Autopsy ; Eye Injuries ; Forensic Medicine ; Humans

AIMTo investigate the pharmacokinetics of mycophenolic acid (MPA), an active metabolite of mycophenolate mofetil (MMF) in Chinese adult liver transplant patients.

METHODSThirty-eight liver transplant patients (male 30, female 8) receiving MMF 1.0 g, twice daily in accordance with the recommended regimen were included in this study. Plasma MPA concentrations were measured by high performance liquid chromatography at 0.5, 1, 1.5, 2, 4, 6, 8, 10 and 12 h after the administration of a single dose. Pharmacokinetic parameters were calculated with 3P97 software.

RESULTSThe plasma MPA concentration-time curve was characterized with an early sharp peak reached at 0.5 - 6.0 h after oral administration. And in some patients there was a small second peak due to enterohepatic circulation of mycophenolic acid glucuronide (MPAG), which underwent deglucuronidation and re-absorption as MPA at 4 to 12 h postdose. The mean peak plasma concentration (C(max)) and area under concentration-time curve (AUC(0-12 h)) were (12 +/- 7) microg x mL(-1) and (44 +/- 16) microg x h x mL(-1), respectively. However, a large variability of pharmacokinetic parameters existed in these patients.

CONCLUSIONIn view of the inter-individual variability of MMF pharmacokinetics, plasma MPA concentration should be monitored routinely after MMF administration for individual patient.

Adult ; Aged ; Area Under Curve ; Female ; Humans ; Immunosuppressive Agents ; pharmacokinetics ; Liver Transplantation ; Male ; Middle Aged ; Mycophenolic Acid ; analogs & derivatives ; pharmacokinetics

BACKGROUND:As the regulators of cytokines, suppressors of cytokine signaling (SOCS) play an important role in the inflammation reaction. Some studies found that SOCS-1 and SOCS-3 were involved in the pathogenesis of some inflammatory diseases such as rheumatoid arthritis, inflammatory bowel disease. But the expressions of SOCS in coronary heart disease have not yet been reported. This study aimed to investigate the expression and clinical significance of SOCS-1 and SOCS-3 in the myocardium of patients with sudden cardiac death (SCD).METHODS:Myocardial autopsy specimens were collected from 24 patients at the Forensic Medicine Department of Sun Yat-Sen University, Guangzhou, China between 2005 and 2006. Of them, 9 patients had autopsy findings consistent with coronary atherosclerosis (non-myocardial infarction) leading to SCD (non-MI group), 7 died of acute myocardial infaction (MI group), and 8 died from traffic accidents and trauma (control group). The expressions of SOCS-1 mRNA and SOCS-3 mRNA in the myocardium of the non-MI, MI and control groups were detected using RT-PCR. The levels of SOCS-1 and SOCS-3 proteins were detected using immunohistochemistry. Statistical analyses were performed using SPSS version 13.0 software and the data were analyzed by ANOVA.RESULTS:The expressions of SOCS-1 mRNA and SOCS-3 mRNA in the non-MI and MI groups were significantly higher than those in the control group[(0.788±0.101), (0.741±0.111) vs. (0.436±0.044), (P<0.01); (0.841±0.092), (0.776±0.070) vs. (0.454±0.076), (P<0.01)] respectively. The antibody-positive cells of SOCS-1 protein in the myocardium of the non-MI and MI groups were significantly higher than those in the myocardium of the control group[(320.00±48.48), (347.14±70.88) vs. (42.50±10.35), (P<0.01)] respectively. The antibody-positive cells of SOCS-3 protein in the myocardium of the non-MI and MI groups were significantly higher than those in the myocardium of the control group[(381.11±59.25) vs. (40.00±10.69), (P<0.01)] and[(332.86±111.91) vs. (40.00±10.69), (P=0.001)].CONCLUSION:The expressions of SOCS-1 and SOCS-3 in the myocardium of patients with SCD from coronary heart disease are significantly increased and contribute to the pathogenesis of SCD.

Objective: To assess the risk of public health emergencies in Zhejiang Province, March 2021. Methods: An expert counsel was conducted to assess the risk of coronavirus disease 2019 ( COVID-19 ) , enteritis due to norovirus, chicken pox and influenza by professionals in Zhejiang CDC, based on the information from infectious disease and public health emergency surveillance in Zhejiang Province, domestic health administrative departments, World Health Organization, and European CDC. Results: In March 2021, the risk of imported COVID-19 epidemic will be high in Zhejiang Province, and the possibility of local spread could not be ruled out. The possibility of a large-scale outbreak of enteritis due to norovirus and a small-scale outbreak of chickenpox in schools and kindergartens could not be ruled out after the new term begins. An increased risk of influenza epidemic is predicted in collective units such as schools and kindergartens, yet the risk of a large-scale one will be low. Conclusion High attention should be paid to COVID-19 and enteritis due to norovirus, and general attention should be paid to chicken pox and influenza outbreak.

AIM To explore the effects of praeruptorin A from Suhuang antitussive capsules on cough variant asthma(CVA).METHODS The rats were randomly divided into the normal group,the model group,the dexamethasone group(0.5 mg/kg),the Suhuang antitussive capsules group(7 g/kg)and the low,medium and high dose praeruptorin A groups(15,30 and 60 mg/kg).The rat model of CVA was established by intraperitoneal injection of sensitizer(1 mg/mL ovalbumin and 10 mg/mL aluminum hydroxide)and aerosol inhalation of 1%ovalbumin followed by the corresponding dosing of drugs by gavage initiated on the 14th day.Another 14 days later,the rats had their pathological pulmonary changes observed by HE,Masson and PAS stainings;their number of inflammatory cells in bronchoalveolar lavage fluid(BALF)detected by hematology analyzer;and their levels of IL-4,IL-5,IL-13 and MUC5AC in BALF detected by ELISA.The RAW264.7 cell inflammatory model induced by lipopolysaccharide(LPS)was treated with 4,8,16 μmol/L praeruptorin A or 0.25 mg/mL Suhuang antitussive capsules,respectively.And the cells had their NO level detected by Griess method,and their ROS expression observed using fluorescence microscopy.The detections of the pulmonary and cellular mRNA expressions of IL-6,IL-1β,COX-2,iNOS and PPAR-γ by RT-qPCR;and the protein expressions of p-P65,P65,p-IκBα,IκBα,NLRP3,caspase-1(p20)and IL-1β by Western blot were conducted in both the cells and the rats.RESULTS The in vivo result showed that praeruptorin A reduced the cough frequency(P＜0.01);prolonged the cough latency(P＜0.05,P＜0.01);reduced the number of eosinophils and neutrophils in BALF(P＜0.05,P＜0.01);decreased the levels of IL-4,IL-5,IL-13 and MUC5AC in BALF and the pulmonary mRNA expressions of IL-6,IL-1β,COX-2 and iNOS(P＜0.05,P＜0.01);and decreased the phosphorylation of P65 and IκBα protein and NLRP3,caspase-1(p20)and IL-1β protein expressions(P＜0.05,P＜0.01)as well.The in vitro result showed that praeruptorin A inhibited the release of LPS-induced NO and reduce the ROS level(P＜0.01);decreased the mRNA expressions of IL-1β,COX-2 and iNOS(P＜0.05,P＜0.01);increased PPAR-γ mRNA expression(P＜0.05),and decreased the phosphorylation of P65 and IκBα protein and the expression of NLRP3 protein(P＜0.05,P＜0.01).CONCLUSION Praeruptorin A,one of the main antitussive components of Suhuang antitussive capsules,may improve CVA because of its anti-inflammatory and antitussive role by inhibiting the activation of NF-κB signaling pathway and reducing the expression of NLRP3 inflammatory corpuscles.

BACKGROUNDArsenic trioxide (As2O3) has been identified as a very potent anti-acute leukemic agent. However its role in apoptosis needs to be elucidated. As2O3 interferes with the proliferation and survival of tumor cells via a variety of mechanisms. Drug-target interactions at the level of nuclear matrix (NM) may be critical events in the induction of cell death by As2O3. This study dealt with As2O3-target interactions at the level of NM in chronic myelogenous leukemia cell line K562 by proteomics.

METHODSK562 cells were cultured in MEM and treated with different concentrations of As2O3. The nuclear matrix proteins were analyzed by high-resolution two-dimensional gel electrophoresis and computer-assisted image analysis.

RESULTSAs2O3 significantly inhibited the growth of chronic myelogenous leukemia cell line K562 at low concentrations. While more than 200 protein spots were shared among the nuclear matrices, about 18 distinct spots in the nuclear matrices were found characteristic for As2O3 treated cells.

CONCLUSIONSAs2O3 induces apoptosis in K562 cells in a dose and time-dependent manner. Our results demonstrated that for the detection of the onset of apoptosis, the alteration in the composition of nuclear matrix proteins was a more sensitive indicator than nucleosomal DNA fragmentation test. These results indicated that As2O3 might be clinically useful in the treatment of chronic myelogenous leukemia. The changes of nuclear matrix proteins in the treated cells can be used as a useful indicator for this treatment.

Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; Arsenicals ; pharmacology ; Dose-Response Relationship, Drug ; Humans ; K562 Cells ; drug effects ; Nuclear Matrix-Associated Proteins ; analysis ; Oxides ; pharmacology ; Proteomics

OBJECTIVETo explore the differential expression of homeobox genes in the normal, wounded human fetal and adult skins and its significance in fetal scarless healing.

METHODSGene chips containing 14 000 human genes were used to investigate homeobox gene expressions of the normal, wounded human fetal and adult skins.

RESULTSThere were significant differences between the expression of homeobox genes, especially for PRX-2, HOXB13, HOXB6 and HOXB7.

CONCLUSIONSThe homeobox gene is in close relation to developmental biology. The different expressions and changes of homeobox genes in the normal, wounded human fetal and adult skin may be a primary cause of different wound healing between fetal and adult skin.

Adolescent ; Adult ; Animals ; Cells, Cultured ; Child ; Female ; Fetus ; Gene Expression ; Gene Expression Profiling ; Genes, Homeobox ; genetics ; Homeodomain Proteins ; genetics ; Humans ; Male ; Mice ; Mice, Inbred BALB C ; Oligonucleotide Array Sequence Analysis ; Skin ; Wound Healing ; genetics ; Young Adult

OBJECTIVETo explore the distribution of deep inferior epigastric perforator vessel and application of the expanded perforator flap for large scar on hand and forearm.

METHODS20 healthy adults were selected to detect the distribution of deep inferior epigastric perforator vessel. 10 cases with cicatricial constriction on hand and forearm were treated with expanded perforator flap.

RESULTS425 perforator points were detected on the skin surface of abdomen in 20 adults. 80% of the points are located within the area which is 1.1 -5.8 cm far from the mid-line of abdomen. According to the Rand method, the percentage of the points in zone I , II , III were 26%, 43%, and 30%, respectively. There were few points in zone IV. The area around navel had a high density of points. The points were distributed asymmetrically at the two sides of abdomen. 10 cases were treated. Vascular deficiency happened at the distal end of one flap. All the other 9 flaps survived.

CONCLUSIONSThe expanded deep inferior epigastric perforator flap is thin and has a large size. It is very suitable for large scar on forearm or hand.

Adolescent ; Adult ; Burns ; complications ; Contracture ; etiology ; surgery ; Epigastric Arteries ; Female ; Humans ; Male ; Reconstructive Surgical Procedures ; methods ; Surgical Flaps ; blood supply ; Tissue Expansion ; Young Adult

OBJECTIVETo investigate effects of low-dose cyclophosphamide and prednisone (CP) metronomic chemotherapy on microvessel density of bone marrow, serum vascular endothelial growth factor (VEGF) and platelet derived growth factor BB (PDGF-BB)in multiple myeloma (MM) patients.

METHODS54 refractory or relapsed MM patients were treated with CP metronomic chemotherapy consisted of oral cyclophosphamide (CTX, 50 mg/d) and prednisone (Pred, 15 mg/d). Bone marrow and peripheral blood of each patient were collected before and 2, 4, 6 months after treatment. Among the 37 assessable patients, 30 cases were responsive with the response rate of 81.08%. Another 17 cases were follow-uped less than 6 months or failure to obtain serum samples or lost to follow-up. Microvessel density of bone marrow was measured by immunohistochemistry and serum VEGF/PDGF-BB expression was analyzed by ELISA in the 37 assessable patients.

RESULTS2, 4, 6 months following CP metronomic chemotherapy, microvessel densities of bone marrow in the responders were 33.1 ± 4.8/HP, 24.8 ± 3.7/HP, 19.7 ± 2.1/HP respectively; the expressions of VEGF were (394 ± 57) ng/L, (268 ± 32) ng/L and (217 ± 20) ng/L respectively; the expressions of PDGF-BB were (304 ± 31) ng/L, (274 ± 31) ng/L and (196 ± 22) ng/L respectively. After CP metronomic chemotherapy, there were significantly lower of microvessel density, VEGF and PDGF-BB levels than pretreatment \[MVD 48.5 ± 5.9/HP, VEGF (517 ± 60) ng/L, PDGF-BB (484 ± 60) ng/L\]in the responders (P < 0.01). While in the non-responders, after treated by CP metronomic chemotherapy for 2 months, microvessel density, the expression of VEGF and the expression of PDGF-BB were 32.5 ± 4.7/HP, 512 ± 39 ng/L and (452 ± 39) ng/L respectively. There were no significant changes of MVD, VEGF and PDGF-BB levels compared with pretreatment \[MVD 33.2 ± 5.6/HP,VEGF (498 ± 55) ng/L, PDGF-BB (488 ± 44) ng/L\] (P > 0.05).

CONCLUSIONSOur findings suggested that continuous low-dose CP metronomic chemotherapy could decrease microvessel density of bone marrow in MM patients. Furthermore, it down-regulated expression of serum VEGF and PDGF-BB to exert its anti-angiogenesis in MM.

Aged ; Aged, 80 and over ; Angiogenesis Inhibitors ; administration & dosage ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Cyclophosphamide ; administration & dosage ; Female ; Humans ; Male ; Microvessels ; drug effects ; Middle Aged ; Multiple Myeloma ; blood ; blood supply ; drug therapy ; Prednisone ; administration & dosage ; Proto-Oncogene Proteins c-sis ; blood ; Vascular Endothelial Growth Factor A ; blood