Objective:To study the expression of MMP1 and TIMP1 in simple and radiation-combined wound healing and their effects on the healing process and tissue remodeling. Methods: A rat model of radiation-combined wound healing was used. Immunohistochemistry and in situ hybridization were performed which enabled the detection of MMP1 and TIMP1 expression in the healing process. Ultrastructural changes were observed with transmission EM. Results: The wound healing process was impaired and delayed. In rats receiving 25 Gy of gamma ray locally the irradiated wounds healed 6 days later than non-irradiated controls. The following changes in MMP1 and TIMP1 expression were found: (1) In the early inflammatory phase and in the period of granulation tissue formation, MMP1 expression in the newly-formed epidermis of irradiated wounds approximated that in the controls. Later, the epidermal expression of MMP1 in radiation wounds was comparatively increased with the delay of the healing process.On days 3 to 14 after wounding, TIMP1 was weakly positive in the proliferating keratinocytes of control wounds and became negative after epidermal covering, whereas no or only slight epidermal expression was detected in radiation wounds before epidermal covering.(2)MMP1 and TIMP　1 expression in radiation wounds was markedlydecreased in fibroblasts　, endotheliocytes and macrophages as compared with the controls. The expression phase was prolonged due to the delay of the healing process.Conclusions:The reduced expression of MMP1 and TIMP1 in granulation tissue retards such important processes as cell migration, angiogenesis and tissue remodeling, thus retarding the healing process. The expression of MMP1 in the newly-formed epidermis may help the process of reepithelialization,but in the late healing period, overexpression of MMP1 and decreased expression of TIMP1 in the epidermis may hinder the establishment of basal membrane and the formation of granulation tissue, and thus affect the matrix remodeling process.

Objective To investigate the effect of autophagy on the apoptosis of H 9C2 cardiomyocytes.Methods H9C2 cardiomyocytes were incubated with different concentrations of high glucose and high lipids ( HGHL ) for different time.The surface area of cardiomyocytes was measured after HE staining .The cell viability and apoptotic rate were measured by flow cytometry.Western blot was used to detect the expression levels of LC3Ⅱ, p62, Beclin-1,LAMP2 and cleaved caspase-3.Results After treatment with HGHL, the cells appeared hypertrophy in a concentration-and time-dependent manner , the cell hypertrophy was most obvious under the condition of HGHL(500 μmol/L,36 h)(P<0.001).Cell apoptosis increased in a concentration-and time-dependent manner, the apoptotic rate was nearly 50%under the condition of HGHL ( 500 μmol/L,36 h) ( P<0.001 ) .After treatment with HGHL for 24 h, compared with the control group , the expression of LC3Ⅱ was very significantly increased ( P<0.01) , the expression of Beclin-1 and LAMP 2 were significantly decreased ( P<0.05) , but the expression of p 62 was significantly increased ( P<0.01 ) .Compared with the control group and the intervention group , the expression of cleaved caspase-3 was significantly increased ( P<0.01 ) after 1 h of chloroquine pretreatment .Conclusions HGHL induced H9C2 cardiomyocytes hypertrophy promote H 9C2 cardiomyocytes apoptosis in a concentration-and time-dependent manner .HGHL may inhibit autophagy formation and degradation of H 9C2 cardiomyocytes at the same time , leading to abnormal autophagy accumulation of cardiomyocytes , and promote apoptosis , suggesting that inhibition of autophagy may be an important cause for promote apoptosis .

Objective:To investigate the clinical and electroencephalogram (EEG) characteristics of pattern-sensitive epilepsy (PSE).Methods:This retrospective case summary study enrolled 4 pediatric patients with PSE treated at the Peking University People′s Hospital from January 2015 to September 2023.The clinical data, EEG findings, treatments, and prognosis were retrospectively analyzed.Results:Among the 4 patients, 3 were female, and 2 had developmental delays before the onset of the disease.Spontaneous seizures occurred in 3 cases, including spasticity and tonic seizures in case 1, atypical absence seizures, myoclonic seizures, and general tonic-clonic seizures in case 3, and eyelid myoclonic seizures in case 4.All 4 cases exhibited pattern-induced reflex seizures, and pattern-induced seizures with photosensitivity were monitored by EEG in 3 cases.Of the 3 cases, 1 had myoclonic seizures, 1 had eyelid myoclonic seizures, and 1 had both myoclonic seizures and focal to bilateral tonic-clonic seizures.Two out of the 4 patients were diagnosed with epilepsy syndromes: Lennox-Gastaut syndrome and epilepsy with eyelid myoclonia.All 4 patients had interictal discharges, including 2 cases of generalized discharges, 1 case of multifocal discharges combined with generalized discharges, and 1 case of anterior head discharges.Three cases underwent the detection of whole exon gene and copy number variation, and 1 case showed a novel heterozygous mutation c. 73T>C(p.W25R) in the MBD5 gene on chromosome 2.Three patients were treated with antiseizure medication (ASM), while 1 did not receive ASM treatment because the seizures were all induced.However, none of the 4 had seizures under control after 5 to 10 years of follow-up. Conclusions:PSE is more common in female children and may co-occur with developmental delays and intellectual disabilities.In PSE children, the EEG shows mostly generalized discharges, spontaneous seizures, induced seizures, and predominantly generalized seizures coexist.Reflex seizures in PSE patients are more difficult to control with ASM treatment.

OBJECTIVE To observe the inhibitory effects of Liuwei Dihuang Pills(LWDHP) on macrophages activation in CCl4-induced liver fibrosis in mice.METHODS C57BL/6 mice were induced liver fibrosis by CCl4 exposure and administered with LWDHP for 6 weeks simultaneously.Liver tissue was investigated by HE and Sirius red staining.α-SMA was analyzed by immunofluorescence,qPCR and Western blot.Liver macrophages were observed by immunohistochemistry of CD68.The pro-inflammatory cytokines and chemokine such as TNF-α,IL-1β,CXCR3 and MCP1 were detected by qPCR or Western blot analysis.RESULTS After 6 weeks of CCl4 administration,the expression ofα-SMA significantly increased,and LWDHP po-tently inhibited the α-SMA expression.Immunohistochemistry showed that the expression of CD68 was very weak in normal group,CD68 was distributed mainly between fibrotic septa with strong positive expression in CCl4 model group;Real-time quantitative PCR showed that TNF-α,IL-1β,MCP1 and CXCR3 expression significantly increased in model group compared with normal group.Compared with the model group,LWDHP significantly reduced the expression of CD68,inflammatory fac-tors and chemotactic factors.CONCLUSION LWDHP shows a potent inhibition of macrophage activation in CCl4-induced liv-er fibrosis.

OBJECTIVETo investigate the changes in the activity of Escherichia coli asparaginase (L-asp) and the concentration of asparagines (ASN) in the plasma of the acute lymphoblastic leukemia (ALL) children receiving L-asp containing chemotherapeutic protocol to explore more reasonable usage of L-asp in the treatment of childhood ALL.

METHODSL-asp containing hemotherapy regimen of VDLP was used, in which L-asp (10,000 U/m(2)) was administered intravenously every other day for 10 doses in 15 children with ALL. A total of 340 peripheral blood samples were collected at scheduled time points during the therapy and plasma L-asp activity (by spectrophotometric assay) and asparagines concentration (by RP-HPLC) were measured.

RESULTSDuring the administration of L-asp, the plasma L-asp activity was increasing gradually peaked after eight doses and then decreased gradually, while the plasma concentration of asparagines maintained in complete or nearly complete depletion status. After the therapy courses finished, a plasma L-asp activity above 100 U/L with asparagines almost complete depletion status was lasting for about seven days.

CONCLUSIONThe current L-asp containing chemotherapeutic protocols in which L-asp was administered in a dose of 10 000/m(2) intravenously every other day, are efficient enough for the depletion of plasma ASN.

Adolescent ; Antineoplastic Combined Chemotherapy Protocols ; blood ; pharmacokinetics ; therapeutic use ; Asparaginase ; administration & dosage ; blood ; pharmacokinetics ; Asparagine ; blood ; Child ; Child, Preschool ; Drug Administration Schedule ; Female ; Humans ; Infusions, Intravenous ; Male ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; blood ; drug therapy ; Treatment Outcome

OBJECTIVETo investigate the effects of intensive insulin therapy on plasma nitric oxide (NO) and endothelin-1 (ET-1) levels in patients undergoing cardiac valve replacement under cardiopulmonary bypass (CPB).

METHODSA total of 36 patients were randomly assigned to routine therapy (RT) group and intensive insulin therapy (IT) group, with 18 patients in each group. The blood glucose levels during surgery were maintained at 3.9 to 10.0 mmol/L and those after surgery at 3.9 to 6.1 mmol/L in IT group, whereas patients in RT group didn't undergo the treatment of controlling glucose levels during operation and maintained below 13.9 mmoVL after operation. Levels of plasma NO and ET-1 in both groups were respectively measured before surgical anesthesia, at the initiation of CPB, and 0 h, 4 h, 12 h, 24 h and 48 h after the termination of CPB.

RESULTSIn RT group, plasma NO concentration was decreased since the initiation of CPB [from (68.2 +/- 16.3) micromol/L to (67.8 +/- 8.4) micromol/L] and reached the trough at the termination of CPB [ (60.0 +/- 10.2) micromol/L, P < 0.05 compared with that before anesthesia]. Then it began to increase and neared to the preoperational level 48 h after the termination of CPB. In contrast, plasma ET-1 concentration was increased since the initiation of CPB [from (62.2 +/- 10.2) ng/L to (68.3 +/- 10.8) ng/L] and reached the peak at the termination of CPB [ (112.5 +/- 18.6) ng/L, P < 0.01 compared with that before anesthesia]. Then it began to decrease and reached the preoperational level 24 h after the termination of CPB. In IT group, however, the changes of NO and ET-1 levels at different time points during CPB and thereafter didn't reach the significance as compared with those before anesthesia.

CONCLUSIONSIntensive insulin therapy may relieve the changes of CPB-induced NO and ET-1 levels during cardiovascular surgery, which suggests its protective effects on cardiovascular function.

Adult ; Cardiopulmonary Bypass ; adverse effects ; Endothelin-1 ; blood ; Female ; Humans ; Hyperglycemia ; drug therapy ; etiology ; Hypoglycemic Agents ; therapeutic use ; Insulin ; therapeutic use ; Insulin Infusion Systems ; Male ; Middle Aged ; Nitric Oxide ; blood

AIM:To investigate the effect of urantide on the liver function and histomorphology in the rats with atherosclerosis (AS).METHODS:The AS Wistar rat model was induced by intraperitoneal injection of vitamin D3 (VD3) and feeding with high-fat diet.The rats were randomly divided into normal control group, AS model group, positive medicine group and urantide group.The liver function indexes of the rats were measured by biochemical test, and the pathological changes of the aorta and liver of the rats were observed by hematoxylin-eosin (HE) staining.The mRNA expression of urotensinⅡ (UII) and GPR14 at mRNA and protein levels in rat livers was determined by RT-qPCR and Western blot.RESULTS:The levels of alanine aminotransferase (ALT) , aspartate aminotransferase (AST) , γ-glutamyltransferase (γ-GT) , lactate dehydrogenase (LDH) , total bilirubin (TBIL) , indirect bilirubin (IBIL) and alkaline phosphatase (ALP) in AS model group were significantly increased compared with normal control group (P<0.05).The above indexes in urantide group were remarkably decreased compared with AS model group (P<0.05).No change of the levels of direct bilirubin (DBIL) , total protein (TP) , globulin (GLB) and albumin (ALB) in each group was observed.Urantide postponed hepatocyte fatty degeneration and repaired hepatocyte injury in the AS rats.Compared with normal control group, the mRNA and protein levels of UII and GPR14 in the liver were significantly increased in AS model group (P<0.05).With the prolongation of dosing time, the mRNA and protein levels of UII and GPR14 in the liver were significantly decreased in urantide group compared with AS model group (P<0.05).CONCLUSION:Urantide significantly attenuates the liver damage caused by liver fatty degeneration in AS rats.

Objective To investigate the distribution of gene polymorphism of CYP450 2C9 and VKORC1-1639A/G in the Chinese population as well as the difference of genetic polymorphism between Chinese Han population and other ethnic populations.Contribution of CYP2C9 and VKORC1 genotype to the maintenance doses on warfarin was also studied.Methods The genotype and allele frequencies were calculated and compared with those in other populations.One hundred and one patients with stable anticoagulation with warfarin under a target international normalized ratio(INR)of 2.0 to 3.0 were enrolled for studying the relationship between the CYP2C9 and VKORC1 gene polymorphism and the warfarin maintaining dosage.Results CYP450 2C9~*3 + 1075C/A allele frequencies were:AA in 449 cases(92.2%),AC in 36 cases(7.4%)and CC in 2 cases(0.4%),respectively.VKORC1-1639A/G allele frequencies were AA in 415 cases(85.2%),GA in 72 cases(14.8%),but GG in no case(0.0%),respectively.When linear stepwise regression analysis was used to identify factors contributing to warfarin stable dose,the final equation was:ln(D)=0.346 + 0.017(weight)-0.376(CYP450 2C9~*3 + 1075C/A)+ 0.148(VKORC1-1639A/G)-0.002(age)(r=0.827,P=0.02).Conclusion There existed significant gene polymorphism CYP450 2C9~*3 + 1075C/A and VKORC1-1639A/G in the Chinese Han population.Both Gene polymorphisms of CYP450 2C9*3 + 1075C/A and VKORC1-1639A/G were significantly affecting the maintaining dose of warfarin in the Chinese population.

Background: The accessory tendon of the extensor hallucis longus (ATEHL) muscle is a common abnormal structure, and its clinical significance remains debatable. In this study, we provide the incidence of the ATEHL and characterize its morphological types in Asian cadavers and investigate its clinical applications. Methods: The tendons from 50 adult cadaveric feet, fixed in 10% formalin, were analyzed. We measured the length and width of both the ATEHL and the extensor hallucis brevis (EHB). Results: All dissected specimens had an ATEHL. The first metatarsophalangeal joint was surrounded by an accessory tendon that inserted onto the joint capsule and the dorsal base of the proximal phalanx. We classified the ATEHL into 3 types based on their directions. Differences in ATEHL type based on sex were not statistically significant. Conclusions We found an ATEHL in all cadaveric specimens in this study. We surmise that the ATEHL acts as an antagonist with the EHB when the toe is extending, which might help prevent the occurrence of hallux valgus deformity.

Background: The accessory tendon of the extensor hallucis longus (ATEHL) muscle is a common abnormal structure, and its clinical significance remains debatable. In this study, we provide the incidence of the ATEHL and characterize its morphological types in Asian cadavers and investigate its clinical applications. Methods: The tendons from 50 adult cadaveric feet, fixed in 10% formalin, were analyzed. We measured the length and width of both the ATEHL and the extensor hallucis brevis (EHB). Results: All dissected specimens had an ATEHL. The first metatarsophalangeal joint was surrounded by an accessory tendon that inserted onto the joint capsule and the dorsal base of the proximal phalanx. We classified the ATEHL into 3 types based on their directions. Differences in ATEHL type based on sex were not statistically significant. Conclusions We found an ATEHL in all cadaveric specimens in this study. We surmise that the ATEHL acts as an antagonist with the EHB when the toe is extending, which might help prevent the occurrence of hallux valgus deformity.