Arsenicals ; pharmacology ; DNA Methylation ; drug effects ; Humans ; Intercellular Signaling Peptides and Proteins ; genetics ; metabolism ; K562 Cells ; Membrane Proteins ; genetics ; metabolism ; Oxides ; pharmacology

AIM:To investigate the imbalance between the expression of metalloproteinases (MMPs) and that of tissue inhibitors of metalloproteinase (TIMPs) during wound healing in diabetic rats. METHODS: Diabetic rats were induced with streptozotocin. All rats were maintained for 6 weeks. A full-thickness excisional wound was created on the back of each rat. Every group was randomly divided into 3 subgroups of 7 rats: 3 d group, 7 d group, 14 d group and animals were killed at 3rd, 7th and 14th day. Routine pathological examination, Masson′s trichrome staining and immunohistochemistry were made to calculate the score of epidermal and dermal regeneration, granulation tissue thickness, angiogenesis, matrix density, and infiltrated cells at different time points. RT-PCR and Western blotting were used to detect the expression of mRNA and protein of MMP-9 and TIMP-1 in the skin at those time points. RESULTS: Six weeks after streptozotocin treatment, Three days after injury, the wound healing rate of normal rats was faster than that of diabetic rats. From 3rd to 14th day, there were a lot of fibroblast and macrophage in normal skin, while few such cells were observed in diabetic skin. The other histological scores in normal skin were higher than those in diabetic rats at 7th and 14th day. Both MMP-9 and TIMP-1 had minimally detectable levels before wounding but exhibited rapid, significantly large increases within 3 d after wounding. Subsequently, they showed a rapid decline by 14 d. The relative values of expression of MMP-9 mRNA and protein in diabetic group were higher than those in normal group at different time points. However, the values of TIMP-1 mRNA and protein in diabetic group were significantly lower than those in control group. Significant difference was observed between two groups with the ratio of MMP-9/TIMP-1, higher in diabetic group than that in normal group. CONCLUSION: Abnormal reepithelialization, angiogenesis, inflammatory cell infiltration, collagen fibers generation, granulation tissue deposition, seem to be the basic histopathology that delays wound healing. The imbalance between MMPs and TIMPs in diabetic skin tissue before and after injury may be one of the important reasons of these alterations of histopathology.

Objective To investigate the change of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in the skin of diabetic rats, and to explore the potential role of MMP-9/TIMP-1. Methods Diabetic rats were induced with streptozotocin (STZ). Then all rats were maintained for 6 weeks. Routine pathological examination and immnnohistochemistry were made to reveal the histological and cytological appearances. RT-PCR and Western blotting were used to detect the expression of mRNA and protein of MMP-9 and TIMP-1 in the skin. Results Six weeks after STZ treatment, examination of HE-stained skin sections from normal and diabetic animals revealed that the epidermis and dermis layers were thinner in diabetic rats than those in control rats. The skin of diabetic rats showed features of atrophy such as disorganization of connective tissue fiber bundles and enlarged space between collagen fiber bundles. In contrast, thick bundles of connective tissue were observed in the dermis of normal rat skin. In normal skin, cells had a bipolar, spindle-shaped appearance in the thick collagen bundles, while in the skin of diabetic animals the interstitial cells had a rounded, shrunken and crenated appearance. The relative values of expression of MMP-9 in diabetic group were higher than those in normal group with significant difference, however, the relative values of expression of TIMP-I in diabetic group were lower than those in control group. Conclusion The changes in cutaneous histology and cytology appear earlier than skin wound. These "underlying disorders" may be associated with the imbalance of MMP-9/TIMP-1.

Objective:To investigate the model,quality as well as effect of teaching-in-English in five-year clinical medicine program of Hainan Medical University.Methods:The questionnaire was carried out among clinical medicine undergraduates of 2012-2015 grades in Hainan Medical University,to investigate studying time,studying habits and the impact of teaching in English.Additionally results of CET-4,CET-6 and overseas internship from undergraduates of 2012-2015 grade,as well as the result of phased medical licensing examination and post-graduate entrance examination from undergraduates of 2012 were accordingly collected from the Teaching Management Department.Results:For the Chinese students in international classes,the average time of self-study was 161.49 min,58.3％ had preview before classes,and 90.7％ had habit of review after classes.Thus the first time pass rate,total pass rate,first time excellent rate and total excellent rate of CET-4 and CET-6 of international classes were significantly higher than those of regular classes.The result of post-graduate entrance examination in 2016 showed that the score,pass rate and acceptance rate of international classes of 2012 grade were significantly higher those of regular classes (P ＜ 0.01).Conclusions:Teaching-in-English reform in Hainan Medical University has achieved initial success.Chinese students from international classes are superior to those from regular classes in many aspects.However,there are still many problems,and effective measures should be implemented to promote teaching quality continuously.

BACKGROUND:The high level of matrix metalloproteinase 9 (MMP9) is thought to slow down the healing of diabetic foot ulcers. Whether it can influence the biological behaviors of skin fibroblasts and affect wound healing is stillunclear. The present study aimed to observe changes in the biological behaviors of rat dermal fibroblasts induced by high expression of MMP9 and to clarify the possible mechanisms of wound healing for diabetic foot. METHODS:A cellmodel of skin fibroblast with high expression of MMP9 was established by co-culture of high glucose (22.0 mmol/L) and homocysteine (100 μmol/L). A control group was incubated with normal glucose (5.5 mmol/L). Realtime PCR, ELISA and gelatin zymography were used to detect the MMP9 mRNA, protein expression and activity of MMP9. Flow cytometry, CCK-8, ELISA assay, scratch test and transwellwere used to detect cellproliferation, viability, collagen (hydroxyproline) secretion, horizontal migration and vertical migration of cells. The data were expressed as mean±SD. P value less than 0.05 was considered statistically significant. RESULTS:The expression of MMP9 mRNA, protein levels and the activity of MMP9 were much higher in the high MMP9 group than in the control group (7.05±1.02 vs. 1.00±0.00, 206.9±33.6 pg/mL vs. 40.4±5.9 pg/mL, and 1.47±0.13 vs. 0.57±0.12, respectively,P<0.01). The proportion of S-phase cells, proliferation index, cellviability, collagen (hydroxyproline) secretion, horizontal migration rate and the number of vertical migration cells were lower in the high MMP9 group than in the control group (P<0.01). CONCLUSION:Fibroblasts with a high expression of MMP9 decreased proliferation, activity, secretion and migration of collagens, suggesting that MMP9 may inhibit the biological behaviors of fibroblasts.

Objective To study the role of inflammation in white matter damage of spontaneously hypertensive rats (SHRs) through observing the pathology changes of tissues after white matter damage and detecting the levels of inflammation-related indicators.Methods Eighteen 40-week-old male SHRs were chosen as experimental group,and seven male Wistar-Kyoto (WKY) rats were used as control group.The animal brain tissues were taken for hematoxylin-eosin staining (HE staining) and immunohistochemical staining to observe the pathological changes,and the levels of myelin basic protein (MBP),neurofilament (NF) and glial fibrillary acidic protein (GFAP).Real-time PCR was employed to detect toll-like receptor 4 (TLR-4),monocyte chemotactic protein 1 (MCP-1) and vascular cell adhesion molecule-1 (VCAM-1) expression levels in the white matter tissues.Results The white matter of 40-week-old SHRs was apparently injured.HE staining displayed sponge-like changes in the white matter and immunohistochemical staining showed astrocyte activation,reduced number of axonal and demyelination in the white matter.As compared with those in the WKY rats,TLR-4,MCP-1 and VCAM-1 mRNA expressions in SHR white matter were significantly increased (P＜0.05); and TLR-4,MCP-1 and VCAM-1 expression levels in SHRs were positively related to the degree of white matter damage.Conclusion The white matter damage in 40-week-old SHRs is similar to that of LA;inflammation is involved in the pathophysiological process of white matter damage,being one of induced factors of white matter injury.

Platinum-based anticancer drugs have been becoming one of the most effective drugs for clinical treatment of malignant tumors for its unique mechanism of action and broad range of anticancer spectrum. But, there are still several problems such as side effects, drug resistance/cross resistance and no-specific targeting, becoming obstacles to restrict its expanding of clinical application. In recent years, supramolecular chemistry drug delivery systems have been gradually concerned for their favorable safety and low toxicity. Supramolecular macrocycles-platinum complexes increased the water solubility, stability and safety of traditional platinum drugs, and have become hot focus of developing novel platinum-based anticancer drugs because of its potential targeting of tumor tissues/organs. This article concentrates in the research progress of the new drug delivery system between platinum-based anticancer drugs with three generations of macrocycles: crown ether, cyclodextrin, cucurbituril and calixarene.
Antineoplastic Agents ; pharmacology ; Calixarenes ; Crown Compounds ; Cyclodextrins ; Drug Delivery Systems ; Humans ; Macrocyclic Compounds ; pharmacology ; Neoplasms ; drug therapy ; Platinum Compounds ; pharmacology

Objective To clarify the clinical features,therapeutic strategy and prognosis of lipid storage myopathy (LSM).Methods The clinical data and therapeutic effects of 42 LSM patients were summarized retrospectively.All patients were followed up to evaluate their prognosis.Results Data of short-term therapeutic results of all the 42 patients were available.Thirty-three cases were placed in low- doses prednisone and 9 cases in riboflavin.All patients showed marked and quick improvement of symptoms within one month.Among thirty-two patients followed up for more than one year,26 cases had a full recovery and 6 remained to have intolerance to heavy exercise.Thirteen patients had relapses of muscle weakness in various degrees and most of which were induced by exertion,exposure to coldness and upper respiratory tract infection.In 5 patients the symptoms were recurred for more than one time.Among 13 cases with relapses, 7 had family history.Conclusions Our data suggest that LSM is a treatable disease and well responsive to low-doses prednisone.The disease tends to recur,especially in patients with family history.Glutaric aciduria type Ⅱ should be considered in LSM patients who are responsive well to riboflavin,indicating drug therapeutic strategy for LSM should be based on the etiology of the disease.

Objective To investigate the clinical,neuroimaging and myopathological features of mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes(MELAS).Methods The clinical manifestations,neuroimaging and myopathological features of 31 patients with MELAS diagnosed in our Neuromuscular Center in the recent 7 years were retrospectively analyzed.A3243G point mutations were analyzed by RFLP method in 10 patients.Results ①Clinical features:There were 18 male patients and 13 female patients.The age of onset ranged from 3 to 43 years,averaging 21.9 years.The averaged duration was 4.9 years.Thirteen patients in this group had family history of maternal inheritance pattern.The main clinical manifestations included short stature(26 patients),recurrent headache and vomiting(24 patients), muscle weakness(22 patients),epileptic seizure(21 patients),cognitive decline(19 patients),visual disturbance(17 patients),sensorineural deafness(16 patients),ataxia(6 patients),psychiatric symptom (8 patients),external ophathalmoplegia(2 patients)and diabetes mellitus(9 patients).The serum CK level was slightly elevated in 6 patients,and the fasting blood lactic acid was increased in 15 of the 18 detected patients.②Neuroimaging features:The stroke-like lesions were mostly confined to cerebral cortex, including temporal lobe(24 patients),occipital lobe(21 patients),parietal lobe(12 patients)and frontal lobe(4 patients).Three patients had deep white matter involvement.Migrating stroke-like lesions were confirmed in 4 patients by repeated cranial CT/MRI examination.In addition,cerebral atrophy(17 patients)and bilateral basilar ganglion calcification(11 patients)were found.③Myopathological features: Scattered ragged red fibers(RRF)in various number were found in all the patients by MGT staining.Other founding included strongly SDH-reactive blood vessel(27 patients),COX enzyme deficiency(19 patients), and mild to moderate lipid storage in RRF(20 patients).④MtDNA analysis showed 9 patients with A3243G point mutation in all the detected 13 patients.Conclusion The clinical and neuroimaging features may offer important clue to the diagnosis of MELAS,but a definite diagnosis of MELAS relies on the myopathology and mtDNA mutation analysis.

Axons ; chemistry ; Myelin Sheath ; chemistry ; Staining and Labeling ; methods