Objective To investigate the therapeutic mechanism of bazedoxifene, the third-generation selective ER modulator (SERM), on endometriosis lesions in a rat model. Methods Endometriosis was induced by transplanting pieces of endometrium from other syngeneic rats that were as donors onto the subcutaneous of other unmated female rats. The rats with successful ectopic implants were divided into two groups:control group (n=10) and bazedoxifene group (n=10). The macroscopic morphology, volume, histopathology of ectopic implant and rats uterine wet weight were determined before and after the treatment. Expression of proliferation cell nuclear antigen (PCNA), ER and PR in the eutopic endometrium and endometriosis lesions detected by immunohistochemistry in the two groups. Results (1) The gross morphology and histological changes of endometriosis lesions in rats after treatment: compared with the control group, it was obviously depauperated and had more less glands and blood vessels in the stroma. (2) The change of rats′weight, the volume of endometriosis lesion before and after treatment and rats uterine wet weigh after treatment respectively in the control group and the bazedoxifene group:rats′ weight were respectively before treatment: (201±17) g, (202±18) g, that were respectively after treatment: (266±16) g, (261±16) g, which showed no significant difference between two groups before and after treatment (P>0.05). The volume of ectopic implant before treatment were respectively (85±17) mm3, (85±12) mm3, and showed no significant difference between two groups;that were respectively (48±11) mm3, (24±9) mm3 afte rtreatment, which was significantly decreased compared with the control group (P<0.05). Rats uterine wet weight after treatment were respectively:(0.77±0.16) g, (0.45±0.18) g, and was significantly reduced compared with the control group (P<0.05). (3) The protein expression levels of PCNA, ER and PR in the endometriosis lesions after treatment were respectively 0.282 ± 0.044, 0.51 ± 0.06, 0.49 ± 0.05 in the control group, 0.191 ± 0.020, 0.23 ± 0.03, 0.48 ± 0.06 in the bazedoxifene group; that in eutopic endometrium were respectively 0.369 ± 0.081, 0.56 ± 0.08, 0.56 ± 0.10 in the control group, 0.211 ± 0.037, 0.27 ± 0.05, 0.54 ± 0.08 in the bazedoxifene group;the protein expression levels of PCNA and ER in endometriosis lesions and the eutopic endometrium were significantly decreased in the bazedoxifene group compared with the control group (P<0.05), but the protein levels of PR in endometriosis lesionsand and the eutopic endometrium were not significantly altered by treatment (P>0.05). Conclusion Bazedoxifene could obviously reduce the size of endometriosis lesions, the mechanism may be related with suppressing estrogen-induced proliferation, the expression of ER and direct ER antagonism by this SERM.

Objective To evaluate the outcomes of open reduction and internal fixation of complex tibial plateau fractures with improved three combined approaches.Methods In the period from July 2014 to February 2016,7 complex tibial plateau fractures underwent surgical treatment.These patients included 5 male and 2 female,aged from 24 to 68 years old (average,39.7± 15.3 years).According to Schatzker classification,they were all of type V.And all of type 41B-3.1 by AO/OTA classification.All these fractures were exposed and reduction via three combined approaches.First let the patients lied in lateral prone position,expose the anterolateral and the posterolateral of the tibia1 plateau,and fix the fractures of the posterior in the posterolateral approach,then fix the fractures of the lateral in the anterolateral approach.Then turn the patients to supine position,fix the fractures of the medial in the anteromedial incision.All patients received regular reexamination.The knee function was evaluated at the final follow-up using The Hospital for Special Surgery (HSS) score,the activity of the knee was evaluated by Lysholm score,and the stability of the knee was checked by Lachmantest and Pivot-shift test.The tibial plateau angle,the posterior slope angle and Rasmussen X-ray score were assessed on the X-ray films.Results The average time of operation is (3.3±0.9) h,and the hemorrhage volume in operation was (341± 106) ml for the 7 patients.The wounds of 6 patients healed by (11.8± 1.3) days,while the wound of the rest one of them occurred fat liquefaction after operation who is very fat (BMI ＞ 30) and suffered from diabetes.His wound healed by 21 days.These patients obtained follow-ups of 8 to 14 months (average,11.4±2.8 months).The average full weight-bearing time was 2-3 months (average,2.5±0.4 months).The fractures healed after 8 to 16 weeks (average,11.1 ±2.8 weeks).No displacement of the fractures or breakage of the implants occurred in our series.Nobody has activity limitation of the knee or pain because of the implant,and no never symptoms were noted postoperatively,so we would not take out the implant for these patients.The mean HSS score was 93.1±4.8 (range,from 85 to 100) at the final follow-up,and the excellent rate is 100％.The Lysholm score was 97.1±3.6 (range,from 90 to 100) at the final follow-up.The Lachman test and the Pivot-shift test were negative in our patients,and the mean knee flexion was 128.6±12.8°(range,from 105°to 140°).The fractures were all anatomical reduction by the X-ray after operation,and there had being no displacement of the fractures or breakage of the implants occurred during the follow-up period.The mean posterior slope angle was 8.29±2.87° (range,from 4 °to 12°),which was 8.71±2.63° (range,from 5 °to 14°) 6months after operation.The mean tibial plateau angle was 86.00± 1.41° (range,from 84 °to 88°),which was 86.43± 1.62° (range,from 84 °to 89°) 6 months after operation.The mean Rasmussen X-ray score was 16.86±1.57 (range,from 14 to 18),which was 16.57±1.51 (range,from 14 to 18) 6 months after operation,and the excellent rate are 100％.Conclusion For the complex tibial plateau fractures which simultaneous involved the medial,the lateral and the posterior,the improved three combined approaches showed the advantages of the convenient operation,the satisfactory results of reduction and fixation,and the less trauma and secondary damage,and could be worth for clinic.

Obj ective To observe the position fertilization (IVF)treatment cycle of in vitro cultivation quality blastocyst formation and analyze its relationship with pieces of D2D3 embryo cleav-age count and rating.Methods Cleavage stage 3 day (D3 )frozen surplus embryos were selected and cultured to blastocyst stage.Quality of blastocyst formation was observed,and at the same time their D2D3 embryo cleavage count and debris were discussed.Results The high quality D3 10 or more cells blastocyst formation rate was 38.9%,which was almost equal to 43.1%of 7 to 9 cells blastocyst formation rate (P>0 .05 ).7 to 9 cell quality blastocyst formation rate was 43 .1%, which was significantly higher than 10.2%of 4 to 6 cells (P<0.05).D2 4 cell quality blastocyst formation rate was 43.1%,which was significantly higher than 28.9%of 5 cells and 12.3%of 2 to 3 cells (P<0 .05 ).5 cells quality blastocyst formation rate was 28 .9%,which was almost equal to 23 .4%of 6 cells blastocyst formation rate (P>0 .05 ).Ⅰand classⅡD3 embryos pieces of high quality blastocyst formation rate was 36.4%,which was significantly higher than 6.1%of gradeⅢorⅣ(P<0 .05 ).Ⅰand class ⅡD2 embryos pieces of high quality blastocyst formation rate was 35.3%,which was significantly higher than 4.7% of grade Ⅲ or Ⅳ (P<0.05).Conclusion Extending IVF can effectively filter the embryo developmental potential.The more D3 embryo cleavage count ,the more high-quality blastocysts .D2 4 cells ,embryo blastocyst development ability is good.Ⅰand classⅡD2 and D3 embryos pieces of high quality blastocyst formation rate is higher.High quality blastocyst formation and D2 and D3 embryo cleavage count and debris are closely related to the ratings.

Obj ective To observe the position fertilization (IVF)treatment cycle of in vitro cultivation quality blastocyst formation and analyze its relationship with pieces of D2D3 embryo cleav-age count and rating.Methods Cleavage stage 3 day (D3 )frozen surplus embryos were selected and cultured to blastocyst stage.Quality of blastocyst formation was observed,and at the same time their D2D3 embryo cleavage count and debris were discussed.Results The high quality D3 10 or more cells blastocyst formation rate was 38.9%,which was almost equal to 43.1%of 7 to 9 cells blastocyst formation rate (P>0 .05 ).7 to 9 cell quality blastocyst formation rate was 43 .1%, which was significantly higher than 10.2%of 4 to 6 cells (P<0.05).D2 4 cell quality blastocyst formation rate was 43.1%,which was significantly higher than 28.9%of 5 cells and 12.3%of 2 to 3 cells (P<0 .05 ).5 cells quality blastocyst formation rate was 28 .9%,which was almost equal to 23 .4%of 6 cells blastocyst formation rate (P>0 .05 ).Ⅰand classⅡD3 embryos pieces of high quality blastocyst formation rate was 36.4%,which was significantly higher than 6.1%of gradeⅢorⅣ(P<0 .05 ).Ⅰand class ⅡD2 embryos pieces of high quality blastocyst formation rate was 35.3%,which was significantly higher than 4.7% of grade Ⅲ or Ⅳ (P<0.05).Conclusion Extending IVF can effectively filter the embryo developmental potential.The more D3 embryo cleavage count ,the more high-quality blastocysts .D2 4 cells ,embryo blastocyst development ability is good.Ⅰand classⅡD2 and D3 embryos pieces of high quality blastocyst formation rate is higher.High quality blastocyst formation and D2 and D3 embryo cleavage count and debris are closely related to the ratings.

Chronic endometritis (CE) is one of the common diseases in women of reproductive age, belonging to pelvic inflammatory disease, and characterized by a persistent localized inflammatory state of the endometrium. Clinically, CE often presents as asymptomatic or with atypical symptoms, leading to frequent neglect by obstetricians and gynecologists. In recent years, the incidence of CE has been increasing annually and has become a significant cause of unexplained infertility, recurrent implantation failure, and miscarriage in women. It also plays a crucial role in influencing the outcomes of assisted reproductive technologies. Therefore, safe, effective, and non-invasive diagnostic and therapeutic methods have garnered increasing attention. This article comprehensively elaborated on the etiology, latest diagnostic methods, and multidimensional treatment modalities of CE, providing novel insights into its diagnosis and treatment.

AIM:To verify the safety application of MIL60 in the treatment of corneal neovascularization both in vivo and in vitro.METHODS:We observed the biological characteristics of human corneal epithelial cells.The cell proliferation was analyzed using CCK-8 assay,which also used to test the toxicity of MIL60 and the solvent on cultured human corneal epithelial (HCE).FACs was used to analyze the apoptosis of HCE after treated with MIL60.Also we evaluated the effect of subconjunctival injection of MIL60 on corneal epithelial healing model in normal rat and rats with epithelium defect through slit lamp-microscopy,Draize scores and histopathology way.RESULTS:The proliferation speed of HCE in three groups was the same.MIL60 did no harm on the proliferation of HCE and the apoptosis of HCE,and has no effect on corneal epithelial healing and other parts of the ocular in rats without inflammation cells infiltration.CONCLUSION:When given subconjunctival injection,Mil60 does no harm to the proliferation and apoptosis of HCE,and is safe with ocular application.

Acute traumatic spinal cord injury (SCI) represents one of the most devastating injuries that afflict the human body. Ascorbic acid ( AA) plays an important role in mammalian central nervous system, especially in SCI. In this study, the change of AA concentration after SCI was investigated by using an on-line electrochemical method integrated with in vivo microdialysis. A microdialysis probe (2 mm in length) was implanted into the spinal cord of an anesthetized rat (Thoracic-10). Microdialysis perfusate (2 μL/ min) was collected in the sample loop of an on-line injector for direct injection onto a glassy carbon electrode which was modified with the heat-treated single-walled carbon nanotubes (SWNTs). Normal ascorbic acid concentration in the extracellular fluids of spinal cords was (26. 17 ± 1. 25) μmol/ L (n =8). The experimental spinal cord injury, induced by a lesion at T-10, significantly increased the extracellular ascorbic acid levels to (53. 24± 1. 95) μmol/ L (n =8). This study provides the experimental evidence on the essential roles of ascorbic acid in spinal cord injuries.

BACKGROUNDAtopic dermatitis (AD) is characterized by defective skin barrier and imbalance in T helper 1/T helper 2 (Th1/Th2) cytokine expression. Filaggrin (FLG) is the key protein to maintaining skin barrier function. Recent studies indicated that Th1/Th2 cytokines influence FLG expression in keratinocytes. However, the role of Th1/Th2 cytokines on FLG processing is not substantially documented. Our aim was to investigate the impact of Th1/Th2 cytokines on FLG processing.

METHODSHaCaT cells and normal human keratinocytes were cultured in low and high calcium media and stimulated by either interleukin (IL)-4, 13 or interferon-γ (IFN-γ). FLG, its major processing proteases and key protease inhibitor lymphoepithelial Kazal-type-related inhibitor (LEKTI) were measured by both real-time quantitative polymerase chain reaction and Western blotting. Their expression was also evaluated in acute and chronic AD lesions by immunohistochemistry.

RESULTSIL-4/13 significantly reduced, while IFN-γ significantly up-regulated FLG expression. IL-4/13 significantly increased, whereas IFN-γ significantly decreased the expression of kallikreins 5 and 7, matriptase and channel-activating serine protease 1. On the contrary, IL-4/13 significantly decreased, while IFN-γ increased the expression of LEKTI and caspase-14. Similar trends were observed in AD lesions.

CONCLUSIONSOur results suggested that Th1/Th2 cytokines differentially regulated the expression of major FLG processing enzymes. The imbalance between Th1 and Th2 polarized immune response seems to extend to FLG homeostasis, through the network of FLG processing enzymes.

Caspase 14 ; metabolism ; Cell Line, Tumor ; Cells, Cultured ; Dermatitis, Atopic ; metabolism ; Humans ; Immunohistochemistry ; Interferon-gamma ; metabolism ; Interleukin-13 ; metabolism ; Interleukin-4 ; metabolism ; Intermediate Filament Proteins ; metabolism ; Keratinocytes ; enzymology ; metabolism ; Proteinase Inhibitory Proteins, Secretory ; metabolism ; Serine Peptidase Inhibitor Kazal-Type 5 ; Th1 Cells ; metabolism ; Th2 Cells ; metabolism

This study aims at making full use of microbial resources, and screening the active endophytic fungi of anti-rheumatoid arthritis from Zanthoxylum simulans. The endophytic fungi were cultured and isolated by tissue culture and scribing method, and the active strain of inhibiting the proliferation of human rheumatoid arthritis synovial fibroblasts (HFLS-RA) was screened by MTT method. Morphological characteristics and rDNA ITS1-5.8S-ITS2 sequences were applied for the taxonomy of endophytic fungi. Strains were isolated from Z. simulans. Among them, MK-05, MK-17, MK-19, MK-23 having inhibiting activity to HFLS-RA, the IC₅₀ were 0.367, 0.775, 0.689, 0.757 g·L⁻¹, respectively. By classic morphologic classification and sequencing the PCR-amplified rDNA ITS1-5.8S-ITS2 regions, four effective strains were identified as Botryosphaeria dothidea, Phomopsis sp., P. liquidambari and Diaporthe perseae. The active endophyic fungi that inhibited the proliferation of HFLS-RA were screened from Z. simulans for the first time, and the results lay the foundation for the development and utilization of the Z. simulans resources.

Calycanthaceae family comprises of four genera including Chimonanthus, Sinocalycanthus, Calycanthus, and Idiospermum. The plants of Calycanthaceae are popular ornamental shrubs and used as foods and medicines, which are mainly distributed in China, North America, and Australia. The plants of Calycanthaceae are rich in volatile components, alkaloids, sesquiterpenes and coumarins. Dimeric piperidinoquinoline and dimeric pyrrolidinoindoline alkaloids, dimeric and/or trimeric coumarins are characteristic compositions in these plants. In order to provide timely reference for further investigation and development of Calycanthaceae plants, we made a systemic review on chemical constituents, i.e. alkaloids, terpenoids, flavonoids, coumarins, and steroids, from Calycanthaceae plants, focusing on their chemical structures and pharmacological activities.