Joint line plate fixation for tibial plateau fractures caused by hyperextension varus.

The present study evaluated the outcomes of internal fixation with a joint line plate in the treatment of tibial plateau fractures caused by hyperextension of the varus. The study included 25 cases (13 males and 12 females; age, 19-71 years) of tibial plateau fracture caused by hyperextension of the varus, which were treated at Puai Hospital, Tongji Medical College (Wuhan, China) between January 2015 and June 2017. Fractures were treated with internal fixations of the inner cortex with a self-clipped joint line plate made of steel. After the surgery, patients were examined immediately and at 3, 6 and 12 months. Healing was evaluated by X-ray examination. All cases were cured during follow-up. After surgery, one patient developed partial necrosis of the skin margin of the incision and recovered after a dressing change. Furthermore, one patient with a concomitant peroneal nerve injury and hypoesthesia recovered after treatment with neurotrophic drugs. No screw loosening, fractures or failure of the internal fixations occurred. According to the X-ray results, there were significant differences in the tibial plateau angle (TPA) and medial posterior slope angle (m-PSA) between the pre-operative stage and 12 months post-operatively (P<0.05). However, no significant differences in either the TPA or m-PSA were present between the immediate post-operative stage and 12 months post-operatively (P>0.05). In conclusion, internal fixation with a joint line plate is an appropriate treatment for tibial plateau fractures involving the anteromedial margin with good clinical efficacy.

Prohibitin 1 (PHB1) controls growth and development and regulates proliferation and apoptosis in Schistosoma japonicum.

Schistosomiasis is a zoonotic parasitic disease caused by the trematode blood flukes of the genus Schistosoma. The prodigious egg output of females is the main cause of the disease in definitive hosts, while the female worm relies on continuous pairing with the male worm to fuel the growth and maturation of the reproductive organs and egg production. Prohibitin, which contains the functionally interdependent PHB1 and PHB2 subunits in human and some other species, has been proposed to participate in the cell proliferation and apoptosis regulation in mammals. However, little is known about the function of PHB homolog in the growth and reproductive development of schistosomes. Here, we reported the Phb1 gene that was structurally and evolutionarily conserved in Schistosoma japonicum when compared with that of other species from Caenorhabditis elegans to human. Real-time PCR detected that SjPhb1 was highly transcribed in the vitellaria of female worms. SjPhb1 knockdown achieved through the dsRNA-mediated RNAi in vivo resulted in retarded growth, decreased pairing, and fecundity in adult worms, as well as attenuated pathogenicity or virulence of worms to their hosts. Cell proliferation and apoptosis examination found decreased cell proliferation and increased cell apoptosis in SjPhb1 dsRNA-treated worms. Therefore, our study provides the first characterization of S. japonicum PHB1 and reveals its fundamental role in the regulation of growth and development of S. japonicum by specific dsRNA-mediated RNAi in vivo. Our findings prompt for a promising molecular of schistosomes that can be targeted to effectively retard the growth and development of the schistosomes.

Comparative Transcriptome Analyses of Schistosoma japonicum Derived From SCID Mice and BALB/c Mice: Clues to the Abnormality in Parasite Growth and Development.

Schistosomiasis, caused by the parasitic flatworms called schistosomes, remains one of the most prevailing parasitic diseases in the world. The prodigious oviposition of female worms after maturity is the main driver of pathology due to infection, yet our understanding about the regulation of development and reproduction of schistosomes is limited. Here, we comparatively profiled the transcriptome of Schistosoma japonicum recovered from SCID and BALB/c mice, which were collected 35 days post-infection, when prominent morphological abnormalities could be observed in schistosomes from SCID mice, by performing RNA-seq analysis. Of the 11,183 identified genes, 62 differentially expressed genes (DEGs) with 39 upregulated and 23 downregulated messenger RNAs (mRNAs) were found in male worms from SCID mice (S_M) vs. male worms from BALB/c mice (B_M), and 240 DEGs with 152 upregulated and 88 downregulated mRNAs were found in female worms from SCID mice (S_F) vs. female worms from BALB/c mice (B_F). We also tested nine DEGs with a relatively higher expression abundance in the gonads of the worms (ovary, vitellaria, or testis), suggesting their potential biological significance in the development and reproduction of the parasites. Gene ontology (GO) enrichment analysis revealed that GO terms such as "microtubule-based process," "multicellular organismal development," and "Rho protein signal transduction" were significantly enriched in the DEGs in S_F vs. B_F, whereas GO terms such as "oxidation-reduction process," "response to stress," and "response to DNA damage stimulus" were significantly enriched in the DEGs in S_M vs. B_M. These results revealed that the differential expression of some important genes might contribute to the morphological abnormalities of worms in SCID mice. Furthermore, we selected one DEG, the mitochondrial prohibitin complex protein 1 (Phb1), to perform double-stranded RNA (dsRNA)-mediated RNA interference (RNAi) in vivo targeting the worms in BALB/c mice, and we found that it was essential for the growth and reproductive development of both male and female S. japonicum worms. Taken together, these results provided a wealth of information on the differential gene expression profiles of schistosomes from SCID mice when compared with those from BALB/c mice, which were potentially involved in regulating the growth and development of schistosomes. These findings contributed to an understanding of parasite biology and provided a rich resource for the exploitation of antischistosomal intervention targets.

Comparative Metabonomic Investigations of Schistosoma japonicum From SCID Mice and BALB/c Mice: Clues to Developmental Abnormality of Schistosome in the Immunodeficient Host.

The growth and development of schistosome has been affected in the immunodeficient hosts. But it remains unresolved about the molecular mechanisms involved in the development and reproduction regulation of schistosomes. This study tested and compared the metabolic profiles of the male and female Schistosoma japonicum worms collected from SCID mice and BALB/c mice at 5 weeks post infection using liquid chromatography tandem mass spectrometry (LC-MS/MS) platform, in which the worms from SCID mice were the investigated organisms and the worms from BALB/c mice were used as the controls. There were 1015 ion features in ESI+ mode and 342 ion features in ESI- mode were identified after filtration by false discovery rate. Distinct metabolic profiles were found to clearly differentiate both male and female worms in SCID mice from those in BALB/c mice using multivariate modeling methods including the Principal Component Analysis (PCA), Partial Least Squares Discriminant Analysis (PLS-DA), and Orthogonal Partial Least Squares Discriminant Analysis (OPLS-DA). There were more differential metabolites in female worms than in male worms between SCID mice and BALB/c mice. And common and uniquely perturbed metabolites and pathways were identified among male and female worms from SCID mice when compared with BALB/c mice. The enriched metabolite sets of the differential metabolites in male worms between SCID mice and BALB/c mice included bile acid biosynthesis, taurine and hypotaurine metabolism, sphingolipid metabolism, retinol metabolism, purine metabolism, etc. And the enriched metabolite sets of differential metabolites in female worms included retinol metabolism, alpha linolenic acid and linoleic acid metabolism, purine metabolism, sphingolipid metabolism, glutamate metabolism, etc. Further detection and comparison in transcript abundance of genes of the perturbed retinol metabolism and its associated meiosis process in worms identified clues suggesting accumulated retinyl ester and perturbed meiotic process. These findings suggested an association between the schistosome with retarded growth and development in SCID mice and their perturbed metabolites and metabolic pathways, and provided a new insight into the growth and development regulation of S. japonicum worms from the metabolic level, which indicated great clues for discovery of drugs or vaccines against the parasites and disease with more researches.

Analysis of Staged Treatment for Gustilo Anderson IIIB/C Open Tibial Fractures.

BACKGROUND: Gustilo Anderson III B/C open tibial fractures are more difficult to manage than I, II, and III A fractures. These open tibial fractures are often associated with wound infection, soft tissue necrosis, bone nonunion, osteomyelitis or amputation. Staged treatment for this severe trauma is very necessary. MATERIALS AND METHODS: 25 cases of Gustilo Anderson IIIB/C open tibial fractures with serious soft-tissue defects treated between January 2010 and January 2015 were included in this study. The treatment was administered in three stages. The first stage included emergency debridement, external fixation, repair of damaged main blood vessels and nerves, covering of the wound, and infection control. The second stage involved skin flap or skin graft placement to repair wounds. The third stage involved replacement of the external fixator with an internal fixator and the placement of bone grafts. RESULTS: All the skin flaps or skin grafts survived, and a small necrotic area in the distal flap was observed in only two cases (which resolved spontaneously after the dressing was changed). Bone union occurred at the predicted time in 23 cases, while it was delayed in 2 cases. The rate of excellent and good was 88%. CONCLUSION: Staged treatment was safe and effective for Gustilo Anderson IIIB/C tibial fractures. The timing for the placement of internal and external fixators and choosing the appropriate skin flap repair technique are important.

Emodin mitigates the oxidative stress induced by cisplatin in osteosarcoma MG63 cells.

Previously, the application of cisplatin in chemotherapy was limited due to the significant side effects on normal cell growth. In the present study, the concomitant application of emodin with cisplatin was demonstrated to ameliorate cisplatin-induced oxidative stress and markedly suppress tumor cell proliferation for the first time. Human osteosarcoma MG-63 cells were treated with cisplatin alone or in combination with emodin. The cell viability was determined by MTS assays and the augmentation of reactive oxygen species were determined by fluorogenic probes; in addition, a stable MG-63 subline bearing antioxidant response element (ARE)-driven luciferase expression was developed to monitor the activation of the nuclear factor erythroid 2-related factor 2 (Nrf2)-ARE signaling pathway. The results indicated that cisplatin or emodin may inhibit MG-63 cell proliferation in a time- or dose-dependent manner, respectively. Concomitant treatment with cisplatin and emodin demonstrated synergic anti-tumor effects. Cisplatin augmented reactive oxygen species in the MG-63 cells, followed by the translocation of Nrf2 from the cytoplasm into the nucleus, which triggered ARE-driven luciferase expression. The addition of emodin diminished the previously described phenomenon, resulting in decreased ROS augmentation, translocation of Nrf2 and ARE-driven luciferase activity. In conclusion, emodin could ameliorate cisplatin-induced oxidative stress and protect the cells from oxidative stress-induced damage. The findings of the present study provide a novel strategy for the treatment of osteosarcoma using emodin and cisplatin.

A free anterolateral thigh flap and iliotibial band for reconstruction of soft tissue defects at children's feet and ankles.

BACKGROUND AND PURPOSE: High-energy injury to children caused by a traffic accident is usually characterised by extensive soft tissue defects with exposure or loss of tendons and bone at the foot. Segmental loss of the Achilles tendon along with soft tissue defects is a great challenge for microsurgical reconstruction. Free anterolateral thigh (ALT) flap is indicated for reconstruction of such defects because limited local tissues are available. Additionally, iliotibial band in the donor area can be used to reconstruct the damaged tendon. MATERIALS AND METHODS: Here we described our successful management of 25 paediatric patients with such high-energy injury at feet and ankles in one-stage transplantation of a free ALT flap and an iliotibial band from January 2008 to January 2013. The tendon defect, ranging from 3 to 16cm in length, was reconstructed with an iliotibial band. The flaps ranged from 5 to 12cm in width and 8 to 18cm in length. RESULTS: All the flaps survived completely and no donor site complications were observed. In two flaps there was a small area of distal necrosis which was healed by dressing changes. The mean follow-up time was 14.2 months (from 6 to 24 months). Limb function was assessed using the Maryland Foot Score. The excellent and good rate was 92%. CONCLUSIONS: We believe a free ALT flap is ideal for reconstruction of massive soft tissue defects at the foot and ankle in children and an iliotibial band from the same donor site can be used for reconstruction of a damaged tendon.

Establishment of a cell model for screening antibody drugs against rheumatoid arthritis with ADCC and CDC.

TNFα played a dominant role in the development and progression of rheumatoid arthritis (RA). Clinical trials proved the efficacies of anti-TNFα agents for curing RA. However, most researchers were concentrating on their abilities of neutralizing TNFα, the potencies of different anti-TNFα agents varied a lot due to the antibody-dependent cell-mediated cytotoxicity (ADCC) or complement dependent cytotoxicity (CDC). For better understanding and differentiating the potentiality of various candidate anti-TNF reagents at the stage of new drug research and development, present study established a cell model expressing the transmembrane TNFα for usage in in vitro ADCC or CDC assay, meanwhile, the assay protocol described here could provide guidelines for screening macromolecular antibody drugs. A stable cell subline bearing transmembrane TNFα was first established by conventional transfection method, the expression of transmembrane TNFα was approved by flow cytometer, and the performance of the stable subline in ADCC and CDC assay was evaluated, using human peripheral blood mononuclear cells as effector cells, and Adalimumab as the anti-TNFα reagent. The stable cell subline demonstrated high level of surface expression of transmembrane TNFα, and Adalimumab exerted both ADCC and CDC effects on this cell model. In conclusion, the stable cell line we established in present research could be used in ADCC or CDC assay for screening antibody drugs, which would provide in-depth understanding of the potencies of candidate antibody drugs in addition to the traditional TNFα neutralizing assay.

Advances in serous tubal intraepithelial carcinoma: correlation with high grade serous carcinoma and ovarian carcinogenesis.

Early serous carcinoma in fallopian tube or serous tubal intraepithelial carcinoma (STIC), an early lesion limited to the epithelium of the fallopian tube and firstly identified from specimen obtained by prophylactic salpingo-oophorectomy, has provided insight into pelvic high grade serous carcinoma (HGSC). Increasing evidence indicates that STIC is a likely precursor for HGSC and several studies have focused on this lesion and its clinical significance. This review addresses recent advances in recognizing STIC and its correlation with HGSC and ovarian carcinogenesis. It also describes evidence regarding the fallopian tube as a source of some HGSCs, the protocol for optimizing histological evaluation of the tubes, the spectrum of tubal lesions from benign to noninvasive carcinoma, changes in diagnostic criteria from purely morphologic characteristics to a combination of morphologic features and molecular biomarkers, and new studies about potential biomarkers. However, the direct evidence regarding STIC as the precursor of HGSC is still tantalizing due to other possibilities that may also explain the origin of pelvic HGSC. Further molecular genetic studies are required to address this important question.

[Effects of miR-135a on HOXA10 expression, proliferation and apoptosis of ovarian cancer cells].

OBJECTIVE: To investigate the effects of miR-135a on HOXA10 expression, proliferation and apoptosis of SKOV3 cells. METHODS: (1) Through computer-aided algorithms,the predicted target gene of miR-135a (HOXA10)were determined. (2) miR-135a mimics, miR-135a inhibitor and negative control were transfected into SKOV3 cells, respectively.Reverse transcription (RT)-PCR, western blot analysis were used to examine the expression levels of HOXA10 at different times (24, 48 and 72 hours). (3) A luciferase reporter assay was used to confirm the direct regulation between miR-135a and HOXA10. (4) SKOV3 cells proliferation at different times (24,48 and 72 hours) was detected by methyl thiazolyl tetrazolium (MTT) assay [quantified by absorbance(A)]. Western blot was used to examine the expression of apoptosis-associated protein bcl-2, bax and caspase-3 in SKOV3 cells after 48 hours transfection. RESULTS: (1) HOXA10 was predicted to be the target gene of miR-135a by computer-aided algorithms. (2) RT-PCR shown that HOXA10 mRNA levels were decreased over time (24, 48 and 72 hours) after miR-135a mimics transfection in SKOV3 cells (0.94 ± 0.04 vs 0.78 ± 0.03 vs 0.70 ± 0.03, P < 0.05). While, the expression of HOXA10 mRNA was increased over time after miR-135a inhibitor transfection (1.14 ± 0.05 vs 1.16 ± 0.03 vs 2.60 ± 0.08,P < 0.05). After transfected with miR-135a mimics or miR-135a inhibitor over 48 and 72 hours, the HOXA10 expression levels in SKOV3 cells were significantly lower or higher than each control group, respectively (all P < 0.01). Western blot analysis of HOXA10 expression in SKOV3 cells confirmed the results of RT-PCR detected. (3) After cotransfection of miR-135a plasmid and pMIR-REPORT luciferase plasmid containing HOXA10, luciferase reporter assays showed that the luciferase activity reduced by 67.8% (P < 0.01). (4) MTT showed that SKOV3 cells growth after miR-135a mimics transfection for 48 and 72 hours were significantly lower than those in control group (0.38 ± 0.03 vs 0.52 ± 0.05, 0.67 ± 0.05 vs 0.75 ± 0.06;respectively,all P < 0.05).While, SKOV3 cells transfected with miR-135a inhibitor for 72 hours grew significantly faster than that in control group (0.95 ± 0.05 vs 0.75 ± 0.06, P < 0.01). After miR-135a mimics transfection, the level of bcl-2 protein was significantly lower than that in control group (0.28 ± 0.06 vs 0.76 ± 0.09,P < 0.01). The activity of caspase-3 was significantly higher than that in control group (115.0 ± 2.4 vs 95.4 ± 2.1, P < 0.01). While, there was no statistical difference of bax expression (P = 0.142). However, after miR-135a inhibitor transfection, the expression level of bcl-2 protein was significantly higher than that in control group (0.92 ± 0.03 vs 0.76 ± 0.09, P = 0.037) and the activity of caspase-3 was significantly lower than that in control group (59.5 ± 4.1 vs 95.4 ± 2.1, P < 0.01). There was also no statistical difference of bax expression (P = 0.066). CONCLUSION: miR-135a may play an important role in cell proliferation and apoptosis of ovarian cancer cells by regulating HOXA10 and its downstream pathways.

[Establishment of a goat model of tibial bone hole defect suitable for repair using injectable bone materials].

OBJECTIVE: To prepare a goat model of tibial bone hole defect suitable for studies of bone defect repair using tissue-engineered injectable bone materials. METHODS: A circular hole bone defect 1.2 cm in diameter was induced below the tibial medial plateau of the goat. X-ray, histological inspection, and image analysis were carried out to evaluate the validity of the model in simulating limb bone defect for the study of tissue-engineered injectable bone materials. RESULTS: At 4 and 8 weeks after the operation, neither X-ray nor histological examination showed obvious bone tissues in the bone defect. Image analysis showed a area of new bone tissue formation of (8.79 - or + 3.63)% in the total defect area at 4 weeks, which increased to (15.41 - or + 4.21)% at 8 weeks. CONCLUSION: The goat model of tibial bone hole defect established in this study is suitable for studying the ability of injectable bone materials for repairing limb bone defect, and offers a simple and reliable means to simulate the local condition of bone regeneration and mechanical environment of bone defect in the limbs.