Animals ; Antibodies, Monoclonal ; pharmacokinetics ; Iodine Radioisotopes ; pharmacokinetics ; Leukocyte Common Antigens ; immunology ; Male ; Mice ; Radiation Monitoring ; methods ; Rats ; Tissue Distribution

OBJECTIVETo study relationship between daunorubicin (DNR) pharmacokinetics and efficacy and toxicity in children with acute leukemia.

METHODS(1) The concentration of DNR in plasma of children with acute leukemia was determined by high performance liquid chromatography (HPLC)-fluorescence detection method. Plasma was sampled frequently from the start of the infusion till the end of 24 h. DNR pharmacokinetics was studied by determination of the concentrations. (2) Efficacy and toxicity were monitored in each period after chemotherapy. Laboratory studies included examination of bone marrow, white blood cell count, electrocardiogram, echocardiogram, myocardial enzymogram, the liver and kidney function.

RESULTS(1) DNR was eliminated from plasma in a two-compartment manner. The maximum concentration was seen 1 - 3 h after infusion. Cmax was 63.50 microg/L. Tmax was 1.45 h. The concentration decreased quickly to a low level of about 11.52 microg/L from the end of 2 hours infusion. There was a large inter-individual difference in pharmacokinetic parameters of DNR. The difference of CL was 9-fold, AUC was 8-fold, Cmax was 5-fold. (2) CL of male patients [57.99 L/(h.m(2))] was significantly lower than that of female patients [93.71 L/(h.m(2))] (P < 0.05). Tmax of children older than 6 years was 1.1 h, and that of children younger than 6 years was 1.8 h (P < 0.05); Cmax of children older than 6 years was 90.77 microg/L, younger than 6 years was 57.44 microg/L (P < 0.05).

CONCLUSION(1) There is a large inter-individual difference in pharmacokinetic parameters of DNR in children. It may predict individual variety of efficacy and toxicity. Therapeutic drug monitoring is important. (2) Male patients and children older than 6 years had a higher bioavailability and lower metabolism, toxicity may easily occur in such children, therefore they may need lower dose.

Antibiotics, Antineoplastic ; adverse effects ; pharmacokinetics ; therapeutic use ; Child ; Child, Preschool ; Chromatography, High Pressure Liquid ; Daunorubicin ; adverse effects ; pharmacokinetics ; therapeutic use ; Drug Monitoring ; Female ; Humans ; Infant ; Leukemia ; drug therapy ; metabolism ; Male

Objective To evaluate the advantages and short term clinical results of arthroscopic release with radiofrequeney vaporization for knee joint stiffness.Methods Arthroscopic release with ra- diofrequency vaporization was done in 32 cases with knee joint stiffness resulted from various causes be- tween January 2002 and June 2005.According to degree of stiffness,32 cases were divided into three groups,ie,Group A(18 cases with suprapatellar bursa adhesions)treated with confectioning at suprapa- tellar bursa and lateral grooves;Group B(eight cases with joint compartment adhesions)managed with debridement at suprapatellar bursa and lateral groove and intereondyloid fossa,bending the knee with pressure and abscising the adhesion part in the joint compartment with radiofrequency vaporization;and Group C(six cases with most part of the joint adhered)treated by making small incision at the lateral or medial upper pole of the patellar as well as a space at the suprapatellar bursa by blunt dissection when it was difficult to insert arthroscope.After that,release combined with massage manipulation and thorough hemostasis by radiofrequency vaporization were carried out.There was no drainage after operation.Pas- sive and active flexion and extension exercises with pressure began two days after operation.Results Pre-operative limitation of flexion was 35?-75?that was increased to 115?-125?three weeks after opera- tion,with mean improvement of 78?in Group A.Pre-operative limitation of flexion was 40?-60?that was increased to 95?-120?three weeks after operation,with mean improvement of 72?in Group B.Pre-opera- tive limitation of flexion was 25?-45?that was increased to 90?-110?three weeks after operation,with mean improvement of 64?in Group C.No haematocele occurred postoperatively,with only slight swelling of the knee.Conclusion Arthroscopic release with radiofrequency vaporization for knee joint stiffness is characterized by less bleeding,minor trauma and reliable release and can be applicable especially for the eases with only adhesion at suprapatellar bursa,lateral groove or joint compartment.

OBJECTIVETo investigate the expression and clinical significance of EphA7 protein in primary hepatocellular carcinoma.

METHODSImmunohistochemistry and Western blot were used to detect the expression of EphA7 protein in 40 cases of primary hepatocellular carcinoma, their corresponding adjacent liver tissues and 10 cases of normal liver tissues. The relations with its clinical pathological parameters were analyzed too.

RESULTSExpression of EphA7 protein was mainly located in the cytoplasm and the blood vessels of the septa, which was found in hepatocellular carcinoma tissues, their corresponding adjacent liver tissues and normal liver tissues. Western blot analysis showed that the expression level of EphA7 protein in hepatocellular carcinoma (0.58 +/- 0.26) was greater than that in corresponding adjacent liver tissues (0.40 +/- 0.22, P < 0.05) and normal liver tissues (0.32 +/- 0.16, P < 0.05). But it had no significant difference between corresponding adjacent liver tissues and normal liver tissues (P > 0.05). EphA7 protein expression was correlated with histological differentiation, tumor thrombi in portal vein, lymph node metastasis and high AFP level (P < 0.05).

CONCLUSIONSEphA7 protein expression is significantly correlated with the biological behavior of primary hepatocellular carcinoma. The high expression of EphA7 protein may play an important role in the malignancy transformation, invasion progression and metastasis of primary hepatocellular carcinoma.

Carcinoma, Hepatocellular ; metabolism ; pathology ; Humans ; Liver Neoplasms ; metabolism ; pathology ; Receptor, EphA7 ; metabolism

Objective:To analyze the research hot topics, knowledge evolution context, potential frontier trends and future breakthrough directions in the field of medical security governance in China.Methods:Subject term retrieval was used to study the literatures related to medical security governance published by CNKI from January 2009 to December 2021. CiteSpace V software was used to draw the keyword co-occurrence network, time zone map, cluster map, and emergent word graph, and to visually analyze and predict the frontier hotspots and evolution trends in the field of medical security governance.Results:A total of 793 literatures were retrieved. The cooperation network among medical security governance research institutions in China needed to be strengthened; the mainstream of research focused on basic research on medical insurance system design, research on medical security governance paths and methods, and empirical research combined with the era background or policy hotspots.Conclusions:There are some problems in the current rerearch on medical security governance, such as imperfect theoretical construction, research content to be expanded, insufficient communication and cooperation, etc. Future research hotspots tend to be innovation of the goal, structure and path of medical security governance, application of big data in the field of medical security governance, and research on crisis response and challenges of medical security governance under public health emergencies. Future research should strengthen multi-cooperation to jointly tackle key problems, pay attention to the cross-integration of disciplines, develop localized medical security governance innovation systems and mechanisms, and enrich problem-oriented empirical research.

Background and Objective:A single nucleotide polymorphism of the tumor necrosis factor β(TNFβ)gene affected the level of tumor necrosis factor α and was associated with prognosis of acute respiratory distress syndrome(ARDS).This study was to investigate the association between the TNFβ and ARDS after operation for esophageal carcinoma.Methods:Thinyfour patients with and 116 patients without ARDS after radicaI resection for thoracotomic esophageal carcinoma were recruited in the Fourth Hospital of Hebei Medical University from January 2005 to June 2007.Peripheral blood samples were collected and DNA extracted.TNFβ genotype was determined by restriction fragment length polymorphism(RPLF).Results:There was no significant difference between the two groups in the TNFβ genotype and allele frequency (P>0.05).The time of mechanicaI ventilation was shorter and that of staying in the intesive care unit was longer for ARDS patients with the 1/2 genotype in the TNFβ than for those with other genotypes ( both P< 0.05).The frequency of the 1/1 genotype and 1 allele in the TNFβ was significantly higher in the group of surviving patients with ARDS than in the group of death patients.The odd ratios for mortality of two groups were 16.5 and 11.2, respectively. Conclusions: TNFβ did not appear to be a contributing factor influencing the morbidity of the patients with ARDS after operation for esophageal carcinoma,however, it might affect the development and prognosis of ARDS.

AIM:To explore the therapeutic effect of a novel Rho kinase inhibitor FSD-C10 onβ-amyloid pro-tein precursor (APP)/presenilin-1 (PS1) double transgenic mice.METHODS: The transgenic mice overexpressing hu-man APP with the Swedish mutation (695) and human PS1 with ΔE9 mutation at the age of 8 months were used in this study.The mice were randomly divided into model group and FSD-C10 intervention group, and wild-type mice at the same age served as normal controls .The mice in FSD-C10 intervention group were treated with FSD-C10 (25 mg· kg-1 · d-1 ) for 2 months by intraperitoneal injection .The mice in model group and the wild-type mice were injected with saline in the similar manner.Morris water maze (MWM) test was applied to examine the capacity of learning and memory .The Aβ1-42 deposition, Tau protein phosphorylation , and the expression of β-site APP-cleaving enzyme ( BACE) as well as inflammato-ry molecules, such as TLR-4 and NF-Κb, and M1/M2 microglial markers, such as Inos and Arg-1, were determined by the methods of immunohistochemistry and Western blot .RESULTS: Compared with model group , FSD-C10 significantly improved the learning and memory abilities of APP/PS1 double transgenic mice , accompanied by reduced Aβ1-42 deposi-tion, Tau protein phosphorylation and BACE expression in the hippocampus .The intervention of FSD-C10 decreased the protein levels of TLR-4 and p-NF-Κb, reduced the expression of Inos and increased the expression of Arg-1 in the brain tissues.CONCLUSION:The novel Rho kinase inhibitor FSD-C10 improves the capacity of spatial learning and memory in APP/PS1 double transgenic mice , which may be related to the inhibition of TLRs/NF-Κb signaling pathway , the reduction of the secretion of inflammatory molecules and the polarization of anti-inflammatory M2 microglia, thus improving the in-flammatory microenvironment of the brain in APP/PS1 double transgenic mice .

Uveal melanoma(UM)is the most frequent and life-threatening ocular malignancy in adults.Aberrant histone methylation contributes to the abnormal transcriptome during oncogenesis.However,a comprehensive understanding of histone methylation patterns and their therapeutic potential in UM remains enigmatic.Herein,using a systematic epi-drug screening and a high-throughput transcriptome profiling of histone methylation modifiers,we observed that disruptor of telomeric silencing-1-like(DOT1L),a methyltransferase of histone H3 lysine 79(H3K79),was activated in UM,especially in the high-risk group.Concordantly,a systematic epi-drug library screening revealed that DOT1 L inhibitors exhibited salient tumor-selective inhibitory effects on UM cells,both in vitro and in vivo.Combining Cleavage Under Targets and Tagmentation(CUT&Tag),RNA sequencing(RNA-seq),and bioinformatics analysis,we identified that DOT1 L facilitated H3K79 methylation of nicotinate phosphoribosyltransferase(NAPRT)and epigenetically activated its expression.Importantly,NAPRT served as an oncogenic accel-erator by enhancing nicotinamide adenine dinucleotide(NAD+)synthesis.Therapeutically,DOT1L inhi-bition epigenetically silenced NAPRT expression through the diminishment of dimethylation of H3K79(H3K79me2)in the NAPRT promoter,thereby inhibiting the malignant behaviors of UM.Conclusively,our findings delineated an integrated picture of the histone methylation landscape in UM and unveiled a novel DOT1L/NAPRT oncogenic mechanism that bridges transcriptional addiction and metabolic reprogramming.

OBJECTIVETo explore an appropriate measure to repair tissue defects and deformities in mandibulo-cervical region.

METHODSEighteen cases with severe tissue defects and deformity in jaw and neck were repaired with thoracic skin flap with multiple blood supply system in our unit from Jan. 2006 to Nov. 2008. Anterior cutaneous branch of transverse cervical artery, intercostal branch of internal thoracic artery and lateral thoracic artery were included in the pedicles.

RESULTSAll skin flaps survived, except in one patient in whom a small belb appeared at the distal end of the island flap with anterior cutaneous branch of transverse cervical artery, and it was healed after a few dressing changes. The functions and appearances were satisfactory after 6-month to 2-year follow-up, without showing secondary deformity.

CONCLUSIONSThe blood supply of thoracic skin flap is abundant and constant, which is an ideal method for repair of tissue defects and deformities in jaw and neck after taking into account some factors, such as the demand of the patient, general physical condition, and the size of the defect.

Adolescent ; Adult ; Child ; Female ; Humans ; Male ; Middle Aged ; Neck ; abnormalities ; surgery ; Reconstructive Surgical Procedures ; methods ; Skin ; blood supply ; Skin Transplantation ; methods ; Surgical Flaps ; blood supply ; Thoracic Wall ; surgery ; Wound Healing ; Young Adult

OBJECTIVETo observe the effect of different concentration of Tamoxifen ointment on the fibroblasts and transforming growth factor (TGF-beta2) of hypertrophic scar at rabbit ears, so as to explore the possibility of treatment of hypertrophic scar with Tamoxifen.

METHODSThe hypertrophic scar model was established in 96 New Zealand rabbits' ears. The wounds were divided into four groups (A, B, C and D), with 144 wounds in each group. Different concentration of tamoxifen ointment (0.5%, 1%, 2%) was topically administered in groups A, B and C respectively, and blank ointment in group D. On postoperative day 30, 60 and 90, the scar samples were harvested. The scar thickness, scar histological change and the content of TGF-beta2 were detected.

RESULTS(1) On the 30th day after operation, the difference of scar tissue thickness among groups A, D and B, C reached statistical significance (group A, D < group B < group C). However, there was a contrary tendency in fibroblasts density and TGF-beta2 content of the scar tissue simultaneously. (2) On 60th, 90th day after injury, there was statistical difference in scar thickness, fibroblasts density and the content of TGF-beta2 in scar of four groups (P < 0.05). The content of TGF-beta2 in group A, B, C, D was (43.97 +/- 3.63) microg/L, (41.92 +/- 3.91) microg/L, (36.69 +/- 4.15) microg/L, (54.90 +/- 4.71) microg/L, respectively, on 60th day; and (45.69 +/- 2.63) microg/L, (40.43 +/- 3.87) microg/L, (38.76 +/- 3.24) microg/L, (52.59 +/- 4.92) microg/L, respectively, on 90th day. The fibroblasts density of scar in groups A, B, C, D was (4392.07 +/- 327.84) point/mm2, (4208.57 +/- 329.76) point/mm2 (4 033.44 +/- 427.91) point/mm2, (4863.03 +/- 387.98) point/mm2, respectively, on 60th day; and (4418.41 +/- 432.52) point/mm2, (4077.65 +/- 386.70) point/mm2, (3844.53 +/- 354.29) point/mm2, (4838.64 +/- 390.52) point/mm2, respectively, on 90th day. The content of TGF-beta2 and fibroblasts density of scar were lined up as group D > group A > group B > group C (P < 0.05).

CONCLUSIONSTopical Tamoxifen can reduce the content of TGF-beta2 and fibroblast, decrease fibroblasts density and the formation of hypertrophic scar at rabbit ears. It offers a new way for the treatment of the hypertrophic scar.

Animals ; Cicatrix, Hypertrophic ; drug therapy ; metabolism ; pathology ; Disease Models, Animal ; Ear Diseases ; drug therapy ; metabolism ; pathology ; Fibroblasts ; drug effects ; pathology ; Ointments ; Rabbits ; Tamoxifen ; pharmacology ; Transforming Growth Factor beta2 ; metabolism