Prediction of high-level fear of cancer recurrence in breast cancer survivors: An integrative approach utilizing random forest algorithm and visual nomogram.

PURPOSE: This study is the first attempt to use a combination of regression analysis and random forest algorithm to predict the risk factors for high-level fear of cancer recurrence and develop a predictive nomogram to guide clinicians and nurses in identifying high-risk populations for high-level fear of cancer recurrence. METHODS: After receiving various recruitment strategies, a total of 781 survivors who had undergone breast cancer resection within 5 years in four Grade-A hospitals in China were included. Besides demographic and clinical characteristics, variables were also selected from the perspectives of somatic, cognitive, psychological, social and economic factors, all of which were measured using a scale with high reliability and validity. This study established univariate regression analysis and random forest model to screen for risk factors for high-level fear of cancer recurrence. Based on the results of the multi-variable regression model, a nomogram was constructed to visualize risk prediction. RESULTS: Fatigue, social constraints, maladaptive cognitive emotion regulation strategies, meta-cognition and age were identified as risk factors. Based on the predictive model, a nomogram was constructed, and the area under the curve was 0.949, indicating strong discrimination and calibration. CONCLUSIONS: The integration of two models enhances the credibility of the prediction outcomes. The nomogram effectively transformed intricate regression equations into a visual representation, enhancing the readability and accessibility of the prediction model's results. It aids clinicians and nurses in swiftly and precisely identifying high-risk individuals for high-level fear of cancer recurrence, enabling the development of timely, predictable, and personalized intervention programs for high-risk patients.

Daphnetin alleviates silica-induced pulmonary inflammation and fibrosis by regulating the PI3K/AKT1 signaling pathway in mice.

Silicosis is a hazardous occupational disease caused by inhalation of silica, characterized by persistent lung inflammation that leads to fibrosis and subsequent lung dysfunction. Moreover, the complex pathophysiology of silicosis, the challenges associated with early detection, and the unfavorable prognosis contribute to the limited availability of treatment options. Daphnetin (DAP), a natural lactone, has demonstrated various pharmacological properties, including anti-inflammatory, anti-fibrotic, and pulmonary protective effects. However, the effects of DAP on silicosis and its molecular mechanisms remain uncover. This study aimed to evaluate the therapeutic effects of DAP against pulmonary inflammation and fibrosis using a silica-induced silicosis mouse model, and investigate the potential mechanisms and targets through network pharmacology, proteomics, molecular docking, and cellular thermal shift assay (CETSA). Here, we found that DAP significantly alleviated silica-induced lung injury in mice with silicosis. The results of H&E staining, Masson staining, and Sirius red staining indicated that DAP effectively reduced the inflammatory response and collagen deposition over a 28-day period following lung exposure to silica. Furthermore, DAP reduced the number of TUNEL-positive cells, increased the expression levels of Bcl-2, and decreased the expression of Bax and cleaved caspase-3 in the mice with silicosis. More importantly, DAP suppressed the expression levels of NLRP3 signaling pathway-related proteins, including NLRP3, ASC, and cleaved caspase-1, thereby inhibiting silica-induced lung inflammation. Further studies demonstrated that DAP possesses the ability to inhibit the epithelial mesenchymal transition (EMT) induced by silica through the inhibition of the TGF-ß1/Smad2/3 signaling pathway. The experimental results of proteomic analysis found that the PI3K/AKT1 signaling pathway was the key targets of DAP to alleviate lung injury induced by silica. DAP significantly inhibited the activation of the PI3K/AKT1 signaling pathway induced by silica in lung tissues. The conclusion was also verified by the results of molecular and CETSA. To further verify this conclusion, the activity of PI3K/AKT1 signaling pathway was inhibited in A549 cells using LY294002. When the A549 cells were pretreated with LY294002, the protective effect of DAP on silica-induced injury was lost. In conclusion, the results of this study suggest that DAP alleviates pulmonary inflammation and fibrosis induced by silica by modulating the PI3K/AKT1 signaling pathway, and holds promise as a potentially effective treatment for silicosis.

Resveratrol-Coated Gold Nanoflowers for CT Imaging and Apoptosis/Photothermal Synergistic Therapy of Malignant Melanoma.

In the past decade, photothermal therapy (PTT) of tumors based on gold nanomaterials has been widely studied because of their strong extinction ability and high photothermal conversion ability in the near-infrared (NIR) region. However, related research still faces two problems: First, the biosafety of the surface ligands on gold nanomaterials is not ideal and even has strong toxicity, so the surface modification or shell coating is very necessary; second, gold nanomaterials only have a single PTT function, which requires high temperature to achieve better treatment effect. Therefore, it is necessary to enrich the antitumor function of gold nanomaterials and realize synergistic therapy. Natural polyphenols can combine with each other or other substances through various supramolecular forces, forming shells on the surface of nanomaterials and reducing biotoxicity. In addition, natural polyphenols represented by resveratrol have antitumor activity and can induce apoptosis of tumor cells. Therefore, the surface coating method of gold nanomaterials with natural polyphenols with antitumor activity can effectively solve the above problems. In this work, we prepared resveratrol-coated gold nanoflowers (Au@Res NFs) and applied them to the treatment of malignant melanoma. Resveratrol in Au@Res NFs can induce the apoptosis of tumor cells, and Au@Res NFs can play a role in PTT under an NIR laser. In cell experiments, the synergistic effect of apoptosis/PTT on the A375 cells was extremely strong. In animal experiments, Au@Res NFs enriched in tumor sites identified the location and boundary of tumors by computed tomography (CT). The apoptosis induced by resveratrol had a certain inhibitory effect on tumor growth. Further applying the NIR laser, under the synergistic effect of apoptosis and PTT, the tumors were completely eliminated without recurrence during the experimental period.

"Reconstruction of large lower lip defect including vermilion using a V-Y advanced flap combined with a musculomucosal stacked flap."

SUMMARY: The reconstruction of large lower lip defect is challenging, especially to repair the vermilion at the same time. We describe a novel method for reconstruction of large lower lip defect including vermilion here. The reconstruction included 2 layers, the anterior layer was reconstructed from the V-Y advanced musculocutaneous flap of the cheek; the posterior layer was reconstructed from the musculomucosal flap from the remnant lower lip, the stacking up of the bilateral musculomucosal flaps raised the height of posterior layer and cover the top of the lower lip to form the new vermillion as well. This is a simple and reliable method with satisfactory cosmetic and functional result.

Jingfang granules ameliorate inflammation and immune disorders in mice exposed to low temperature and high humidity by restoring the dysregulation of gut microbiota and fecal metabolites.

The dramatic changes in global climate on human health have been extremely severe. The immune disorder caused by low temperature and high humidity (LTHH) have become a severe public health issue. Clinically, Jingfang granule (JF) has the effect of dispelling cold and eliminating dampness, and is widely used in the treatment of cold caused by wind and cold, autoimmune diseases, and COVID-19 with cold-dampness stagnating in the lung pattern. Our study aims to elucidate the effect of JF on LTHH-induced immune disorders in mice as well as the underlying mechanisms. In this study, JF increased the spleen index, improved fecal character, repaired the intestinal barrier and alleviated intestinal inflammatory responses. Most importantly, JF ameliorated immune disorder in LTHH mice, which was manifested primarily by the significant increase in gdT, CD8+ Tcm, and CD8+ Tem cells, as well as the decrease in TH1, TH17, CD4+ Tem1, CD4+ Tem2, immature NK, mature NK cells, and M1-like macrophages. Interestingly, the JF treatment not only regulated the gut microbiota by decreasing the abundance of harmful bacteria, as well as up-regulating the abundance of beneficial bacteria, but also ameliorated the metabolic disorders by reversing the levels of fecal metabolites to normality. The results of the correlation analysis demonstrated a significant association among gut microbiota, fecal metabolites and immune cells. In addition, JF inhibited the TLR4/NF-κB/NLRP3 pathway in LTHH mice. In conclusion, our results suggested that JF alleviated inflammation and immune disorders in LTHH mice by restoring gut microbiota and fecal metabolism.

[Jingfang Mixture regulates balance of spleen T lymphocyte subsets in urticaria mice by inhibiting JAK2-STAT3 signaling pathway].

Urticaria is an immune-mediated allergic disease. This study explored the effect of Jingfang Mixture on spleen T lymphocyte subsets of urticaria mice. A total of 50 Kunming mice were randomized into normal group(C), model group(V), and low-(JF-L, 0.5 g·kg~(-1)), medium-(JF-M, 1 g·kg~(-1)) and high-dose(JF-H, 2 g·kg~(-1)) Jingfang Mixture groups, with 10 mice in each group. The mixture of ovalbumin and aluminum hydroxide(0.1 mg + 0.1 mL) was used(intraperitoneal injection) to induce urticaria in mice. The administration began 6 days after the first immunization, and the second immunization was carried out 10 days after the first immunization. The pruritus index was detected within 30 min after the second immunization. The administration lasted 21 days. After 21 days, the serum was taken to detect the total IgE level. Based on hematoxylin and eosin(HE) staining, the pathological changes of skin tissue were observed, and Western blot was used to detect the levels of p-Janus kinase 2(JAK2)/JAK2 and p-signal transducer and activator of transcription 3(STAT3)/STAT3 in skin tissue. The spleen was taken to detect the spleen index, and flow cytometry was employed to determine the expression of lymphocyte subsets. The results showed that group V had obvious pathological changes in skin tissue compared with group C. Moreover, group V showed more scratches, higher spleen index, and higher level of total serum IgE than group C. In addition, higher levels of p-JAK2 and p-STAT3, lower proportions of CD4~+T, Th1, and Treg, higher proportions of CD8~+T, Th2, and Th17, and lower ratios of CD4~+/CD8~+, Th1/Th2, and Terg/Th17 were observed in group V than in group C. Compared with group V, each administration group showed alleviation of the pathological morphology of skin tissue, obvious epidermal thickening, relatively intact collagen fiber structure of dermal reticular layer, alleviated edema, and relief of vasodilation and peripheral inflammatory cell infiltration. Moreover, less scratching, lower spleen index, lower p-JAK2/JAK2 and p-STAT3/STAT3 were observed in the administration groups than in group V. JF-M group and JF-H group demonstrated lower levels of total IgE, larger proportions of CD4~+T, Th1, and Treg, smaller proportions of CD8~+ T, Th2, and Th17, and higher ratios of CD4~+/CD8~+, Th1/Th2, and Terg/Th17. In conclusion, Jingfang Mixture may improve the symptoms of urticaria mice by regulating the balance of spleen T lymphocyte subsets through JAK2-STAT3 signaling pathway.

A simple method for eyelid reconstruction with an advancement flap after resection of a minor nevus on the eyelid margin.

We developed a simple and effective method for eyelid reconstruction after resection of a minor nevus on the eyelid margin. With a vertical advancement flap to repair the defect, all patients were satisfied with the cosmetic and functional results of the eyelids, and no significant complications occurred.

[Effect of Jingfang Granules on carrageenan-induced tail thrombosis in mice based on ERK/p38 MAPK signaling pathway].

The present study explored the anti-inflammatory and anti-thrombotic mechanism of Jingfang Granules on tail thrombosis induced by carrageenan in mice. Thirty-two male ICR mice were randomly divided into a control group, a model group, a Jingfang Granules group, and a positive drug(aspirin) group, with eight mice in each group. The thrombosis model was induced by intraperitoneal injection of carrageenan(45 mg·kg~(-1)) combined with low-temperature stimulation, and the mice were treated with drugs for 7 days before modeling. Twenty-four hours after modeling, blood was detected for four blood coagulation indices in each group. The enzyme-linked immunosorbent assay(ELISA) was used to detect the activity of plasma interleukin-6(IL-6), interleukin-1ß(IL-1ß), tumor necrosis factor-α(TNF-α), and other inflammatory factors. The tails of mice in each group were cut off to observe tail lesions and measure the length of the thrombus. The protein expression and phosphorylation level of extracellular signal-regulated kinase 1/2(ERK1/2) and p38 mitogen-activated protein kinase(p38 MAPK) in spleen tissues were detected by Western blot. The results showed that dark red thrombus appeared in the tails of mice in each group. The length of the black part accounted for about 40% of the total tail in the model group. Additionally, the model group showed prolonged prothrombin time(PT), increased fibrinogen(FIB) content, and shortened activated partial thromboplastin time(APTT). Compared with the model group, the groups with drug intervention displayed shortened black parts in the tail and improved four blood coagulation indices(P<0.05). As revealed by ELISA, the expression levels of TNF-α, IL-1ß, and IL-6 in the mouse plasma were significantly up-regulated in the model group, and those in the groups with drug intervention were reduced as compared with the model group(P<0.05). As demonstrated by Western blot, the protein expression and phosphorylation levels of ERK1/2 and p38 MAPK in the spleen tissues were significantly elevated in the model group, while those in the Jingfang Granules group were down-regulated as compared with the model group with a significant difference. Jingfang Granules can inhibit tail thrombosis of mice caused by carrageenan presumedly by inhibiting the activation of ERK1/2 and p38 MAPK signaling pathways.

MicroRNA-193b-3p reduces oxidative stress and mitochondrial damage in rats with cerebral ischemia-reperfusion injury via the seven in absentia homolog 1/Jun N-terminal kinase pathway.

Ischemic stroke is one of the major causes of death and disability among adults. This study sought to explore the mechanism of microRNA (miR)-193b-3p in rats with cerebral ischemia-reperfusion (I/R) injury. The cerebral I/R injury models of rats were established using the suture-occluded method. The pathological changes were observed, and oxidative stress (OS) and mitochondrial function indexes in rat brain tissue were examined. The levels of miR-193b-3p and seven in absentia homolog 1 (SIAH1) were detected. miR-193b-3p agomir or antagomir was injected into the lateral ventricle of I/R rats to overexpress or inhibit miR-193b-3p expression. The targeting relationship between miR-193b-3p and SIAH1 was verified. The effect of SIAH1 overexpression on brain injury in I/R rats was investigated by injecting the lentivirus vector into the lateral ventricle. The phosphorylation level of Jun N-terminal kinase (JNK) was identified. miR-193b-3p was lowly expressed in I/R rats. Overexpression of miR-193b-3p alleviated the pathological damage of I/R rats and limited the OS and mitochondrial damage. miR-193b-3p targeted SIAH1. Overexpression of SIAH1 partially reversed the protection of miR-193b-3p overexpression against cerebral I/R injury. p-JNK was up-regulated in I/R rats and overexpression of miR-193b-3p inhibited p-JNK. Overall, overexpression of miR-193b-3p targeted SIAH1 to inhibit the activation of the JNK pathway and protect rats against cerebral I/R injury.

Combined serum free light chain predicts prognosis in acute kidney injury following cardiovascular surgery.

OBJECTIVES: Increased polyclonal free light chains (FLCs) are found in inflammatory conditions. Inflammation is recognized in the progression of acute kidney injury (AKI). This study was aimed to determine whether polyclonal combined FLC (cFLC) was associated with prognosis of AKI patients. METHODS: This prospective cohort included 145 adults with hospital-acquired AKI following cardiovascular surgery between 2014 and 2016, according to the KDIGO creatinine criteria. The primary end point of the study was all-cause death during follow-up. RESULTS: The median of serum cFLC concentration in the cohort was 42.0 (31.9-60.3 mg/L) and levels of cFLC in patients with AKI stage 3 were higher than those in AKI stage 1 and stage 2. cFLC levels correlated significantly with renal function biomarkers, high sensitivity C-reactive protein (hsCRP), and sequential organ failure assessment (SOFA) score. Patients were organized into the following two groups: the low-cFLC group (cFLC <43.3 mg/L) and the high-cFLC group (cFLC ≥ 43.3 mg/L). A total of 17 (11.0%) patient deaths occurred within 90 d, 13 (18.8%) in the high-cFLC group. Kaplan-Meier analysis revealed that the two groups differed significantly with respect to 90-d survival (log-rank p = .012), and Cox regression analysis showed that an cFLC level ≥43.3 mg/L was significantly associated with a 5.0-fold increased risk of death (adjusted hazard ratio [HR], 5.95; 95% confidence interval [CI], 1.04- 33.91; p = .045) compared with an cFLC level <43.3 mg/L. CONCLUSIONS: Serum cFLC levels were significantly elevated and might be an independent predictor of mortality in patients with AKI following cardiovascular surgery.

Dexamethasone Induces Apoptosis of Embryonic Palatal Mesenchymal Cells Through the GATA-6/Bone Morphogenetic Protein-2/p38 MAPK Pathway.

ABSTRACT: Exposure to dexamethasone (DEX) causes cleft palate at high rates. Our previous studies proved that GATA binding protein 6 (GATA-6)/bone morphogenetic protein-2 (BMP-2) mediated apoptosis is related to DEX-induced cleft palate, but the specific mechanism is still unclear. The goal of this research was to understand the mechanism of apoptosis in cleft palate formation induced by DEX. Palatal mesenchymal cells from mouse embryos on embryonic day 13 were isolated as the experimental group, GATA-6 was silenced by GATA-6 small interfering Ribonucleic Acid (RNA). Cell Counting Kit-8, flow cytometry and Western Blot were applied to detect cell proliferation ability, cell cycle, the proportion of apoptotic cells, and the expression of apoptosis- related proteins of GATA-6 knockdown palatal mesenchymal cells. Further proteins on the BMP-2/Mitogen-activated protein kinase (MAPK) pathways were detected using Western Blot. T results showed that knockdown of GATA-6 by siRNA significantly decreased cell proliferation and increased the expression of apoptosis-related proteins. Bone morphogenetic protein-2/P38 mitogen Activated protein kinase (P38 MARK) pathway proteins decreased significantly among the GATA-6 knockdown group, DEX-cleft palate group and control +DEX groups. The results indicated that the GATA-6/BMP-2/P38 MAPK athway was involved in the apoptosis caused by GATA-6 silencing, which may be the possible mechanism of DEX inducing cleft palate.

The Role of Rigid Suspension and Fixation in Treating Lagophthalmos After Lower Eyelid Reconstruction.

ABSTRACT: A patient with severe eyelid defects caused by a car accident was admitted to the Plastic Surgery Department of the First Hospital of Jilin University. The lower eyelid was first reconstructed with autogenous palatal mucosa and a temporal musculocutaneous flap, which provided adequate tissue volume. Postoperatively, eyelid closure was good. After long-term follow-up, the reconstructed lower eyelid showed laxity and downward movement. The eyelid could not close completely and lagophthalmos occurred. Then, the lower eyelid was suspended by the fascia lata. The suture at the point of fixation became loose again after the operation. Incomplete eyelid closure recurred. Finally, palmaris longus tendon graft suspension combined with screw fixation was used to obtain a satisfactory therapeutic effect. in summary, rigid suspension and fixation can provide adequate lateral tension to resist lower reconstructed eyelid shifting and lagophthalmos, which is important for the maintenance of lasting effects.

Daphnetin inhibits corneal inflammation and neovascularization on a mouse model of corneal alkali burn.

Alkali burn is a significant contributor to corneal injury. Alkali burn-induced corneal inflammation often causes vision loss due to corneal neovascularization. Daphnetin (DAP) has been studied for its anti-inflammatory and antiangiogenic properties with encouraging results. Driven by those encouraging results, we sought to explore the effects of DAP in treating alkali burn-induced corneal inflammation and neovascularization and its mechanism of action. We found that the angiogenesis processes of human umbilical vein endothelial cells (HUVECs) induced by vascular endothelial growth factor A (VEGF-A) were primarily attenuated by treatment with DAP, including proliferation, migration, and tube formation. Treatment of DAP significantly suppressed the VEGF-A-induced protein expression of VEGF receptor2 (VEGFR2), as well as the activation of downstream signal transducer and activator of transcription 3 (STAT3), AKT, and extracellular signal-regulated kinase (ERK) signaling. In the mouse corneal alkali burn model, the inflammatory cell infiltrations and neovascularization in the cornea caused by alkali burn were inhibited by 10 µM DAP eye drops. Alkali burn-induced corneal protein expression of VEGF-A, VEGFR2, phosphorylated (p-)STAT3, p-AKT, and p-ERK in corneal tissue were reduced mainly by DAP. Moreover, the upregulation of inflammatory caused by alkali burn in the pathological process was significantly neutralized by DAP. Mechanistically, the inflammatory response could be alleviated by DAP in the way of inhibiting the expression levels of TLR4, p-NF-κB, NLRP3, ASC, Cleaved-caspase-1 (p20), mature-IL-1ß (p17), and N-GSDM. In conclusion, our findings confirmed that the corneal inflammation and neovascularization caused by alkali burn could be inhibited by DAP in vitro and in vivo, elucidating the underlying mechanisms of its protective effects. DAP may have tremendous therapeutic potential for the treatment of corneal alkali burn.

Pericytes of Indirect Contact Coculture Decrease Integrity of Inner Blood-Retina Barrier Model In Vitro by Upgrading MMP-2/9 Activity.

Inner blood-retina barrier (iBRB) is primarily formed of retinal microvascular endothelial cells (ECs) with tight junctions, which are surrounded and supported by retinal microvascular pericytes (RMPs) and basement membrane. Pericytes are believed to be critically involved in the physiology and pathology of iBRB. However, the underlying mechanism remains to be fully elucidated. We developed a novel in vitro iBRB model which was composed of primary cultures of rat retinal ECs and RMPs based on Transwell system. We tested the involvement of pericytes in the migration and invasion of ECs, examined the expression and activity of matrix metalloproteinase- (MMP-) 2/MMP-9 in the culture, evaluated the TEER and permeability of iBRB, and assessed the expression of ZO-1, occludin, claudin-5, and VE-cadherin of endothelial junctions. We found that RMPs with indirect contact of ECs can increase the expression of MMP-2 and upgrade the activity of MMP-2/9 in the coculture, which subsequently decreased TJ protein abundance of ZO-1 and occludin in ECs, promoted the migration of ECs, and finally reduced the integrity of iBRB. Taken together, our data show that RMP relative location with ECs is involved in the integrity of iBRB via MMP-2/9 and has important implications for treating diabetic retinopathy and other retinal disorders involving iBRB dysfunction.

High-Fat Diet Induced Gut Microbiota Alterations Associating With Ghrelin/Jak2/Stat3 Up-Regulation to Promote Benign Prostatic Hyperplasia Development.

The role of high-fat diet (HFD) induced gut microbiota alteration and Ghrelin as well as their correlation in benign prostatic hyperplasia (BPH) were explored in our study. The gut microbiota was analyzed by 16s rRNA sequencing. Ghrelin levels in serum, along with Ghrelin and Ghrelin receptor in prostate tissue of mice and patients with BPH were measured. The effect of Ghrelin on cell proliferation, apoptosis, and induction of BPH in mice was explored. Our results indicated that BPH mice have the highest ratio of Firmicutes and Bacteroidetes induced by HFD, as well as Ghrelin level in serum and prostate tissue was significantly increased compared with control. Elevated Ghrelin content in the serum and prostate tissue of BPH patients was also observed. Ghrelin promotes cell proliferation while inhibiting cell apoptosis of prostate cells. The effect of Ghrelin on enlargement of the prostate was found almost equivalent to that of testosterone propionate (TP) which may be attenuated by Ghrelin receptor antagonist YIL-781. Ghrelin could up-regulate Jak2/pJak2/Stat3/pStat3 expression in vitro and in vivo. Our results suggested that Gut microbiota may associate with Ghrelin which plays an important role in activation of Jak2/Stat3 in BPH development. Gut microbiota and Ghrelin might be pathogenic factors for BPH and could be used as a target for mediation.

Topical Timolol Combined Intralesional Injection of Diprospan in the Treatment of Elevated Localized Mixed Infantile Hemangiomas and a Discussion for Proper Timing for Injection.

BACKGROUND: Although infantile hemangiomas (IHs) are usually self-limiting, residual elevated appearance may remain. Topical beta-blockers are effective in superficial IHs management, while intralesionally injected diprospan is effective at treating deep, localized IHs. A single application of topical timolol or injected diprospan has obvious limitations. Therefore, for elevated, localized mixed IHs, we applied topical timolol combined with intralesionally injected diprospan, using their respective advantages to maximize benefits. PURPOSE: To evaluate the clinical efficacy and safety of topical timolol combined with intralesionally injected diprospan for the treatment of elevated, localized mixed IHs and identify the optimal injection time. METHODS: Infants with elevated, localized mixed IHs in the proliferative phase were treated with injected diprospan combined with topical timolol between March 2018 and March 2020. The injection was administered only when the tumor surface was higher than that of the surrounding tissue. The patients were asked to return every 4 weeks for a treatment response evaluation, and complications were recorded. RESULTS: Thirty-six patients with elevated, localized mixed IHs (thickness >3 mm on Doppler ultrasound) were recruited. The mean age at treatment initiation was 3.58 ±â€Š1.50 months (range: 1.00-6.00 months). The follow-up period ranged from 9 to 24 months. Considering the size of the IH at the end of treatment, regression was observed in 31 (86.1%) cases, stabilization was observed in 5 (13.9%) cases, and no treatment failure was observed. All the IHs improved in color and height after treatment. CONCLUSION: Topical timolol combined with intralesionally injected diprospan is an effective and safe treatment for elevated, localized mixed IH. The injection is needed only when we forecast the elevated tissue may remain after regression.

Mitochondrial gene COX2 methylation and downregulation is a biomarker of aging in heart mesenchymal stem cells.

The mitochondria have been proven to be involved in processes of aging; however, the mechansims through which mitoepigenetics affect the cytological behaviors of cardiomyocytes during the aging process are not yet fully understood. In the present study, two senescence models were constructed, replicative senescence (RS) and stress­induced premature senescence (SIPS), using human heart mesenchymal stem cells (HMSCs). First, the differences in age­related gene expression levels and telomere length were compared between the HMSCs in the RS and SIPS models by PCR. Subsequently, protein expression and the mitochondrial DNA (mtDNA) methylation status of cytochrome c oxidase subunit II (COX2) was measured by western blot analysis and bisulfite genomic sequencing (BSP). Finally, the value of the DNA methyltransferase (Dnmt) inhibitor, 5­aza­2'­deoxycytidine (AdC), in delaying the senescence of HMSCs was evaluated. It was found that the p16, p27 and p53 mRNA expression levels increased in the senescent cells, whereas p21 mRNA expression did not. It was also found that telomere shortening only occurred in the RS model, but not in the SIPS model. Along with the senescence of HMSCs, COX2 gene methylation increased and its protein expression level significantly decreased. It was demonstrated that AdC inhibited COX2 methylation and downregulated COX2 expression. The addition of exogenous COX2 or the administration of AdC promoted cell proliferation and delayed cell aging. On the whole, the present study demonstrates that COX2 methylation and downregulation are biomarkers of HMSC senescence. Thus, COX2 may have potential for use as a therapeutic target of cardiovascular diseases and this warrants further investigation.

Crosstalk between the COX2-PGE2-EP4 signaling pathway and primary cilia in osteoblasts after mechanical stimulation.

Primary cilia have been found to function as mechanosensors in low-magnitude high-frequency vibration (LMHFV)-induced osteogenesis. The PGE2 also regulates bone homeostasis and mechanical osteogenesis through its receptor EP4 signaling, but its involvement in LMHFV-induced or in primary cilia-induced osteogenesis has not been investigated. We hypothesized that LMHFV stimulates osteoblast (OB) differentiation by activating the COX2-PGE2-EP pathway in a manner dependent on primary cilia and that primary cilia are also affected by the PGE2 pathway. In this study, through western blot analysis, RNA interference, enzyme-linked immunosorbent assay, real-time quantitative polymerase chain reaction, and cytochemical staining, we observed that COX2, mPGES-1, and PGE2 levels were markedly elevated in cells treated with LMHFV and were greatly decreased in LMHFV-treated cells following IFT88 silencing. EP4 expression was significantly increased in OBs following LMHFV treatment, but IFT88 silencing significantly blocked this increase. EP4 localized to the bases of primary cilia. LMHFV reduced the length and abundance of primary cilia, but the cells could self-repair their primary cilia after mechanical damage. EP4 antagonism significantly blocked the LMHFV-induced increase in IFT88 expression and blocked the recovery of primary cilia length and the proportion of cells with primary cilia. In addition, COX2 or EP4 antagonism disrupted LMHFV-induced osteogenesis. These results demonstrate the integration of and crosstalk between primary cilia and the COX2-PGE2-EP4 signaling pathway under mechanical stimulation.

Popliteal artery transection associated with a minimally displaced tibial plateau fracture: a case report and review of the literature.

BACKGROUND: Poplital artery transection injury is potentially catastrophic, or even life-threatening. Severe traumas, including open fracture, gunshot, stabs, and knee dislocation and complex fracture of proximal tibia or distal femur, are the common causes of high rate of amputation due to popliteal artery trauma. No report mentions vascular injury associated with minimally displaced tibial plateau fracture in adult. CASE PRESENTATION: A 30-year-old male presented with popliteal artery transection injury associated with minimally displaced tibial plateau fracture. He presented to emergency department, 6 h after fall from ground into a 1-m height hole. Physical examination suggested acute ischemia, with signs of paleness, coldness, anesthesia, hemorrhagic bullae below the right knee level. There was severe swelling and ecchymosis in popliteal fossa and around the leg with significant calf tenderness and pedal edema. Tibialis posterior, dorsalis pedis, and popliteal arterial pulses were not palpable. Radiograph suggested minimally displaced tibial plateau fracture with no evidence of knee dislocation. The patient was taken up for emergency surgery after consultation with vascular surgeon. During the closed reduction external fixation and compartment decompression, popliteal artery trunk was found transected and end-to-end repair was performed. During the post-operational period, no complication was developed and the patient was followed-up for 1 year. At the one-year follow-up, he acquired good stability of his right knee with full range of motion. CONCLUSION: Significant swelling and ecchymosis should alert the surgeons to the possibility of vascular injury in knee joint injury, even if there is no fracture or dislocation, or fracture is minimally displaced.

Association between mineral and bone disorder in patients with acute kidney injury following cardiac surgery and adverse outcomes.

BACKGROUND: Numerous studies have evaluated the prevalence and importance of mineral and bone disorders among patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD). However, little is known about dysregulated mineral and bone metabolism in acute kidney injury (AKI). METHODS: We evaluated the association between mineral and bone metabolites and clinical outcomes in 158 patients who underwent cardiac surgery and developed AKI between June 2014 and January 2016. The baseline characteristics of the patients were recorded, and the levels of mineral and bone metabolites, including calcium, phosphate, intact parathyroid hormone (iPTH), 25-hydroxyvitamin D (25D), bone-specific alkaline phosphatase (BAP), tartrate-resistant acid phosphatase 5b (TRACP-5b) and C-terminal fibroblast growth factor 23 (cFGF23) were measured within 12 h after establishing the clinical diagnosis. RESULTS: The serum phosphate, iPTH and cFGF23 levels were significantly associated with the 28-day mortality (phosphate: Hazard Ratio [HR] =2.620, 95% CI: 1.083 to 6.338, p = 0.035; iPTH: HR = 1.044, 95% CI: 1.001 to 1.090, p = 0.046; cFGF23: HR = 1.367, 95% CI: 1.168 to 1.599, p < 0.001). Moreover, higher serum cFGF23 and BAP levels were independently associated with an increased risk of adverse outcomes. Additionally, we found that the serum cFGF23 levels rose most significantly and were associated with the severity of AKI (P < 0.001). CONCLUSIONS: Mineral and bone metabolites are dysregulated and are associated with adverse clinical outcomes among patients with AKI. TRIAL REGISTRATION: www.clinicaltrials.gov NCT00953992. Registered 6 August 2009.