Denosumab treatment for progressive Enneking stage II cervical giant-cell tumor conservatively.

Cervical giant cell tumor of the bone (GCTB) is a rare, primary benign bone tumor in pediatric patients. Surgery remains the primary choice for treating resectable cervical GCTB. Additional adjuvant therapeutic options are available for patients with unresectable cervical GCTB, including the anti-RANKL monoclonal antibody, denosumab. We represented a case incidentally found in a 7-year-old female, who complained severe craniocervical pain, grade 2-3 dysphagia, dysphonia, hypesthesia, and extremity weakness. The patient showed an impressive clinical response to denosumab, both clinically and radiologically, without adverse events or recurrence. To date, this is the youngest patient ever reported to have a progressive Enneking stage II C3 GCTB treated with denosumab alone. Denosumab can be administered as a single and conservative therapy for pediatric patients with unresectable upper cervical GCTB, avoiding the risks and morbidity of surgical and radiative treatment.

The relationship between adjuvant radiotherapy and survival of osteosarcoma: a case-control study.

To investigate whether adjuvant radiotherapy (RT) is associated with survival rate of osteosarcoma patients. A total of 3938 osteosarcoma patients between 1975 and 2016 from Surveillance, Epidemiology, and End Results (SEER) database were enrolled in this study. Survival rate was obtained by Kaplan-Meier method, with log-rank test identifying the difference. Multivariate Cox regression analysis was used to explore independent prognostic factors. The 5-year overall survival (OS) and cancer-specific survival (CSS) rates in surgery plus adjuvant RT group and surgery alone group were 38.2%, 66.3% (OS), and 41.6%, 68% (CSS), respectively. Multivariate analysis showed that adjuvant RT served as the independent unfavorable prognostic factor for OS and CSS. Based on the propensity score matching (PSM) method, the patients who received adjuvant RT had a poorer prognosis. Adjuvant RT showed an association with survival of osteosarcoma. Patients who received adjuvant RT had poorer survival. In the clinical use of adjuvant RT for osteosarcoma, the potential for reduced survival should be considered.

Surgical strategy and outcomes for thoracolumbar disc herniation with Autologous Bone-Fusion or Cage-Fusion surgery: case series and literature review.

To analyze the clinical characteristics and surgical outcomes of TLDH with Autologous Bone-Fusion for T10-L1 TLDH or Cage-Fusion for T12-L3 TLDH. This is a retrospective multi-center clinical study, involving a total of 43 patients with TLDH who underwent surgery in our institutions from December 2013 to January 2021. In all, 15 of 43 patients (34.9%) with T10-11(2)/T11-12(5)/T12-L1 (8) TLDH underwent Autologous Bone-Fusion surgery and 28 of 43 patients (65.1%) with T12-L1(3)/L1-L2(12)/L2-L3(13) TLDH underwent Cage-Fusion surgery. Demographic data, clinical characteristics and perioperative outcomes were recorded. During the follow-up, pre- to post-operative ODI, VAS back and leg pain scores significantly decreased (P1.2 = 0.001) and the score changes had no significant difference between two groups (P3 = 0.81, 0.59, 0.68). The intraoperative blood loss and operation time showed no significant difference between two groups (P = 0.056, 0.072). The patients showed prominent improvement of hypokinesia and satisfactory rate in two groups (5/7, 71.4% VS 9/12, 75.0%, P = 0.633; 11, 73.3% VS 25, 89.3%, P = 0.281). Notably, no recurrence and severe complications were reported. The choice of surgery approach should be individualized by clinical characteristics and radiology. Selectively Autologous Bone-Fusion for T10-L1 TLDH or Cage-Fusion for T12-L3 TLDH provided adequate nerve decompression and immediate stability. The overall fusion surgical outcomes were satisfactory without major complications during follow-up.

Elevated procalcitonin levels in the absence of infection in procalcitonin-secretin hepatocellular carcinoma: A case report.

BACKGROUND: Serum procalcitonin (PCT) is widely used to diagnose bacterial infection and sepsis. However, PCT may be elevated in some neoplasms. It is important to distinguish infection from no infection in such neoplasms. The relationship between hepatocellular carcinoma (HCC) and PCT is unknown. CASE SUMMARY: A 62-year-old male was admitted due to a hepatic lesion of unknown origin. The patient had an elevated PCT level. Infectious diseases were excluded after appropriate examination. He then underwent exploratory laparotomy and a left lateral hepatectomy was performed. The patient recovered with an uneventful postoperative course and PCT level decreased gradually and was normal on day 16. HCC was diagnosed by histopathology and no evidence of infection was observed. Furthermore, immunohistochemical analyses revealed that tumor cells were positive for PCT. CONCLUSION: HCC cells can secrete PCT in the absence of infection and PCT may be used as a marker to monitor the efficacy of tumor therapy.

CT45A1 promotes the metastasis of osteosarcoma cells in vitro and in vivo through ß-catenin.

Increased expression of cancer/testis antigens (CTAs) is reported in various tumors. However, the unique role of CTAs in tumor genesis has not yet been verified. Here, we first report the functional role of CT45A1 in the carcinogenesis of osteosarcoma. RNA sequencing and immunohistochemistry confirmed that elevated expression of CT45A1 was detected in osteosarcoma, especially in metastatic tissues of osteosarcoma. Furthermore, osteosarcoma patients with poorer prognosis showed high expression of CT45A1. In cell tests, CT45A1 overexpression was shown to strengthen the proliferation, migration, and invasion abilities of osteosarcoma cells, while silencing CT45A1 markedly elicited the opposite effects in these tests by disrupting the activation of ß-catenin. In summary, we identify a novel role of CT45A1 in osteosarcoma. Furthermore, our results suggested that CT45A1 may contribute to the development of osteosarcoma and could be a possible therapeutic target for osteosarcoma patients.

Successful laparoscopic treatment for sustained abdominal pain due to fish bone migrating into the neck of the pancreas: a case report and thinking about surgical approach through the literature review.

BACKGROUND: The majority of ingested foreign bodies pass through the gastrointestinal tract smoothly, with less than 1% requiring surgery. Fish bone could perforate through the wall of stomach or duodenum and then migrate to other surrounding organs, like the pancreas and liver. CASE PRESENTATION: We report herein the case of a 67-year-old male who presented with sustained mild epigastric pain. Abdominal computed tomography revealed a linear, hyperdense, foreign body along the stomach wall and pancreatic neck. We made a final diagnosis of localized inflammation caused by a fish bone penetrating the posterior wall of the gastric antrum and migrating into the neck of the pancreas. Upper gastrointestinal endoscopy was performed firstly, but no foreign body was found. Hence, a laparoscopic surgery was performed. The foreign body was removed safely in one piece and was identified as a 3.2-cm-long fish bone. The patient was discharged from the hospital on the fifth day after surgery without any postoperative complications. CONCLUSION: Laparoscopic surgery has proven to be a safe and effective way to remove an ingested fish bone embedded in the pancreas.

Intrahepatic cholangiocarcinoma is more complex than we thought: A case report.

BACKGROUND: Brain metastasis from intrahepatic cholangiocarcinoma is rare. To the best of our knowledge, only a few cases have been reported. The biological behavior was complex, and treatment requires further investigation. CASE SUMMARY: A 62-year-old woman complained of left limb weakness. Abdominal computed tomography showed a 5.0 cm × 5.6 cm lesion in the left lobe of the liver. Tumor markers were normal. Serological analysis indicated absence of hepatitis virus. Brain magnetic resonance imaging revealed a 1.0 cm × 1.3 cm mass in the right frontal lobe. Intrahepatic cholangiocarcinoma with brain metastasis was diagnosed by our liver cancer multidisciplinary team. After sufficient preparation, the patient underwent partial frontal lobotomy and left hemihepatectomy. Histopathological results confirmed that both the lesions were cholangiocarcinoma. Six cycles of gemcitabine combined with S1 were administered. During a 39 mo postoperative follow-up, no sign of local recurrence or distant metastasis was observed. CONCLUSION: This case expands our knowledge concerning the complex and heterogeneous nature of tumor metastasis.

Blueberry anthocyanin­enriched extract ameliorates transverse aortic constriction­induced myocardial dysfunction via the DDAH1/ADMA/NO signaling pathway in mice.

Blueberry anthocyanin­enriched extract (BAE) has been demonstrated to protect against cardiovascular diseases by activating multiple target genes. The present study investigated the effects of BAE on transverse aortic constriction (TAC)­induced myocardial dysfunction in mice and explored its possible molecular mechanisms. A total of 30 male mice were divided randomly into control, TAC and TAC + BAE groups. Mice in the TAC + BAE groups were administered BAE by oral gavage for 6 consecutive weeks. Myocardial dysfunction was assessed using echocardiogram, histopathology, TUNEL assay, immunofluorescence staining, reverse transcription­quantitative PCR and western blot analysis. The results demonstrated that BAE treatment significantly ameliorated heart weight, left ventricular weight, myocardial dysfunction, left ventricular hypertrophy and fibrosis. In addition, BAE treatment alleviated TAC­induced inflammation, oxidative stress and apoptosis. Notably, BAE treatment markedly reduced asymmetric dimethylarginine (ADMA) concentration and significantly increased dimethylarginine dimethylaminohydrolase 1 (DDAH1) expression and nitric oxide (NO) production. The present data indicated that BAE treatment ameliorated TAC­induced myocardial dysfunction, oxidative stress, inflammatory response and apoptosis via the DDAH1/ADMA/NO signaling pathway.

Inhalation cancer risk estimation of source-specific personal exposure for particulate matter-bound polycyclic aromatic hydrocarbons based on positive matrix factorization.

In previous studies, inhalation cancer risk was estimated using conventional risk assessment method, which was normally based on compound-specific analysis, and cannot provide substantial data for source-specific particulate matter concentrations and pollution control. In the present study, we applied an integrated risk analysis method, which was a synthetic combination of source apportionment receptor model and risk assessment method, to estimate cancer risks associated to individual PAHs coming from specific sources. Personal exposure particulate matter samples referring to an elderly panel were collected in a community of Tianjin, Northern China, in 2009, and 12 PAH compounds were measured using GC-MS. Positive matrix factorization (PMF) was used to extract the potential sources and quantify the source contributions to the PAH mixture. Then, the lung cancer risk of each modeled source was estimated by summing up the cancer risks of all measured PAH species according to the extracted source profile. The final results indicated that the overall cancer risk was 1.12 × 10-5, with the largest contribution from gasoline vehicle emission (44.1%). Unlike other risk estimation studies, this study was successful in combining risk analysis and source apportionment approaches, which allow estimating the potential risk of all source types and provided suitable information to select prior control strategies and mitigate the main air pollution sources that contributing to health risks.

Simvastatin With PRP Promotes Chondrogenesis of Bone Marrow Stem Cells In Vitro and Wounded Rat Achilles Tendon-Bone Interface Healing In Vivo.

BACKGROUND: Tendons and ligaments are joined to bone in a specialized interface that transmits force from muscle to bone and permits body movement. Tendon/ligament injuries always occur in the interface areas, and injured tendons/ligaments have a limited healing response because the insertion site is composed of a fibrocartilaginous zone. PURPOSE: To study the effect of simvastatin with platelet-rich plasma (PRP) on chondrogenesis of rat bone marrow stem cells (BMSCs) in vitro and wounded rat Achilles tendon-bone interface healing in vivo. STUDY DESIGN: Controlled laboratory study. METHODS: The in vitro model was performed by the culture of rat BMSCs with various concentrations of simvastatin (0, 10, 50, 100 nM) for 2 weeks. The effect of simvastatin on the chondrogenic differentiation of the BMSCs was examined by histochemical analysis and real-time quantitative reverse transcription polymerase chain reaction. The in vivo model was carried out by testing the healing effect of simvastatin with PRP on 12 wounded rat Achilles tendon-bone interfaces. RESULTS: Simvastatin induced chondrogenic differentiation of rat BMSCs in a concentration-dependent manner as evidenced by histological staining and real-time quantitative reverse transcription polymerase chain reaction. The wounds treated with simvastatin alone or with simvastatin-containing PRP gel healed much faster than the wounds treated with saline alone or PRP alone. Histological analysis showed that higher percentages of healed tissues were positively stained with safranin O and fast green in wounds treated with simvastatin-containing PRP gel than in the other 3 groups. Immunohistochemical analysis further demonstrated these findings, as evidenced by more positively stained healed tissues with collagen I and II antibodies in the wound areas treated with simvastatin-containing PRP gel than the other 3 groups. CONCLUSION: The combination of simvastatin with PRP induced chondrogenesis of BMSCs in vitro and enhanced fibrocartilage formation in vivo. The simvastatin-PRP gel treatment promotes wounded tendon-bone interface healing in clinical treatment. CLINICAL RELEVANCE: The combination of simvastatin with PRP may be a good clinical treatment for wounded tendon/ligament junction healing, especially for acute sports-related tendon/ligament injuries.

A novel curcumin-loaded nanoparticle restricts atherosclerosis development and promotes plaques stability in apolipoprotein E deficient mice.

Although curcumin possesses anti-atherogenic and anti-inflammatory properties, its application is limited because of its low aqueous solubility and poor oral bioavailability. Recently, our group synthesized a novel linear-dendrimer methoxy-poly (ethylene glycol)-b-poly(ε-caprolactone) copolymer nanoparticle loading curcumin (Cur-NPs) which could improve solubility and release property of curcumin. In the present study, we further evaluated its anti-atherosclerotic effect in apolipoprotein E-/- mice. Our results demonstrated that the Cur-NPs significantly decreased atherosclerotic lesion areas and were more effective in stabilizing vulnerable plaques compared with free curcumin. The anti-atherosclerotic mechanisms of Cur-NPs include decreasing the number of introplaque microvessels, inhibiting the matrix metalloproteinase 2 and 9 activity, reducing the inflammatory response and regulating lipoprotein cholesterol metabolism more effectively compared with free curcumin. Furthermore, Cur-NPs could increase the amount of curcumin in the thoracic aorta and no significant toxicity was observed in the blood biochemical parameters in Cur-NPs-treated groups. Overall, our findings suggested that Cur-NPs could be a stabilized aqueous formulation for application with improved curcumin activity, which could be a potential treatment strategy for arteriosclerosis in the future.

Bioinformatics analysis of the gene expression profiles in human intervertebral disc degeneration associated with inflammatory cytokines.

BACKGROUND: To investigate the microarray data on the gene expression profiles of intervertebral disc degeneration related to cytokine exposure. The purpose of the study was to identify the key genes that were differentially expressed in these disc cells compared to cells without inflammatory cytokine treatment, using bioinformatics analyses, and to explore the related signaling pathways and interaction networks, providing clues to the molecular mechanisms of disc degeneration for future experimental studies. METHODS: The gene expression profiles data were obtained using the same microarray platform for two groups of patients suffering from degenerative disc diseases: GSE41883 (Human annulus disc cells exposed to TNF-a; 4 samples) and GSE27494 (Human annulus disc cells exposed to IL-1ß; 4 samples). The genes that were differentially expressed in these two datasets compared to control disc cells (without cytokine exposure; 4 samples each) were identified using the R language, and were pooled using the Excel software program to select the common differentially expressed genes in the two datasets. The initial functional clustering, signaling pathways and protein-protein interaction relationship analyses were conducted using the DAVID and STRING software programs. RESULTS: Of the 255 concomitantly and differentially expressed genes identified after respective treatment with TNF-α and IL-1ß, 141 were up-regulated and 114 were down-regulated. The gene ontology annotation analysis showed that these differentially expressed genes were primarily associated with cytokine activity, growth factor activity, the inflammatory reaction and the response to injury. The signaling pathway analysis showed that these differentially expressed genes were mainly related to the interactions of cytokines, apoptosis and NOD-like receptor signaling pathways. The interaction network analysis indicated that PTGS2, ICAM1, NOV and other genes may play a role in disc degeneration. CONCLUSIONS: We found that ICAM1 and other genes may play a role in the development of disc degeneration induced by inflammatory reactions using a bioinformatics analysis of the gene expression profiles of degenerative intervertebral disc cells stimulated with inflammatory factors, suggesting that bioinformatics methods can be used to identify potential target for intervertebral disc degeneration.

Effect of Clonidine on Hemodynamic Responses During Laparoscopic Cholecystectomy: A Systematic Review and Meta-Analysis.

BACKGROUND: Clonidine might be beneficial to the patients undergoing laparoscopic cholecystectomy. This meta-analysis focused on the influence of clonidine on hemodynamic responses in patients undergoing laparoscopic cholecystectomy. METHODS: We searched several databases including PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases. This meta-analysis included randomized controlled trials regarding the influence of clonidine versus placebo on laparoscopic cholecystectomy. The primary outcomes were mean arterial pressure (MAP) and heart rate (HR) at pneumoperitoneum. The random-effect model was applied for this study. RESULTS: Compared with control intervention, clonidine intervention was found to significantly reduce the MAP at pneumoperitoneum [standard mean difference=-2.58; 95% confidence interval (CI),-4.63 to -0.53; P=0.01), HR at pneumoperitoneum (standard mean difference=-3.67; 95% CI, -6.57 to -0.76; P=0.01), MAP at intubation (standard mean difference=-2.40; 95% CI, -4.75 to -0.06; P=0.04), HR at intubation (standard mean difference=-3.39; 95% CI, -5.75 to -1.02; P=0.005), propofol requirement (standard mean difference=-2.25; 95% CI, -4.01 to -0.48; P=0.01), as well as postoperative nausea and vomiting (risk ratio, 0.35; 95% CI, 0.19-0.63; P=0.0005). CONCLUSIONS: Compared with control intervention, clonidine intervention was found to significantly reduce MAP and HR at pneumoperitoneum and intubation, propofol requirement, as well as postoperative nausea and vomiting in patients undergoing laparoscopic cholecystectomy.

Determination of urine-derived odorous compounds in a source separation sanitation system.

Source separation sanitation systems have attracted more and more attention recently. However, separate urine collection and treatment could induce odor issues, especially in large scale application. In order to avoid such issues, it is necessary to monitor the odor related compounds that might be generated during urine storage. This study investigated the odorous compounds that emitted from source-separated human urine under different hydrolysis conditions. Batch experiments were conducted to investigate the effect of temperature, stale/fresh urine ratio and urine dilution on odor emissions. It was found that ammonia, dimethyl disulfide, allyl methyl sulfide and 4-heptanone were the main odorous compounds generated from human urine, with headspace concentrations hundreds of times higher than their respective odor thresholds. Furthermore, the high temperature accelerated urine hydrolysis and liquid-gas mass transfer, resulting a remarkable increase of odor emissions from the urine solution. The addition of stale urine enhanced urine hydrolysis and expedited odor emissions. On the contrary, diluted urine emitted less odorous compounds ascribed to reduced concentrations of odorant precursors. In addition, this study quantified the odor emissions and revealed the constraints of urine source separation in real-world applications. To address the odor issue, several control strategies are recommended for odor mitigation or elimination from an engineering perspective.

TNF-α promotes osteoclastogenesis through JNK signaling-dependent induction of Semaphorin3D expression in estrogen-deficiency induced osteoporosis.

Tumor necrosis factor α (TNF-α)-induced osteoclast formation have been demonstrated to play an important role in the pathogenesis of estrogen deficiency-mediated bone loss, but the exact mechanisms by which TNF-α enhanced osteoclast differentiation were not fully elucidated. The class III semaphorins members were critical to regulate bone homeostasis. Here, we identified a novel mechanism whereby TNF-α increasing Semaphorin3D expression contributes to estrogen deficiency-induced osteoporosis. In this study, we found that Semaphorin3D expression was upregulated by TNF-α during the process of RANKL-induced osteoclast differentiation. Inhibition of Semaphorin3D in pre-osteoclasts could attenuate the stimulatory effects of TNF-α on osteoclast proliferation and differentiation. Mechanistically, blocking of the Jun N-terminal kinase (JNK) signaling markedly rescued TNF-α-induced Semaphorin3D expression, suggesting that JNK signaling was involved in the regulation of Semaphorin3D expression by TNF-α. In addition, silencing of Semaphorin3D in vivo could alleviate estrogen deficiency-induced osteoporosis. Our results revealed a novel function for Semaphorin3D and suggested that increased Semaphorin3D may contribute to enhanced bone loss by increased TNF-α in estrogen deficiency-induced osteoporosis. Thus, Semaphorin3D may provide a potential therapeutic target for the treatment of estrogen-deficiency induced osteoporosis.

Direct and indirect photodegradation pathways of cytostatic drugs under UV germicidal irradiation: Process kinetics and influences of water matrix species and oxidant dosing.

The ever-increasing consumption of various cytostatic drugs (CSDs) has attracted growing public concern in recent years. The photodegradation of 8 CSDs was investigated using a low-pressure UV-254Hg lamp, resulting in fluence-based first-order kinetic rate constants in the range of (0.20-6.97)×10-4cm2mJ-1. The influence of water matrix components, including natural dissolved organic matter (DOM), bicarbonate (HCO3-), nitrate (NO3-), chloride (Cl-), and sulfate (SO42-), was investigated. The degradation rates of CSDs decrease in the presence of DOM due to the competition for the UV light, but increase with addition of NO3- due to an indirect production of HO. Further investigation was carried out to evaluate the viability of UV treatment performances using two real water samples, namely treated water from a water treatment plant and secondary effluent from a wastewater treatment plant. The primary photodegradation byproducts of CSDs were identified using LC/MS/MS to investigate the mechanism of direct UV photolysis and indirect NO3--induced and DOM-induced photolysis. The degradation rates of CSDs increase significantly with the addition of H2O2 or S2O82- under UV irradiation, due to the generation of non-selective HO or selective SO4-. As an electrophilic radical, SO4- mainly reacts via electron transfer and selectively attacks certain electron-donating functional groups of CSDs.

Assessment on personal exposure to particulate compounds using an empirical exposure model in an elderly community in Tianjin, China.

Using central site measurement data to predict personal exposure to particulate matter (PM) is challenging, because people spend most of their time indoors and ambient contribution to personal exposure is subject to infiltration conditions affected by many factors. Efforts in assessing and predicting exposure on the basis of associated indoor/outdoor and central site monitoring were limited in China. This study collected daily personal exposure, residential indoor/outdoor and community central site PM filter samples in an elderly community during the non-heating and heating periods in 2009 in Tianjin, China. Based on the chemical analysis results of particulate species, mass concentrations of the particulate compounds were estimated and used to reconstruct the PM mass for mass balance analysis. The infiltration factors (Finf) of particulate compounds were estimated using both robust regression and mixed effect regression methods, and further estimated the exposure factor (Fpex) according to participants' time-activity patterns. Then an empirical exposure model was developed to predict personal exposure to PM and particulate compounds as the sum of ambient and non-ambient contributions. Results showed that PM mass observed during the heating period could be well represented through chemical mass reconstruction, because unidentified mass was minimal. Excluding the high observations (>300µg/m3), this empirical exposure model performed well for PM and elemental carbon (EC) that had few indoor sources. These results support the use of Fpex as an indicator for ambient contribution predictions, and the use of empirical non-ambient contribution to assess exposure to particulate compounds.

Assessing the inhalation cancer risk of particulate matter bound polycyclic aromatic hydrocarbons (PAHs) for the elderly in a retirement community of a mega city in North China.

Assessment of the health risks resulting from exposure to ambient polycyclic aromatic hydrocarbons (PAHs) is limited by the lack of environmental exposure data among different subpopulations. To assess the exposure cancer risk of particulate carcinogenic polycyclic aromatic hydrocarbon pollution for the elderly, this study conducted a personal exposure measurement campaign for particulate PAHs in a community of Tianjin, a city in northern China. Personal exposure samples were collected from the elderly in non-heating (August-September, 2009) and heating periods (November-December, 2009), and 12 PAHs individuals were analyzed for risk estimation. Questionnaire and time-activity log were also recorded for each person. The probabilistic risk assessment model was integrated with Toxic Equivalent Factors (TEFs). Considering that the estimation of the applied dose for a given air pollutant is dependent on the inhalation rate, the inhalation rate from both EPA exposure factor book was applied to calculate the carcinogenic risk in this study. Monte Carlo simulation was used as a probabilistic risk assessment model, and risk simulation results indicated that the inhalation-ILCR values for both male and female subjects followed a lognormal distribution with a mean of 4.81 × 10-6 and 4.57 × 10-6, respectively. Furthermore, the 95 % probability lung cancer risks were greater than the USEPA acceptable level of 10-6 for both men and women through the inhalation route, revealing that exposure to PAHs posed an unacceptable potential cancer risk for the elderly in this study. As a result, some measures should be taken to reduce PAHs pollution and the exposure level to decrease the cancer risk for the general population, especially for the elderly.