The fertility-sparing treatment and outcome of epithelioid trophoblastic tumor isolated to lung: a case report and review literature.

Background: Epithelioid trophoblastic tumor (ETT) is the rarest gestational trophoblastic tumor, with poor response to chemotherapy. Hysterectomy, as the cornerstone therapy for early ETT, is particularly challenging in reproductive-age women who often have a strong desire for fertility preservation. The management of extra-uterine ETT could be even more complicated and inconsistent. Here we reported a case of isolated ETT lesions in lungs managed with thoracic surgery without hysterectomy. Case presentation: A 32-year-old woman presented with amenorrhea for 2 months. Her serum ß- human chorionic gonadotropin (hCG) levels fluctuated between 52 and 75 mIU/mL. The patient underwent removal of intrauterine device and suction and curettage, but only proliferative endometrium was found. Methotrexate was given for a provisional diagnosis of ectopic pregnancy of unknown location, while ß-hCG had no significant decline. She complained of mild chest pain during the past half year, and the chest computed tomography (CT) result showed two mixed ground-glass nodules of 24 mm × 14.2 mm in right upper lobe and 10 mm × 8 mm in the right lower lobe and a thin-walled cavity in the posterior segment of the left lower lobe. Right upper wedge resection and right lower segmentectomy were performed 3 months later. The result of the pathological examination of pulmonary mass indicated an epithelioid trophoblastic tumor. She was diagnosed with ETT at stage III (with right lung metastasis) according to FIGO 2000. Her menstrual cycle recovered within 1 month after the first thoracic surgery. However, ß-hCG was elevated again to 9 mIU/mL, and the positron emission tomography/computed tomography (PET/CT) scans revealed the consolidation of the nodule in the left lower lobe which enlarged to about 1.0 cm × 1.7 cm. Her second pulmonary surgery without hysterectomy was conducted. Followed for 12 months for postoperative monitoring, the patient was found to be disease-free with negative results of serial serum ß-hCG and chest CT. Conclusion: Our case highlights the efficacy of fertility-sparing surgery for isolated ETT in lungs. The surgical management of pulmonary isolated ETT could be individualized under long-term supervision. Sporadic reports on the favorable outcome of extra-uterine ETT with fertility-sparing surgery were described in the last decades. The safety of this surgical strategy might be warranted only if enough reliable data is accumulated.

[Adsorption behavior of low density lipoprotein on titanium surface].

PURPOSE: The purpose of this study was to investigate the adsorption of low density lipoprotein (LDL) on titanium surface. METHODS: Pure titanium specimens were soaked with different concentrations of LDL (0, 1, 2 mg/mL). Low density lipoprotein essay was used to analyze the change of LDL adsorption on titanium surface with time going on. Scanning electron microscope(SEM) and X-ray photoelectron spectroscopy(XPS) were used to observe and analyze the adsorption of LDL on titanium surface and its effect on element composition of titanium surface. Contact angle of titanium surface was detected before and after LDL adsorption. SPSS 22.0 software package was used for statistical analysis of the data. RESULTS: The adsorption amount of LDL on titanium surface gradually increased as time went on. XPS analysis results showed that LDL was adsorbed on the titanium surface, the content of titanium and oxygen elements seemed to decrease on the titanium surface, and the hydrophilicity of the titanium surface declined. CONCLUSIONS: LDL can adsorb on titanium surface, which can change the physical and chemical properties of titanium surface to a certain extent.

Osseointegration of titanium dental implant under fluoride exposure in rabbits: Micro-CT and histomorphometry study.

OBJECTIVE: This study aims to investigate the influence of fluoride exposure on implant osseointegration. METHODS: A total of 24 male New Zealand white rabbits were randomly divided into the control group and the fluoride exposure group. Rabbits in the control group were fed with tap water, while those in the fluoride exposure group were given 200 mg/L sodium fluoride solution. After 2-month feeding, implants were inserted into the extraction socket immediately after extraction of rabbit mandibular anterior teeth. Four rabbits in each group were sacrificed to collect the implants samples at 1, 2, and 3 months post-implantation, respectively. Radiographic and histomorphometry examinations were performed to evaluate the condition of implant osseointegration. RESULTS: Bone volume around the implants increased in a time-dependent manner in both groups. Micro-CT images illustrated that the bone mineral density (BMD) in the fluoride exposure group was significantly lower than that in the control group after implantation for 2 and 3 months. The bone-implant contact ratio (BIC) in the fluoride exposure group was much lower than that of the control group at 3 months post-implantation according to histomorphometry examination. CONCLUSIONS: In rabbit animal model, high fluoride exposure affected the quality of bone surrounding the implant and significantly reduced bone integration of the implant, especially in the late stage of osseointegration.

Regulation of osteoblast behaviors via cross-talk between Hippo/YAP and MAPK signaling pathway under fluoride exposure.

Titanium is widely used in implant materials, while excessive fluoride may have negative effects on the osseointegration between the titanium and osteoblasts. Although the underlying mechanisms are still not clear, the mitogen-activated protein kinase (MAPK) or Yes-associated protein (YAP) signaling pathways are thought to be involved. This study evaluated the role of Hippo/YAP and MAPK signaling pathway in osteoblast behaviors under excessive fluoride exposure in vitro and in vivo. Commercially pure Ti (cp-Ti) samples were exposed to fluoride (0, 0.1, and 1.0 mM NaF) for 7 days. Cell adhesion was observed using a laser scanning confocal microscope. Cell viability and apoptosis were evaluated by CCK-8 assay and flow cytometry, respectively. The expressions of osteoblast markers and key molecules in MAPK and YAP pathway were detected by Western blot. In vivo studies were evaluated by histology methods in C57/BL6 mice model. Our results showed that 1.0 mM NaF destroyed the passivation film on cp-Ti surface, which further inhibited the osteoblast adhesion and spreading. Meanwhile, compared to other groups, 1.0 mM NaF led to a remarkable reduction in cell viability (P < 0.05), as well as increased apoptosis (P < 0.05) and downregulation of osteogenesis protein expression (P < 0.05). MAPK and YAP signaling pathways were also activated under 1.0 mM NaF exposure, and JNK seemed to regulate YAP phosphorylation in response to NaF impacts on osteoblasts. In vivo fluorosis mouse model further indicated that 100 ppm NaF group (high fluoride group) increased bone resorption and inhibited the nuclear translocation of YAP. The osteoblast behaviors were negatively altered under excessive fluoride, and MAPK/JNK axis contributed to YAP signaling activation in regulating NaF-induced osteoblast behaviors. KEY MESSAGES: • Excessive fluoride inhibited osteoblast behaviors and bone formation. • YAP and MAPK signaling pathways were activated in osteoblasts under fluoride exposure. • Fluoride regulated osteoblast behaviors via the cross-talk between YAP and MAPK.

Effect of titanium ions on the Hippo/YAP signaling pathway in regulating biological behaviors of MC3T3-E1 osteoblasts.

Titanium (Ti) and its corresponding alloys have been widely applied in dental and orthopedic implants. Owing to abrasion and corrosion of implants in the unfavorable electrolytic aqueous environment of the host body, Ti ions could be released from implants and accumulated in local tissues. Recent studies have found that excessive Ti ions were toxic to osteoblasts in adjacent bone tissues and subsequently influenced long-term effects on implant prostheses. However, the potential molecular mechanisms underlying the damage to osteoblasts induced by Ti ions remained unclear. Hippo signaling has been confirmed to be involved in organ size and tissue regeneration in many organs, while its roles in osteoblasts differentiation and bone repair remained elusive. Therefore, we hypothesize that YAP, a regulator of Hippo pathway, inhibited osteoblast growth, skeletal development and bone repair, as well as excessive Ti ions promoted the progression of YAP activation. This study aimed to explore the role of Hippo/YAP signaling pathway in the biotoxicity effect of Ti ions on osteoblast behaviors. Here, we confirmed that 10 ppm Ti ions, a minimum concentration gradient previously reported that was capable of suppressing osteoblasts growth, induced nuclear expression of YAP in osteoblasts in our study. Furthermore, 10 ppm Ti ion-induced YAP activation was found to downregulate osteogenic differentiation of MC3T3-E1 cells. Most importantly, the hypothesis we proposed that knockdown of YAP did reverse the inhibitory effect of 10 ppm Ti ions on osteogenesis has been verified. Taken together, our work provides insights into the mechanism of which YAP is involved in regulating osteoblast behaviors under the effect of Ti ions, which may help to develop therapeutic applications for Ti implant failures and peri-implantitis.