AIM:To investigate the role of specific long noncoding RNA SLC25a6(lncSLC25a6)in homocys-teine(Hcy)-induced cuproptosis in cardiomyocytes.METHODS:Rat cardiomyocytes were cultured in vitro and divided into control group and Hcy group.After 48 h of intervention,the expression levels of cuproptosis-related proteins,ferre-doxin 1(FDX1)and heat shock protein 70(HSP70),were detected by Western blot and immunofluorescence staining.The oxidative stress state of cardiomyocytes was assessed using fluorescence staining,and the intracellular Cu2+levels were measured using a copper ion assay kit.Furthermore,the impact of Hcy on the expression of cuproptosis-related proteins in cardiomyocytes was analyzed following overexpression of lncSLC25a6.RESULTS:Compared with the control group,80 μmol/L Hcy significantly accelerated cardiomyocyte damage,with a notable underexpression of lncSLC25a6(P<0.05).Western blot results indicated that,compared with the control group,the expression level of FDX1 in the Hcy intervention group was significantly reduced(P<0.05),while the expression level of HSP70 was significantly elevated(P<0.05),and the expression level of copper ions in cardiomyocytes of the Hcy group was increased(P<0.05).Immunofluorescence staining showed a significant reduction in FDX1 fluorescence intensity and a significant increase in HSP70 fluorescence in-tensity in the Hcy group.Further overexpression of lncSLC25a6 significantly mitigated Hcy-induced cuproptosis in cardio-myocytes,resulting in elevated expression of FDX1 and reduced expression of HSP70(P<0.05).Pearson correlation analysis demonstrated that the expression level of lncSLC25a6 was negatively correlated with FDX1 protein expression(r=-0.676,P=0.046)and positively correlated with HSP70 expression(r=0.680,P=0.044).CONCLUSION:lnc-SLC25a6 significantly mitigates Hcy-induced cuproptosis in cardiomyocytes,positioning it as a potential therapeutic target for managing Hcy-induced cardiac injury.

Objective To identify and conduct antimicrobial susceptibility testing on Vibrio species isolated from blood culture specimens of two patients with bloodstream infection(BSI),analyze the microbiological characteristics of non-O1/non-O139 Vibrio cholerae(NOVC),and provide evidence for the diagnosis,prevention and control of Vibrio cholerae infection.Methods Two Vibrio strains were identified by matrix-assisted laser desorption/ioniza-tion time-of-flight mass spectrometry(MALDI-TOF MS),API bacterial biochemical reaction identification test strip,VITEK 2 Compact identification instrument and 16S rRNA gene sequencing.Serological typing,virulence gene molecular detection,and drug resistance phenotype detection were performed to the Vibrio strains.Results Two strains were identified as Vibrio cholerae,classified as NOVC by serological typing,and were negative for ctxAB virulence gene detection.Antimicrobial susceptibility testing showed that one strain was sensitive to ampici-llin,azi-thromycin,doxycycline and chloramphenicol,while resistant to tetracycline and trimethoprim-sulfametho-xazole.The other strain was sensitive to all tested antimicrobial agents.Conclusion BSI caused by NOVC is rarely reported in China.Accurate identification,typing and drug-resistant phenotype detection of Vibrio cholerae isolated from blood culture specimens are valuable for the diagnosis,treatment,prevention and control of Vibrio cholerae-associated infection.

Objective To study the role of ubiquitin-conjugating enzyme 9(UBC9)in the pyroptosis of homocysteine-induced macrophages mediated by small ubiquitin-like modifier(SUMO)modification.Methods First,the effects of homocysteine at different concentrations(0 μmol/L,50 μ.mol/L,100 μmol/L,150 μmol/L and 200 μmol/L)on the viability and pyrodeath of mouse macrophages(RAW264.7)were detected by CCK-8 and Western blot.Western blot was used to detect the expression levels of UBC9,SUMO-1,and the inflammatory cytokine IL-1β in different groups of cells.qRT-PCR was used to detect the mRNA expression of UBC9 before and after RNA interference and the expression of UBC9,pyrogen-related protein,and SUMO-1 after RNA interference.Results After stimulation with 100 μmol/L homocysteine,the effect of macrophage activity was minimal,and NLRP3 and Caspase-1 were the proteins with the most obvious increase in expression(P＜0.05).Compared with the Control group,the Hcy group's expression of IL-1β and SUMO-1 was increased(P＜0.01).Compared with the Control group,the Hcy group's UBC9 protein and mRNA levels were increased(P＜0.05).The expression of NLRP3,Caspase-1,IL-1β,UBC9,and SUMO-1 was decreased in the si-UBC9+Hcy group compared with the si-NC+Hcy group(P＜0.01).Conclusions Homocysteine induces pyroptosis in macrophages,and its mechanism of action is related to the up-regulation of UBC9 to induce SUMO modification.

Oral and maxillofacial space infections (OMSI) are common diseases of the facial region involving fascial spaces. Recently, OMSI shows trends of multi drug-resistance, severe symptoms, and increased mortality. OMSI treatment principles need to be updated to improve the cure rate. Based on the clinical experiences of Chinese experts and with the incorporation of international counterparts′ expertise, the principles of preoperative checklist, interpretation of examination results, empirical medication principles, surgical treatment principles, postoperative drainage principles, prevention strategies of wisdom teeth pericoronitis-related OMSI, blood glucose management, physiotherapy principles, Ludwig′s angina treatment and perioperative care were systematically summarized and an expert consensus on the diagnosis and treatment of OMSI was reached. The consensus aims to provide criteria for the diagnosis and treatment of OMSI in China so as to improve the level of OMSI treatment.

BACKGROUND: Resting heart rate (RHR) is considered as a strong predictor of total mortality and hospitalization due to heart failure in hypertension patients. Bisoprolol fumarate, a second-generation beta-adrenoreceptor blockers (β-blocker) is commonly prescribed drug to manage hypertension. The present study was to retrospectively evaluate changes in the average RHR and its association with cardiovascular outcomes in bisoprolol-treated coronary artery disease (CAD) patients from the CAD treated with bisoprolol (BISO-CAD) study who had comorbid hypertension. METHODS: We performed ad-hoc analysis for hypertension sub-group of the BISO-CAD study (n = 866), which was a phase IV, multination, multi-center, single-arm, observational study carried out from October 2011 to July 2015 across China, South Korea, and Vietnam. Multivariate regression analysis was used to identify factors associated with incidence of composite cardiac clinical outcome (CCCO), the results were presented as adjusted odds ratio (OR) along with 95% confidence interval (CI) and adjusted P value. RESULTS: A total of 681 patients (mean age: 64.77 ± 10.33 years) with hypertension from BISO-CAD study were included in the analysis. Bisoprolol improved CCCOs in CAD patients with comorbid hypertension, with RHR <65 and <70 beats/min compared with RHR ≥65 and ≥75 beats/min, respectively, in the efficacy analysis (EA) set. In addition, it lowered RHR in both intent-to-treat (ITT) and EA groups after 6, 12, and 18 months of treatment. Further, RHR 70 to 74 beats/min resulted in significantly higher risk of CCCOs EA set of patients (adjusted OR: 4.34; 95% CI: 1.19-15.89; P = 0.03). Also, events of hospitalization due to acute coronary syndrome were higher when RHR 69 to 74 beats/min compared to RHR <69 beats/min in ITT patients. CONCLUSION Bisoprolol can effectively reduce RHR in Asian CAD patients with comorbid hypertension and hence, improve CCCO without affecting their blood pressure.

ABSTRACT OBJECTIVE：To study pharmacokinetic characteristics of single dose and multiple dose administration of Gefitinib emulsion in rats. METHODS：The rats were divided into single administration group and multiple administration group. Single administration group was subdivided into Gefitinib raw medicine group（50 mg/kg，i.g.）and Gefitinib emulsion group（50 mg/kg，i.g.），with 6 rats in each group，gavage once. Multiple administration group were subdivided into Gefitinib raw medicine group （50 mg/kg）and Gefitinib emulsion group（50 mg/kg），with 8 rats in each group；they were given relevant medicine intragastricaly for consecutive 7d，once a day. 0.3 mL blood of rats in Gefitinib raw medicine group was taken before medication and 1，2，2.5， 3，3.5，3.75，4，4.25，4.5，6，8，12 and 24 h after medication；0.3 mL blood of rats in Gefitinib emulsion group was taken before medication and 2，4，6，8，9，10，11，12，13，14，16，24，36 and 48 h after administration（Multiple administration group is after 7 d of administration）. HPLC method was used to determine the plasma concentration of gefitinib in rat，and plasma concentration-time curves were drawn. Pharmacokinetic parameters were fitted by using DAS 2.0 software. RESULTS：After single administration，compared with the tmax（[ 2.67±0.75）h]，MRT0-24 h （[ 8.68±0.91）h]，MRT0- ∞ （[ 14.20±3.45）h] of Gefitinib raw medicine group，tmax （[ 8.33±4.41）h]，MRT0-48 h （[ 15.00±1.60）h]，MRT0-∞ （[ 17.60±2.66）h] of Gefitinib emulsion group were increased significantly（P＜0.05）. After multiple administration，compared with the tmax （[ 6.79±3.75）h]，AUC0-48 h （[ 41.10±8.92） mg·h/L]，Vz/F [（16.30±5.45）L/kg]，CLz/F [（0.94±0.19） L/（h·kg）]，MRT0-48 h （[ 10.10 ± 0.36） h] of Gefitinib raw medicine group，Vz/F [（44.20±30.3）L/kg]，CLz/F[（1.89± 1.56） L/（h·kg）]，MRT0-48 h （[ 16.20 ± 2.52） h] of Gefitinib emulsion group were increased significantly （P＜0.05） AUC0-48 h （[ 38.70±26.20）mg·h/L] was decreased significantly （P＜0.05），and tmax （[ 10.40±3.25）h] was increased，without statistical significance. CONCLUSIONS： Compared with Gefitinib raw medicine，single and multiple administration of Gefitinib emulsion can effectively prolong the peak time，the results of this study can provide reference for new delivery system study of Gefitinib.

Bone tissue engineering (BTE) is a rapidly developing strategy for repairing critical-sized bone defects to address the unmet need for bone augmentation and skeletal repair. Effective therapies for bone regeneration primarily require the coordinated combination of innovative scaffolds, seed cells, and biological factors. However, current techniques in bone tissue engineering have not yet reached valid translation into clinical applications because of several limitations, such as weaker osteogenic differentiation, inadequate vascularization of scaffolds, and inefficient growth factor delivery. Therefore, further standardized protocols and innovative measures are required to overcome these shortcomings and facilitate the clinical application of these techniques to enhance bone regeneration. Given the deficiency of comprehensive studies in the development in BTE, our review systematically introduces the new types of biomimetic and bifunctional scaffolds. We describe the cell sources, biology of seed cells, growth factors, vascular development, and the interactions of relevant molecules. Furthermore, we discuss the challenges and perspectives that may propel the direction of future clinical delivery in bone regeneration.
Animals ; Bone Regeneration ; Cell Differentiation ; Humans ; Intercellular Signaling Peptides and Proteins ; metabolism ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stem Cells ; cytology ; Osteogenesis ; Tissue Engineering ; methods ; Tissue Scaffolds

Objective To explore the clinical characteristics and treatment of a family with inherited generalized epilepsy with febrile seizures plus (GEFS+) caused by STX1B gene mutation and to review the literature.Methods Clinical data of a child with GEFS+ and his family members who visited Guangzhou Women and Children Medical Center in August 2017 were collected.DNA samples of the proband and his parents,his grandparents were analyzed by the next-generation sequencing and confirmed by Sanger sequencing.A literature search with "STX1B " as the key word was conducted at PubMed,China National Knowledge Infrastructure and Wanfang databases to include recently published studies (up to May 2018).Results The proband was a 2-year-old boy who was admitted to our hospital because of frequent epileptic seizures in a month,with focal seizures evolving into the generalized bilateral tonic-clonic epileptic attacks after febrile seizure.His seizures were well controlled by levetiracetam.His father presented febrile seizure in early childhood stage and epilepsy in adult stage,which were under control with lamotrigine.The proband's grandmother had a history of febrile seizure.Other family members had no history of convulsion.Ictal electroencephalogram showed low voltage fast activities (8-10 Hz) originating from the central region of the brain.Heterozygous mutation of STX1B gene (c.705C＞G,p.Asn235Lys) was detected in the proband,his father and grandmother.The mutation has not been reported previously.Furthermore,no other family members carried the mutation at c.705 locus of STX1B gene.No article in Chinese was found,and 4 articles in a language other than Chinese provided the complete case data of 9 mutation loci in 33 patients (4 families and 4 sporadic cases).With this research data (3 cases in 1 family) included,there were 36 cases and 10 mutation sites in STX1B gene.Of these mutations,there were 5 missense mutations,3 nonsense mutations,1 insert mutation and 1 deletion mutation;and according to the mutation distribution,there were 4 mutation sites in exon 3,2 in exon 8,2 in exon 9,and 1 in exon 1.There was incomplete penetrance in the family,so different types of epileptic attacks occurred among different family members.Conclusions In this study,a de novo mutation of STX1B gene in a family with GEFS+ was defined,which would expand the gene mutation spectrum and provide basis for family genetic counseling.Clinical heterogeneity was found in this family.Seizures caused by STX 1B gene mutation were sensitive to antiepileptic drugs.

OBJECTIVE To explore the effect of BoFa for neuropathic pain in rats from the perspective of inflammatory reaction.METHODS The CCI model rats were intervened qualitatively and quantitatively by the massage simulation instrument.Observe the variation of rats' behavior though solar-thermal pain threshold resistance.Observe the variation of IL-6 and SOCS3 in spinal cord in rats through Immunohistochemical technique.RESULTS After seven days of surgery,the results of solar-thermal pain threshold resistance of the model group were significance changed than that of normal group(P<0.01),the results of IL-6 and SOCS3 in spinal cord in rats were significantly increased than that of normal group(P<0.01).After twenty times of BoFa therapy,the results of solar-thermal pain threshold resistance of the BoFa group were significance changed than that of model group(P<0.05),and near normal group level;the results of IL-6 in spinal cord in rats were significantly reduce than that of model group(P<0.01);the results of SOCS3 in spinal cord in rats were significantly increased than that of model group(P<0.01).CONCLUSION BoFa can improve the pain sense and temperature sense of CCI rats in a certain extent,and it also can inhibit the expression of pro-inflammatory factors in rats.

BACKGROUNDHypotension induced by combined spinal epidural anesthesia in parturient with hypertensive disorders of pregnancy (HDP) can easily compromise blood supply to vital organs including uteroplacental perfusion and result in fetal distress. The aim of this study was to investigate whether the goal-directed fluid therapy (GDFT) with LiDCO rapid system can improve well-being of both HDP parturient and their babies.

METHODSFifty-two stable HDP parturient scheduled for elective cesarean delivery were recruited. After loading with 10 ml/kg lactated Ringer's solution (LR), parturient were randomized to the GDFT and control group. In the GDFT group, individualized fluid therapy was guided by increase in stroke volume (ΔSV) provided via LiDCO rapid system. The control group received the routine fluid therapy. The primary endpoints included maternal hypotension and the doses of vasopressors administered prior to fetal delivery. The secondary endpoints included umbilical blood gas abnormalities and neonatal adverse events.

RESULTSThe severity of HDP was similar between two groups. The total LR infusion (P < 0.01) and urine output (P < 0.05) were higher in the GDFT group than in the control group. Following twice fluid challenge tests, the systolic blood pressure, mean blood pressure, cardiac output and SV in the GDFT group were significantly higher, and the heart rate was lower than in the control group. The incidence of maternal hypotension and doses of phenylephrine used prior to fetal delivery were significantly higher in the control group than in the GDFT group (P < 0.01). There were no differences in the Apgar scores between two groups. In the control group, the mean values of pH in umbilical artery/vein were remarkably decreased (P < 0.05), and the incidences of neonatal hypercapnia and hypoxemia were statistically increased (P < 0.05) than in the GDFT group.

CONCLUSIONSDynamic responsiveness guided fluid therapy with the LiDCO rapid system may provide potential benefits to stable HDP parturient and their babies.

Adult ; Anesthesia, Epidural ; methods ; Anesthesia, Spinal ; methods ; Blood Pressure ; Cesarean Section ; methods ; Female ; Fluid Therapy ; methods ; Humans ; Hypertension, Pregnancy-Induced ; Infant, Newborn ; Isotonic Solutions ; Pregnancy ; Pregnancy Outcome