Extrapulmonary Comorbidities Associated with Chronic Obstructive Pulmonary Disease: A Review.

Most patients with chronic obstructive pulmonary disease (COPD) suffer from at least one additional, clinically relevant chronic disease. To a degree, the high global prevalence and mortality rate of COPD is closely related to its extrapulmonary effects. Moreover, the various of comorbidities of COPD and itself interact with each other, resulting in diverse clinical manifestations and individual differences, and thus further influencing the prognosis as well as healthcare burden of COPD patients. This is closely related to the common risk factors of chronic diseases (aging, smoking, inactivity, etc.). Additionally, some pathophysiological mechanisms caused by COPD, including the systemic inflammatory response, hypoxia, oxidative stress, and others, also have an impact on other systems. But comprehensive management and medical interventions have not yet been established. The clinicians should improve their knowledge and skills in diagnosing as well as treating the comorbidities of COPD, and then aim to develop more individualized, efficient diagnostic and therapeutic strategies for different patients to achieve greater clinical benefits. In this article, we will review the risk factors, mechanisms, and treatment strategies for extrapulmonary comorbidities in chronic obstructive pulmonary disease, including cardiovascular diseases, diabetes, anemia, osteoporosis, emotional disorders, and gastroesophageal reflux disease.

Glucocorticoid Alleviates Mechanical Stress-Induced Airway Inflammation and Remodeling in COPD via Transient Receptor Potential Canonical 1 Channel.

Background: Increased airway resistance and hyperinflation in chronic obstructive pulmonary disease (COPD) are associated with increased mechanical stress that modulate many essential pathophysiological functions including airway remodeling and inflammation. Our present study aimed to investigate the role of transient receptor potential canonical 1 (TRPC1), a mechanosensitive cation channel in airway remodeling and inflammation in COPD and the effect of glucocorticoid on this process. Methods: In patients, we investigated the effect of pathological high mechanical stress on the expression of airway remodeling-related cytokines transforming growth factor ß1 (TGF-ß1), matrix metalloproteinase-9 (MMP9) and the count of inflammatory cells in endotracheal aspirates (ETAs) by means of different levels of peak inspiratory pressure (PIP) under mechanical ventilation, and analyzed their correlation with TRPC1. Based on whether patients regularly used inhaled corticosteroid (ICS), COPD patients were further divided into ICS group (n = 12) and non-ICS group (n=15). The ICS effect on the expression of TRPC1 was detected by Western blot. In vitro, we imitated the mechanical stress using cyclic stretch and examined the levels of TGF-ß1 and MMP-9. The role of TRPC1 was further explored by siRNA transfection and dexamethasone administration. Results: Our results revealed that the TRPC1 level and the inflammatory cells counts were significantly higher in COPD group. After mechanical ventilation, the expression of TGF-ß1 and MMP-9 in all COPD subgroups was significantly increased, while in the control group, only high PIP subgroup increased. Meanwhile, TRPC1 expression was positively correlated with the counts of inflammatory cells and the levels of TGF-ß1 and MMP-9. In vitro, mechanical stretch significantly increased TGF-ß1 and MMP-9 levels and such increase was greatly attenuated by TRPC1 siRNA transfection and dexamethasone administration. Conclusion: Our results suggest that the increased TRPC1 may play a role in the airway inflammation and airway remodeling in COPD under high airway pressure. Glucocorticoid could in some degree alleviate airway remodeling via inhibition of TRPC1.

Anteroposterior Cannulated Screw Fixation of Coronoid Fractures in Terrible Triad Injuries: A Simple Syringe-guided Technique.

OBJECTIVE: The fixation of the coronoid fractures in terrible triad injuries is quite challenging. In this study, we introduce a minimally invasive technique using a syringe as a guide for insertion of the cannulated screw in an anterior to posterior fashion to fix the coronoid fracture in patients with terrible triad injuries. METHODS: In this retrospective study, clinical data of patients suffering from terrible triad injuries between 2012 and 2019 were analyzed. Fifteen patients with an average age of 38.2 years old (21-56 years) were enrolled in this study, of which 12 were males and three were females. The Regan-Morrey type II and type III coronoid fractures in these patients were treated with cannulated screws, inserted anteriorly using a 1 mL syringe as a guide. Outcome measures included pain, range of motion, stability and daily function using Mayo Elbow Performance scores (MEPs). The anteroposterior and lateral radiographs were used for evaluating a healing fracture. RESULTS: After a mean follow up of 44.2 months (range 13-80), the mean elbow flexion was 128.2°, extension was 12.3°, forearm pronation was 74.6° and supination was 73.6°. A concentric reduction was maintained without severe pain, stiffness, and radiographic evidence of instability in all patients during the follow-up period. The mean MEPs was 89.7 points. CONCLUSION: The anteroposterior cannulated screw fixation via simple syringe guide is a minimally invasive and safe option for surgical treatment of coronoid fractures in terrible triad injuries.

Association between environmental exposure to perchlorate, nitrate, and thiocyanate and serum α-Klotho levels among adults from the National Health and nutrition examination survey (2007-2014).

BACKGROUND & AIMS: Aging is a pathophysiological process driven by a diverse set of complex biological processes, and environmental pollution plays an important role in this process. This study aimed to explore the association between serum α-Klotho levels and urinary perchlorate, nitrate, and thiocyanate levels. METHODS: This secondary dataset analysis included 4875 participants (mean age, 57.69 year; male, 49.58%; non-Hispanic White, 47.67%) from the US National Health and Nutrition Examination Survey (2007-2014). Enzyme-linked immunosorbent assay was used to quantify α-Klotho levels, and ion chromatography coupled with electrospray tandem mass spectrometry was used to quantify thiocyanate, nitrate, and perchlorate levels. Multivariate linear regression models were applied to estimate the association between perchlorate, nitrate, and thiocyanate levels and serum α-Klotho levels. RESULTS: Urinary thiocyanate levels were negatively associated with α-Klotho levels (ß = - 0.006; 95% confidence interval, - 0.010 to - 0.003; P = 0.0004) after adjusting for age, sex, body mass index, race, alcohol consumption, estimated glomerular filtration rate, underlying disease, physical activity, smoking status, usual energy intake, and urinary creatinine and serum cotinine levels and mutual adjustment of urinary perchlorate, urinary nitrate, and urinary thiocyanate levels. The α-Klotho level in participants in the highest quartile was higher by 50.567 ng/mL (ß = 50.567; 95% confidence interval, 14.407 to 86.726; P = 0.009) than that in participants in the lowest quartile of urinary perchlorate. A linear relationship was observed between urinary thiocyanate and α-Klotho levels. CONCLUSIONS: Urinary thiocyanate levels were negatively associated with serum α-Klotho levels. Urinary thiocyanate should be further investigated as a potential mediator of aging and age-related diseases.

Effect of Bi, Sb, and Ti on Microstructure and Mechanical Properties of SAC105 Alloys.

The Sn-Ag-Cu (SAC) solder alloys with a low Ag (Ag < 3 wt.%) content have attracted great attention owing to their low cost, increased ability in bulk compliance, and plastic energy dissipation. However, some of their mechanical properties are generally lower than the SAC alloys with a higher Ag content. Adding alloying elements is an effective approach for improving the mechanical properties of the SAC alloys. In this study, the effect of Bi, Sb, and Ti on Sn-1 wt.%Ag-0.5 wt.%Cu (SAC105) solder alloys was investigated. The SAC solders with four compositions: SAC105-1 wt.%Bi, SAC105-1 wt.%Sb, SAC105-1 wt.%Bi-1 wt.%Sb, SAC105-1 wt.%Bi-1 wt.%Sb-0.4 wt.%Ti were prepared. The microstructure and phase compositions were characterized using electron scanning microscopy, and X-ray diffraction. The thermal properties and wettability were also examined. Uniaxial tensile tests and nano-indentation tests were conducted to evaluate the mechanical properties. The results show that adding Bi or Sb could increase the strength of SAC105 alloys mainly due to the solid solution strengthening effect. The creep resistance of SAC105 alloys was also improved with the additions of Bi and Sb. The co-additions of Bi and Sb into SAC105 alloys exhibit an enhanced creep resistance than that calculated by the theoretical calculation. The further addition of Ti into SAC105-1Bi-1Sb alloys demonstrated a much-improved creep resistance, which could be attributed to the synergistic effects of both solid solution strengthening and the precipitation hardening effects.

Differences between novel hybrid mode flaps and traditional perforator flaps at the level of metabolites using LC-MS.

The multi-territory perforator flaps are widely used in plastic surgery. However, partial necrosis flap in the potential territory remains a challenge to plastic surgeons. We raised a novel "hybrid nourished mode" (HNM) flap based on the multi-territory deep inferior epigastric perforator (DIEP) flap to improve flap survival. Thirty-two rabbits were randomly divided into DIEP and HNM groups. Untargeted metabolic mechanisms between the DIEP and HNM groups were performed using LC-MS under the filter criteria of fold change >20.0 times or <0.05, and variable importance in projection (VIP) value was set at ≥1, P < 0.05. Between the two groups, flap survival, perfusion, microvasculature, histopathology, and immunohistochemistry of CD31 were assessed on post-operative day 7. We screened 16 different metabolites that mainly participated in biosynthesis of secondary metabolites, aminoacyl transfer RNA biosynthesis, phenylalanine metabolism, arginine and proline metabolism, among others. The results of the HNM flaps were higher than those of the DIEP flaps (P < 0.05) in the aspects of flap survival, flap perfusion, and microvasculature. Compared with the DIEP flaps, HNM has a stronger advantage in tissue metabolism. This study provided us with a better understanding and strong evidence in terms of metabolites on how HNM achieves the survival of large multi-territory perforator flaps.

Association between serum cotinine and α-Klotho levels among adults: Findings from the National Health and Nutrition Examination Survey 2007-2016.

INTRODUCTION: Serum cotinine is a sensitive and specific marker of tobacco smoke exposure. α-Klotho is an anti-ageing molecule, which plays an important role in several diseases. We aimed to examine the association between smoke exposure indicated by the serum cotinine and α-Klotho levels, as previous reports regarding the level of α-Klotho in smokers have been inconsistent. METHODS: This secondary dataset analysis included 9833 participants (aged 40-79 years; 47.0% females and 53.0% males) from the US National Health and Nutrition Examination Survey 2007-2016. Independent variables were serum cotinine level, age, sex, race, body mass index (BMI), and alcohol consumption. The outcome variable was serum α-Klotho level. Multiple linear regression analysis was used to examine the association between serum cotinine and α-Klotho levels. RESULTS: The serum cotinine level was negatively associated with the α-Klotho level (ß= -0.107, 95% CI: -0.155 to -0.059, p<0.0001) after adjusting for age, BMI, sex, race, and alcohol consumption. The α-Klotho level in participants with cotinine ≥3 ng/mL decreased by 44.514 pg/mL (p<0.0001) compared to that in participants with cotinine <3 ng/mL. There is a non-linear relationship between serum cotinine and α-Klotho levels. The piecewise linear models indicated a significant threshold effect between serum cotinine and α-Klotho levels. On the left of the inflection point (cotinine <130 ng/mL), the serum cotinine level increased with decreased α-Klotho level (ß= -0.519, 95% CI: -0.682 to -0.356). On the right of the inflection point (cotinine ≥130 ng/mL), the serum cotinine level increased with increased α-Klotho level (ß=0.085, 95% CI: 0.000 to 0.170). CONCLUSIONS: Based on our study results, serum cotinine level was associated with the serum α-Klotho level.

Exploring the Correlation Between the Regulation of Macrophages by Regulatory T Cells and Peripheral Neuropathic Pain.

OBJECTIVE: Intractable pain after peripheral nerve injury has become a major concern in the field of pain. Current evidence shows that routine medications or surgical treatment is associated with inconsistent results and different curative effects. Stable and effective treatment methods in clinical practice are also lacking. To date, there is no consensus on the pathophysiological mechanisms of pain. The present study investigates the potential regulatory role of regulatory T cells in the differentiation of macrophages on dorsal root ganglion (DRG) and explores the mechanism of nociceptive signals in the signal transfer station. The findings are expected to guide the prevention of various types of peripheral neuropathic pain. METHODS: Thirty-six male Sprague Dawley (SD) rats and 18 male Nude rats, of equal weight (250-300g), were used in this study. The rats were divided into 3 groups: SD rat sciatic nerve transection group (SNT group, n = 18), SD rat nerve transection experimental group (SNT/RAPA group, n = 18) and Nude rat nerve transection experimental group (SNT/NUDE group, n = 18). The behavior related to neuropathic pain of animals were comprehensively evaluated in all groups. Furthermore, we analyzed the degree of neuroma development, histology, gene, and protein expression, and compared their correlation with the ultrastructural changes of M1/M2 type differentiation of macrophages in DRG. RESULTS: Sciatic nerve transection (SNT), induced the aggregation of several types of macrophages in lumbar DRG of SD rats leading to a higher ratio of M1/M2. Following the inhibition of the M1 type polarization of macrophages, axon outgrowth increased significantly. A significantly lower average autotomy score was reported in the SNT/NUDE group (*p < 0.05) and the SNT/RAPA group (@ p < 0.05) as compared to that of the SNT group. The SNT/NUDE group showed no noticeable neuroma formation 30 days after the nerve transection. However, bulbous neuromas were observed in the nerve stumps of both the SNT control and SNT/RAPA groups. Immunofluorescence staining revealed a significant decrease in the proportion of M1/M2 macrophages in lumbar DRG of the SNT/NUDE group (** p < 0.001) and the SNT/RAPA group (@ p < 0.05) compared to the SNT group. The expression of pain-related proteins was also decreased (@ p < 0.05, *p < 0.05,** p < 0.001). Also, the expression of alpha-smooth muscle actin (α-SMA), neurofilament 200 (NF-200), and nerve growth factor low-affinity receptor p75 were significantly down-regulated in the nerve tissue (@ p < 0.05, @@ p < 0.001, ** p < 0.001). CONCLUSION: M1/M2 type differentiation of macrophages on DRG plays a significant role in the formation of traumatic painful neuroma after neurotomy. In combination with our previous study, the results of this study suggest that regulatory T cells reduce the ratio of M1/M2 macrophages and alleviate the pain of neuroma by regulating the polarization direction of macrophages on neuroma. These findings provide key insights into developing new strategies to manage painful neuroma.

A new insight on peripheral nerve repair: the technique of internal nerve splinting.

OBJECTIVE: Neuropathic pain produced by symptomatic neuromas is an important problem after peripheral nerve injury (PNI). End-to-end anastomosis of the nerve stump for PNI is well established but cannot efficiently prevent neuroma-in-continuity formation. METHODS: Sciatic nerve injury was used in the experimental model. Seventy-two rats were randomly divided into four groups: rats with nerve anastomosis sites supported with silicone tubes represented the internal nerve splinting (INS) group (n = 18); rats with end-to-end nerve anastomosis represented control group 1 (CON1) (n = 18); rats with INS and the nerve anastomosis site represented control group 2 (CON2) (n = 18); and rats that underwent the same surgical procedures for skin and muscle operations but without sciatic nerve injury represented the normal group (n = 18). RESULTS: Gross evaluations of the nerve anastomosis sites, gastrocnemius muscle atrophy, axonal regeneration and remyelination, neuropathic pain, and scar hyperplasia of the neuromas were performed, as well as motor function evaluations. Axonal regeneration, remyelination, and gastrocnemius muscle atrophy were similar between the INS group and CON1 (p > 0.05). However, neuropathic pain and scar hyperplasia-as evaluated according to the expression of anti-sigma-1 receptor antibody and anti-α-smooth muscle actin, respectively-and the weight ratios of the neuromas were reduced in the INS group compared with those of CON1 and CON2 (p < 0.05). CONCLUSIONS: Application of INS in nerve repair effectively prevented traumatic neuroma-in-continuity formation and inhibited neuropathic pain without influencing nerve regeneration in rats.

Notoginseng Triterpenes Inhibited Autophagy in Random Flaps via the Beclin-1/VPS34/LC3 Signaling Pathway to Improve Tissue Survival.

Random flaps are widely used in tissue reconstruction, attributed to the lack of vascular axial limitation. Nevertheless, the distal end of the flap is prone to necrosis due to the lack of blood supply. Notoginseng triterpenes (NTs) are the active components extracted from Panax notoginseng, reducing oxygen consumption and improving the body's tolerance to hypoxia. However, their role in random flap survival has not been elucidated. In this study, we used a mouse random skin flap model to verify that NT can promote cell proliferation and migration and that increasing blood perfusion can effectively improve the survival area of a skin flap. Our study also showed that the autophagy of random flaps after NT treatment was activated through the Beclin-1/VPS34/LC3 signaling pathway, and the therapeutic effect of NT significantly decreased after VPS34 IN inhibited autophagy. In conclusion, we have demonstrated that NT can significantly improve the survival rate of random flaps through the Beclin-1/VPS34/LC3 signaling pathway, suggesting that it might be a promising clinical treatment option.

Incidence, prognosis and nomograms of breast cancer with bone metastases at initial diagnosis: a large population-based study.

BACKGROUND: Bone is the most common metastatic site for breast cancer, and patients' condition will deteriorate when it occurs. METHODS: We performed a retrospective analysis on 6482 breast cancer patients with bone metastases (BCBM), who were selected from the Surveillance, Epidemiology, and End Result (SEER) 18 registry database. The optimal age cut-points were generated by using the X-tile software. By using Cox regression, we selected independent prognostic factors from 21 variables, and plotted a visual nomogram to predict the probability of surviving to the median survival time. We also diagrammed a competing risk nomogram on the basis of competitive risk model. RESULTS: Compared with other three common metastatic sites, the incidence of bone metastasis was the highest for patients with breast cancer. The incidence of BCBM peaked around the age of 60, and a large majority of patients were between the ages of 50 and 70. The survival rate decreased with age, and the median survival time was about 19 months. Factors of age, race, marital status, grade, human epidermal growth factor receptor-2 (HER2) receptor, hormone receptor, concurrent brain metastasis, concurrent liver metastasis, concurrent lung metastasis, surgery and chemotherapy are strongly related to the prognosis of patients with BCBM. It was revealed that the C-index of the nomogram was 0.72 and the calibration curves showed good agreement between the nomogram prediction and actual observation. CONCLUSION: Our practical nomograms provide a visual and user-friendly tool in the risk evaluation and prognostic prediction for breast cancer patients with bone metastases.

Effect of hirudin on arterialized venous flap survival in rabbits.

Arterialized venous flap (AVF) is limited in clinical application because its survival remains inconsistent and its exact survival mechanism is still unclear. Hirudin is an effective thrombin specific inhibitor, which is isolated from the salivary gland secretions of the leech. Our study evaluated the impact of hirudin on the viability of AVFs in rabbits. Thirty-six rabbits were randomly divided into three groups: sham group (physiological perfusion), control group (AVF), and hirudin group (AVF + hirudin). In hirudin group, 20 antithrombin units (ATU) hirudin (2.5 ml) were injected into each flap. In sham group and control group, the same amount of normal saline was injected into each flap. Status of flap survival, water content, vascular perfusion, histopathology, expression of CD34, VEGF, eNOS and HIF-1α were analyzed in each group. Analysis of oxidative stress was performed by measuring the activity of superoxide dismutase (SOD) and malondialdehyde (MDA). Compared with flaps in sham group with physiological perfusion mode, results of survival rate, perfusion status, SOD activity, expression of CD34, VEGF, and eNOS of AVFs in control group were significantly lower, while water content, MDA level and expression of HIF-1α were higher. The flap condition of AVFs injected with hirudin in hirudin group was improved significantly, and the results were similar to sham group. Our findings revealed that hirudin can effectively improve survival of AVF.

Meigs' syndrome caused by granulosa cell tumor accompanied with intrathoracic lesions: A case report.

BACKGROUND: Meigs' syndrome is regarded as a benign ovarian tumor accompanied by pleural effusion and ascites, both of which resolve after removal of the tumor. Patients often seek treatment in the Department of Respiratory and Critical Care Medicine or other internal medicine departments due to symptoms caused by ascites or hydrothorax. Here, we report a rare case of Meigs' syndrome caused by granulosa cell tumor accompanied with intrathoracic lesions. CASE SUMMARY: A 52-year-old women was admitted to the Department of Respiratory and Critical Care Medicine due to coughing and expectoration accompanied with shortness of breath. Chest X-ray and chest computed tomography showed a modest volume of pleural fluid with pleural thickening in the right lung. The carbohydrate antigen 125 (CA125) concentration was 150.8 U/mL (normal, 0-35 U/mL) and no tumor cells were observed in pleural fluid. Nodules and a neoplasm with a fish meat-like appearance in the parietal pleura and nodules with a 'string of beads'-like appearance in the diaphragm were found by thoracoscopic examination. Furthermore, pelvic magnetic resonance revealed a pelvic mass measuring about 11.6 cm × 10.0 cm × 12.4 cm with heterogeneous signal intensity and multiple hypointense separations. Total abdominal hysterectomy, bilateral adnexectomy, and separation of pelvic adhesion were performed under general anesthesia. The pathology results showed granulosa cell tumor. At the 2-mo follow-up after the surgery, the hydrothorax subsided, and the CA125 level returned to normal. CONCLUSION: For postmenopausal women with unexplained hydrothorax and elevated CA125, in addition to being suspected of having gynecological malignancy, Meigs' syndrome should be considered.

AGAP2-AS1 May Promote the Occurrence and Development of Glioblastoma by Sponging miR-9-5p: Evidence From a ceRNA Network.

Glioblastoma (GBM), the primary malignant brain tumor, is typically associated with a poor prognosis and poor quality of life, mainly due to the lack of early diagnostic biomarkers and therapeutic targets. However, gene sequencing technologies and bioinformatics analysis are currently being actively utilized to explore potential targets for the diagnosis and management of malignancy. Herein, based on a variety of bioinformatics tools for the reverse prediction of target genes associated with the prognosis of GBM, a ceRNA network of AGAP2-AS1-miR-9-5p-MMP2/MMP9 was constructed, and a potential therapeutic target for GBM was identified. Enrichment analysis predicted that the ceRNA regulatory network participates in the processes of cell proliferation, differentiation, and migration.

ceRNA Network Analysis Shows That lncRNA CRNDE Promotes Progression of Glioblastoma Through Sponge mir-9-5p.

Glioblastoma accounts for 45.2% of central nervous system tumors. Despite the availability of multiple treatments (e.g., surgery, radiotherapy, chemotherapy, biological therapy, immunotherapy, and electric field therapy), glioblastoma has a poor prognosis, with a 5-year survival rate of approximately 5%. The pathogenesis and prognostic markers of this cancer are currently unclear. To this end, this study aimed to explore the pathogenesis of glioblastoma and identify potential prognostic markers. We used data from the GEO and TCGA databases and identified five genes (ITGA5, MMP9, PTPRN, PTX3, and STX1A) that could affect the survival rate of glioblastoma patients and that were differentially expressed between glioblastoma patients and non-tumors groups. Based on a variety of bioinformatics tools for reverse prediction of target genes associated with the prognosis of GBM, a ceRNA network of messenger RNA (STX1A, PTX3, MMP9)-microRNA (miR-9-5p)-long non-coding RNA (CRNDE) was constructed. Finally, we identified five potential therapeutic drugs (bacitracin, hecogenin, clemizole, chrysin, and gibberellic acid) that may be effective treatments for glioblastoma.

Trans-Cinnamaldehyde Increases Random Pattern Flap Survival Through Activation of the Nitric Oxide Pathway.

BACKGROUND: The application of random pattern skin flaps is limited in plastic surgery reconstruction due to necrosis. Trans-cinnamaldehyde has antibacterial, anticancer, and antioxidant properties. In this study, we aimed to investigate the effect of trans-cinnamaldehyde on skin flap survival and its possible mechanism regarding nitric oxide. MATERIALS AND METHODS: One hundred forty male Sprague-Dawley rats were randomly divided into seven groups (n = 20 each group). After the dorsal flap was raised, different doses of trans-cinnamaldehyde (10, 20, and 30 mg/kg) were immediately given by oral gavage in the three different groups. To assess the possible involvement of the nitric oxide system, NG-nitro-L-arginine methyl ester (L-NAME, a nonselective nitric oxide synthase inhibitor) was used in this study. All flap samples were incised on postoperative day 7. RESULTS: Our results showed that flap survival was increased significantly in the 20 mg/kg (P < 0.001) trans-cinnamaldehyde (TC) group compared to the control group or 30 mg/kg TC group. This protective function was restrained by coadministration of L-NAME with 20 mg/kg TC. The results of histopathology, laser Doppler, arteriography mediated with oxide-gelatine, and fluorescent staining all showed a significant increase in capillary count, collagen deposition, angiogenesis, and flap perfusion. Immunohistochemistry results revealed a significant increase in the expression of CD34, eNOS, and VEGF. CONCLUSION: Trans-cinnamaldehyde increased flap survival through the nitric oxide synthase pathway and contributed to angiogenesis. A concentration of 20 mg/kg trans-cinnamaldehyde was recommended in this study.

A metabolic investigation of arterialized venous flaps in rabbits using mass spectrometry-based metabolomics.

An arterialized venous flap (AVF) is an ideal choice of flap to repair wounds. However, the survival of these flaps remains the source of some concern. This study used metabolomic analysis to investigate the mechanisms underlying survival in AVF flaps in order to guide the clinical application of these flaps. Thirty-six male Japanese rabbits were randomly divided into a sham group and an AVF group. They were used for histology and hemodynamic investigations. Three days after surgery, tissue samples were analyzed by mass spectroscopy-based metabolomics. The results of the study revealed a reduction in blood flow, infiltration of inflammatory cells, and necrosis of flaps in the AVF group. In addition, notable changes were evident in the levels of several metabolites in the AVF group, including lactic acid, acetoacetic acid, inositol phosphate, arachidonic acid, and other metabolites. Our results indicate that the AVF group experienced changes in several biological pathways, including energy metabolism, cell membrane stability, and inflammatory response. There is a significant metabolic difference between AVFs and physiological flaps. The dysregulation in certain metabolites may be related to the specific hemodynamics and insufficient energy metabolism of the AVFs.

Gastrodin Promotes the Survival of Random-Pattern Skin Flaps via Autophagy Flux Stimulation.

The random-pattern flap has a significant application in full mouth restoration (reconstructive surgery) and plastic surgery owing to an easy operation with no axial vascular restriction. However, distal necrosis after flap operation is still considered the most common complication which makes it the Achilles heel in the clinical application of random-pattern flaps. A Chinese medicinal herb named gastrodin is an effective active ingredient of Gastrodia. Herein, the existing study explored the significant potential of gastrodin on flap survival and its underlying mechanism. Our obtained results show that gastrodin will significantly improve flap survival, reduce tissue edema, and increase blood flow. Furthermore, our studies reveal that gastrodin can promote angiogenesis and reduce the apoptotic process as well as oxidative stress. The results of immunohistochemistry and immunoblotting revealed that gastrodin has a role in the elevation of autophagy flux which results in induced autophagy. The use of 3MA (3-methyladenine) for the inhibition of induced autophagy significantly weakened the underlying benefits of gastrodin treatment. Taken together, our obtained results confirmed that gastrodin is an effective drug that can considerably promote the survival rate of flaps (random pattern) via enhancing autophagy. Enhanced autophagy is correlated with the elevation of angiogenesis, reduced level of oxidative stress, and inhibition of cell apoptosis.

Improvement of multiterritory perforator flap survival supported by a hybrid perfusion mode: A novel strategy and literature review.

Perforator flaps have been widely used in clinical Settings, however, unexpected necrosis was still commonly encountered in the distal portions of multiterritory flaps known as Choke zone III. In this study, we introduced a novel hybrid perfusion technique which is different from the established one of arterial supercharging or venous superdrainage to improve multiterritory flap survival with success. In order to ensure the entire flap survival of multiterritory flaps extending to choke zone III, a "hybrid perfusion" mode by anastomosing a distal vein of the flap with a recipient artery was carried out in two cases based on our previous basic study. In addition, a systematic literature review regarding the established microsurgical assistant techniques of arterial supercharging and venous superdrainage techniques were performed. Both flaps survived uneventfully. At a minimal follow-up of six months, both patients were satisfied with the results. This novel hybrid perfusion technique provides a simple new concept in solving partial necrosis of multiterritory flaps. Further practice is guaranteed for better understanding this unconventional attempt.

Butylphthalide Inhibits Autophagy and Promotes Multiterritory Perforator Flap Survival.

Multiterritory perforator flap is an important plastic surgery technique, yet its efficacy can be limited by partial necrosis at the choke Ⅱ zone. Butylphthalide (NBP) has been used for many diseases but has not been studied in the multiterritory perforator flap. With the effect of NBP, we observed increasing in capillary density, inhibition of autophagy and oxidative stress, and a reduction in apoptosis of cells, all consistent with increased flap survival. However, the protective effect of NBP on multiterritory perforator flap was lost following administration of the autophagy agonist rapamycin (Rap). Through the above results, we assumed that NBP promotes flap survival by inhibiting autophagy. Thus, this study has found a new pharmacological effect of NBP on the multiterritory perforator by inhibiting autophagy to prevent distal postoperative necrosis and exert effects on angiogenesis, oxidative stress, and apoptosis within the flap.