Metformin-induced PCSK9 inhibition further decreases LDL-C following statin treatment in patients with coronary artery disease and without diabetes.

In vitro investigations have established metformin's capacity to downregulate PCSK9 expression, suggesting a potential beneficial effect on atherogenic lipoprotein particles when combined with metformin therapy. Our objective was to assess whether metformin could mitigate statin-induced adverse effects on PCSK9, thereby improving lipid profiles in patients with coronary artery disease (CAD) but without diabetes. Employing an open-label, placebo-controlled, randomized trial, we randomized patients with CAD but without diabetes into CLA (Cholesterol-Lowering Agents alone: atorvastatin+/-ezetimibe, n=38) and Met+CLA groups (metformin plus CLA, n=33) at a 1:1 ratio. The primary endpoint was the therapeutic impact of one-month metformin combination treatment on LDL-C and PCSK9 levels. Baseline LDL-C and PCSK9 levels were 76.18 mg·dL-1 and 80.54 ng·mL-1, respectively. After one month, metformin significantly reduced LDL-C (-20.81%, P<0.001), enabling 72% of patients to attain guideline-recommended LDL-C goals. Noteworthy reductions in PCSK9 levels (-15.03%, P<0.001) were observed. Moreover, Met+CLA markedly reduced LDL particle number more than CLA alone (-10.65% vs 1.45%, P=0.009), primarily due to diminished small-dense LDL particle count. Mechanistically, our study demonstrated metformin's inhibition of statin-induced PCSK9 expression in human hepatocellular cells. In summary, a one-month metformin combination regimen reduced LDL-C levels in patients with CAD but without diabetes by inhibiting PCSK9 expression.

Using the Super Learner algorithm to predict risk of major adverse cardiovascular events after percutaneous coronary intervention in patients with myocardial infarction.

BACKGROUND: The primary treatment for patients with myocardial infarction (MI) is percutaneous coronary intervention (PCI). Despite this, the incidence of major adverse cardiovascular events (MACEs) remains a significant concern. Our study seeks to optimize PCI predictive modeling by employing an ensemble learning approach to identify the most effective combination of predictive variables. METHODS AND RESULTS: We conducted a retrospective, non-interventional analysis of MI patient data from 2018 to 2021, focusing on those who underwent PCI. Our principal metric was the occurrence of 1-year postoperative MACEs. Variable selection was performed using lasso regression, and predictive models were developed using the Super Learner (SL) algorithm. Model performance was appraised by the area under the receiver operating characteristic curve (AUC) and the average precision (AP) score. Our cohort included 3,880 PCI patients, with 475 (12.2%) experiencing MACEs within one year. The SL model exhibited superior discriminative performance, achieving a validated AUC of 0.982 and an AP of 0.971, which markedly surpassed the traditional logistic regression models (AUC: 0.826, AP: 0.626) in the test cohort. Thirteen variables were significantly associated with the occurrence of 1-year MACEs. CONCLUSION: Implementing the Super Learner algorithm has substantially enhanced the predictive accuracy for the risk of MACEs in MI patients. This advancement presents a promising tool for clinicians to craft individualized, data-driven interventions to better patient outcomes.

Solvent Effects on the 1 H-NMR Chemical Shifts of Imidazolium-Based Ionic Liquids.

The 1 H nuclear magnetic resonance (1 H-NMR) spectrum is a useful tool for characterizing the hydrogen bonding (H-bonding) interactions in ionic liquids (ILs). As the main hydrogen bond (H-bond) donor of imidazolium-based ILs, the chemical shift (δH2 ) of the proton in the 2-position of the imidazolium ring (H2) exhibits significant and complex solvents, concentrations and anions dependence. In the present work, based on the dielectric constants (ϵ) and Kamlet-Taft (KT) parameters of solvents, we identified that the δH2 are dominated by the solvents polarity and the competitive H-bonding interactions between cations and anions or solvents. Besides, the solvents effects on δH2 are understood by the structure of ILs in solvents: 1) In diluted solutions of inoizable solvents, ILs exist as free ions and the cations will form H-bond with solvents, resulting in δH2 being independent with anions but positively correlated with ßS . 2) In diluted solutions of non-ionzable solvents, ILs exist as contact ion-pairs (CIPs) and H2 will form H-bond with anions. Since non-ionizable solvents hardly influence the H-bonding interactions between H2 and anions, the δH2 are not related to ßS but positively correlated with ßIL .

Short-term efficacy and safety of personalized antiplatelet therapy for patients with acute ischaemic stroke or transient ischaemic attack: A randomized clinical trial.

AIMS: The aim of this study was to determine whether the testing strategy for clopidogrel and/or aspirin resistance using CYP2C19 genotyping or urinary 11-dhTxB2 testing has an impact on clinical outcomes. METHODS: A multicentre, randomized, controlled trial was conducted at 14 centres in China from 2019 to 2021. For the intervention group, a specific antiplatelet strategy was assigned based on the CYP2C19 genotype and 11-dhTxB2, a urinary metabolite of aspirin, and the control group received nonguided (ie, standard of care) treatment. 11-dhTXB2 is a thromboxane A2 metabolite that can help quantify the effects of resistance to aspirin in individuals after ingestion. The primary efficacy outcome was new stroke, the secondary efficacy outcome was a poor functional prognosis (a modified Rankin scale score ≥3), and the primary safety outcome was bleeding, all within the 90-day follow-up period. RESULTS: A total of 2815 patients were screened and 2663 patients were enrolled in the trial, with 1344 subjects assigned to the intervention group and 1319 subjects assigned to the control group. A total of 60.1% were carriers of the CYP2C19 loss-of-function allele (*2, *3) and 8.71% tested positive for urinary 11-dhTxB2- indicating aspirin resistance in the intervention group. The primary outcome was not different between the intervention and control groups (P = .842). A total of 200 patients (14.88%) in the intervention group and 240 patients (18.20%) in the control group had a poor functional prognosis (hazard ratio 0.77, 95% confidence interval [CI] 0.63 to 0.95, P = .012). Bleeding events occurred in 49 patients (3.65%) in the intervention group and 72 patients (5.46%) in the control group (hazard ratio 0.66, 95% CI 0.45 to 0.95, P = .025). CONCLUSIONS: Personalized antiplatelet therapy based on the CYP2C19 genotype and 11-dhTxB2 levels was associated with favourable neurological function and reduced bleeding risk in acute ischaemic stroke and transient ischaemic attack patients. The results may help support the role of CYP2C19 genotyping and urinary 11-dhTxB2 testing in the provision of precise clinical treatment.

Thyroidectomy for thyroid cancer via transareola single-site endoscopic approach: results of a case-match study with large-scale population.

BACKGROUND: Due to technical challenges, single-site endoscopic thyroidectomy (SSET) is seldom reported and has been attempted in only limited cases. This large-scale study aimed to compare the clinical outcomes of standardized transareola SSET (TASSET) with those of conventional open thyroidectomy (COT) for thyroid cancer. METHODS: The data were prospectively collected, and case-match study was performed at a ratio of 1:1 according to age, sex, body mass index, lesion size, number of lesion foci, lesion side, recurrent laryngeal nerve (RLN) exploration and pathology. Two hundred eligible patients underwent TASSET, and the same number of patients was selected for propensity score matching from 2256 patients who underwent COT. Perioperative data, including surgical profile, oncological and traumatic burdens, and cosmetic satisfaction, were analyzed. RESULTS: No significant differences were observed in blood loss or drainage between TASSET and COT groups. There were no differences in operation time between TASSET and COT (106.39 ± 28.44 vs 102.55 ± 23.10 min, p = 0.154). A total of 3.63 ± 1.82 lymph nodes (LNs) were retrieved from CND with 0.96 ± 1.42 positive in TASSET. In COT, the total and positive LN yields were 3.77 ± 1.91 and 0.99 ± 1.40 (p = 0.445, p = 0.802). Cancer recurrence was not observed in either group. There were no differences in the occurrence of permanent and transient hoarseness or RLN injuries. Postoperative flap seroma or hematoma occurred in 12 TASSET patients and 58 COT patients (p < 0.001). The pain score, CRP level and ESR in TASSET group were lower than those in COT group. TASSET yielded significantly better incision recovery and cosmetic scores than did COT at both the proliferation and stabilization stages. CONCLUSIONS: TASSET is technically feasible and yields enhanced recovery with minimally invasive and cosmetic advantages without compromising the level of safety or cancer eradication.

The role of anlotinib-mediated EGFR blockade in a positive feedback loop of CXCL11-EGF-EGFR signalling in anaplastic thyroid cancer angiogenesis.

BACKGROUND: Hypoxia-induced angiogenesis functions importantly in anaplastic thyroid cancer (ATC) progression. However, the therapeutic potential of broad-spectrum anti-angiogenic agent remains undefined. Anlotinib conventionally targets VEGFR, FGFR and PDGFR. Here, a novel role of anlotinib on ATC angiogenesis was illustrated. METHODS: Molecular expressions were established via tissue microarray. Multiple assays (tubule formation, 3D sprouting and chicken chorioallantoic membrane model) were used for angiogenic evaluation. Panels of molecular screening were achieved by antibody and PCR arrays. The loop binding motif of EGFR for homology modelling was prepared using Maestro. RESULTS: Anlotinib could dose- and time-dependently inhibit cell viability under normoxia and hypoxia and could repress hypoxia-activated angiogenesis more efficiently in vitro and in vivo. CXCL11 and phospho-EGFR were hypoxia-upregulated with a positive correlation. The cancer-endothelium crosstalk could be mediated by the positive CXCL11-EGF-EGFR feedback loop, which could be blocked by anlotinib directly targeting EGFR via a dual mechanism by simultaneous inhibitory effects on cancer and endothelial cells. The AKT-mTOR pathway was involved in this regulatory network. CONCLUSIONS: The newly identified CXCL11-EGF-EGFR signalling provided mechanistic insight into the interaction between cancer and endothelial cells under hypoxia, and EGFR was a novel target. Anlotinib may be the encouraging therapeutic candidate in ATC.

Polymer solubility in ionic liquids: dominated by hydrogen bonding.

Polymer solubility in ionic liquids (ILs) cannot be predicted by the solubility parameter approach based on the "like dissolves like" principle. According to the Kamlet-Abraham-Taft (KAT) multi-parameter polarity scale, ILs can be categorized on the basis of hydrogen-bond acidity or basicity ones. The experimental observations, that acidic ILs easily dissolve basic polymers and basic ILs dissolve acidic polymers, reflect the complementary nature of hydrogen-bonding interactions. A quantitative hydrogen-bonding analysis is proposed for predicting the solubility by taking the product of ΔαΔß as an indicator of the competition between cross-association and self-association hydrogen bonding (H-bonding), where Δα is the difference of acidity parameters between the polymer and IL, and Δß is the difference of basicity. This solubility criterion has been validated by the solubility data of 19 polymers (11 acidic and 8 basic) in 11 ILs (7 acidic and 4 basic). These principles based on KAT parameters can be applied to other systems dominated by hydrogen bonding.

Comparison of calculated remnant lipoprotein cholesterol levels with levels directly measured by nuclear magnetic resonance.

BACKGROUND: Remnant cholesterol (RC) can partly explain the residual risk in atherosclerotic cardiovascular disease (ASCVD). A consensus method of measuring RC levels has not been established yet. In clinical practice, RC levels are usually calculated from the standard lipid profile, which are not true RC. Nuclear magnetic resonance (NMR) can measure RC levels directly. This study aimed to characterize RC at fasting and non-fasting states in more details and establish the performance of calculated RC and NMR-measured RC. METHODS: Blood samples at fasting state and at 2 h and 4 h postprandial states were collected in 98 subjects. Lipid parameters including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), subfractions 3, 4, and 5 of very low-density lipoprotein cholesterol (VLDL3-C, VLDL4-C, and VLDL5-C, respectively), and intermediate-density lipoprotein cholesterol (IDL-C) were measured by enzymatic method and NMR. RC levels calculated from the standard lipid profile or measured by NMR were referred here as RCe or RCn. RESULTS: The RCe and RCn levels were different, but both of them increased after a meal (P < 0.05), especially at 4 h postprandial state. Low correlations were found between RCe and RCn in the 1st, 2nd, and 3rd quartiles of TG, but RCn showed great correlation with RCe in the highest quartile regardless of the fasting or non-fasting state (R = 0.611, 0.536, and 0.535 for 0 h, 2 h, and 4 h, respectively). However, across the 2nd and 3rd quartiles, RCe levels were nearly close to RCn levels. RCe levels tended to overestimate RCn levels in the 1st quartile of TGe levels with median differences of 0.23(- 0.13, 0.63) and underestimate RCn levels with median differences of - 0.23(- 0.33, 0.07) in the highest quartile of TGe levels. CONCLUSIONS: RC calculated from the standard lipid profile as TC minus LDL-C minus HDL-C is different from the NMR-measured RC. According to different TG levels, RC could overestimate or underestimate the actual RC level. Developing a consensus clinical method to measure RC levels is necessary, so that results from different studies and platforms can be more directly compared. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1900020873. Registered in 21 January 2019 - Retrospectively registered.

Reference value for the TUGT in healthy older people: A systematic review and meta-analysis.

The timed up and go test (TUGT) was recently proposed as a strong predictor of adverse outcomes. Few reviews have been conducted to identify a standard for the TUGT in healthy older people, and the aims of this study were to explore the source of heterogeneity and evaluate the range of reference values for the TUGT in healthy people over 60 years old stratified by age and sex. The VIP, EMBASE, Web of Science and PubMed databases were searched from January 1, 2000, to December 31, 2018. A subgroup analysis and meta-regression were used to assess heterogeneity. Thirty-four eligible studies were included. The mean TUGT results for the total population, males and females in the sample were 9.21 s [95% CI (9.11, 9.31)], 9.33 s [95% CI (7.82, 11.08)] and 8.87 s [95% CI (8.40, 9.38)], respectively. The mean TUGT results for older people in their 60 s, 70 s, and 80 s were 7.91 s [95% CI (6.62, 9.20)], 8.67 s [95% CI (7.23, 10.12)] and 11.68 s [95% CI (8.11, 15.26)], respectively. The meta-regression analysis results showed that the heterogeneity was related to age (P < 0.01). Age affects the results of the TUGT, and it is necessary to take age into consideration when conducting stratified physical evaluations for the evaluation of older people individuals' physical fitness.

A randomized, double-blind, placebo-controlled trial of probiotics to reduce the severity of oral mucositis induced by chemoradiotherapy for patients with nasopharyngeal carcinoma.

BACKGROUND: The objective of this study was to evaluate the effect of a probiotic combination on the severity of oral mucositis (OM), which is a common, unpreventable complication induced by radiochemotherapy in patients with nasopharyngeal carcinoma who undergo concurrent radiochemotherapy (CCRT). METHODS: Eligible patients (n = 99) with locally advanced nasopharyngeal carcinoma who were undergoing CCRT were randomly assigned (2:1) to receive a probiotic combination or placebo during radiochemotherapy, and the incidence of severe OM (grade 3 or higher) was the primary endpoint. RESULTS: Patients taking the probiotic combination showed a significant reduction in the severity of OM. The incidences of grade 0, 1, 2, and 3 OM in the placebo group and the probiotic combination group were 0% and 12.07%, 0% and 55.17%, 54.29% and 17.24%, and 45.71% and 15.52%, respectively. Furthermore, CCRT greatly lowered the number of immune cells, whereas the probiotic combination markedly lowered the reduction rates of CD4+ T cells (76.59% vs 52.85%; P < .05), CD8+ T cells (62.94% vs 29.76%; P < .05), and CD3+ T cells (69.72% vs 45.49%; P < .05) in an A-CCRT-P (after treatment with radiotherapy plus chemotherapy plus the probiotic combination) group. High-throughput sequencing results indicated that CCRT had obviously disturbed the intestinal diversity of patients in an A-CCRT (after treatment with radiotherapy plus chemotherapy plus a placebo) group, whereas the probiotic combination distinctly restored the microbial diversity in the A-CCRT-P group toward that of healthy people and a B-CCRT-P (before the treatment of radiotherapy plus chemotherapy plus the probiotic combination) group. CONCLUSIONS: A probiotic combination significantly enhances the immune response of patients and reduces the severity of OM through modification of gut microbiota.

Practical gigahertz quantum key distribution robust against channel disturbance.

Quantum key distribution (QKD) provides an attractive solution for secure communication. However, channel disturbance severely limits its application when a QKD system is transferred from the laboratory to the field. Here a high-speed Faraday-Sagnac-Michelson QKD system is proposed that can automatically compensate for the channel polarization disturbance, which largely avoids the intermittency limitations of environment mutation. Over a 50 km fiber channel with 30 Hz polarization scrambling, the practicality of this phase-coding QKD system was characterized with an interference fringe visibility of 99.35% over 24 h and a stable secure key rate of 306 k bits/s over seven days without active polarization alignment.

Apatinib Inhibits Angiogenesis Via Suppressing Akt/GSK3ß/ANG Signaling Pathway in Anaplastic Thyroid Cancer.

BACKGROUND/AIMS: Anaplastic thyroid carcinoma (ATC) is one of the most lethal human malignancies, and there is no efficient method to slow its process. Apatinib, a novel tyrosine kinase inhibitor (TKI), has been confirmed for its efficacy and safety in the treatment of advanced gastric carcinoma patients. However, the effects of Apatinib in ATC are still unknown. METHODS: In this study, we explored the effects and mechanisms of Apatinib on tumor growth and angiogenesis in vitro and in vitro in ATC cells. Angiogenesis antibodies array was utilized to detect the expression of angiogenesis-related genes after Apatinib treatment in ATC cells. In addition, we used Akt activator, Akt inhibitor and GSK3ß inhibitor to further study the mechanism for how Apatinib suppressed angiogenesis. RESULTS: Apatinib treatment could suppress the growth of ATC cells in a dose- and time-dependent manner via inducing apoptosis and blocking cell cycle progression at G0/G1 phase. Moreover, Apatinib treatment decreased the expression of angiogenin (ANG) and inhibited angiogenesis of ATC cells in vitro and in vitro. We further confirmed that recombinant human ANG (rhANG) significantly abrogated Apatinib-mediated anti-angiogenic ability in ATC cells. Additionally, Apatinib treatment decreased the level of p-Akt and p-GSK3ß. Moreover, the Apatinib-mediated decrease of ANG and anti-angiogenic ability were partly reversed when an Akt activator, SC79, was administered. Furthermore, the anti-angiogenic ability of Apatinib can be enhanced in the presence of Akt inhibitor, and the inhibition of GSK3ß attenuated the anti-angiogenic ability of Apatinib. CONCLUSION: Our results demonstrated that Apatinib treatment inhibited tumor growth, and Apatinib-induced suppression of Akt/GSK3ß/ANG signaling pathway may play an important role in the inhibition of angiogenesis in ATC, supporting a potential therapeutic approach for using Apatinib in the treatment of ATC.

Clinical factors influencing the effectiveness of microplasma fractional radiofrequency treatment for atrophic acne scars: A retrospective analysis.

BACKGROUND: Microplasma fractional radiofrequency (MP FRF) technology has been increasingly used for acne scars. Nevertheless, little evidence has analyzed the factors influencing its effectiveness before and during treatment. AIMS: To evaluate the clinical factors affecting the effectiveness of MP FRF therapy for atrophic acne scars. METHODS: We analyzed retrospectively the clinical data of 79 acne scar patients treated with MP FRF technology. The outcome of interest included the effectiveness and adverse events after MP FRF treatment. Multivariable logistic regression was utilized to evaluate clinical factors associated with effectiveness after the initial session. RESULTS: All patients received 115 sessions of MP FRF therapy (average: 1.5 sessions). Twenty-eight (35.4%) patients improved moderately to excellently after one session. We found that the severe grade before treatment was negatively correlated with the effectiveness according to Goodman-Baron qualitative scores (OR = 0.02, 95% CI [0.001, 0.37], p = 0.009). The presence of icepick scars was also a negative correlation factor for the effectiveness (OR = 0.06, 95% CI [0.004, 1.00], p = 0.049). Furthermore, after excluding the effects of icepick scars and Goodman-Baron scores before treatment, ECCA scores were also correlated with effectiveness (OR = 1.04, 95% CI [1.01, 1.06], p = 0.009). CONCLUSION: MP FRF therapy was effective in treating atrophic acne scars with no permanent adverse events. The severity of Goodman-Baron qualitative scores and icepick scars were independent clinical factors affecting effectiveness, suggesting the possible requirement for additional treatments other than MP FRF for severe acne scars and icepick scars.

Machine Learning for Early Prediction of Major Adverse Cardiovascular Events After First Percutaneous Coronary Intervention in Patients With Acute Myocardial Infarction: Retrospective Cohort Study.

BACKGROUND: The incidence of major adverse cardiovascular events (MACEs) remains high in patients with acute myocardial infarction (AMI) who undergo percutaneous coronary intervention (PCI), and early prediction models to guide their clinical management are lacking. OBJECTIVE: This study aimed to develop machine learning-based early prediction models for MACEs in patients with newly diagnosed AMI who underwent PCI. METHODS: A total of 1531 patients with AMI who underwent PCI from January 2018 to December 2019 were enrolled in this consecutive cohort. The data comprised demographic characteristics, clinical investigations, laboratory tests, and disease-related events. Four machine learning models-artificial neural network (ANN), k-nearest neighbors, support vector machine, and random forest-were developed and compared with the logistic regression model. Our primary outcome was the model performance that predicted the MACEs, which was determined by accuracy, area under the receiver operating characteristic curve, and F1-score. RESULTS: In total, 1362 patients were successfully followed up. With a median follow-up of 25.9 months, the incidence of MACEs was 18.5% (252/1362). The area under the receiver operating characteristic curve of the ANN, random forest, k-nearest neighbors, support vector machine, and logistic regression models were 80.49%, 72.67%, 79.80%, 77.20%, and 71.77%, respectively. The top 5 predictors in the ANN model were left ventricular ejection fraction, the number of implanted stents, age, diabetes, and the number of vessels with coronary artery disease. CONCLUSIONS: The ANN model showed good MACE prediction after PCI for patients with AMI. The use of machine learning-based prediction models may improve patient management and outcomes in clinical practice.

Leukotriene B4 receptor knockdown affects PI3K/AKT/mTOR signaling and apoptotic responses in colorectal cancer.

Colorectal cancer (CRC) presents a landscape of intricate molecular dynamics. In this study, we focused on the role of the leukotriene B4 receptor (LTB4R) in CRC, exploring its significance in the disease's progression and potential therapeutic approaches. Using bioinformatics analysis of the GSE164191 and the Cancer Genome Atlas-colorectal adenocarcinoma (TCGA-COAD) datasets, we identified LTB4R as a hub gene influencing CRC prognosis. Subsequently, we examined the relationship between LTB4R expression, apoptosis, and the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) signaling pathway through cellular and mice experiments. Our findings revealed that LTB4R is highly expressed in CRC samples and is pivotal for determining prognosis. In vitro experiments demonstrated that silencing LTB4R significantly impeded CRC cell viability, migration, invasion, and colony formation. Correspondingly, in vivo tests indicated that LTB4R knockdown led to markedly slower tumor growth in mice models. Further in-depth investigation revealed that LTB4R knockdown significantly amplified the apoptosis in CRC cells and upregulated the expression of apoptosis-related proteins, such as caspase-3 and caspase-9, while diminishing p53 expression. Interestingly, silencing LTB4R also resulted in a significant downregulation of the PI3K/AKT/mTOR signaling pathway. Moreover, pretreatment with the PI3K activator 740Y-P only partially attenuated the effects of LTB4R knockdown on CRC cell behavior, emphasizing LTB4R's dominant influence in CRC cell dynamics and signaling pathways. LTB4R stands out as a critical factor in CRC progression, profoundly affecting cellular behavior, apoptotic responses, and the PI3K/AKT/mTOR signaling pathway. These findings not only shed light on LTB4R's role in CRC but also establish it as a potential diagnostic biomarker and a promising target for therapeutic intervention.

Parathyroidectomy for solitary parathyroid adenoma via trans-areola single site endoscopic approach: Results of a case-match study.

BACKGROUND: This study aimed to establish the standardized procedure of trans-areola single site endoscopic parathyroidectomy (TASSEP), and to compare the performance of TASSEP with that of conventional open parathyroidectomy (COP). METHODS: This study enrolled 40 patients with primary hyperparathyroidism (PHPT) who underwent TASSEP, and included 40 of 176 PHPT patients who underwent COP based on propensity score matching. The retrospective analysis was conducted based on prospectively collected data. Perioperative outcomes, including surgical profile, surgical burden and cosmetic results and follow-up were reported. The learning curve was described using a cumulative sum (CUSUM) analysis. RESULTS: 40 TASSEPs were completed successfully without conversions or severe complications. There was no statistically significant difference in operation time between TASSEP and COP groups (80.83 ± 11.95 vs. 76.95 ± 7.30 min, p = 0.084). Experience of 17 cases was necessitated to reach the learning curve of TASSEP. Postoperative pain score and traumatic index (C-reactive protein and erythrocyte sedimentation rate) in TASSEP were apparently lower than those in COP group (p < 0.05). During the proliferation and stabilization phases, TASSEP was associated with significantly better incision recovery and cosmetic scores. Postoperative serum calcium and PTH levels throughout the follow-up period indicated satisfactory surgical qualities in both groups. CONCLUSION: Based on precise preoperative localization and intraoperative planning facilitated by three-dimensional (3D) virtual modeling, TASSEP can be feasibly performed on selected patients with satisfactory success rates and low complication rates, providing preferable cosmetic results and alleviating the surgical burden to a certain extent.

Fractional picosecond laser for atrophic acne scars: A meta-analysis.

BACKGROUND: Conventional fractional lasers (FLs) are well-established treatments for acne scars with some inevitable adverse events. Fractional picosecond laser (FPL) is increasingly used for acne scars. AIMS: To compare the efficacy and safety of FPL with non-picosecond FLs for acne scars. METHODS: PubMed, Embase, Ovid, Cochrane Library, and Web of Science databases were searched. We also searched ClinicalTrials, WHO ICTRP, and ISRCTN websites. A meta-analysis was conducted to assess the clinical improvement and adverse events after FPL compared with other FLs. RESULTS: Overall, seven eligible studies were included. Three physician evaluation systems showed no difference between FPL and other FLs in clinical improvement of atrophic acne scars (MD = 0.64, 95% CI:-9.67 to 10.94; MD = -0.14, 95% CI:-0.71 to 0.43; RR = 0.81, 95% CI:0.32 to 2.01). Patient-assessed effectiveness was also not significantly different between FPL and other FLs (RR = 1.00, 95% CI:0.69 to 1.46). Although temporary pinpoint bleeding was more common after FPL (RR = 30.33, 95% CI:6.14 to 149.8), the incidence of post-inflammatory hyperpigmentation (PIH) and pain level were lower for FPL (RR = 0.16, 95% CI:0.06 to 0.45; MD = -1.99, 95% CI:-3.36 to -0.62). Additionally, edema severity after treatment did not differ between the two groups (MD = -0.35, 95% CI:-0.72 to 0.02). As for the duration of erythema, no difference between FPL and nonablative FL groups (MD = -1.88, 95% CI:-6.28 to 2.51). CONCLUSIONS: FPL seems similar to other FLs regarding clinical improvement of atrophic acne scars. With lower PIH risk and pain scores, FPL is more suitable for acne scar patients prone to PIH or sensitive to pain.

Diffusion kurtosis imaging and MRI-detected extramural venous invasion in rectal cancer: correlation with clinicopathological prognostic factors.

OBJECTIVE: To investigate the prognostic value of the diffusion kurtosis imaging (DKI)-derived parameters D value, K value, diffusion-weighted imaging (DWI) parameter apparent diffusion coefficient (ADC) value, and magnetic resonance imaging (MRI)-detected extramural venous invasion (EMVI) (mrEMVI) in rectal cancer patients. METHODS: Forty patients who underwent MRI for rectal cancer were retrospectively evaluated. DKI-derived parameters D and K were measured using the Medical Imaging Interaction Toolkit. Conventional ADC values were measured from the corresponding DWI images. An experienced radiologist evaluated the mrEMVI status on MR images using the mrEMVI scoring system. An independent sample t-test or analysis of variance was used to analyze and compare the measurement data. The x2 test or Fisher exact test was used for categorical variables. Receiver operating characteristic curves were used to assess the diagnostic performance of these parameters. RESULTS: Among the 40 patients, MRI showed positive EMVI in 15 patients and negative EMVI in 25 patients. Positive mrEMVI status was associated with age, positive circumferential resection margin, pT-stage, lymphovascular invasion (LVI), distant metastasis, and serum carcinoembryonic antigen (CEA) level (P = 0.004-0.036). The dispersion coefficient (D) values and ADC values were significantly higher in the mucinous adenocarcinoma (MC) group than in the common adenocarcinoma (AC) group (P = 0.001), while kurtosis coefficient (K) values were lower in the MC group than in the AC group (P = 0.022). D values were significantly higher in the KRAS-mutated group than in the wild-type group (P < 0.05), whereas K values were lower in the KRAS-mutated group than in the wild-type group (P < 0.05). All three parameters (D, K, and ADC values) showed good diagnostic performance for discriminating MC from AC. Both the D and K values showed certain diagnostic performance for discriminating KRAS mutation. CONCLUSION: DKI-derived parameters, conventional ADC values, and mrEMVI are associated with different histopathological prognostic factors. All DKI-derived parameters and conventional ADC values may distinguish MC from AC. DKI-derived parameters may also be used to discriminate KRAS mutation.

Trifunctional nanoprecipitates ductilize and toughen a strong laminated metastable titanium alloy.

Metastability-engineering, e.g., transformation-induced plasticity (TRIP), can enhance the ductility of alloys, however it often comes at the expense of relatively low yield strength. Here, using a metastable Ti-1Al-8.5Mo-2.8Cr-2.7Zr (wt.%) alloy as a model material, we fabricate a heterogeneous laminated structure decorated by multiple-morphological α-nanoprecipitates. The hard α nanoprecipitate in our alloy acts not only as a strengthener to the material, but also as a local stress raiser to activate TRIP in the soft matrix for great uniform elongation and as a promoter to trigger interfacial delamination toughening for superior fracture resistance. By elaborately manipulating the activation sequence of lamellar-thickness-dependent deformation mechanisms in Ti-1Al-8.5Mo-2.8Cr-2.7Zr alloys, the yield strength of the present submicron-laminated alloy is twice that of equiaxed-coarse grained alloys with the same composition, yet without sacrificing the large uniform elongation. The desired mechanical properties enabled by this strategy combining the laminated metastable structure and trifunctional nanoprecipitates provide new insights into designing ultra-strong and ductile materials with great toughness.

Outcomes of Surgical Treatment for Graves' Disease: A Single-Center Experience of 216 Cases.

BACKGROUND: The role of surgery in the treatment of Graves' disease (GD) needs to be revisited. The aims of the present retrospective study were to evaluate the outcomes of the current surgical strategy as a definitive treatment of GD at our center and to explore the clinical association between GD and thyroid cancer. METHODS: A patient cohort of 216 cases from 2013 to 2020 was involved in this retrospective study. The data of the clinical characteristics and follow-up results were collected and analyzed. RESULTS: There were 182 female and 34 male patients. The mean age was 43.9 ± 15.0 years old. The mean duration of GD reached 72.2 ± 92.7 months. Of the 216 cases, 211 had been treated with antithyroid drugs (ATDs) and hyperthyroidism had been completely controlled in 198 cases. A total (75%) or near-total (23.6%) thyroidectomy was performed. Intraoperative neural monitoring (IONM) was applied to 37 patients. The failure of ATD therapy (52.3%) was the most common surgical indication, followed by suspicion of a malignant nodule (45.8%). A total of 24 (11.1%) patients had hoarseness after the operation and 15 (6.9%) patients had transient vocal cord paralysis; 3 (1.4%) had this problem permanently. No bilateral RLN paralysis occurred. A total of 45 patients had hypoparathyroidism and 42 of them recovered within 6 months. Sex showed a correlation with hypoparathyroidism through a univariate analysis. A total of 2 (0.9%) patients underwent a reoperation because of hematomas. A total of 104 (48.1%) cases were diagnosed as thyroid cancer. In most cases (72.1%), the malignant nodules were microcarcinomas. A total of 38 patients had a central compartment node metastasis. A lateral lymph node metastasis occurred in 10 patients. Thyroid carcinomas were incidentally discovered in the specimens of 7 cases. The patients with concomitant thyroid cancer had a significant difference in body mass index, duration of GD, gland size, thyrotropin receptor antibodies and nodule(s) detected. CONCLUSION: Surgical treatments for GD were effective, with a relatively low incidence of complications at this high-volume center. Concomitant thyroid cancer is one of the most important surgical indications for GD patients. Careful ultrasonic screening is necessary to exclude the presence of malignancies and to determine the therapeutic plan.