OBJECTIVETo evaluate the effect of importing triamcinolone acetonide into hypertrophic scars with skin roller needles.

METHODSThirty-two cases with burn hypertrophic scar were treated. The skin roller needles were moved back and forth on the hypertrophic scars with triamcinolone acetonide dropping on the scar surface at the same time. So the triamcinolone acetonide could be imported into the scar through needles and needle holes. The effect was evaluated as cured, effective, and no effect. The Vancouver scaring criteria and visual analogue scale was used to assess the scar color, thickness, texture and feeling before and after treatment, as well as at the untreated scar area (control).

RESULTSThirty-two cases were treated 1-3 times, including 28 cases with cured result and 4 cases with effective result. The total effective rate was 100%. The scar color, thickness, texture and feeling was significantly different between the scar before and after treatment, or between the treated and untreated scar (P < 0.05).

CONCLUSIONSImporting triamcinolone acetonide into hypertrophic scars with skin roller needles is effective. It is a new method for the treatment of large hypertrophic scar with medicine.

Burns ; complications ; Cicatrix, Hypertrophic ; drug therapy ; etiology ; Humans ; Injections, Intralesional ; instrumentation ; Needles ; Treatment Outcome ; Triamcinolone Acetonide ; administration & dosage

OBJECTIVEChronic myocardial ischemia (CMI) has become the most important cause of heart failure (HF) all over the world. The aim of the current study was to investigate the effects of Sarco-endoplasmic reticulum calcium ATPase 2a (SERCA2a) gene transfer on cardiac function and endoplasmic reticulum stress (ERS) associated myocardial apoptosis in a minipig HF animal model induced by CMI.

METHODSHF was induced in minipigs by implantation of ameroid constrictor in the initial segment of left anterior descending (LAD) branch of coronary artery. After confirmation of myocardial perfusion defects and cardiac function impairment by myocardial perfusion imaging and echocardiography, animals were divided into 4 groups (n = 4 each): HF group, HF + enhanced green fluorescent protein (EGFP) group, HF + SERCA2a group, and shamed animals as control group. A total amount of 1 × 10(12) v.g. of rAAV1-EGFP or rAAV1-SERCA2a were injected intramyocardially to each animal of HF + EGFP and HF + SERCA2a groups. Sixty days after gene transfer, protein level and activity of SERCA2a were examined, cardiac functions and changes of serum inflammatory and neuro-hormonal factors were determined. Apoptotic index of the ischemic myocardium, protein levels of ER stress marker glucose regulated protein 78 (GRP 78) and ER stress specific apoptotic marker caspase-12 were also assayed.

RESULTSAt the study end, echocardiographic and hemo dynamic measurements indicated a significant improvement of both cardiac systolic and diastolic function in HF + SERCA2a group compared with HF/HF + EGFP groups [LVEF (60.2 ± 8.6)% vs (44.2 ± 7.1)% and (46.8 ± 6.7)%, Ev/Av 1.28 ± 0.24 vs 0.77 ± 0.17 and 0.80 ± 0.21, +dp/dt(max) (2713.9 ± 434.0) mm Hg/s (1 mm Hg = 0.133 kPa) vs (1892.3 ± 434.2) mm Hg/s and (1931.2 ± 397.4) mm Hg/s, -dp/dt(max) (1422.1 ± 334.4) mm Hg/s vs (848.3 ± 308.3) mm Hg/s and (849.5 ± 278.3) mm Hg/s, P < 0.05], along with increase in both SERCA2a protein level (1.13 ± 0.26 vs 0.73 ± 0.17 and 0.64 ± 0.18, P < 0.05) and activity [(16.2 ± 5.5) IU/ml vs (7.9 ± 3.1) IU/ml and (7.5 ± 2.8) IU/ml, P < 0.05] compared with HF/HF + EGFP groups. Serum concentrations of inflammatory factor tumor necrotic factor α [(382.3 ± 114.4) ng/L vs (732.3 ± 201.4) ng/L and (689.8 ± 192.5) ng/L, P < 0.05], neural-hormonal factors brain natriuretic peptide [(142.6 ± 45.3) ng/L vs (422.3 ± 113.6) ng/L and (393.7 ± 103.3) ng/L, P < 0.01], endothelin-1 [(111.4 ± 37.5) ng/L vs (193.5 ± 54.3) ng/L and (201.0 ± 72.1) ng/L, P < 0.05] and angiotensin II [(189.7 ± 65.2) µg/L vs (538.3 ± 135.2) µg/L and (525.5 ± 144.1) µg/L, P < 0.01] were also significantly decreased in HF + SERCA2a group compared with HF/HF + EGFP groups. The apoptotic index [(12.71 ± 4.11)% vs (23.22 ± 7.23)% and (24.31 ± 6.38)%, P < 0.05], protein levels of GRP 78 (1.27 ± 0.33 vs 3.23 ± 1.14 and 4.18 ± 1.13, P < 0.05) and protein level ratios of cleaved caspase-12 to total caspase-12 [(4.62 ± 1.93)% vs (9.71 ± 2.70)% and (10.14 ± 2.81)%, P < 0.05] were also significantly reduced in the ischemic myocardium of HF + SERCA2a group compared with the HF/HF + EGFP groups.

CONCLUSIONOverexpression of SERCA2a significantly improved cardiac systolic and diastolic function in this HF model partly through attenuation of ER stress related myocardial apoptosis, suggesting its therapeutic potential for CMI related heart failure.

Animals ; Chronic Disease ; Disease Models, Animal ; Genetic Therapy ; Heart Failure ; therapy ; Myocardial Ischemia ; therapy ; Sarcoplasmic Reticulum Calcium-Transporting ATPases ; genetics ; Swine ; Swine, Miniature

AIMTo investigate the effects of human urotensin II (hUII) on in vivo pia mater microcirculation in rats.

METHODSAdult SD rats were randomly assigned to the following groups: control, sodium chloride injection (NS), UII(10(-6) mol/L), noradrenaline (NA, 10(-6) mol/L), and UII (10(-6) mol/L) + NA (10(-6) mol/L) groups. For recording of microcirculation images in pia mater, skull windows were performed and mounted on the stage of an intravital microscope equipped with a TV camera. Video images of microcirculation were stored by a video cassette recorder. Temporal changes in internal diameter and microcirculatory velocity of microvessels were measured by computer using the Image Pro software. The blood flow in cerebral tissues were measured with PIMII laser Doppler perfusion Imager (Lisca, Sweden).

RESULTSThe internal diameters of arterioles and venules in control group were (35.4 +/- 3.6) microm and (40.6 +/- 8.5) microm, respectively. In UII group, the arterioles and venules contracted immediately after treated with UII and up to the peak at 1 min, the internal diameters of arterioles and venules were (25.6 +/- 3.4) microm and (23.4 +/- 3.3) microm, respectively (P < 0.05). Both microcirculatory velocity in arterioles and venules had no significant changes in UII group (P > 0.05). The blood flow in meninges increased 1 min after treated with UII and up to high peak at 5 min (3.5 +/- 0.4 perfusion unit vs. control 2.3 +/- 0.6, P < 0.05).

CONCLUSIONhUII can contract microvessels in pia mater of rats and increase microcirculatory blood perfusion to cerebral tissue involved.

Animals ; Cerebrovascular Circulation ; drug effects ; Humans ; Male ; Microcirculation ; drug effects ; Rats ; Rats, Sprague-Dawley ; Urotensins ; pharmacology

Objective To investigate modified technique of renal transplantation model in rats.Methods Sprague-Dawley rats were selected as donors ( n=21 ) and Wistar rats as recipients ( n=42 ) .Renal allografts of both sides were harvested from the donors for renal transplantation.After resection of left kidney , end-to-end anastomosis of renal arteries between donor and recipient was performed by the assistance of home-made catheter.And end-to-end anastomosis between recipient's renal vein and donor's inferior vena cava was also performed.The donor's ureter with bladder patch was anastomosed to the recipient's bladder.Finally the right kidney was removed , cefminox (10 mg) was injected intraperitoneally , and then the abdominal cavity was closed.The operation data were recorded , including the operation time , artery and vein anastomosis time , cold and warm ischemia time and so on.Living for 3 days after operation was regarded as a success model.The success rate of modeling was calculated and the cause of death was analyzed.Results The operation time of donor was (32.7 ±5.6) min, and repair time for kidney was (4.2 ±1.1) min.The operation time of recipient was (42.3 ±42.3) min, including (10.1 ±3.2) min of the artery anastomosis time , (13.9 ±2.5) min of vein anastomosis time, (6.3 ±1.4) min of urinary tract reconstruction time.Warm ischemia time was (5.4 ± 1.8) s, and cold ischemia time was (56.2 ±7.3) min.In 42 recipient rats, 40 rats were successful modeling and the success rate was 95.2%.Two rats died.One died of artery anastomosis hemorrhage , and the other died of diffuse peritonitis caused by urine leakage.Conclusions Renal transplantation model in rats with modified vascular end-to-end anastomosis has the characters of simple handling , short operation time and high success rate.

Objective To construct a three-dimensional (3D) dynamic head-neck finite element model which ac cords with the anatomical structure,and study its dynamic responses under the extemal force.Methods By using the neck CT images of a Chinese adult male volunteer and obtaining the 3D cervical point cloud data,the finite element model of cervical spine was established using ICEM-CFD and HyperMesh software.This model,including vertebrae,intervertebral discs,facet joints,ligaments and cartilage tissues,and combining with the es tablished and verified head finite element model,was assembled as human head-neck finite element model with detailed anatomical structures.Results The model was validated by data of head-neck axial impact experiments reported in previously published literature.The simulation results showed that the neck deformation,head acceleration,head force and injury positions were preferably consistent with the experimental data.Conclusions The established 3D dynamic finite element model can be used to study head-neck dynamic responses and damage mechanism in the fields of traffic safety and impact injuries.

Objective To investigate the correlation between red cell volume distribution width (RDW) and the mortality rate of acute respiratory distress syndrome (ARDS) patients after renal transplantation. Methods Clinical data of 106 ARDS patients undergoing renal transplantation were retrospectively analyzed. According to RDW, all patients were assigned into the normal (≤15.0%, n=68) and increasing RDW groups (>15.0%, n=38). Baseline data and the incidence of adverse events were statistically compared between two groups. Kaplan-Meier survival curve was adopted to compare the 50 d-mortality rate between two groups. Cox's proportional hazards regression model was utilized to identify the risk factors of the mortality of ARDS patients. Results Among 106 patients, the 50 d-mortality rate was calculated as 43.4% (46/106). The sequential organ failure assessment (SOFA) score, serum creatinine, hemoglobin and platelet count significantly differed between two groups (all P<0.05). In the increasing RDW group, the 50 d-mortality rate and the incidence of infectious shock were significantly higher than those in the normal RDW group (both P<0.05). Kaplan-Meier survival curve demonstrated that the 50 d-mortality rate significantly differed between two groups (P<0.01). Cox's proportional hazards regression model univariate analysis revealed that hemoglobin level<100 g/L, serum creatinine>133 μmol/L, platelet count<100×109/L, severe ARDS and RDW>15.0% were the potential risk factors of the 50 d-mortality rate in ARDS patients (all P<0.05). Multivariate analysis demonstrated that severe ARDS [odd ratio (OR)=12.77, 95%confidence interval (CI) 11.63-15.39, P<0.001] and RDW>15.0% (OR=2.01, 95%CI 1.02-3.94, P<0.043) were the independent risk factors of the 50 d-mortality rate in ARDS patients. Conclusions RDW elevation is correlated with the severity of disease and 50 d-mortality rate in ARDS patients following renal transplantation. RDW can serve as a clinical parameter to predict the prognosis of ARDS patients after renal transplantation.

Objective:To summarize the clinical characteristics and the features of electroencephalograph (EEG) of children with DEPDC5 gene variants related epilepsy.Methods:The clinical data, gene variation, EEG and head magnetic resonance image (MRI) of 20 epileptic children with DEPDC5 gene variants admitted to Department of Pediatrics, Peking University First Hospital from May 2017 to November 2020 were retrospectively analyzed.Results:Twenty patients with heterozygous DEPDC5 gene variants were enrolled, 8 of 20 patients were nonsense variants, 6 were missense variants, 3 were frame-shift variants, 2 were splicing variants, and 1 was large fragment deletion. Sixteen cases had hereditary variation and 4 had de novo variation. Fifteen of variations were novel. Nine were male, while 11 were female. Their latest follow-up age ranged from 10 months to 13 years and one month.The epilepsy onset age ranged from 3 hours to 11 years and 3 months, the median age was 10.5 months. Twelve (60%) patients had developmental delay. Nineteen patients had focal seizures, 7 had epileptic spasms, 1 had multiple seizure types including tonic, atypical absence, dystonic and myoclonic seizures. Epileptic form discharges were observed in 18 patients during the interictal phase, and 11 were focal discharges, 7 were multifocal discharges. Ten (50%) patients had abnormal brain MRI, including focal cortical dysplasia in 5 patients, undefined malformation of cortical development in 4 patients, hemimegalencephaly in 1 patient. Four patients were diagnosed as West syndrome and one patient was diagnosed as Lennox-Gastaut syndrome. Fourteen (70%) patients were diagnosed as drug-resistant epilepsy. Four patients became seizure-free by treatment with anti-epileptic drugs. Three children were treated with surgery, and 2 of them became seizure-free, 1 had more than 75% reduction in seizures.Conclusions:DEPDC5 gene variant epilepsy is inherited with incomplete penetrance and focal seizure is the major seizure type. However, epileptic spasms, generalized seizures can also be observed. Half of the patients brain malformations. Most of the patients are drug-resistant epilepsy. Patients with clear epileptogenic zones can be treated with surgery. Treatment-resistant patients are more likely to be complicated with developmental delay.

AIM To establish a two reference substances for determination of multiple components(TRSDMC)method for the simultaneous content determination of neochlorogenic acid,chlorogenic acid,cryptochlorogenic acid,luteolin-7-O-glucuronide,isochlorogenic acid B,isochlorogenic acid A,isochlorogenic acid C,deoxyelephantopin,isodeoxyelephantopin,isoscabertopin and scabertopin in Elephantopus scabre L..METHODS The analysis was performed on a 35℃thermostatic Waters Symmetry C18,Phenomenex C18,Agilent ZORBAX Eclipse Plus C18 columns(4.6 mm×250 mm,5.0 μm),with the mobile phase comprising of acetonitrile and 0.1%phosphoric acid flowing at 1.0 mL/min in a gradient elution manner,and the detection wavelengths were set at 220,326 nm.Chlorogenic acid was used as an internal standard to calculate the relative correction factors of neochlorogenic acid,cryptochlorogenic acid,luteolin-7-O-glucuronide,isochlorogenic acid B,isochlorogenic acid A and isochlorogenic acid C,while isodeoxyelephantopin was used as an internal standard to calculate the relative correction factors of deoxyelephantopin,scabertopin and isoscabertopin,after which the content determination was made.Subsequently,cluster analysis,principal component analysis and orthogonal partial least squares-discriminant analysis were conducted.RESULTS Eleven constituents showed good linear relationships within their own ranges(r≥0.999 0),whose average recoveries were 95.3%-103.4%with the RSDs of 0.32%-3.45%.The result obtained by TRSDMC approximated those obtained by external standard method.Isochlorogenic acid A,isochlorogenic acid C,isochlorogenic acid B,chlorogenic acid,luteolin-7-O-glucuronide and cryptochlorogenic acid were taken as quality differential constituents.CONCLUSION This reliable and stable method can be used for the quality control of E.scabre.

Background::Pancreatic adenocarcinoma (PAAD) is an extremely lethal malignancy. Identification of the functional genes and genetic variants related to PAAD prognosis is important and challenging. Previously identified prognostic genes from several expression profile analyses were inconsistent. The regulatory genetic variants that affect PAAD prognosis were largely unknown.Methods::Firstly, a meta-analysis was performed with seven published datasets to systematically explore the candidate prognostic genes for PAAD. Next, to identify the regulatory variants for those candidate genes, expression quantitative trait loci analysis was implemented with PAAD data resources from The Cancer Genome Atlas. Then, a two-stage association study in a total of 893 PAAD patients was conducted to interrogate the regulatory variants and find the prognostic locus. Finally, a series of biochemical experiments and phenotype assays were carried out to demonstrate the biological function of variation and genes in PAAD progression process.Results::A total of 128 genes were identified associated with the PAAD prognosis in the meta-analysis. Fourteen regulatory loci in 12 of the 128 genes were discovered, among which, only rs4887783, the functional variant in the promoter of Ring Finger and WD Repeat Domain 3 ( RFWD3), presented significant association with PAAD prognosis in both stages of the population study. Dual-luciferase reporter and electrophoretic mobility shift assays demonstrated that rs4887783-G allele, which predicts the worse prognosis, enhanced the binding of transcript factor REST, thus elevating RFWD3 expression. Further phenotypic assays revealed that excess expression of RFWD3 promoted tumor cell migration without affecting their proliferation rate. RFWD3 was highly expressed in PAAD and might orchestrate the genes in the DNA repair process. Conclusions::RFWD3 and its regulatory variant are novel genetic factors for PAAD prognosis.

Curcumae Rhizoma is a Chinese medicinal herb that is contraindicated during pregnancy. Cold-congelation and blood-stasis are corresponding syndromes to Curcumae Rhizoma. Whether syndrome-based treatment is associated with developmental neurotoxicity of Curcumae Rhizoma remains to be unclear. To verify the theory of traditional Chinese medicine of "syndrome-based treatment during pregnancy", the present study induced the mice blood stasis model by immersing mice in ice water. Pregnant C57 BL/6 wild type(WT) mice and pregnant Nrf2 knock out(KO) mice were randomly divided into control groups and Rhizoma Curcumae exposure groups. The mice were exposed to Rhizoma Curcumae during day 5 to day 18 after pregnancy. The neurodevelopment was examined to evaluate the differences of developmental neurotoxicity between normal and blood-stasis pregnant mice exposed to Rhizoma Curcumae. caspase-3 and caspase-9 activity in brain of the offspring were measured by colorimetric assays. Bcl-2 mRNA and protein expression in brain of the offspring were examined by Real-time RT-PCR and Western blot, respectively. According to the findings, C57 BL/6 mice exposed to Rhizoma Curcumae(10.0 g·kg~(-1)) had a longer positive occurring time of the surface righting reflex test of offspring and higher caspase-3 and caspase-9 activities in brain of offspring, compared with the normal control group, but with no significant change in those of blood-stasis pregnant mice offspring. However, mice exposed to Rhizoma Curcumae(10.0 g·kg~(-1)) showed no change in Bcl-2 gene expression and p38 MAPK phosphorylation in brain of the offspring. Nrf2 gene knockout using CRISPR/Cas9 resulted in a longer positive occurring time of the surface righting reflex test of offspring and higher caspase-3 and caspase-9 activities in brain of offspring. In conclusion, developmental neurotoxicity of the blood-stasis pregnant mice exposed to Rhizoma Curcumae was weaker than that of the normal pregnant mice. Nrf2 activation involved in the phenomenon of Rhizoma Curcumae of "syndrome-based treatment during pregnancy", but the upstream signal pathway mechanism value shall be further investigated.
Animals ; Apoptosis ; Brain ; drug effects ; Caspases ; genetics ; Curcuma ; chemistry ; Drugs, Chinese Herbal ; pharmacology ; Female ; Maternal Exposure ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; NF-E2-Related Factor 2 ; genetics ; Pregnancy ; Proto-Oncogene Proteins c-bcl-2 ; genetics ; Random Allocation ; Rhizome ; chemistry ; Signal Transduction