In vitro and in vivo protective potential of quercetin-3-glucuronide against lipopolysaccharide-induced pulmonary injury through dual activation of nuclear factor-erythroid 2 related factor 2 and autophagy.

In vitro and in vivo models of lipopolysaccharide (LPS)-induced pulmonary injury, quercetin-3-glucuronide (Q3G) has been previously revealed the lung-protective potential via downregulation of inflammation, pyroptotic, and apoptotic cell death. However, the upstream signals mediating anti-pulmonary injury of Q3G have not yet been clarified. It has been reported that concerted dual activation of nuclear factor-erythroid 2 related factor 2 (Nrf2) and autophagy may prove to be a better treatment strategy in pulmonary injury. In this study, the effect of Q3G on antioxidant and autophagy were further investigated. Noncytotoxic doses of Q3G abolished the LPS-caused cell injury, and reactive oxygen species (ROS) generation with inductions in Nrf2-antioxidant signaling. Moreover, Q3G treatment repressed Nrf2 ubiquitination, and enhanced the association of Keap1 and p62 in the LPS-treated cells. Q3G also showed potential in inducing autophagy, as demonstrated by formation of acidic vesicular organelles (AVOs) and upregulation of autophagy factors. Next, the autolysosomes formation and cell survival were decreased by Q3G under pre-treatment with a lysosome inhibitor, chloroquine (CQ). Furthermore, mechanistic assays indicated that anti-pulmonary injury effects of Q3G might be mediated via Nrf2 signaling, as confirmed by the transfection of Nrf2 siRNA. Finally, Q3G significantly alleviated the development of pulmonary injury in vivo, which may result from inhibiting the LPS-induced lung dysfunction and edema. These findings emphasize a toxicological perspective, providing new insights into the mechanisms of Q3G's protective effects on LPS-induced pulmonary injury and highlighting its role in dual activating Nrf2 and autophagy pathways.

Anti-Hypertensive Effect of Solanum muricatum Aiton Leaf Extract In Vivo and In Vitro.

Hypertension is a global health problem and leads to cardiovascular disease and renal injury. Solanum muricatum Aiton leaf extract, rich in flavonoids, is known for its antioxidant capacity. However, the effects of Solanum muricatum Aiton leaf extract on hypertension combined with inflammatory complications were unknown. This study aimed to investigate the impact of Solanum muricatum Aiton leaf extract on hypertension in vivo and in vitro. In vivo, Solanum muricatum Aiton leaf extract led to decrease high blood pressure, improve heart, aorta, and kidney pathology, and enhance the antioxidative activity in spontaneously hypertensive rats (SHR). Our study demonstrated Solanum muricatum Aiton leaf extract inhibited angiotensin-converting enzyme (ACE), epithelial sodium channel (ENaC), sodium glucose co-transporters-1 (SGLT-1), nuclear factor kappa B (NF-κB), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6). In vitro, Solanum muricatum Aiton leaf extract improved the angiotensin II-induced reactive oxygen species (ROS) and mitochondrial membrane depolarization in NRK-52E cells. Besides, Solanum muricatum Aiton leaf extract could also decrease the expressions of ENaC, SGLT-1, and NF-κB in angiotensin II-treated NRK-52E cells. Solanum muricatum Aiton leaf can be suggested as a novel antihypertensive agent ameliorating hypertension via ACE inhibition, inflammation reduction, and ROS. PLE is a novel anti-hypertensive agent to ameliorate hypertension and its complications, including inflammation.

Outcomes for 160 Consecutive Lateral Arm Free Flaps for Head and Neck Reconstruction.

OBJECTIVE: Examine outcomes for lateral arm autologous tissue transfer in head and neck reconstruction. STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary cancer center. METHODS: All patients who underwent traditional lateral arm, extended lateral arm, and lateral forearm flaps for head and neck reconstruction from 2012 to 2022 were assessed. Disabilities of the arm, shoulder, and hand (DASH) was measured. Factors associated with complications and enteral or mixed diet were evaluated by multivariable regression. RESULTS: Among 160 patients followed for a median of 2.3 ± 2.1 years, defects were 54% oral tongue, 18% external, 9% maxilla, 8% buccal mucosa, 9% floor of mouth, and 3% pharynx. Flap types (and median pedicle lengths) were 41% traditional lateral arm (8 cm), 25% extended lateral arm (11.5 cm), and 34% lateral forearm (14 cm). All donor sites were closed primarily; 19.6% and 0% of patients had increased DASH scores 2 and 12 weeks after reconstruction. Major complications occurred in 18.1% of patients, including 6.3% reoperation, 6.9% readmission, 3.7% fistula, and 1.8% flap loss. Complications were independently associated with peripheral vascular disease (odds ratio [OR]: 5.71, 95% confidence interval [CI]: 1.5-21.6, P = .01), pharyngeal defects (OR: 11.3, 95% CI: 1.4-94.5, P = .025), and interposition vein grafts (OR: 3.78, 95% CI: 1.1-13.3, P = .037). CONCLUSION: The lateral arm free flap was safe, versatile, and reliable for head and neck reconstruction with low donor-site morbidity. Complications occurred in a fifth of patients and were associated with peripheral vascular disease, pharyngeal defects, and vein grafts.

The lateral forearm flap versus traditional upper extremity flaps: A comparison of donor site morbidity and flap thickness.

INTRODUCTION: The lateral forearm flap (LFF) is a thin fasciocutaneous flap with a donor site that can be closed primarily. METHODS: A retrospective analysis of donor site morbidity and hand function was performed in patients who underwent a radial forearm flap (RFF), ulnar artery perforator flap (UAPF), or LFF. Flap thickness was evaluated radiographically in 50 control patients. RESULTS: Of 134 patients (lateral forearm flap: n = 49, RFF: n = 47, UAPF: n = 38), the LFF demonstrated significantly faster return to baseline hand grip strength (3 months vs. 12 months in RFF and UAPF; p < 0.001), had significantly fewer donor site complications (6.1% compared to 6.4% in RFF and 28.9% in UAPF; p = 0.003) and fewer sensory deficits (2.0% compared to 6.4% in RFF and 15.8% in UAPF sites; p = 0.013). The radiographic study confirmed the LFF to be the thinnest of all upper extremity flap options. CONCLUSIONS: The LFF is an excellent forearm-based flap option with thin, pliable tissue and low donor site morbidity.

The inhibitory effect of quercetin-3-glucuronide on pulmonary injury in vitro and in vivo.

Pulmonary injury is defined as a progressive inflammation. Extensive pro-inflammatory cytokines are secreted from alveolus, associated with the production of reactive oxygen species (ROS) and apoptosis. The model of endotoxin lipopolysaccharide (LPS)-stimulated lung cells has been applied to mimic the pulmonary injury. Some antioxidants and anti-inflammatory compounds can be used as chemopreventive agents of pulmonary injury. Quercetin-3-glucuronide (Q3G) has been showed to exert antioxidant, anti-inflammatory, anti-cancer, anti-aging and anti-hypertension effects. The aim of the study is to examine the inhibitory potential of Q3G on pulmonary injury and inflammation in vitro and in vivo. Firstly, human lung fibroblasts MRC-5 cells pre-treated with LPS were demonstrated to cause survival loss and ROS generation, were recovered by Q3G. Q3G also exhibited the anti-inflammatory effects on the LPS-treated cells with a reduction in the activation of NLRP3 [nucleotide-binding and oligomerization domain (NOD)-like receptor protein 3] inflammasome, leading to pyroptosis. Also, Q3G showed the anti-apoptotic effect in the cells might be mediated via inhibition of mitochondrial apoptosis pathway. To further explore in vivo pulmonary-protective effect of Q3G, C57BL/6 mice were intranasally exposed to a combination of LPS and elastase (LPS/E) to perform the pulmonary injury model. The results revealed that Q3G ameliorated pulmonary function parameters and lung edema in the LPS/E-induced mice. Q3G also suppressed the LPS/E-stimulated inflammation, pyroptosis and apoptosis in the lungs. Taken together, this study suggested the lung-protective potential of Q3G via downregulation of inflammation, pyroptotic and apoptotic cell death, contributing to its chemopreventive activity of pulmonary injury.

Profunda Artery Perforator Flap Tongue Reconstruction: An Effective and Safe Alternative to the Anterolateral Thigh Flap.

BACKGROUND: The anterolateral thigh (ALT) perforator flap is a workhorse flap for tongue reconstruction. The authors present an alternative option using the profunda artery perforator (PAP) flap for glossectomy reconstruction compared to the ALT flap. METHODS: A retrospective review was conducted of 65 patients who underwent subtotal or total glossectomy reconstruction between 2016 and 2020 (46 ALT vs. 19 PAP flaps). Flap volume was assessed using CT scans at two different time points. Quality of life and functional outcomes were measured using the MD Anderson Symptom Inventory for head and neck cancer (MDASI-HN). RESULTS: Patients undergoing a PAP flap had significantly lower BMI compared to ALT flaps (22.7±5.0 vs. 25.8±5.1; p=0.014). Donor site and recipient site complications were similar as was the mean flap volume seven months after surgery (30.9% for ALT vs. 28.1% for PAP; p=0.93). Radiation and chemotherapy did not appear to have a significant effect on flap volume change over time. The most frequently reported high-severity items in MDASI-HN were swallowing/chewing and voice/speech for both cohorts. Patients who had reconstruction with a PAP flap had significantly better swallowing function (p=0.034). CONCLUSION: Both the PAP and ALT flaps appear to be safe and effective choices for subtotal and total tongue reconstruction. The PAP flap can serve as an alternative donor site, especially in the setting of malnourished patients with thin lateral thigh thickness undergoing reconstruction of extensive glossectomy defects.

Pre-epithelialized cryopreserved tracheal allograft for neo-trachea flap engineering.

Background: Tracheal reconstruction presents a challenge because of the difficulty in maintaining the rigidity of the trachea to ensure an open lumen and in achieving an intact luminal lining that secretes mucus to protect against infection. Methods: On the basis of the finding that tracheal cartilage has immune privilege, researchers recently started subjecting tracheal allografts to "partial decellularization" (in which only the epithelium and its antigenicity are removed), rather than complete decellularization, to maintain the tracheal cartilage as an ideal scaffold for tracheal tissue engineering and reconstruction. In the present study, we combined a bioengineering approach and a cryopreservation technique to fabricate a neo-trachea using pre-epithelialized cryopreserved tracheal allograft (ReCTA). Results: Our findings in rat heterotopic and orthotopic implantation models confirmed that tracheal cartilage has sufficient mechanical properties to bear neck movement and compression; indicated that pre-epithelialization with respiratory epithelial cells can prevent fibrosis obliteration and maintain lumen/airway patency; and showed that a pedicled adipose tissue flap can be easily integrated with a tracheal construct to achieve neovascularization. Conclusion: ReCTA can be pre-epithelialized and pre-vascularized using a 2-stage bioengineering approach and thus provides a promising strategy for tracheal tissue engineering.

Simultaneous Scalp, Skull, Kidney, and Pancreas Transplant from a Single Donor: Insights from a 5-Year Follow-Up.

SUMMARY: This report provides a 5-year follow-up on the first reported simultaneous scalp, calvarium, kidney, and pancreas transplant. The previously published case report represented both the first composite calvarial-scalp transplant and combination of a vascularized composite allotransplantation with double organ transplantation. Over the ensuing 5 years, the patient underwent a single episode of acute scalp rejection successfully managed with intravenous Solu-Medrol, one resection of a basal cell carcinoma on the native scalp, hardware removal, and bony contouring. In addition, the patient developed seizures secondary to delayed, postirradiation cerebral necrosis requiring craniotomy and resection. His seizures were ultimately controlled. Currently, more than 5 years after his multiorgan transplant, the patient continues to have excellent allograft function and a very satisfactory aesthetic outcome, demonstrating that in certain cases, combined vascularized composite allotransplantation with solid organ transplantation can be performed safely without compromising the solid organ transplantation.

The Use of Machine Learning for Predicting Complications of Free-Flap Head and Neck Reconstruction.

BACKGROUND: Machine learning has been increasingly used for surgical outcome prediction, yet applications in head and neck reconstruction are not well-described. In this study, we developed and evaluated the performance of ML algorithms in predicting postoperative complications in head and neck free-flap reconstruction. METHODS: We conducted a comprehensive review of patients who underwent microvascular head and neck reconstruction between January 2005 and December 2018. Data were used to develop and evaluate nine supervised ML algorithms in predicting overall complications, major recipient-site complication, and total flap loss. RESULTS: We identified 4000 patients who met inclusion criteria. Overall, 33.7% of patients experienced a complication, 26.5% experienced a major recipient-site complication, and 1.7% suffered total flap loss. The k-nearest neighbors algorithm demonstrated the best overall performance for predicting any complication (AUROC = 0.61, sensitivity = 0.60). Regularized regression had the best performance for predicting major recipient-site complications (AUROC = 0.68, sensitivity = 0.66), and decision trees were the best predictors of total flap loss (AUROC = 0.66, sensitivity = 0.50). CONCLUSIONS: ML accurately identified patients at risk of experiencing postsurgical complications, including total flap loss. Predictions from ML models may provide insight in the perioperative setting and facilitate shared decision making.

The effect of isovitexin on lipopolysaccharide-induced renal injury and inflammation by induction of protective autophagy.

Chronic kidney disease (CKD) is a systemic inflammatory syndrome that includes tubulointerstitial inflammation. Lipopolysaccharide (LPS), the outer membrane of Gram-negative bacteria, can increase reactive oxygen species production (ROS) that triggers cell inflammation. Isovitexin (IV) is a flavone that has the potential for anticancer, antioxidant, and anti-inflammatory. This study aimed to hypothesize that IV inhibited LPS-induced renal injury in vitro and in vivo. In vitro study, IV prevented LPS-induced ROS production and increased cell viability on SV40-MES-13 cells. Additionally, IV ameliorated mitochondrial membrane potential, downregulated inflammation and pyroptosis factors on LPS treatment. We found that LPS treatment reduced the expression of autophagy, however, this effect was reversed by IV. In vivo study, the renal injury model in C57BL/6 mice cotreatment with IV was examined. In addition, IV decreased LPS-induced glomerular atrophy and reduced inflammation-related cytokines releases. Further showed that IV could significantly reduce LPS-induced inflammation and pyroptosis factors in mice. Under the immunostaining, increased fluorescence of LC3 autophagy-related protein was recovered by IV. In summary, IV ameliorated renal injury, inflammation and increased protected autophagy by anti-ROS production, anti-inflammation, and anti-pyroptosis. In the future, the safety of isovitexin as a novel perspective for CKD patients should be evaluated in further clinical studies.

The Cost Utility of Virtual Surgical Planning and Computer-Assisted Design/Computer-Assisted Manufacturing in Mandible Reconstruction Using the Free Fibula Osteocutaneous Flap.

BACKGROUND: The use of virtual surgical planning and computer-assisted design and computer-assisted manufacturing (CAD/CAM) has become widespread for mandible reconstruction with the free fibula flap. However, the cost utility of this technology remains unknown. METHODS: The authors used a decision tree model to evaluate the cost utility, from the perspective of a hospital or insurer, of mandible reconstruction using CAD/CAM relative to the conventional (non-CAD/CAM) technique for the free fibula flap. Health state probabilities were obtained from a published meta-analysis. Costs were estimated using 2018 Centers for Medicare and Medicaid Services data. Overall expected cost and quality-adjusted life-years (QALYs) were assessed using a Monte Carlo simulation and sensitivity analyses. Cost effectiveness was defined as an incremental cost utility ratio (ICUR) less than the empirically accepted willingness-to-pay value of $50,000 per QALY. RESULTS: Although CAD/CAM reconstruction had a higher expected cost compared with the conventional technique ($36,487 vs. $26,086), the expected QALYs were higher (17.25 vs. 16.93), resulting in an ICUR = $32,503/QALY; therefore, the use of CAD/CAM in free fibula flap mandible reconstruction was cost-effective relative to conventional technique. Monte Carlo sensitivity analysis confirmed CAD/CAM's superior cost utility, demonstrating that it was the preferred and more cost-effective option in the majority of simulations. Sensitivity analyses also illustrated that CAD/CAM remains cost effective at an amount less than $42,903 or flap loss rate less than 4.5%. CONCLUSION: This cost utility analysis suggests that mandible reconstruction with the free fibula osteocutaneous flap using CAD/CAM is more cost effective than the conventional technique.

In Vitro and In Vivo Nephroprotective Effects of Nelumbo nucifera Seedpod Extract against Cisplatin-Induced Renal Injury.

Cisplatin has been considered a chemotherapeutic drug for treating human tumors, and one of the noteworthy side effects of cisplatin is nephrotoxicity. Amelioration of cisplatin-induced nephrotoxicity is necessary. Lotus seedpod extract (LSE) mainly composed of quercetin-3-glucuronide has been revealed for antioxidant and anti-tumor effects. However, the effects of LSE on cisplatin-induced nephrotoxicity are still unknown. This study aims to explore the in vitro and in vivo protective effect and possible mechanism of LSE on cisplatin-induced nephrotoxicity. Results showed that co-treatment of LSE with cisplatin raised the viability of rat renal tubular epithelial NRK-52E cells and decreased oxidative stress and cell apoptosis when compared to the cells treated with cisplatin alone. The molecular mechanisms analyzed found that LSE could reduce the expressions of apoptotic factors, including Bax, Bad, t-Bid, and caspases. In the in vivo study, LSE improved the cisplatin-induced levels of serum markers of kidney function, glomerular atrophy, and the degree of apoptosis in the kidneys. This is the first study to display that LSE prevents cisplatin-induced nephrotoxicity by reducing oxidative stress and apoptosis. Thus, LSE could be a novel and natural chemoprotective agent for cisplatin chemotherapy in the future.

Outcomes for recurrent oral cavity squamous cell carcinoma.

OBJECTIVES: We sought to determine overall survival (OS), prognostic factors, cost, and functional outcomes after surgery for locally recurrent oral cavity squamous cell carcinoma (OCSCC). MATERIALS AND METHODS: We retrospectively reviewed 399 cases of locally recurrent OCSCC from 1997 to 2011, of which 259 patients were treated with salvage surgery. Survival and prognostic factors were evaluated using univariable and multivariable Cox regression, the Kaplan-Meier method, and the log-rank test. RESULTS: The 5-year OS for patients undergoing surgical salvage, nonsurgical therapy, or supportive care was 44.2%, 1.5%, and 0%, respectively. For patients who underwent surgical salvage, 133 (51%) patients experienced a second recurrence at a median of 17 months. Factors associated with OS included disease-free interval ≤ 6 months (P =.0001), recurrent stage III-IV disease (P <.0001), and prior radiation (P =.0001). Patients with both advanced stage and prior radiation had a 23% 5-year OS, compared with 70% for those with neither risk (P <.001). Functionally, 85% of patients had > 80% speech intelligibility and 81% were able to eat by mouth following salvage surgery. Of the patients who required tracheostomy, 78% were decannulated. The adjusted median hospital and professional charges for patients were $129,696 (range $9,238-$956,818). CONCLUSIONS: Patients with recurrent OCSCC who underwent salvage surgery have favorable functional outcomes with half of alive at 5 years but poorer OS for advanced disease, disease-free interval ≤ 6 months, and prior radiation. Additionally, treatment is associated with high cost, and about half of patients ultimately develop another recurrence.

On the quest for novel bio-degradable plastics for agricultural field mulching.

Plasticulture, the practice of using plastic materials in agricultural applications, consumes about 6.7 million tons of plastics every year, which is about 2% of the overall global annual plastics production. For different reasons, plastic material used for agriculture is difficult to recycle. Therefore, most of it is either buried in fertile soils, thereby significantly causing deterioration of their properties, or, at best case, end in landfills where its half-life is measured in decades and even centuries. Hence, developing biodegradable plastic materials that are suitable for agricultural applications is a vital and inevitable need for the global human society. In our labs, two types of potentially biodegradable plastic polymer films were prepared and characterized imidazolium in terms of their bio-degradability. In the first approach, polymers made of ionic liquid monomers were prepared using photo radical induced polymerization. The second approach relies on formation of polyethylene-like n-alkane disulfide polymers from 1,ω-di-thiols through thermally activated air oxidation. These two families of materials were tested for their biodegradability in soils by using a simulation system that combines a controlled environment chamber equipped with a respirometer and a proton-transfer-reaction time of flight mass spectrometer (PTR-TOF-MS) system. This system provides a time-dependent and comprehensive fingerprint of volatiles emitted in the degradation process. The results obtained thus far indicate that whereas the ionic-liquid based polymer does not show significant bio-degradability under the test conditions, the building block monomer, 1,10-n-decane dithiol, as well as its disulfide-based polymer, are bio-degradable. The latter reaching, under basic soil conditions and in room temperature, ∼20% degradation within three months. These results suggest that by introduction of disulfide groups into the polyethylene backbone one may be able to render it biodegradable, thus considerably shortening its half-life in soils. Principal component analysis, PCA, of the data about the total volatiles produced during the degradation in soil indicates a distinctive volatile "fingerprint" of the disulfide-based bio-degradable products which comes from the volatile organic compounds portfolio as recorded by the PTR-TOF-MS. The biodegradation volatile fingerprint of this kind of film was different from the "fingerprint" of the soil background which served as a control. These results can help us to better understand and design biodegradable films for agricultural mulching practices.

Impact of Body Mass Index on Surgical Outcomes in Oncologic Microvascular Head and Neck Reconstruction.

BACKGROUND: Despite increasing recognition, obesity continues to represent a major health issue for millions of people in the USA and worldwide. There is a paucity in the literature regarding the effect of body mass index (BMI) on microsurgical head and neck reconstruction. The present study hypothesized that high BMI is predictive of postoperative recipient- and donor-site complications with longer operative times. PATIENTS AND METHODS: Retrospective review of patients who underwent free flap surgery for head and neck reconstruction was performed between January 2005 and December 2018. Patients were categorized into four groups based on BMI: < 20 kg/m2, 20-30 kg/m2, 30-40 kg/m2, and ≥ 40 kg/m2. Patient characteristics and surgical outcomes were compared between the four groups. RESULTS: Overall, 4000 free flap surgeries were included in the present study, performed on 3753 patients, of whom 9.9% had a BMI < 20 kg/m2, 64.9% had a BMI between 20 and 30 kg/m2, 21.6% had a BMI between 30 and 40 kg/m2, and 3.6% had a BMI ≥ 40 kg/m2. After adjusting for potential confounders, multivariate analysis showed no association between BMI and any complication, major recipient complications, or total flap loss. However, multivariate linear regression model showed BMI 30-40 kg/m2 and BMI ≥ 40 kg/m2 to be independently associated with longer operative times compared with BMI < 20 kg/m2. CONCLUSION: Obesity and high BMI increase operative times; however, with meticulous surgical technique and diligent postoperative care, microvascular head and neck reconstructions can be performed safely and reliably in the majority of patients regardless of BMI with similar overall, recipient-site, and donor-site complications.

Outcomes after definitive surgery for mandibular osteoradionecrosis.

OBJECTIVES: To analyze charges, complications, survival, and functional outcomes for definitive surgery of mandibular osteoradionecrosis (ORN). MATERIALS AND METHODS: Retrospective analysis of 76 patients who underwent segmental mandibulectomy with reconstruction from 2000 to 2009. RESULTS: Complications occurred in 49 (65%) patients and were associated with preoperative drainage (odds ratio [OR] 4.40, 95% confidence interval [CI] 1.01-19.27). The adjusted median charge was $343 000, and higher charges were associated with double flap reconstruction (OR 8.15, 95% CI 2.19-30.29) and smoking (OR 5.91, 95% CI 1.69-20.72). Improved swallow was associated with age <67 years (OR 3.76, 95% CI 1.16-12.17) and preoperative swallow (OR 3.42, 95% CI 1.23-9.51). Five-year ORN-recurrence-free survival was 93% while overall survival was 63% and associated with pulmonary disease (HR [hazard ratio] 3.57, 95% CI 1.43-8.94). CONCLUSIONS: Although recurrence of ORN is rare, surgical complications are common and charges are high. Poorer outcomes and higher charges are associated with preoperative factors.

A Comprehensive Approach for Measuring Spatial Deviations of Computer-Assisted Mandibular Reconstruction.

BACKGROUND: Computer-assisted surgery has become the mainstream in mandibular reconstruction, but the lack of a standard measuring approach for spatial deviations of mandible hinders postoperative verification and the comparison of different subjects. This study aims to set up a comprehensive approach for measuring spatial deviations of computer-assisted mandibular reconstruction. METHODS: A systematic review was conducted to extract all measurements for computer-assisted mandibular reconstruction. Thereafter, eligible measurements were included in the authors' comprehensive approach, which categorized the measurements according to different anatomical structures and landmarks. RESULTS: A total of 80 studies were included in the authors' systematic review, and 31 measurements were extracted. The authors established a comprehensive panel of anatomical landmarks to facilitate measurement, including parts, points, lines, planes, and angles. These measurements encompassed spatial deviations of the overall mandible, condyle, gonial angle, bone grafts, midline, surgical plate, osteotomy, and miscellaneous indicators. A calculation spreadsheet was developed to collect landmarks and compute deviations automatically with built-in formulas. Finally, a simplified panel of measurements was recommended for spatial deviations of mandibular reconstruction. CONCLUSIONS: A comprehensive approach for measuring spatial deviations of computer-assisted mandibular reconstruction was established. Future studies will confirm this approach as an effective and scientific system for postoperative verification of computer-assisted mandibular reconstruction.

Anti-Atherosclerotic Effect of Gossypetin on Abnormal Vascular Smooth Muscle Cell Proliferation and Migration.

Gossypetin (GTIN), known as 3,5,7,8,3',4'-hexahydroxyflavone, has been demonstrated to exert anti-atherosclerotic potential against apoptotic injury in oxidized low-density lipoprotein-incubated endothelial cells, and atherosclerotic lesions of cholesterol-fed rabbits. However, the effect and underlying mechanism of GTIN on abnormal vascular smooth muscle cells (VSMCs) proliferation and migration, a major event in the pathogenesis of atherosclerosis, is still unknown. In this study, non-cytotoxic doses of GTIN abolished the VSMCs A7r5 proliferation and cell-cycle S phase distribution. The GTIN-arrested G0/G1 phase might be performed by increasing the expressions of phosphorylated p53 and its downstream molecules that inhibit the activation of cyclin E/cyclin-dependent kinase (cdk)-2, blocking retinoblastoma protein (Rb) phosphorylation and the subsequent dissociation of Rb/transcription factor E2F1 complex. In addition, the results indicated that GTIN inhibited VSMCs wound-healing and migratory abilities through reducing matrix metalloproteinase (MMP)-9 activity and expression, as well as down-regulating protein kinase B (PKB)/nuclear factor-kappaB (NF-κB) signaling. GTIN also revealed potential in diminishing reactive oxygen species (ROS) generation. These findings suggested the inhibitory effects of GTIN on VSMCs dysfunction could likely lead to the containment of atherosclerosis and other cardiovascular illness.