Comparison of intraoperative blood loss and perioperative complications between preoperative embolization and nonembolization combined with spinal tumor surgeries: a systematic review and meta-analysis.

PURPOSE: The present study aimed to comparatively evaluate intraoperative blood loss (IBL) and perioperative complications between preoperative embolization (PE) and nonembolization (NE) combined with spinal tumor surgeries as well as to determine the subgroup of spinal tumor surgeries suitable for PE. METHODS: A systematic search in PubMed and EMBASE and an additional search by reference lists of the retrieved studies were undertaken by two reviewers. The mean IBL and perioperative complication rate were employed as the effect size in the general quantitative synthesis through direct calculation. Meta-analysis was performed using standardized mean difference (SMD) and weighted mean difference (WMD) of IBL and the odds ratio (OR) of complications. Heterogeneity was assessed using the I2 statistic. RESULTS: The reviewers selected 17 published studies for the general quantitative synthesis and meta-analyses. The mean IBL of spinal tumor surgeries was 1786.3 mL in the NE group and 1716.4 mL in the PE group. The mean IBL between the two groups was similar. The pooled WMD and SMD of IBL in spinal tumor surgeries was 324.15 mL (95% CI 89.50-1640.9, p = 0.007) and 0.398 (95% CI 0.114-0.682, p = 0.006), respectively. The reduction of the PE group compared with the NE group for the rates of major complications and major hemorrhagic complications were 7.80% and 5.71%, respectively. The risk of PE-related complications in the PE group was only 1.53% more than in the PE group. The pooled OR of major complications in spinal tumor surgeries was 1.426 (95% CI 0.760-2.674; p = 0.269). CONCLUSIONS: PE may be suitable for spinal tumor surgeries and some subgroups. From the perspective of complications, PE may also be a feasible option for spinal tumor surgeries.

Quantile regression-based prediction of intraoperative blood loss in patients with spinal metastases: model development and validation.

PURPOSE: To develop and evaluate a quantile regression-based blood loss prediction model for open surgery of spinal metastases. METHODS: This was a multicenter retrospective cohort study. Over a 11-year period, patients underwent open surgery for spinal metastases at 6 different institutions were reviewed. The outcome measure is intraoperative blood loss (in mL). The effects of baseline, histology of primary tumor and surgical procedure on blood loss were evaluated by univariate and multivariate analysis to determine the predictors. Multivariate ordinary least squares (OLS) regression and 0.75 quantile regression were used to establish two prediction models. The performance of the two models was evaluated in the training set and the test set, respectively. RESULTS: 528 patients were included in this study. Mean age was 57.6 ± 11.2 years, with a range of 20-86 years. Mean blood loss was 1280.1 ± 1181.6 mL, with a range of 10 ~ 10,000 mL. Body mass index (BMI), tumor vascularization, surgical site, surgical extent, total en bloc spondylectomy and microwave ablation use were significant predictors of intraoperative blood loss. Hypervascular tumor, higher BMI, and broader surgical extent were related with massive blood loss. Microwave ablation is more beneficial in surgery with substantial blood loss. Compared to the OLS regression model, the 0.75 quantile regression model may decrease blood loss underestimate. CONCLUSION: In this study, we developed and evaluated a prediction model for blood loss in open surgery for spinal metastases based on 0.75 quantile regression, which may minimize blood loss underestimate.

The Association Between Dry Eye and Sleep Disorders: The Evidence and Possible Mechanisms.

Dry eye is a disease that severely affects patients' quality of life, increasing the global burden on public health and finance. There is growing evidence that a poor lifestyle is a significant risk factor for dry eye. Along with the development of society, sleep, as a way of life, is also constantly changing. The main manifestations of sleep disorders are reduced sleep time, circadian rhythm disturbances, and sleep breathing disturbances. Sleep disorders and their secondary systemic diseases have attracted wide attention in recent years. This review mainly explored the correlation between sleep disorders and dry eye, and found that sleep-related problems and other factors potentially leading from sleep disorders could be critical factors for dry eye. These results suggest that ophthalmologists should pay attention to the sleep health problems in patients with dry eye, and we hope that this paper can provide help for future research in this field.

The Relationship Between Circadian Typology and Dry Eye Symptoms in Chinese College Students.

Purpose: To explore the relationship between symptomatic dry eye and circadian typology in college students. Methods: This study included 269 students from 3 Chinese universities. All participants completed the ocular surface disease index (OSDI) questionnaire, the morningness-eveningness questionnaire (MEQ), and the Pittsburgh sleep quality index (PSQI) questionnaire. Participants were grouped into 3 types by the reduced MEQ (rMEQ) score:E-Type, N-Type, and M-Type. All these parameters were then analyzed for the effect on the severity of dry eye. Results: The occurrence rates of poor sleep quality (PSQI>5) and symptomatic dry eye (OSDI > 13) in the college students were 53.2% and 40.2%, respectively. The distribution of the circadian typology differed significantly among the college students with different dry eye severities (χ 2 = 59.44, P = 0. 000), and E-type was associated with the most severe dry eye symptoms. The OSDI and PSQI scores were both significantly different among college students with different chronotypes (F = 22.14, P = 0.000; F = 15.21, P = 0.000; respectively). For both scores, the E-type scored the highest, followed by N-type, and M-type was the lowest. The circadian typology was an independent factor for dry eye. The risk of E-Type was 6.99 times higher than that of M-Type (P = 0.000), and the risk of N-types was 3.23 times higher than that of M-Type (P = 0.000). Sleep quality was also an independent risk factor for dry eye (P = 0.000). Gender and awareness of dry eye were not risk factors for dry eye. Conclusion: The severity of dry eye symptoms and sleep quality were associated with different circadian typologies. The more the circadian preference tended to be E-type, the worse the sleep quality and the more serious dry eye symptoms would appear.

New Insights Into Cancer Chronotherapies.

Circadian clocks participate in the coordination of various metabolic and biological activities to maintain homeostasis. Disturbances in the circadian rhythm and cancers are closely related. Circadian clock genes are differentially expressed in many tumors, and accelerate the development and progression of tumors. In addition, tumor tissues exert varying biological activities compared to normal tissues due to resetting of altered rhythms. Thus, chronotherapeutics used for cancer treatment should exploit the timing of circadian rhythms to achieve higher efficacy and mild toxicity. Due to interpatient differences in circadian functions, our findings advocate an individualized precision approach to chronotherapy. Herein, we review the specific association between circadian clocks and cancers. In addition, we focus on chronotherapies in cancers and personalized biomarkers for the development of precision chronotherapy. The understanding of circadian clocks in cancer will provide a rationale for more effective clinical treatment of tumors.

TGFBIp mediates lymphatic sprouting in corneal lymphangiogenesis.

Corneal lymphangiogenesis plays a key role in diverse pathological conditions of the eye. Here, we demonstrate that a versatile extracellular matrix protein, transforming growth factor-ß induced protein (TGFBIp), promotes lymphatic sprouting in corneal lymphangiogenesis. TGFBIp is highly up-regulated in inflamed mouse corneas. Immunolocalization of TGFBIp is detected in infiltrating macrophages in inflamed mouse corneas. Subconjunctival injection of liposomal clodronate can significantly reduce macrophage infiltration in inflamed mouse cornea, and decrease the expression of TGFBIp and areas of corneal lymphangiogenesis and angiogenesis after corneal suture placement. In brief, these results indicate that the up-regulation of TGFBIp in sutured cornea correlates with macrophage infiltration. Although TGFBIp alone cannot significantly stimulate corneal lymph vessel ingrowth in vivo, it can enhance the effect of vascular endothelial growth factor-C in promoting corneal lymphangiogenesis. The in vitro results show that TGFBIp promotes migration, tube formation and adhesion of human lymphatic endothelial cells (HLECs), but it has no effect on HLECs' proliferation. We also find that the in vitro effect of TGFBIp is mediated by the integrin α5ß1-FAK pathway. Additionally, integrin α5ß1 blockade can significantly inhibit lymphatic sprouting induced by TGFBIp. Taken together, these findings reveal a new molecular mechanism of lymphangiogenesis in which the TGFBIp-integrin pathways plays a pivotal role in lymphatic sprouting.

Identification of Circular RNA Related to Inflammation-Induced Lymphangiogenesis by Microarray Analysis.

Circular RNAs (circRNAs), as with other noncoding RNAs, have emerged as novel molecules of interest in gene regulation and in the development of many diseases. However, the expression and function of circRNAs in inflammation-induced lymphangiogenesis (LG) are still unknown. Microarray profiling in inflamed human lymphatic endothelial cells identified 82 differentially expressed circRNAs, including 6 downregulated and 76 upregulated circRNAs. One of the top 10 upregulated circRNAs, cZNF609, was selected for subsequent quantitative real-time PCR validation, and was found to be significantly upregulated in inflamed corneas from both mouse and human eyes. The expression of miR-184 was significantly lower in inflamed corneas than in control ones, which suggested that cZNF609 might serve as a sponge for miR-184. The expression of heparanase, a potential target gene of miR-184, was significantly increased in inflamed corneas. Therefore, circRNAs may serve as potential regulators of corneal LG. These findings lay a foundation for functional research on circRNAs in corneal LG pathogenesis.

Selective Serotonin Reuptake Inhibitors Aggravate Depression-Associated Dry Eye Via Activating the NF-κB Pathway.

Purpose: Our study aimed to evaluate the side effects of selective serotonin reuptake inhibitors (SSRIs) on the ocular surface. Methods: Twenty patients with depression and dry eye disease (DED) were randomly picked to receive SSRI treatment, whereas another 20 patients received placebo treatment. The serotonin, inflammatory cytokine, and proapoptotic protein levels were determined by using protein chip, qRT-PCR, and ELISA analyses. A rat depression model was established, and SSRIs were applied for 3 or 6 weeks. Tear production and corneal epithelial barrier function were evaluated. The serotonin and inflammatory cytokine levels were analyzed by qRT-PCR, immunohistochemical staining, and ELISA. Human corneal epithelial cells were subjected to serotonin, a HTR antagonist, and/or an NF-κB signaling inhibitor. The inflammatory cytokine and proapoptotic protein levels were determined by qRT-PCR, Western blot analysis, and ELISA. The cell apoptosis rate was assessed by using flow cytometry. Results: The SSRI group had higher tear serotonin levels and more serious inflammation and cell apoptosis on the ocular surface. In the rat depression model, depression decreased tear secretion and increased IL-1ß and TNF-α production, whereas the serotonin, TLR2, and TLR4 levels were not increased. SSRI aggravated DED, disrupted the corneal epithelial barrier, and promoted an inflammatory response on the ocular surface by increasing the tear serotonin levels. In addition, serotonin induced an inflammatory response and cell apoptosis in corneal epithelial cells by activating NF-κB signaling. Conclusions: SSRIs aggravate depression-associated DED via activating the NF-κB pathway. The antagonist of HTRs or the inhibitor of NF-κB signaling presents a potential therapeutic strategy for depression-associated DED. (Trial registration number, ChiCTR1800015592).

Proline-rich protein 11 silencing inhibits hepatocellular carcinoma growth and epithelial-mesenchymal transition through ß-catenin signaling.

Proline-rich protein 11 (PRR11) has been shown to play an critical roles in the development of cancer. However, the clinical significance and the biological role of PRR11 in hepatocellular carcinoma (HCC) remains unknown. The present study aimed to investigate the expression pattern, prognostic value and the biological role of PRR11 in HCC. PRR11 expression in 80 HCC surgical specimens was examined, and its clinical significance was analyzed. The role of PRR11 in cell proliferation, colony formation, migration and invasion were also determined. The results showed that PRR11 mRNA was significantly up-regulated in 56.25% (45/80) HCC from that in matched adjacent non-tumor tissues. High PRR11 was correlated with tumor size (P = 0.01) and TNM stage (P = 0.006). Patients with higher PRR11 expression had poor overall survival time (P < 0.001). Furthermore, PRR11 silencing obviously inhibited cell proliferation, colony formation, as well as cell migration and invasion of HCC cell lines in vitro. Mechanistically, knockdown of PRR11 significantly decreased the expression of ß-catenin, cyclinD1, c-myc and N-cadherin in HCC cell lines. Additionally, the inhibitory effects of PRR11 silencing on cell migration was significantly enhanced by ß-catenin inhibition. PRRl1 mRNA expression was found positively correlated with ß-catenin (R = 0.5472, P ˂ 0.0001), c-myc (R = 0.5527, P ˂ 0.0001) and cyclinD1 (R = 0.3948, P = 0.0003) in HCC tissues. Collectively, our data demonstrate that PRR11 plays an oncogenic role in HCC progression, through activating the Wnt/ß-catenin signaling pathway, and may represent a valuable prognostic marker and therapeutic target for HCC.

Therapeutic Effect of Intense Pulsed Light on Ocular Demodicosis.

PURPOSE: To evaluate the clinical efficacy of Lumenis® M22TM intense pulsed light (IPL) in reduction of ocular Demodex infestation in eyelashes in a prospective study. METHODS: Forty patients with ocular demodicosis were recruited. Then half were randomly picked to receive the IPL treatment, while the other half got 5% tea tree oil (as the control group). Demodex counts, the ocular surface disease index (OSDI) score, lid margin abnormalities, conjunctival congestion, tear break-up time (TBUT), corneal staining with fluorescein, meibomian gland (MG) expressibility, meibum quality, modified Schirmer I test with anaesthetic (SIT), were assessed on the day before treatment and after treatment of 30 and 90 days, respectively. Changes in the parameters were compared between the IPL group and the control group on the days after treatment of 30 and 90 days. RESULTS: No differences were observed in Demodex counts, lid margin abnormalities, conjunctival congestion, corneal staining with fluorescein, MG expressibility, SIT in the two groups on the days after treatment of 30 and 90 days (p > 0.05), whereas there was a statistically significant difference in the OSDI score, TBUT, meibum quality (p < 0.05). The Demodex eradication rate was more thorough in the IPL group (100%) than in the control group (75%). CONCLUSIONS: IPL shows the preferably therapeutic potential for ocular Demodicosis.

Treatment of dry eye by intracanalicular injection of a thermosensitive chitosan-based hydrogel: evaluation of biosafety and availability.

Chitosan has been increasingly considered for the design of implant materials in the field of translational medicine. However, implant properties addressing the complexity of the desired tissue still need to be developed. The focus of this study lies in the evaluation of a thermosensitive chitosan-based hydrogel for intracanalicular injection. Hydroxybutyl chitosan (HBC) solution was prepared, and its cytocompatibility was investigated by the CCK-8 assay using primary human corneal epithelial cells (HCEpiCs). Minimal cytotoxicity was seen in cultures with the HBC-extracting solution at a concentration of 0.2 g ml-1 for up to 72 h incubation. The biocompatibility and effectiveness, based on both a rabbit model and a human pilot study, were evaluated anatomically and functionally. The flow flux significantly decreased after HBC injection, with 76.9% of the flow flux occurring 10 min after HBC injection. Tear secretion significantly improved in the rabbit model. The density of PAS-positive cells gradually increased in the animal model. Various clinical indicators, which include the ocular surface disease index (OSDI) and tear break up time, have been improved greatly. Thermosensitivity promotes greater suitability for HBC intracanalicular injection to obstruct the lacrimal drainage system at body temperature. These results demonstrate that the thermosensitive chitosan-based hydrogel is suitable as a liquid plug for tear flow blockage and thus represents a promising candidate for translational medicine.

[Surgical treatment for osteoarthritis secondary to Crowe type IV developmental dysplasia of hip in adults].

OBJECTIVE: To investigate the mothod and therapeutic efficacy of total hip anthroplasties (THA) for osteoarthritis secondary to Crowe type IV developmental dysplasia of hip in adults. METHODS: From May 2006 to December 2013, THA was performed on 15 adult patients (17 hips) with Growe type IV acetabular dysplasia, including 13 females and 2 males, with a mean age of 30.9 years old (22 to 58 years old) and an average preoperative Harris score of (34.0 ± 6.5) points. Traction of the affected limb was not performed before surgery. After extensive release and lengthening of soft tissues, sub-trochanteric osteotomy of the femur was performed, hip joint center was rebuilt and the abduction function was restored. RESULTS: The patients were followed up with a mean period of 33 months (ranged from 6 months to 5 years). The postoperative Harris score was 85.0 ± 7.3,higher than the preoperative score. The extended length of limb ranged from 1.6 to 5.4 cm, with a mean of (3.42 ± 0.65) cm. The shortening and malformation of the affected limb were corrected in the most patients,with the difference in length of the two legs less than 1.5 cm. After surgery, 1 patient experienced partial sciatic nerve injury, which was largely recovered after 3 months of conservative treatment. One patient experienced complete sciatic nerve injury, which was partially recovered after 6 months of conservative treatment; a foot-drop varus deformity was formed in the distal end of the affected limb, which was improved after tendon transposition and transplantation. Joint pain was relieved, and the joint function was restored significantly. Over the follow-up period, no severe complications such as dislocation, infection, prosthesis loosening, or subsiding occurred. CONCLUSION: Satisfactory efficacy can be achieved for adult Growe type IV acetabular dysplasia associated with osteoarthritis by THA, with proper soft tissue release and lengthening, sub-trochanteric osteotomy of femur, joint functional restoration, appropriate choice of prosthesis, and careful protection of nerves and vessels.

New Method for Removing Thermosensitive Acrylic Punctal Plugs From Lacrimal Puncta.

PURPOSE: This study explored a new method for removing thermosensitive acrylic punctal plugs from lacrimal puncta. METHODS: A total of 14 dry eye patients (14 eyes), who required the removal of thermosensitive acrylic punctal plugs from the lacrimal puncta because of serious complications, were recruited. Among the 14 patients, lacrimal punctal granuloma formation occurred in 3 patients, tearing occurred in 6 patients, canaliculitis occurred in 3 patients, and chronic inflammation of the ocular surface occurred in 2 patients. The plugs were removed using a new method. Briefly, after local anesthesia was administered, a small lid clamp was used to flip the eyelid outward. After the application of the lid clamp, the plug could be removed without the use of any additional tools if the lacrimal punctum was large enough. If the lacrimal punctum was not large enough, microforceps were used to expand the lacrimal punctum before the application of the lid clamp. If the plug still could not be removed after the expansion of the lacrimal punctum, we moved the small lid clamp from the distal side of the lacrimal ductule to the lacrimal punctum. RESULTS: Using this method, the plug was successfully removed in all of the patients. CONCLUSIONS: This is a simple and effective method for removing thermosensitive acrylic punctal plugs from lacrimal puncta. CLINICAL TRIAL REGISTRATION-URL: : http://www.clinicaltrials.gov. Unique identifier: ChiCTR-IPR-14005476.

Association between PNPLA3 rs738409 polymorphisms and risk of hepatocellular carcinoma and its development in patients with cirrhosis: a meta-analysis.

Genetic variants of PNPLA3 have been implicated in hepatocellular carcinoma (HCC) susceptibility; however, published findings have been both conflicting and inconclusive. To obtain a more precise estimate of the association of the PNPLA3 rs738409 (C > G) polymorphism with the overall risk of HCC and in patients with cirrhosis, we performed a meta-analysis of nine eligible studies identified through an online search of Ovid, PubMed, EBSCO, the Cochrane Library, the Web of Science, the China National Knowledge Infrastructure, Wanfang, and Chinese Biomedicine databases. The studies comprised 1175 patients with HCC, 876 with cirrhosis, and 3026 healthy controls. Pooled odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were calculated to assess associations, using fixed-effects models. Etiology subgroup and sensitivity analyses were also performed. Our results showed that rs738409 was associated with overall HCC risk and in patients with cirrhosis in the genetic contrast modes: G vs. C, GG + CG vs. CC, GG vs. CG + GG, and GG vs. CC. Stratification by etiology did not reveal any significant association between this polymorphism and hepatitis C virus (HCV)-related HCC in patients with HCV-related cirrhosis (P > 0.05). However, healthy individuals harboring two copies of the rs738409 G variant had a higher risk of HCC (GG vs. CC: OR = 4.40, 95% CI: 3.28-5.91) than those carrying a single G allele (CG vs. CC: OR = 1.62, 95% CI: 1.34-1.59); these significant association were also present in each subgroup. Furthermore, the association was more pronounced in alcohol vs. HCV-related HCC. The present meta-analysis suggests that the PNPLA3 rs738409 G allele is a risk factor for HCC except in patients with HCV-related cirrhosis, and that two copies of the rs738409 G variant conferred a higher risk for HCC in controls, especially for alcohol-related HCC. Further studies with a larger sample size are needed to ascertain the association in different ethnicities.

Preconditioning with glycyrrhizic, ferulic, paeoniflorin, cinnamic prevents rat hearts from ischemia/reperfusion injury via endothelial nitric oxide pathway.

OBJECTIVE: The objective was to investigate the endothelial nitric oxide synthase (eNOS/NO) pathway is involved or not in the protective effects of glycyrrhizic, ferulic, paeoniflorin, cinnamic (GFPC) in myocardial ischemia-reperfusion injury Sprague-Dawley rats. MATERIALS AND METHODS: Ischemia-reperfusion (I/R) model was made by ligating the left anterior descending branch of the coronary artery for 30 min and releasing for 120 min, then the left ventricular apical was fixed and sliced, morphological changes of myocardial microvascular endothelial cell (MMVEC) was observed by electron microscopy, apoptosis index of MMVEC was observed by means of TUNEL, serum NO was tested by methods of nitrate reduction, lactate dehydrogenase (LDH), creatine kinase MB (CK-MB) was detected by automatic biochemical analyzer; Phosphorylated eNOS (PeNOS) and inducible NOS (iNOS) protein were measured by means of western blot. RESULTS: In positive product control group, the serum levels of NO, LDH, CK-MB significantly increased (P < 0.05); MMVEC apoptosis was significantly decreased (P < 0.05); incidence of area at risk decreased significantly (P < 0.05); PeNOS protein increased (P < 0.05); iNOS protein decreased significantly (P < 0.05). CONCLUSION: Ischemic preconditioning of GFPC from GFPC plays a protective role in I/R heart through regulating the eNOS/NO signal pathway by increasing the PeNOS protein expression and decreasing the expression of iNOS protein.