive oxygen species (ROS), peroxisome proliferator-activated receptor (PPAR) and other signaling or dependent pathways in ARDS.

Cardiovascular disease (CVD) and its complications are the leading cause of morbidity and mortality in the world. Because of the side effects and incomplete recovery from current therapy, stem cell therapy emerges as a potential therapy for CVD treatment, and endothelial progenitor cell (EPC) is one of the key stem cells used for therapeutic applications. The effect of this therapy required the expansion of EPC function. To enhance the EPC activation, proliferation, and angiogenesis using dronedarone hydrochloride (DH) is the purpose of this study. DH received approval for atrial fibrillation treatment and its cardiovascular protective effects were already reported. In this study, DH significantly increased EPC proliferation, tube formation, migration, and maintained EPCs surface marker expression. In addition, DH treatment up-regulated the phosphorylation of AKT and reduced the reactive oxygen species production. In summary, the cell priming by DH considerably improved the functional activity of EPCs, and the use of which might be a novel strategy for CVD treatment.

The present study explored the effects and its underlying mechanisms of four active fractions of Camellia nitidissima(leaf polyphenols, leaf saponins, flower polyphenols, and flower saponins in C. nitidissima) in inhibiting the proliferation and migration of non-small cell lung cancer(NSCLC) by suppressing the epidermal growth factor receptor(EGFR). MTT assay was used to detect the effect of four active fractions on the proliferation of NCI-H1975 and HCC827 cells. Wound healing assay and Transwell assay were adopted to evaluate the effect of four active fractions on the migration of NSCLC. The effect of four active fractions on the enzyme activity of EGFR was detected. Molecular docking was carried out to explore the direct action capacity and action sites between representative components of the four active fractions and EGPR. Western blot assay was employed to investigate the effect of four active fractions on the protein expression in EGFR downstream signaling pathways. The results of the MTT assay indicated that the cell viability of NCI-H1975 and HCC827 cells was significantly inhibited by four active fractions at 50, 100, 150, and 200 μg·mL~(-1) in a dose-dependent manner. Wound healing assay and Transwell assay revealed that the migration of NCI-H1975 and HCC827 cells was significantly suppressed by four active fractions. In addition, the results of the protein activity assay showed that the enzyme activity of EGFR was significantly inhibited by four active fractions. The molecular docking results confirmed that various components in four active fractions possessed strong binding activity to EGFR enzymes. Western blot assay revealed that four active fractions down-regulated the protein expression of EGFR and its downstream signaling pathways. It is concluded that the four active fractions of C. nitidissima can inhibit NSCLC. The mechanism may be related to EGFR and its downstream signaling pathways. This study provides a new scientific basis for the clinical treatment of NSCLC with active fractions of C. nitidissima, which is of reference significance for further research on the anti-tumor mechanism of C. nitidissima.
Apoptosis ; Camellia ; Carcinoma, Non-Small-Cell Lung/drug therapy* ; Cell Line, Tumor ; Cell Proliferation ; ErbB Receptors/genetics* ; Humans ; Lung Neoplasms/drug therapy* ; Molecular Docking Simulation