BACKGROUND:The research and application of platelet-rich plasma in tissue regeneration and restoration have always been an issue of concern in the medicine and bioengineering fields.OBJECTIVE:To analyze the effects of platelet-rich plasma in combination with tendon stem cells on histomorphology change and matrix metalloproteinase 1 expression of the tendon tissues in a rabbit model of Achilles tendinopathy.METHODS:Forty New Zealand white rabbits were randomly divided into model group (n=32) and blank control group (n=8).In the model group,the animals were injected about 2 cm distant to the attachment point of the left calcaneus with prostaglandin E2 (once a week,for totally 4 weeks) to make the animal model of tendinopathy.The rabbits in the blank control group were injected the equal amount of normal saline.After 4 weeks,model rabbits were randomly divided into four subgroups:combination group,tendon stem cell group,platelet-rich plasma group and model control group,with eight rabbits in each group.Platelet-rich plasma and tendon stem cells,alone or in combination,and normal saline were injected into the corresponding group,twice with an interval of 3 weeks.At 6 weeks after injection,the tendon tissue was collected and stained for histological examination and detection of matrix metalloproteinasa 1 expression.RESULTS AND CONCLUSION:(1) Hematoxylin-eosin staining:the tendon fibers in the combinationgroup were intact and arranged orderly;in the tendon stem cell group,the tendon fibers were almost arranged orderly despite some fractured fibers;in the platelet-rich plasma group,fiber breakage and loose fiber structure were observed;in the model control group,there were no intact tendon fibers,with the presence of inflammatory cell filtration.(2) Masson staining:The tendon fibers in the combination group had slight wave-shaped changes but the fibers were not cut off;in the tendon stem cell group,the tendon fibers were slightly in disorder,but with the intact structure,and obvious inflammatory cell filtration was observed;in the platelet-rich plasma group,fiber breakage,reduced collagen fibers and inflammatory cell filtration were obviously observed;in the model control group,there were no intact tendon fibers,and inflammatory cell filtration was clearly visible.(3) The expression of matrix metalloproteinase 1:Compared with the blank control group,the expression of matrix metalloproteinase 1 was significantly higher in the other groups except the combination group (P ＜ 0.05).There was no significant difference in the expression of matrix metalloproteinase 1 between the combination group and blank control group (P ＞ 0.05).To conclude,the combination of platelet-rich plasma and tendon stem cells can inhibit the vicious cycle of degeneration of collagen and extracellular matrix,reduce the expression of matrix metalloproteinase 1 in tenocytes,and delay inflammation responses and degeneration due to tendinopathy.

OBJECTIVETo study the mechanism of microelement including Cu and Zn on the accumulation of three danshinones in Salviae miltiorrhizae root and build a theory basis for its good quality and high yield.

METHODSand culture experiments were conducted to study the effect of Cu and Zn on the accumulation of three danshinones and oxidase including peroxidase and polyphenol oxidase activity in the plant root. The correlation between available Cu and Zn contents in matrix and oxidase activity in the plant root and, the correlation between available Cu and Zn contents in matrix and contents of tanshinones in the root were discussed.

RESULTContents of danshinones in the root increased with the increasing of Cu and Zn concentration. Dynamic monitoring on contents of dan-shinones of the plant roots growing in the pots with different Cu and Zn concentration in the whole growing season showed that the contents of danshinones for 60 days were the lowest, for 120 days the highest and then dropped for 150 days. In addition, among available Cu and Zn contents of matrix, oxidase including peroxidase and polyphenol oxidase activity and contents of tanshinones in the root,the correlation between two factors were significant difference (P < 0.05 or P < 0.01).

CONCLUSIONThe mechanism of Cu and Zn on the accumulation of danshinones may be that Cu and Zn improve the activity of peroxidase and polyphenol oxidase, which promote transformation of phenolic compounds to terpenes and therefore to increase contents of danshinones.

Catechol Oxidase ; metabolism ; Copper ; metabolism ; Diterpenes, Abietane ; Drugs, Chinese Herbal ; analysis ; metabolism ; Peroxidase ; metabolism ; Phenanthrenes ; metabolism ; Plant Proteins ; metabolism ; Salvia miltiorrhiza ; enzymology ; metabolism ; Zinc ; metabolism

With the advent of Twenty-First century, more and more genome-wide association studies (GWAS) showed that idiosyncratic adverse drug reactions (ADRs) were closely related with human leukocyte antigen (HLA) alleles, such as the associations of abacavir-HLA-B*5701, allopurinol-HLA-B*5801, and carbamazepine-HLA-B*1502, etc. To explore the mechanisms of these idiosyncratic drug reactions, hapten hypothesis, danger signal hypothesis, pharmacological interaction (P-I) concept and autoimmune mechanism are proposed. In this paper, recent GWAS studies on the HLA-mediated adverse drug reactions and underlying mechanism are reviewed in detail.
Alleles ; Allopurinol ; adverse effects ; Anti-HIV Agents ; adverse effects ; Anticonvulsants ; adverse effects ; Carbamazepine ; adverse effects ; Dideoxynucleosides ; adverse effects ; Drug Hypersensitivity Syndrome ; etiology ; immunology ; Drug-Related Side Effects and Adverse Reactions ; genetics ; immunology ; Enzyme Inhibitors ; adverse effects ; Genome-Wide Association Study ; HLA Antigens ; genetics ; HLA-B Antigens ; immunology ; HLA-B15 Antigen ; immunology ; Humans ; Stevens-Johnson Syndrome ; etiology ; immunology

OBJECTIVETo investigate the effect of Compound Qingqin Liquid (CQL) on the expression level of angiotensin II (Ang II) and COX-2 mRNA transcription and protein expression in the renal tissue of rats with uric acid nephropathy.

METHODSSD rats were randomly divided into the blank control group, the model group, the positive drug group, the high, moderate, and low dose CQL group according to number randomization principle. The model was established by gastrogavage of adenine, accompanied with yeast feeding. Distilled water was given by gastrogavage to rats in the blank control group and the model group. Allopurinol at the daily dose of 9.33 mg/kg was given by gastrogavage to rats of the positive control group. CQL at the daily dose of 3.77 g/kg, 1.89 g/kg, and 0.09 g/kg was respectively given by gastrogavage to rats in the high, moderate, and low dose CQL groups. All treatment lasted for 6 weeks. Rats were randomly divided at week 4 (3 in the blank control group, and 6 in the rest groups), and the rest rats were killed at week 6. The renal tissue was extracted. The expression level of Ang II and COX-2 mRNA transcription were detected by RT-PCR. The expression level of Ang II was detected by ELISA. The expression level of COX-2 protein was detected by Western blot and immunohistochemical assay.

RESULTSCompared with the blank control group, except the mRNA expression of Ang II at week 4, the mRNA and protein expression of Ang II and COX-2 obviously increased at week 4 and 6 in the model group (P < 0.01, P < 0.05). The COX-2 protein expression at week 4 was obviously lower in the high and moderate dose CQL groups than in the model group and the low dose CQL group (P < 0.05); the average integral of optical density value was obviously lower in the positive control group than in the model group. Except the mRNA expression of Ang II in the high dose CQL group at week 6, the mRNA and protein expression of Ang II obviously decreased in the positive control group and each dose CQL group (P < 0.01, P < 0.05). Of them, the effects were better in the high and moderate dose CQL groups than in the positive control group and the low dose CQL group (P < 0.05, P < 0.01). Besides, the mRNA expression of COX-2, the average integral of optical density value were obviously lower in the positive control group and each dose CQL group than in the model group (P < 0.05). The protein expression of COX-2 was obviously lower in the high and moderate dose CQL groups than in the model group (P < 0.05). Of them, the mRNA expression of COX-2 was better in the moderate dose CQL group than in the positive control group (P < 0.05); the protein expression of COX-2 was better in the high dose CQL group than in the low dose CQL group (P < 0.05).

CONCLUSIONCQL was capable of lowering the expression level of Ang II, COX-2 mRNA transcription and protein expression, thus suppressing the inflammatory pathological injury of the renal tissue.

Angiotensin II ; metabolism ; Animals ; Cyclooxygenase 2 ; genetics ; metabolism ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; Kidney ; metabolism ; Kidney Diseases ; drug therapy ; metabolism ; Male ; RNA, Messenger ; genetics ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Uric Acid

OBJECTIVETo investigate the effect of compound qingqin liquid (CQL) on Toll-like receptor 2 (TLR2) and toll-like receptor 4 (TLR4) in rats with urate nephropathy, and to explore its renal protection mechanism.

METHODSTotally 55 SD rats were randomly divided into 5 groups, i.e., the normal control group (n =5), the model group (n =10), the positive drug group (n=10), and the high-, medium-, low-dose CQL groups (n=10) respectively. The urate nephropathy model was induced by intragastrically administering adenine and feeding yeast. Distilled water was intragastrically administered at the daily dose of 10 mL/kg to rats in the normal control group and the model group. Allopurinol was intragastrically administered at the daily dose of 9.33 mg/kg to rats in the positive control group. CQL was intragastrically administered at the daily dose of 3.77, 1.89, 0.94 g/kg to rats in the high-, medium-, and low-dose CQL groups. Rats of each group were executed in batches at the 4th and 6th week respectively. Their kidney tissues were taken out to determine the mRNA transcription level of TLR2 and TLR4 by reverse transcription-polymerase chain reaction (RT-PCR). The protein expression level of TLR2 and TLR4 were determined by Western blot. The protein expression level of TLR4 was also detected by immunohistochemical assay.

RESULTSAt week 4 and 6, the protein expression of TLR2 and TLR4 as well as the mRNA transcription of TLR4 increased in the model group, when compared with the control group (P < 0.05, P < 0.01). Compared with the model group, there was no statistical difference in the transcription level of TLR2 mRNA or TLR4 mRNA among the 3 CQL groups (P > 0.05) at week 4 and 6. Additionally, at week 6, the protein expression of TLR4 and TLR2 could be reduced by CQL (P < 0.05, P < 0.01).

CONCLUSIONCQL might protect kidney tissue against inflammatory injury by inhibiting the protein expression levels of TLR2 and TLR4.

Animals ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; Kidney ; drug effects ; metabolism ; Kidney Diseases ; drug therapy ; metabolism ; Male ; RNA, Messenger ; genetics ; Rats ; Rats, Sprague-Dawley ; Toll-Like Receptor 2 ; genetics ; metabolism ; Toll-Like Receptor 4 ; genetics ; metabolism ; Uric Acid

Objective To study the influence on the tumor after percutaneous intra-tumor injection of ~(32)P-GMS in liver cancer as well as its suitable dose.Methods 24 New Zealand rabbits were used to establish the animal model of VX-2 liver cancer,and divided into A,B,C and D groups with individually 37,74,111 and 148 MBq of ~(32)P-GMS being injected,respectively;and then pathological changes of tumor were observed by light and electron microscope respectively.Result The dose of ~(32)P-GMS was obviously correlated with the radioactivity damage of tumor cells.In the A and B groups,the tumor cells were not observed to disappear completely after injection of ~(32)P-GMS,but in C group,tumor cells were almost completely disappeared and surrounded by a lot of connective tissue.Although the tumor cells were found to disappear completely in D group,normal liver tissues were also involved.Conclusion Percutaneous intra-tumor injection of ~(32)P-GMS with suitable dose that may induce the tumor tissue to be maximally damaged and may also provide some significances to prevent the tumor metastasis.

This study was aimed to investigate the expression and activity of membrane surface tissue factor (TF) of monocytes and platelets in peripheral blood cells from patients with cerebral infarction and their clinical significance. The TF expressions in monocytes and platelets from 25 patients with cerebral infarction were detected by flow cytometry, the TF activity was detected by chromogenic reaction method, and compared with 24 normal people used as control. The results showed that the TF expressions of monocytes and platelets in peripheral blood cells from patients with cerebral infarction were significantly higher than that in normal controls (p<0.01), and TF activity was also higher in patients than that in controls (p<0.01). In conclusion, the expression and activity of membrane surface in patients with cerebral infarction were enhanced, the hematocyte-derived tissue factor as a trigger in coagulation pathway is involved in pathological thrombosis in patients with cerebral infarction.
Aged ; Blood Cells ; metabolism ; Case-Control Studies ; Cerebral Infarction ; blood ; metabolism ; Erythrocyte Membrane ; metabolism ; Female ; Flow Cytometry ; Humans ; Male ; Middle Aged ; Monocytes ; metabolism ; Thromboplastin ; metabolism

BACKGROUNDAccording to the National Institutes of Health consensus criteria, gastrointestinal stromal tumors (GISTs) smaller than 2 cm in diameter with less than 5 mitotic figures per 50 high-power fields are considered very-low-risk GISTs, but these two indices alone cannot reliably predict a benign outcome during long-term follow-ups. Therefore, identification of additional parameters for predicting the clinical behavior of GISTs is necessary.

METHODSEighty-eight patients with tumors that meet the very-low-risk GIST criteria were retrospectively investigated and morphological parameters of tumors associated with the biological behavior of very-low-risk GISTs were evaluated in the present study. The Kaplan-Meier method was used to calculate disease-free survival rates.

RESULTSEighty-one patients were followed up for one to 16.3 years. Five cases of relapses were identified in the patients. Distinctive infiltrative growth patterns such as muscularis propria, muscularis mucosa, or nerve infiltration were identified by microscopy in 4 patients with the relapse, including three patients who experienced multiple recurrences. The infiltrative growth features became more obvious in multiple recurrent tumors compared to the single recurrent tumor, while only one developed relapse in 76 patients without infiltration (P < 0.0001).

CONCLUSIONMicroscopic infiltrative growth patterns of the tumor may have clinical significance in predicting the prognosis of very-low-risk GISTs.

Adult ; Aged ; Aged, 80 and over ; Disease-Free Survival ; Female ; Gastrointestinal Stromal Tumors ; pathology ; Humans ; Male ; Middle Aged ; Prognosis ; Retrospective Studies

OBJECTIVE: To investigate the expression of haptoglobin in the lesions of condyloma acuminatum (CA) at the mRNA and protein level, and to explore its role in the pathogenesis of CA. METHODS: The expressions of haptoglobin protein and mRNA in the skin tissues of 30 patients with CA and 20 normal controls were detected by immunohistochemistry(IHC), Western blot, and hybridization in situ. RESULTS: The in situ hybridization study showed that haptoglobin mRNA was expressed in the epidermal cells in the lesions of CA. The distribution of haptoglobin mRNA expression in the lesions of CA was similar to that of the normal controls, and the expression of haptoglobin mRNA in CA was higher than that of the normal controls. There was a significant difference in the positive expression of haptoglobin mRNA between the CA group and the control group (P<0.05). The immunohistochemical study showed that haptoglobin protein was expressed in the whole layers of epidermal keratinocytes in the lesions of CA at a high level and stronger staining was seen in the stratum basale and stratum spinosum. Haptoglobin protein was expressed predominantly in the stratum basale in normal skin tissues, while weak staining was seen below the stratum spinosum.There was a significant difference in the mean gray value between the CA group and control group (P<0.05). Western blot showed that the haptoglobin expression in CA lesions significantly increased compared with the normal skins (P<0.05). CONCLUSION The expression of haptoglobin mRNA in the CA lesions obviously increases and the epidermal cells in the CA lesions are able to synthesize haptoglobin protein. Haptoglobin in the CA lesions may involve in the local immunity escape by preventing Langerhans cell functional maturation and inhibiting the immunocompetence of keratinocyte.
Adolescent ; Adult ; Aged ; Blotting, Western ; Case-Control Studies ; Condylomata Acuminata ; genetics ; metabolism ; Epidermal Cells ; Haptoglobins ; genetics ; metabolism ; Humans ; In Situ Hybridization ; Keratinocytes ; metabolism ; Male ; Middle Aged ; RNA, Messenger ; genetics ; Young Adult

Objective To understand the developmental effects induced by CdSe /ZnS quantum dots(QDs)on zebrafish embryos.Methods Zebrafish embryos were exposed to 0,0.5,1,2,4,8 and 16 nmol/L of CdSe /ZnS QDs,and the typical toxicological indexes were recorded at five time points respectively (24 hours post fertilization (hpf),48 hpf, 72 hpf,96 hpf,120 hpf).Results The results showed that the median lethal concentration (LC50 )for zebrafish embryos after 120 hpf was 21.38 nmol/L(95% CI =17.21 -26.57).The frequency of spontaneous movement in 60 seconds after 24 hpf,the frequency of heart beat in 60 seconds after 48 hpf,the hatching rate and the mortality rate were obviously affected by CdSe /ZnS QDs.Several abnormalities and toxic symptoms caused by CdSe /ZnS QDs at 8 nmol/L and 16 nmol/L were observed including pericardial edema,liver atrophy,non -depleted yolk,intestinal abnormal development and muscle degeneration after 120 hpf.Conclusion High level of CdSe /ZnS QDs (more than 8 nmol/L)could induce toxic effects on zebrafish embryonic development.