Semaglutide ameliorates pressure overload-induced cardiac hypertrophy by improving cardiac mitophagy to suppress the activation of NLRP3 inflammasome.

Pathological cardiac hypertrophy is an important cause of heart failure(HF). Recent studies reveal that glucagon-like peptide-1 receptor (GLP1R) agonists can improve mortality and left ventricular ejection fraction in the patients with type 2 diabetes and HF. The present study aims to investigate whether semaglutide, a long-acting GLP1R agonist, can ameliorate cardiac hypertrophy induced by pressure overload, and explore the potential mechanism. The rats were performed transverse aortic constriction (TAC) to mimic pressure overload model. The rats were divided into four groups including Sham, TAC, TAC + semaglutide, and TAC + semaglutide + HCQ (hydroxychloroquine, an inhibitor of mitophagy). The rats in each experimental group received their respective interventions for 4 weeks. The parameters of left ventricular hypertrophy(LVH) were measured by echocardiography, Hematoxylin-eosin (HE) staining, western-blot and immunohistochemistry (IHC), respectively. The changes of mitophagy were reflected by detecting cytochrome c oxidase subunit II (COXII), LC3II/LC3I, mitochondria, and autophagosomes. Meanwhile, NLRP3, Caspase-1, and interleukin-18 were detected to evaluate the activation of NLRP3 inflammasome in each group. The results suggest that LVH, impaired mitophagy, and activation of NLRP3 inflammasome were present in TAC rats. Semaglutide significantly reduced LVH, improve mitophagy, and down-regulated NLRP3 inflammatory signal pathway in TAC rats. However, the reversed effect of semaglutide on cardiac hypertrophy was abolished by HCQ, which restored the activation of NLRP3 inflammasome suppressed by improved mitophagy. In conclusion, semaglutide ameliorates the cardiac hypertrophy by improving cardiac mitophagy to suppress the activation of NLRP3 inflammasome. Semaglutide may be a novel potential option for intervention of cardiac hypertrophy induced by pressure overload.

LILRB2 promotes immune escape in breast cancer cells via enhanced HLA-A degradation.

PURPOSE: Increased expression of leukocyte immunoglobulin-like receptor subfamily B member 2 (LILRB2) is associated with immune evasion in breast cancer (BC). The aim of this study to elucidate the role of LILRB2 in BC progression. METHODS: LILRB2 expression in tumor tissues was detected by immunohistochemical staining. Human leukocyte antigen A (HLA-A) expression in BC cells was detected by Western blotting, and HLA-A ubiquitination was detected by immunoprecipitation and histidine pulldown assay. An in-situ tumor model was established in nude BALB/c mice to verify the role of LILRB2 in immune escape. Finally, the functions and potential mechanisms of LILRB2 in BC progression were explored using in silico data. RESULTS: LILRB2 was upregulated in BC tissues and cells, and correlated positively with poor prognosis. LILRB2 promoted BC progression by downregulating HLA-A expression. Mechanistically, LILRB2 facilitates the ubiquitination and subsequent degradation of HLA-A by promoting the interaction between the ubiquitin ligase membrane-associated ring finger protein 9 (MARCH9) and HLA-A. In syngeneic graft mouse models, LILRB2-expressing BC cells evaded CD8 + T cells and inhibited the secretion of cytokines by the cytotoxic CD8 + T cells. CONCLUSION: LILRB2 downregulates HLA-A to promote immune evasion in BC cells and is a promising new target for BC treatment.

Associations between cardiovascular diseases and cancer mortality: insights from a retrospective cohort analysis of NHANES data.

BACKGROUND: This study explored the association of cardiovascular disease (CVD) with cancer mortality risk in individuals with or without a history of cancer, to better understand the interplay between CVD and cancer outcomes. METHODS: Utilizing data from the National Health and Nutrition Examination Survey (NHANES) spanning 1999 to 2018, a retrospective cohort analysis was conducted. This analysis accounted for the survey's complex design to ensure national representativeness. The association of CVD with cancer mortality was assessed through multivariable Cox proportional hazards models. RESULTS: The present study included 59,653 participants, of whom 54,095 did not have cancer and 5558 had a history of cancer. In individuals without cancer, heart failure (HF) was associated with an increased risk of mortality from cancer (HR, 1.36; 95% CI, 1.09-1.69; P = 0.005). In participants with cancer, HF correlated with a higher risk of mortality from cancer (HR, 1.76; 95% CI, 1.32-2.34; P < 0.001). Diabetes (DM), hypertension (HBP) and coronary heart disease (CHD) were not significantly associated with an increased risk of mortality from cancer. Significant differences were observed in the interaction between cancer and CHD (HR, 0.68; 95% CI, 0.53-0.87; P = 0.002). For cancer and HBP, a similar trend was noted (HR, 0.75; 95% CI, 0.62-0.91; P = 0.003). No significant differences were found in interactions between HF, DM and cancer. CONCLUSIONS: HF was associated with an increased risk of mortality from cancer, regardless of cancer history, while HBP, CHD and DM showed no significant association. These findings underscore the importance of understanding the mechanisms behind the increased risk of cancer mortality following HF.

A Novel Conchal Cartilage Harvesting Technique.

BACKGROUND: Conchal cartilage is generally favored in rhinoplasty with a satisfied aesthetic outcome. However, patients may suffer from postoperative donor auricle deformities. OBJECTIVES: This study introduced a novel conchal cartilage harvesting technique which can minimize the deformity of auricle and harvest the sufficient amounts of grafts. METHODS: This study proposed preservation of the concha cymba and cavum support structures to minimize the deformity of auricle and harvest of cartilage hidden in the craniofacial region to obtain the sufficient amounts. The medical records of 60 patients who underwent the novel conchal cartilage harvesting were reviewed retrospectively. Postoperative aesthetic outcomes were assessed by comparing pre- and postoperative photographs according to the deformation extent of auricular subunits (cymba concha, cavum concha, antihelix, helix crus and intertragal notch) on a four-point Likert scale. Additionally, function and complications were analyzed. RESULTS: 56 patients performed unilateral conchal cartilage harvesting (8 with right-side and 48 with left-side) and 4 performed bilateral harvesting. The average aesthetic score, rated on a four-point Likert scale (1 = significant deformation, 2 = moderated deformation, 3 = slight deformation, 4 = complete no deformation), were 3.83 ± 0.03 points, respectively. The functional scores, rated on a four-point Likert scale (1 = significant damage, 2 = moderated damage, 3 = slight damage, 4 = complete no damage), was 3.94±0.03. Complications included hematoma, delayed wound healing and hypopigmentated scar in six ears (9.4%). CONCLUSIONS: This novel technique can minimize the deformity of auricle, as shown by the outcome scores, and allows for sufficient amount of grafting material acquired. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Evaluation of the association between glutathione S-transferase polymorphisms and susceptibility to cutaneous melanoma: a systematic review and meta-analysis.

Introduction: Glutathione S-transferase (GST) enzymes play a crucial role in detoxification by catalysing the conjugation of many hydrophobic and electrophilic compounds with reduced glutathione. Polymorphisms in GST genes may influence the susceptibility to various cancers, including melanoma. Aim: We reported a systematic review and meta-analysis to evaluate the association between GST polymorphisms and susceptibility to cutaneous melanoma. Material and methods: A comprehensive search of four databases, namely PubMed, Scopus, Cochrane Library, and Web of Science, was conducted to gather pertinent studies up until 24 August 2023. No restrictions were imposed during the search. The analysis included 32 studies and was broken down into subgroups based on ethnicity, control source, control matching, quality score, and sample size. Results: The forest plot analyses on GSTM1, GSTT1, combined GSTM1/GSTT1, and GSTP1 polymorphisms in relation to melanoma risk showed no statistically significant differences between the case and control groups, except for the recessive model of GSTP1 polymorphism. The analysis revealed significant associations between GSTM1 polymorphisms and melanoma risk in Asians and in studies with a sample size of less than 200. For the combined GSTM1/GSTT1 polymorphisms, a significant association was found in hospital-based controls. Conclusions: While this study enhances our understanding of the genetic factors influencing melanoma risk, it also highlights the need for further research. The current evidence is not sufficient to confirm or reject the intervention effect. Future research should consider gene-gene and gene-environment interactions, which could offer a more comprehensive understanding of the complex biology of melanoma.

Associations of different type of physical activity with all-cause mortality in hypertension participants.

Few studies explored the association of different type of physical activity with all-cause mortality in hypertension (HBP) participants. A retrospective cohort analysis was performed using National Health and Nutrition Examination Survey (NHANES) data to explore association of moderate-intensity physical activity (MPA), vigorous-intensity physical activity (VPA), sedentary behavior with mortality in HBP individuals. Among 10,913 HBP participants followed for a median of 6.2 years, VPA was not associated with a reduction in all-cause mortality compared to participants without VPA in multivariate Cox survival analysis. MPA was linked to lower all-cause mortality at durations of 0-150 min/week (HR, 0.72; 95% CI 0.58-0.88), 150-300 min/week (HR, 0.71; 95% CI 0.52-0.96), and > 300 min/week (HR, 0.61; 95% CI 0.49-0.77) compared to no MPA. Sedentary behavior of 6-8 h/day (HR, 1.35; 95% CI 1.15-1.59) and > 8 h/day (HR, 1.55; 95% CI 1.34-1.79) were associated with increased mortality risk versus < 6 h/day. Further research is needed to explore whether VPA can improve outcomes for HBP individuals and to determine the optimal duration of VPA.MPA is linked to lower mortality risk, indicating its potential as the best physical activity intensity for HBP individuals.

Uncut Roux-en-Y reconstruction after distal gastrectomy for gastric cancer.

BACKGROUND: Choosing an optimal reconstruction method is pivotal for patients with gastric cancer undergoing distal gastrectomy. The uncut Roux-en-Y reconstruction, a variant of the conventional Roux-en-Y approach (or variant of the Billroth II reconstruction), employs uncut devices to occlude the afferent loop of the jejunum. This modification is designed to mitigate postgastrectomy syndrome and enhance long-term functional outcomes. However, the comparative benefits and potential harms of this approach compared to other reconstruction techniques remain a topic of debate. OBJECTIVES: To assess the benefits and harms of uncut Roux-en-Y reconstruction after distal gastrectomy in patients with gastric cancer. SEARCH METHODS: We searched CENTRAL, PubMed, Embase, WanFang Data, China National Knowledge Infrastructure, and clinical trial registries for published and unpublished trials up to November 2023. We also manually reviewed references from relevant systematic reviews identified by our search. We did not impose any language restrictions. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs comparing uncut Roux-en-Y reconstruction versus other reconstructions after distal gastrectomy for gastric cancer. The comparison groups encompassed other reconstructions such as Billroth I, Billroth II (with or without Braun anastomosis), and Roux-en-Y reconstruction. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. The critical outcomes included health-related quality of life at least six months after surgery, major postoperative complications within 30 days after surgery according to the Clavien-Dindo Classification (grades III to V), anastomotic leakage within 30 days, changes in body weight (kg) at least six months after surgery, and incidence of bile reflux, remnant gastritis, and oesophagitis at least six months after surgery. We used the GRADE approach to evaluate the certainty of the evidence. MAIN RESULTS: We identified eight trials, including 1167 participants, which contributed data to our meta-analyses. These trials were exclusively conducted in East Asian countries, predominantly in China. The studies varied in the types of uncut devices used, ranging from 2- to 6-row linear staplers to suture lines. The follow-up periods for long-term outcomes spanned from 3 months to 42 months, with most studies focusing on a 6- to 12-month range. We rated the certainty of evidence from low to very low. Uncut Roux-en-Y reconstruction versus Billroth II reconstruction In the realm of surgical complications, very low-certainty evidence suggests that uncut Roux-en-Y reconstruction compared with Billroth II reconstruction may make little to no difference to major postoperative complications (risk ratio (RR) 0.98, 95% confidence interval (CI) 0.24 to 4.05; I² = 0%; risk difference (RD) 0.00, 95% CI -0.04 to 0.04; I² = 0%; 2 studies, 282 participants; very low-certainty evidence) and incidence of anastomotic leakage (RR 0.64, 95% CI 0.29 to 1.44; I² not applicable; RD -0.00, 95% CI -0.03 to 0.02; I² = 32%; 3 studies, 615 participants; very low-certainty evidence). We are very uncertain about these results. Focusing on long-term outcomes, low- to very low-certainty evidence suggests that uncut Roux-en-Y reconstruction compared with Billroth II reconstruction may make little to no difference to changes in body weight (mean difference (MD) 0.04 kg, 95% CI -0.84 to 0.92 kg; I² = 0%; 2 studies, 233 participants; low-certainty evidence), may reduce the incidence of bile reflux into the remnant stomach (RR 0.67, 95% CI 0.55 to 0.83; RD -0.29, 95% CI -0.43 to -0.16; number needed to treat for an additional beneficial outcome (NNTB) 4, 95% CI 3 to 7; 1 study, 141 participants; low-certainty evidence), and may have little or no effect on the incidence of remnant gastritis (RR 0.27, 95% CI 0.01 to 5.06; I2 = 78%; RD -0.15, 95% CI -0.23 to -0.07; I2 = 0%; NNTB 7, 95% CI 5 to 15; 2 studies, 265 participants; very low-certainty evidence). No studies reported on quality of life or the incidence of oesophagitis. Uncut Roux-en-Y reconstruction versus Roux-en-Y reconstruction In the realm of surgical complications, very low-certainty evidence suggests that uncut Roux-en-Y reconstruction compared with Roux-en-Y reconstruction may make little to no difference to major postoperative complications (RR 4.74, 95% CI 0.23 to 97.08; I² not applicable; RD 0.01, 95% CI -0.02 to 0.04; I² = 0%; 2 studies, 256 participants; very low-certainty evidence) and incidence of anastomotic leakage (RR 0.34, 95% CI 0.05 to 2.08; I² = 0%; RD -0.02, 95% CI -0.06 to 0.02; I² = 0%; 2 studies, 213 participants; very low-certainty evidence). We are very uncertain about these results. Focusing on long-term outcomes, very low-certainty evidence suggests that uncut Roux-en-Y reconstruction compared with Roux-en-Y reconstruction may increase the incidence of bile reflux into the remnant stomach (RR 10.74, 95% CI 3.52 to 32.76; RD 0.57, 95% CI 0.43 to 0.71; NNT for an additional harmful outcome (NNTH) 2, 95% CI 2 to 3; 1 study, 108 participants; very low-certainty evidence) and may make little to no difference to the incidence of remnant gastritis (RR 1.18, 95% CI 0.69 to 2.01; I² = 60%; RD 0.03, 95% CI -0.03 to 0.08; I² = 0%; 3 studies, 361 participants; very low-certainty evidence) and incidence of oesophagitis (RR 0.82, 95% CI 0.53 to 1.26; I² = 0%; RD -0.02, 95% CI -0.07 to 0.03; I² = 0%; 3 studies, 361 participants; very low-certainty evidence). We are very uncertain about these results. Data were insufficient to assess the impact on quality of life and changes in body weight. AUTHORS' CONCLUSIONS: Given the predominance of low- to very low-certainty evidence, this Cochrane review faces challenges in providing definitive clinical guidance. We found the majority of critical outcomes may be comparable between the uncut Roux-en-Y reconstruction and other methods, but we are very uncertain about most of these results. Nevertheless, it indicates that uncut Roux-en-Y reconstruction may reduce the incidence of bile reflux compared to Billroth-II reconstruction, albeit with low certainty. In contrast, compared to Roux-en-Y reconstruction, uncut Roux-en-Y may increase bile reflux incidence, based on very low-certainty evidence. To strengthen the evidence base, further rigorous and long-term trials are needed. Additionally, these studies should explore variations in surgical procedures, particularly regarding uncut devices and methods to prevent recanalisation. Future research may potentially alter the conclusions of this review.

Advancements in tissue engineering for articular cartilage regeneration.

Articular cartilage injury is a prevalent clinical condition resulting from trauma, tumors, infection, osteoarthritis, and other factors. The intrinsic lack of blood vessels, nerves, and lymphatic vessels within cartilage tissue severely limits its self-regenerative capacity after injury. Current treatment options, such as conservative drug therapy and joint replacement, have inherent limitations. Achieving perfect regeneration and repair of articular cartilage remains an ongoing challenge in the field of regenerative medicine. Tissue engineering has emerged as a key focus in articular cartilage injury research, aiming to utilize cultured and expanded tissue cells combined with suitable scaffold materials to create viable, functional tissues. This review article encompasses the latest advancements in seed cells, scaffolds, and cytokines. Additionally, the role of stimulatory factors including cytokines and growth factors, genetic engineering techniques, biophysical stimulation, and bioreactor systems, as well as the role of scaffolding materials including natural scaffolds, synthetic scaffolds, and nanostructured scaffolds in the regeneration of cartilage tissues are discussed. Finally, we also outline the signaling pathways involved in cartilage regeneration. Our review provides valuable insights for scholars to address the complex problem of cartilage regeneration and repair.

Midline and off-midline wound closure methods after surgical treatment for pilonidal sinus.

BACKGROUND: Pilonidal sinus disease is a common and debilitating condition. Surgical treatment remains the mainstay for managing chronic disease, with options including midline and off-midline wound closure methods. However, the optimal approach remains uncertain. Recent developments in tension-free midline techniques require further exploration. OBJECTIVES: To assess the effects of midline and off-midline wound closure methods for pilonidal sinus, and to determine the optimal off-midline flap procedures. SEARCH METHODS: In June 2022, we searched the Cochrane Wounds Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL Plus EBSCO, and clinical trials registries. We also scanned the reference lists of included studies, as well as reviews, meta-analyses, and health technology reports. We applied no language, publication date, or study setting restrictions. SELECTION CRITERIA: We included parallel RCTs involving participants undergoing midline closure without flap techniques and off-midline closure for pilonidal sinus treatment. We excluded quasi-experimental studies and studies that enroled participants presenting with an abscess. DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methodology. The critical outcomes included wound healing (time to wound healing, proportion of wounds healed), recurrence rate, wound infection, wound dehiscence, time to return to work, and quality of life. We assessed biases in these outcomes utilising the Cochrane risk of bias 2 tool and appraised evidence certainty via the GRADE approach. MAIN RESULTS: We included 33 studies with 3667 analysed participants. The median or average age of the participants across the included studies ranged from 21.0 to 34.2 years, with a predominant male representation. Geographically, the trials were primarily conducted in the Middle East. We identified nine intervention comparisons. In this abstract, we focus on and present the summarised findings for the three primary comparisons. Off-midline closure versus conventional midline closure Off-midline closure probably reduces the time to wound healing (mean difference (MD) -5.23 days, 95% confidence interval (CI) -7.55 to -2.92 days; 3 studies, 300 participants; moderate-certainty evidence). However, there may be little to no difference between the two methods in the proportion of wounds healed (100% versus 88.5%, risk ratio (RR) 1.13, 95% CI 0.92 to 1.39; 2 studies, 207 participants; very low-certainty evidence). Off-midline closure probably results in lower rates of recurrence (1.5% versus 6.8%, RR 0.22, 95% CI 0.11 to 0.45; 13 studies, 1492 participants; moderate-certainty evidence) and wound infection (3.8% versus 11.7%, RR 0.32, 95% CI 0.22 to 0.49; 13 studies, 1568 participants; moderate-certainty evidence), and may lower rates of wound dehiscence (3.9% versus 8.9%, RR 0.44, 95% CI 0.27 to 0.71; 11 studies, 1389 participants; low-certainty evidence). Furthermore, off-midline closure may result in a reduced time to return to work (MD -3.72 days, 95% CI -6.11 to -1.33 days; 6 studies, 820 participants; low-certainty evidence). There were no data available for quality of life. Off-midline closure versus tension-free midline closure Off-midline closure may reduce the time to wound healing (median 14 days in off-midline closure versus 51 days in tension-free midline closure; 1 study, 116 participants; low-certainty evidence) and increase wound healing rates at three months (94.7% versus 76.4%, RR 1.24, 95% CI 1.06 to 1.46; 1 study, 115 participants; low-certainty evidence), but may result in little to no difference in rates of recurrence (5.4% versus 7.8%, RR 0.69, 95% CI 0.30 to 1.61; 6 studies, 551 participants; very low-certainty evidence), wound infection (2.8% versus 6.4%, RR 0.44, 95% CI 0.16 to 1.17; 6 studies, 559 participants; very low-certainty evidence), and wound dehiscence (2.5% versus 3.0%, RR 0.82, 95% CI 0.17 to 3.84; 3 studies, 250 participants; very low-certainty evidence) compared to tension-free midline closure. Furthermore, off-midline closure may result in longer time to return to work compared to tension-free midline closure (MD 3.00 days, 95% CI 1.52 to 4.48 days; 1 study, 60 participants; low-certainty evidence). There were no data available for quality of life. Karydakis flap versus Limberg flap Karydakis flap probably results in little to no difference in time to wound healing compared to Limberg flap (MD 0.36 days, 95% CI -1.49 to 2.22; 6 studies, 526 participants; moderate-certainty evidence). Compared to Limberg flap, Karydakis flap may result in little to no difference in the proportion of wounds healed (80.0% versus 66.7%, RR 1.20, 95% CI 0.77 to 1.86; 1 study, 30 participants; low-certainty evidence), recurrence rate (5.1% versus 4.5%, RR 1.14, 95% CI 0.61 to 2.14; 9 studies, 890 participants; low-certainty evidence), wound infection (7.9% versus 5.1%, RR 1.55, 95% CI 0.90 to 2.68; 8 studies, 869 participants; low-certainty evidence), wound dehiscence (7.4% versus 6.2%, RR 1.20, 95% CI 0.41 to 3.50; 7 studies, 776 participants; low-certainty evidence), and time to return to work (MD -0.23 days, 95% CI -5.53 to 5.08 days; 6 studies, 541 participants; low-certainty evidence). There were no data available for quality of life. AUTHORS' CONCLUSIONS: This Cochrane review examines the midline and off-midline wound closure options for pilonidal sinus, predominantly based on young adult studies. Off-midline flap procedures demonstrate there may be benefits over conventional midline closure for pilonidal sinus, with various off-midline flap techniques. When off-midline flap closures were compared to tension-free midline closure, low-certainty evidence indicated there may be improved wound healing and increased time to return to work for off-midline closure, whilst very low-certainty evidence indicated there may be no evidence of a difference in other outcomes. There may be no evidence of an advantage found amongst the off-midline techniques evaluated. The choice of either procedure is likely to be based on a clinician's preference, experience, patient characteristics, and the patients' preferences. To more accurately determine the benefits and potential harms of these closure techniques, further large-scale and meticulously-designed trials are essential. Specifically, there is a pressing need for more studies addressing the paediatric population, in addition to adult studies.

Practical Classification and Management of Accessory Auricle.

BACKGROUND: Accessory auricle is a common congenital abnormal auricular appendage with various forms of presentation. The authors proposed a practical classification system based on the involved anatomical subunits (tragus, the anterior notch and the intertragal notch) and described the corresponding surgical procedures. METHODS: The authors reviewed and analyzed 80 patients (96 ears) who underwent accessory auricle excisions form January 2018 to December 2021. Accessory auricles were classified into three categories: simple (no deformed subunits), complex (several deformed subunits) and compound (coexistence of simple and complex type). The complex type was subclassified into notch and tragal subtypes. The tragal subtype was subclassified into subtype A, B and C, according to the location, contour and size of the involved tragus. Surgical methods were described, and postoperative outcomes were assessed. RESULTS: Simple type was the most common type (54%) and compound type was less common (15%). In addition, there were 28 (29%) tragal subtype accessory auricles and 2 (2%) notch subtype. Among the tragal subtype, A was the most commonly observed (25%), followed by B (2%) and C (2%). Patients were followed for an average of 11.3 months. One patient experienced delayed wound healing and 6 patients showed hypertrophic scars. The average aesthetic score, evaluated by a 4-point Likert scale (1 = poor, 2 = fair, 3 = good, 4 = excellent), was 3.67 ± 0.06 points. The OSAS and PSAS scores were 9.29 ± 0.44 and 10.84 ± 0.40, respectively. CONCLUSIONS: The innovative classification system of accessory auricles can reflect whether there was a combined deformity and the deformed subunits, and guide decisions on surgical approaches. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Highly Sensitive and Quantitative Magnetic Nanoparticle-Based Lateral Flow Immunoassay with an Atomic Magnetometer.

Lateral flow immunoassay (LFIA) is a simple point-of-care method for detecting various analytes. However, the lack of test result precision and poor quantification are the main bottlenecks of LFIA. Although magnetic nanoparticles (MNPs) have gained prominence as potent labels in LIFA, the quantitative detection method for trace biomarkers remains to be improved. Here, we propose a promising real-time biosensing platform based on a highly sensitive atomic magnetometer to fulfill the quantitative detection of MNP-based lateral flow immunochromatographic assays. The strategy entails obtaining the residual flux density component spectrum by continuously and linearly scanning the trace MNP label and then resolving the magnetization and quantity from the spectrum. Moreover, we exploit the theoretical model of the magnetic dipole to verify the method's reliability. Regarding carcinoembryonic antigen detection, the atomic magnetometer exhibits a low detection limit of ∼0.01 ng mL-1 with a 100-fold enhancement factor compared to optical detection methods and a more straightforward mechanism than other magnetic detection approaches. Together, these results provide valuable insight for the potential application of atomic magnetometer quantum measurement techniques in intelligent diagnosis and treatment.

Ear reconstruction stage I: Minor modifications in sculpting the auricle support using the 7th and 8th costal cartilages.

BACKGROUND: The verisimilitude of the reconstructed auricle and its long-term stability largely depends on the framework sculpting. This study described three kinds of minor modifications based on Firmin's way of sculpting the auricle framework and reported the clinical outcomes achieved with them. METHODS: We conducted a retrospective study of congenital microtia patients undergoing detail-improved auricular reconstruction from June 2016 to June 2020. The three kinds of minor modifications included: (1) fabricating the base frame using the 7th costal cartilage, (2) fabricating the helix and the antihelix complex using the 8th costal cartilage, and (3) fabricating the helix using the combination of the 8th and 9th costal cartilage. RESULTS: Ninety-eight patients (aged 9-27 years, 62.2% male) were included. Ninety-five patients (97.0%) adopted minor modifications 1, 2, and 3 patients (3.0%) adopted minor modifications 1, 2, and 3. All patients achieved an excellent auricle appearance and a well-laid foundation for subsequent operations. During the follow-up period, 89 patients (90.8%) were satisfied with the reconstructed auricles, 6 (6.1%) complained of hypertrophic scars in the retroauricular sulcus or pigmentation in the skin graft area, and 3 (3.1%) developed surgery-related complications. CONCLUSIONS: Three minor modifications of the auricle framework sculpting can make more satisfactory use of cartilage and adjust with the flexibility of the reconstructed auricle in different situations, making it similar to the contralateral auricle, thus, improving patients' satisfaction.

ZIKV infection differentially affects the transcriptional profiles in HTR8 and U251 cells.

The mechanism by which Zika virus (ZIKV) causes severe birth defects in pregnant women remains unclear. Cell tropisms in placenta and brain play a crucial role in ZIKV pathogenesis, leading to congenital Zika syndrome (CZS). To identify the host factors involved in ZIKV infection, we compared the transcriptional profiles of ZIKV-infected human first-trimester placental trophoblast cells HTR8/SVneo and a human glioblastoma astrocytoma cell line U251. Our results demonstrated that ZIKV exhibited lower rates of mRNA replication and protein expression in HTR8 than in U251 cells, while showing a higher release of infectious viral particles. However, a greater number of differentially expressed genes (DEGs) were found in ZIKV-infected U251 cells than in ZIKV-infected HTR8 cells. Several of these DEGs were enriched in distinct biological processes related to the characteristics of each cell type that may contribute to foetal damage. Both cell types exhibited activation of common interferons, inflammatory cytokines, and chemokine production upon ZIKV infection. Moreover, the neutralization of tumour necrosis factor-alpha (TNF-α) promoted ZIKV infection in both trophoblasts and glioblastoma astrocytoma cells. Overall, we identified multiple DEGs associated with ZIKV pathogenesis.

Activatable Near-Infrared Fluorescent and Photoacoustic Dual-Modal Probe for Highly Sensitive Imaging of Sulfatase In Vivo.

Sulfatase is an important biomarker closely associated with various diseases. However, the state-of-the-art sulfatase probes are plagued with a short absorption/emission wavelength and limited sensitivity. Developing highly sensitive fluorescent probes for in vivo imaging of sulfatase remains a grand challenge. Herein, for the first time, an activatable near-infrared fluorescence/photoacoustic (NIRF/PA) dual-modal probe (Hcy-SA) for visualizing sulfatase activity in living cells and animals is developed. Hcy-SA is composed of a sulfate ester moiety as the recognition unit and a NIR fluorophore hemicyanine (Hcy-OH) as the NIRF/PA reporter. The designed probe exhibits a rapid response, excellent sensitivity, and high specificity for sulfatase detection in vitro. More importantly, cells and in vivo experiments confirm that Hcy-SA can be successfully applied for PA/NIRF dual-modal imaging of sulfatase activity in living sulfatase-overexpressed tumor cells and tumor-bearing animals. This probe can serve as a promising tool for sulfatase-related pathological research and cancer diagnosis.

Repair of Congenitally Defective Type of Earlobe Clefts With Residual Lobular Tissue: A Convenient and Effective Surgical Technique.

BACKGROUND: For patients with a congenitally defective type of earlobe cleft, repair techniques similar to those utilized for earlobe lacerations are not suitable due to the presence of certain tissue defects. However, traditional earlobe reconstruction techniques imply the need to form complex flaps with adjacent normal tissues, which may lead to many complications. OBJECTIVES: In this study, we developed a technique to repair the earlobe with residual lobular tissue based on the characteristics of congenitally defective earlobe clefts. METHODS: We designed a triangular random flap out of the remnant lobular tissue, rotated and embedded into the edge of the remnant earlobe to repair the earlobe. RESULTS: In the past 3 years, this technique was applied to 15 patients with congenitally defective earlobe clefts. With this technique, the new earlobe achieved the desired aesthetic results, such as smooth edges and fullness of form, without complicated and unnecessary incisions. It also solved the aesthetic problem of residual lobular tissue on the face. CONCLUSIONS: Based on the characteristics of the congenitally defective type of earlobe cleft, we innovatively proposed the utilization of residual lobular tissues for earlobe repair, and the feasibility and multiple advantages of this technique have been demonstrated in practice.

MRI Fat-Saturated T2-Weighted Radiomics Model for Identifying the Ki-67 Index of Soft Tissue Sarcomas.

BACKGROUND: Ki-67 expression has been shown to be an important risk factor associated with prognosis in patients with soft tissue sarcomas (STSs). Its assessment requires fine-needle biopsy and its accuracy can be influenced by tumor heterogeneity. PURPOSE: To develop and test an MRI-based radiomics nomogram for identifying the Ki-67 status of STSs. STUDY TYPE: Retrospective. POPULATION: A total of 149 patients at two independent institutions (training cohort [high Ki-67/low ki-67]: 102 [52/50], external validation cohort [high Ki-67/low ki-67]: 47 [28/19]) with STSs. FIELD STRENGTH/SEQUENCE: Fat-saturated T2-weighted imaging (FS-T2WI) with a fat-suppressed fast spin/turbo spin echo sequence at 1.5 T or 3 T. ASSESSMENT: After radiomics feature extraction, logistic regression (LR), random forest (RF), support vector machine (SVM), and k-nearest neighbor (KNN) were used to construct radiomics models to distinguish between high and low Ki-67 status. Clinical-MRI characteristics included age, gender, location, size, margin, and MRI morphological features (size, margin, signal intensity, and peritumoral hyperintensity) were assessed. Univariate and multivariate logistic regression analysis were applied for screening significant risk factors. Radiomics nomogram was constructed by radiomics signature and risk factors. STATISTICAL TESTS: Model performances (discrimination, calibration, and clinical usefulness) were validated in the validation cohort. The nomogram was assessed using the Harrell index of concordance (C-index), calibration curve analysis. The clinical utility of the model was assessed by decision curve analysis (DCA). RESULTS: LR, RF, SVM, and KNN models represented AUCs of 0.789, 0.755, 0.726, and 0.701 in the validation cohort (P > 0.05). The nomogram had a C-index of 0.895 (95% CI: 0.837-0.953) in the training cohort and 0.852 (95% CI: 0.796-0.957) in the validation cohort and it demonstrated good calibration and clinical utility (P = 0.972 for the training cohort and P = 0.727 for the validation cohort). DATA CONCLUSION: This MRI-based radiomics nomogram developed showed good performance in identifying Ki-67 expression status in STSs. TECHNICAL EFFICACY STAGE: 2.

Identification of Endoplasmic Reticulum Stress-Related Subtypes, Infiltration Analysis of Tumor Microenvironment, and Construction of a Prognostic Model in Colorectal Cancer.

Recently, endoplasmic reticulum (ER) stress has been shown to influence tumor progression and immune cell function in the tumor microenvironment (TME). However, the underlying role of ER stress-related gene patterns in colorectal cancer (CRC) development remains unclear. We analyzed the ER stress-related gene patterns in 884 patients with CRC from the Gene Expression Omnibus database and evaluated the cell-infiltrating patterns in the TME. Two ER stress-related patterns were identified in patients with CRC that had distinct cell-infiltrating patterns in the TME and clinical characteristics. A risk score and nomogram based on 14 screened prognosis-correlated genes was built and validated to predict patient survival. Patients with a higher risk score were shown to have an unfavorable prognosis, and the risk score was associated with cell infiltration and drug sensitivity. Furthermore, spatial transcriptomics data were utilized to explore ER stress-related gene patterns in CRC tissues, and it was shown that ER stress phenotype involves in the formation of the immunosuppressive TME. This study demonstrated that ER stress-related gene patterns play a role in influencing the TME and predicting prognosis. These analyses of ER stress in the TME of CRC might deepen our understanding of CRC progression and immune escape and provide novel insights into therapeutic strategies.

Overexpression of SHARPIN promotes tumor progression in ovarian cancer.

SHARPIN (Shank-associated RH domain interacting protein) plays an important role in tumorigenesis. However, its role in ovarian cancer remains largely unknown. To investigate this issue, we systematically analyzed the amplification and expression of the SHARPIN in the TCGA database. From the database, we found that SHARPIN was amplified in ovarian cancer compared to normal ovarian tissue, and the mRNA level of SHARPIN was significantly elevated in ovarian cancer compared to non-tumorigenic ovarian tissue. In addition, we observed similar results from ovarian cancer cell lines and clinical samples from ovarian cancer patients, which indicated that increased SHARPIN expression is associated with tumorigenesis in ovarian cancer. SHARPIN knockdown inhibited the migration and invasion of ovarian cancer cells, also inhibited cell cycle and promoted apoptosis, thereby suppressing cell proliferation. RNA-seq results showed that SHARPIN significantly increased the expression of P53 and P21 and decreased the expression of Cyclin D1 and c-Myc, all of which are involved in the regulation of cell proliferation. Subsequent mechanistic exploration revealed that SHARPIN knockdown increased the expression of caspases 3 and 9, leading to apoptosis of ovarian cancer cells. We also found that high expression of SHARPIN was associated with poor prognosis of ovarian cancer patients. Collectively, we demonstrated a positive correlation between SHARPIN and ovarian cancer progression and provide a basis for combined targeted therapy strategies for future ovarian cancer treatment.