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1.
BMC Pediatr ; 24(1): 368, 2024 May 28.
Article En | MEDLINE | ID: mdl-38807073

BACKGROUND: Lip infantile hemangiomas tend to show less volumetric regression and are more susceptible to visible sequelae in the involuted stage. Some of them still require surgical management after propranolol therapy. This study aimed to evaluate the efficacy and safety of the Stepwise, Multi-Incisional, and Single-Stage (SMISS) approach applied to lip reduction for those with involuted lip hemangiomas. METHODS: A retrospective review was performed to evaluate patients with lip hemangioma who received previous propranolol treatment and underwent the aforementioned procedure. Demographic characteristics, lesion morphology, and medical history were reviewed. The Visual Analog Scale was applied to assess the postoperative appearance. Complications within 12 months postoperatively were recorded. RESULTS: A total of 18 patients with lip hemangioma were eligible. All patients received oral propranolol therapy before surgery, with treatment duration ranging from 6.0 to 23.0 months. Their age at surgery ranged from 2.5 to 9.0 years. The median Visual Analog Scale scores were 8.0, ranging from 4.0 to 10.0. No severe complications were reported. CONCLUSIONS: This modified technique based on the SMISS approach has proven reliable and effective in improving the aesthetic outcome for involuted lip infantile hemangiomas. Practical surgical techniques still play an important part in the propranolol era.


Hemangioma , Lip Neoplasms , Propranolol , Humans , Retrospective Studies , Male , Female , Hemangioma/surgery , Lip Neoplasms/surgery , Propranolol/therapeutic use , Child, Preschool , Child , Infant , Lip/surgery , Treatment Outcome , Lipoma/surgery
2.
Head Face Med ; 20(1): 13, 2024 Feb 20.
Article En | MEDLINE | ID: mdl-38378686

BACKGROUND: Facial infiltrating lipomatosis (FIL) is a rare condition characterized by congenital facial enlargement. Beyond its impact on physical appearance, FIL can also impair essential facial functions such as swallowing, chewing, vision, and breathing, imposing a substantial physiological and psychological burden. Currently, fewer than 80 cases of FIL have been reported, and the characteristics and management strategies for FIL remain unclear. METHODS: We reviewed the clinical, surgical, and radiological records of 39 FIL patients who were treated at our center. Of these, genetic testing was performed for 21 patients. RESULTS: Aberrant overgrowth involves subcutaneous fat, bones, muscles, glands, tongue, lips, and teeth. Epidermal nevi could be observed in the dermatomes innervated by the three branches of the trigeminal nerve, with the highest frequency seen in the dermatome of the mandibular branch. Four patients exhibited concurrent hemimegalencephaly (HMEG), with one case presenting HMEG on the opposite side of the FIL. Nineteen patients were confirmed to harbor the PIK3CA mutation. Thirty-three patients underwent surgical procedures, with a post resection recurrence rate of approximately 25%. CONCLUSIONS: A variety of maxillofacial structures may be involved in FIL. PIK3CA mutations are important pathogenic factors. Emerging targeted therapies could present an additional treatment avenue in the future. However, surgery currently remains the predominant treatment choice for FIL. The timing and modality of surgery should be individually customized, taking into account each patient's unique circumstances. Notably, there is a significant possibility of postoperative recurrence during childhood and adolescence, necessitating early strategic planning of disease management.


Face , Lipomatosis , Adolescent , Humans , Lipomatosis/diagnostic imaging , Lipomatosis/surgery , Lipomatosis/genetics , Subcutaneous Fat , Lip/pathology , Mandible/pathology
3.
Cell Rep ; 43(2): 113796, 2024 Feb 27.
Article En | MEDLINE | ID: mdl-38367240

The acidic metabolic byproducts within the tumor microenvironment (TME) hinder T cell effector functions. However, their effects on T cell infiltration remain largely unexplored. Leveraging the comprehensive The Cancer Genome Atlas dataset, we pinpoint 16 genes that correlate with extracellular acidification and establish a metric known as the "tumor acidity (TuAci) score" for individual patients. We consistently observe a negative association between the TuAci score and T lymphocyte score (T score) across various human cancer types. Mechanistically, extracellular acidification significantly impedes T cell motility by suppressing podosome formation. This phenomenon can be attributed to the reduced expression of methyltransferase-like 3 (METTL3) and the modification of RNA N6-methyladenosine (m6A), resulting in a subsequent decrease in the expression of integrin ß1 (ITGB1). Importantly, enforced ITGB1 expression leads to enhanced T cell infiltration and improved antitumor activity. Our study suggests that modulating METTL3 activity or boosting ITGB1 expression could augment T cell infiltration within the acidic TME, thereby improving the efficacy of cell therapy.


Integrin beta1 , Neoplasms , Humans , Cell- and Tissue-Based Therapy , Hydrogen-Ion Concentration , Integrin beta1/genetics , Methyltransferases/genetics , T-Lymphocytes , Tumor Microenvironment
4.
Plast Reconstr Surg ; 153(2): 346-350, 2024 02 01.
Article En | MEDLINE | ID: mdl-36988638

SUMMARY: Adequate nasal tip projection remains a challenge in aesthetic rhinoplasty for East Asians. Various surgical techniques have been developed to reshape the nasal tip using auricular cartilage. In this article, we introduce the new ram graft to increase nasal tip projection by using one complete piece of conchal cartilage. Between 2019 and 2021, 19 patients who underwent nasal tip reconstruction using ram grafts were reviewed in a single hospital. The complication rate, satisfaction rate, and changes in nasolabial angle and nasal proportion were recorded. Nineteen patients with a mean age (± SD) of 28.9 ± 6.1 years underwent nasal tip reconstruction. The mean follow-up time was 15.4 ± 6.6 months. Nasolabial angle increased from 87.4 ± 10.0 degrees to 91.2 ± 10.2 degrees ( P > 0.05). Sixteen of 19 patients (84.2%) were satisfied with their results. The nasal length-to-nasal tip projection-to-dorsal height-to-radix height ratio is 2:0.8:0.62:0.19 preoperatively and 2:0.92:0.77:0.35 postoperatively. Complications including alloplast-related infection (two of 19) and septal extension graft-related decrease of nasal tip projection (one of 19) were recorded. By using one complete piece of conchal cartilage, the ram graft is a simple and effective approach to increase nasal tip projection for East Asians. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.


Ear Auricle , Rhinoplasty , Humans , Young Adult , Adult , Nose/surgery , Rhinoplasty/methods , Ear Cartilage/surgery , Esthetics , Ear Auricle/surgery , Nasal Septum/surgery , Retrospective Studies , Treatment Outcome
5.
J Plast Reconstr Aesthet Surg ; 87: 54-60, 2023 12.
Article En | MEDLINE | ID: mdl-37804648

Infantile hemangiomas (IHs) of the lips are associated with an increased risk of incomplete involution and ulceration, causing disfigurement. Treatment with oral propranolol (OPT) has credible efficacy but takes months to complete. Thus, this study aimed to investigate the efficacy of intralesional betamethasone injection (IBI) as an alternative treatment for protruding localized IHs of the lips. To investigate the efficacies of OPT and IBI, we designed a prospective, noninferiority, parallel-group study. The primary outcome assessed was treatment response rate. Secondary outcome assessments included lesion size changes and surgical rate. Additionally, complication rates and treatment durations of OPT and IBI were compared. The treatment response rate of IBI was not inferior to that of OPT (95.7% vs. 76.0%, respectively; a difference of 19.7%, 95% confidence interval [CI], -4.4% to 41.6%). The average surgical rate in the IBI group was significantly lower than that in the OPT group (8.7% vs. 40%, respectively; p = 0.012), and the average duration of treatment for IBI was shorter than that of OPT (2.1 months vs. 6.3 months, respectively; p < 0.001). There were no severe adverse drug events in either group. If not managed properly, small, localized lip IHs may cause disfigurement in a child. Our study demonstrated that IBI is as effective as OPT in treating protruding localized lip IHs. Moreover, IBI treatment has a shorter duration and lower surgical rate than OPT. With proper care, IBI is an effective treatment modality for small and localized lip IHs.


Hemangioma , Skin Neoplasms , Child , Humans , Infant , Propranolol/adverse effects , Lip/pathology , Hemangioma/drug therapy , Betamethasone/therapeutic use , Prospective Studies , Treatment Outcome , Skin Neoplasms/drug therapy , Adrenergic beta-Antagonists/therapeutic use
6.
Orphanet J Rare Dis ; 18(1): 189, 2023 Jul 14.
Article En | MEDLINE | ID: mdl-37452404

BACKGROUND: Facial infiltrating lipomatosis (FIL) is a rare congenital disorder characterized by unilateral facial swelling, for which surgery is the prevailing therapeutic option. Several studies have shown that the development of FIL is closely associated with PIK3CA mutations. This study aimed to further identify rare clinical features and underlying molecular variants in patients with FIL. RESULTS: Eighteen patients were included in this study, and all patients presented with infiltrating adipose tissues confirmed by magnetic resonance imaging. Macrodactyly, polydactyly, hemimegalencephaly and hemihyperplasia were also observed in patients with FIL. In total, eight different PIK3CA mutations were detected in tissues obtained from sixteen patients, including the missense mutations p.His1047Arg (n = 4), p.Cys420Arg (n = 2), p.Glu453Lys (n = 2), p.Glu542Lys (n = 2), p.Glu418Lys (n = 1), p.Glu545Lys (n = 1), and p.His1047Tyr (n = 1) and the deletion mutation p.Glu110del (n = 3). Furthermore, the GNAQ mutation p.Arg183Gln was detected in the epidermal nevus tissue of one patient. Imaging revealed that several patients carrying hotspot mutations had more severe adipose infiltration and skeletal deformities. CONCLUSIONS: The abundant clinical presentations and genetic profiles of FIL make it difficult to treat. PIK3CA mutations drive the pathogenesis of FIL, and PIK3CA hotspot mutations may lead to more extensive infiltration of lipomatosis. Understanding the molecular variant profile of FIL will facilitate the application of novel PI3K-targeted inhibitors.


Face , Lipomatosis , Humans , Face/pathology , Lipomatosis/genetics , Phenotype , Genotype , Mutation/genetics , Class I Phosphatidylinositol 3-Kinases/genetics
7.
Front Oncol ; 13: 1063673, 2023.
Article En | MEDLINE | ID: mdl-37182177

Objective: Infantile hemangioma (IH), the most common infantile vascular neoplasm, is uniquely characterized by rapid proliferation followed by slow spontaneous involution lasting for years. In IH lesions, perivascular cells are the most dynamic cell subset during the transition from the proliferation phase to the involution phase, and we aimed to systematically study this kind of cell. Methods and results: CD146-selective microbeads were used to isolate IH-derived mural-like cells (HemMCs). Mesenchymal markers of HemMCs were detected by flow cytometry, and the multilineage differentiation potential of HemMCs was detected by specific staining after conditioned culture. CD146-selected nonendothelial cells from IH samples showed characteristics of mesenchymal stem cells with distinct angiogenesis-promoting effects detected by transcriptome sequencing. HemMCs spontaneously differentiated into adipocytes 2 weeks after implantation into immunodeficient mice, and almost all HemMCs had differentiated into adipocytes within 4 weeks. HemMCs could not be induced to differentiate into endothelial cells in vitro. However, 2 weeks after implantation in vivo, HemMCs in combination with human umbilical vein endothelial cells (HUVECs) formed GLUT1+ IH-like blood vessels, which spontaneously involuted into adipose tissue 4 weeks after implantation. Conclusions: In conclusion, we identified a specific cell subset that not only showed behavior consistent with the evolution of IH but also recapitulated the unique course of IH. Thus, we speculate that proangiogenic HemMCs may be a potential target for the construction of hemangioma animal models and the study of IH pathogenesis.

8.
BMC Cardiovasc Disord ; 23(1): 181, 2023 04 04.
Article En | MEDLINE | ID: mdl-37016312

OBJECTIVE: The aim of this work was to evaluate the predictive value of FAR combined with CACS for MACCEs. BACKGROUND: The fibrinogen-albumin-ratio (FAR), a novel biomarker of inflammation, is associated with the severity of coronary artery disease (CAD). Coronary calcification score (CACS) is associated with the severity of coronary stenosis and is closely related to the prognosis of CAD patients. What is the prognostic value of FAR in patients with chest pain, which has not been reported. This study aims to evaluate the relationship between CACS and FAR and their impact on prognosis in patients with suspected CAD. METHODS: We used information from 12,904 individuals who had coronary computed tomography angiography (CTA) for chest pain and tracked down any significant adverse cardiac and cerebrovascular events (MACCEs). The following formula was used to calculate FAR: fibrinogen (g/L)/albumin (g/L). Patients were separated into groups with greater levels of FAR (FAR-H) and lower levels of FAR (FAR-L) in accordance with the ideal cut-off value of FAR for MACCEs prediction. In addition, patients were divided into three groups based on their CACS scores (CACS ≤ 100, 100 < CACS ≤ 400, and CACS > 400). RESULTS: 4946 patients [62(55-71) years, 64.4% male] were ultimately enrolled in the present study. During follow-up, a total of 234 cases (4.7%) of MACCEs were documented. Linear regression analysis results showed that CACS (R2 = 0.004, Standard ß = 0.066, P < 0.001) was positively associated with FAR in patients with chest pain.Compared to ones with FAR-L, FAR-H had an increased risk for MACCEs (adjusted HR 1.371(1.053-1.786) P = 0.019). Multivariate Cox regression showed that age (adjusted HR 1.015 95% CI 1.001-1.028;p = 0.03), FAR (adjusted HR 1.355 95% CI 1.042-1.763;p = 0.023),FBG (adjusted HR 1.043 95% CI 1.006-1.083;p = 0.024) and CACS (adjusted HR 1.470 95% CI 1.250-1.727;p < 0.001) were the independent risk factors for MACCEs. The FAR and CACS significantly improved MACCEs risk stratification, contributing to substantial net reclassification improvement ( NRI 0.122, 95% CI 0.054-0.198, P < 0.001) and integrated discrimination improvement(IDI 0.011, 95% CI 0.006-0.017, P < 0.001). CONCLUSION: FAR was an independent risk factor for MACCEs. The results showed that CACS was positively associated with FAR in patients with suspected CAD. A higher level of FAR and heavier coronary calcification burden was associated with worse outcomes among patients with suspected CAD. FAR and CACS improved the risk identification of patients with suspected CAD, leading to a significant reclassification of MACCEs.


Coronary Artery Disease , Vascular Calcification , Female , Humans , Male , Chest Pain , Coronary Angiography/methods , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/complications , Predictive Value of Tests , Prognosis , Risk Assessment , Risk Factors , Vascular Calcification/diagnostic imaging , Middle Aged , Aged
9.
Clin Exp Dermatol ; 48(3): 193-198, 2023 Mar 01.
Article En | MEDLINE | ID: mdl-36763678

BACKGROUND: The distribution and response to propranolol of problematic facial infantile haemangiomas (IHs) has rarely been described in the literature. AIM: To map problematic facial IHs and observe their response to propranolol. METHODS: Eligible patients were categorized according to focal location and cohorts corresponding to these (buccal, medial, zygomatic, lateral and multiregional) were created. The primary efficacy variable was regression score ranging from 1 to 4, calculated using results of colour Doppler ultrasonography. RESULTS: In total, 104 patients met the inclusion criteria. There were 32 (30·8%) IHs located in the buccal area, 12 (11·5%) in the medial area, 49 (47·1%) in the lateral area and 1 (1·0%) in the zygomatic area, with 10 (9·6%) IH cases having multiregional lesions. We found that the distribution pattern of most IHs matched the surface projection of the trunk of the external carotid and the facial arteries. Further analysis showed that the median regression score in the buccal and medial groups were significantly lower than those in the lateral and multiregional groups. CONCLUSION: Treatment of buccal and medial haemangiomas tends to be more challenging and their distribution pattern mainly reflects the direction of the facial vessels.


Hemangioma, Capillary , Hemangioma , Skin Neoplasms , Humans , Infant , Propranolol/therapeutic use , Retrospective Studies , Hemangioma, Capillary/pathology , Administration, Oral , Treatment Outcome , Skin Neoplasms/drug therapy , Adrenergic beta-Antagonists/therapeutic use
10.
Nat Metab ; 5(2): 314-330, 2023 02.
Article En | MEDLINE | ID: mdl-36717749

The accumulation of acidic metabolic waste products within the tumor microenvironment inhibits effector functions of tumor-infiltrating lymphocytes (TILs). However, it remains unclear how an acidic environment affects T cell metabolism and differentiation. Here we show that prolonged exposure to acid reprograms T cell intracellular metabolism and mitochondrial fitness and preserves T cell stemness. Mechanistically, elevated extracellular acidosis impairs methionine uptake and metabolism via downregulation of SLC7A5, therefore altering H3K27me3 deposition at the promoters of key T cell stemness genes. These changes promote the maintenance of a 'stem-like memory' state and improve long-term in vivo persistence and anti-tumor efficacy in mice. Our findings not only reveal an unexpected capacity of extracellular acidosis to maintain the stem-like properties of T cells, but also advance our understanding of how methionine metabolism affects T cell stemness.


Acidosis , Neoplasms , Animals , Mice , Neoplasms/metabolism , Cell Differentiation , Tumor Microenvironment , Acidosis/metabolism , Carbon
11.
Facial Plast Surg Aesthet Med ; 25(6): 466-471, 2023.
Article En | MEDLINE | ID: mdl-36459124

Background: The optimal timing of laser epilation with expanded forehead flaps in facial defect reconstruction remains undetermined. Objective: To compare the efficacy and safety of hair removal during or after flap expansion. Methods: This prospective exploratory study included 15 (11 women and 4 men, 16.47 ± 16.331 years of age) and 26 (19 women and 7 men, 10.69 ± 10.899 years of age) patients who underwent 755 nm long-pulsed alexandrite laser epilation during flap expansion and after surgery, respectively. Facial reconstruction was performed in these patients because of congenital melanin nevus, scar or port-wine stains. Evaluation included hair reduction rate, patient satisfaction, and adverse events. Results: The median number of laser sessions for hair removal during flap expansion was significantly lower than that after surgery (2.00 vs. 3.00, p < 0.01), and the hair reduction rate was also significantly higher during flap expansion (79.5% ± 21.93% vs. 68.3% ± 17.44%, p < 0.05). No severe adverse events were reported. Conclusion: Laser hair removal is safe and efficient when performed both during flap expansion period and after surgery, but its efficacy was significantly higher, and fewer sessions were required when performed during tissue expansion. Clinical trial registration information: ChiCTR1900026090.


Forehead , Hair Removal , Plastic Surgery Procedures , Skin Neoplasms , Adult , Female , Humans , Male , Forehead/surgery , Lasers , Prospective Studies , Skin Neoplasms/surgery , Tissue Expansion , Infant, Newborn , Infant , Child, Preschool , Child , Adolescent , Young Adult
12.
Clin Cardiol ; 46(2): 195-203, 2023 Feb.
Article En | MEDLINE | ID: mdl-36484372

OBJECTIVES: The aim of this study was to examine the independent and joint associations of baseline coronary artery calcium score (CACS) and cystatin C (Cys-C) with the risk of major adverse cardiac and cerebrovascular events (MACCEs) and all-cause death in symptomatic populations. METHODS: The study included 7140 patients with symptom of chest pain who underwent cardiac computerized tomography examinations to measure CACS. All of them had serum Cys-C results. Endpoints were set for MACCEs and all-cause death events. RESULTS: A total of 7140 participants were followed for a median of 1106 days. A total of 305 patients had experienced MACCEs and 191 patients had experienced all-cause death. CACS ≥ 100 and Cys-C ≥ 0.995 mg/L were independently associated with an increased risk of MACCEs (adjusted hazard ratio [HR]: 1.46; 95% confidence interval [CI]: 1.15-1.85; p = .002 and adjusted HR: 1.57; 95% CI: 1.24-2.00; p < .001, respectively). Compared with CACS < 100 and Cys-C < 0.995 mg/L patients, CACS ≥ 100 and Cys-C ≥ 0.995 mg/L patients had the highest risk of MACCEs and all-cause death (adjusted HR: 2.33; 95% CI: 1.64-3.29; p < .001 and adjusted HR: 2.85; 95% CI: 1.79-4.55; p < .001, respectively). Even in patients with CACS < 100, Cys-C ≥ 0.995 mg/L was also associated with a higher risk of MACCEs and all-cause death than Cys-C < 0.995 mg/L (adjusted HR: 1.76; p = .003 and adjusted HR: 2.02; p = .007, respectively). CONCLUSIONS: The combined stratification of CACS and Cys-C showed an incremental risk of MACCEs and all-cause death, reflecting complementary prognostic value. Our results support the combination of the two indicators for risk stratification and event prediction.


Calcium , Coronary Artery Disease , Humans , Coronary Angiography/methods , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/complications , Coronary Vessels/diagnostic imaging , Cystatin C , Predictive Value of Tests , Prognosis , Risk Assessment/methods , Risk Factors
13.
J Invest Dermatol ; 143(4): 566-577.e12, 2023 04.
Article En | MEDLINE | ID: mdl-36243122

Infantile hemangioma (IH), the most common benign tumor in infancy, is generally sensitive to propranolol treatment. However, the challenge remains because resistance or recurrence could occur in some patients, and the mechanism or target of propranolol remains unknown. Therefore, advancement in the drug development is needed. In this study, we explored whether apelin receptor (APJ) can become a candidate target. We found that APJ is expressed only in endothelial cells of IH (HemECs) but not in other vascular anomalies, and its antagonist, ML221, can negatively regulate cellular viability and functions of HemECs. This inhibitory effect could be replicated in a murine hemangioma model. Importantly, in vitro experiments also indicated that ML221 failed to affect the proliferation or angiogenesis of normal endothelial cells or APJ-knockout HemECs. Through analysis of the phosphoantibody microarray data, ML221 was revealed to have an inhibitory effect on HemECs by suppressing the activation of mitogen-activated protein kinase/extracellular signal-regulated kinase pathway. These results verified the distinctive expression of APJ in IH and specific inhibition of HemEC activity caused by ML221. In addition, APJ was also detected in propranolol-resistant IH. Collectively, we propose that APJ can act as a specific marker and a promising therapeutic target for IH, which will facilitate further drug development.


Endothelial Cells , Hemangioma , Humans , Animals , Mice , Endothelial Cells/metabolism , Propranolol/pharmacology , Propranolol/therapeutic use , Apelin Receptors/metabolism , Apelin Receptors/therapeutic use , Cell Proliferation , Hemangioma/drug therapy
14.
Front Cardiovasc Med ; 9: 824955, 2022.
Article En | MEDLINE | ID: mdl-35958403

Background: Platelet-related parameters and HDL-C have been regarded as reliable and alternative markers of coronary heart disease (CHD) and the independent predictors of cardiovascular outcomes. PDW is a simple platelet index, which increases during platelet activation. Whether the PDW/HDL-C ratio predicts major adverse cardiovascular and cerebrovascular events (MACCEs) in patients who complained of chest pain and confirmed coronary artery calcification remains to be investigated. This study aimed to investigate the prognostic value of the PDW/HDL-C ratio in patients with chest pain symptoms and coronary artery calcification. Methods: A total of 5,647 patients with chest pain who underwent coronary computer tomography angiography (CTA) were enrolled in this study. Patients were divided into two groups according to their PDW/HDL-C ratio or whether the MACCE occurs. The primary outcomes were new-onset MACCEs, defined as the composite of all-cause death, non-fatal MI, non-fatal stroke, revascularization, malignant arrhythmia, and severe heart failure. Results: All patients had varying degrees of coronary calcification, with a mean CACS of 97.60 (22.60, 942.75), and the level of CACS in the MACCEs group was significantly higher than that in non-MACCE (P<0.001). During the 89-month follow-up, 304 (5.38%) MACCEs were recorded. The incidence of MACCEs was significantly higher in patients with the PDW/HDL-C ratio > 13.33. The K-M survival curves showed that patients in the high PDW/HDL-C ratio group had significantly lower survival rates than patients in the low PDW/HDL-C ratio group (log-rank test: P < 0.001). Multivariate Cox hazard regression analysis reveals that the PDW/HDL ratio was an independent predictor of MACCEs (HR: 1.604, 95% CI: 1.263-2.035; P < 0.001). Cox regression analysis showed that participants with a lower PDW/HDL-C ratio had a higher risk of MACCEs than those in the higher ratio group. The incidence of MACCEs was also more common in the PDW/HDL-C ratio > 13.33 group among different severities of coronary artery calcification. Furthermore, adding the PDW/HDL-C ratio to the traditional prognostic model for MACCEs improved C-statistic (P < 0.001), the NRI value (11.3% improvement, 95% CI: 0.018-0.196, P = 0.01), and the IDI value (0.7% improvement, 95% CI: 0.003-0.010, P < 0.001). Conclusion: The higher PDW/HDL-C ratio was independently associated with the increasing risk of MACCEs in patients with chest pain symptoms and coronary artery calcification. In patients with moderate calcification, mild coronary artery stenosis, and CAD verified by CTA, the incidence of MACCEs increased significantly in the PDW/HDL-C ratio > 13.33 group. Adding the PDW/HDL-C ratio to the traditional model provided had an incremental prognostic value for MACCEs.

15.
Pharmaceutics ; 14(8)2022 Aug 01.
Article En | MEDLINE | ID: mdl-36015233

Infantile hemangiomas (IH) leave sequelae after involution. Topical application of timolol maleate (TM) is the mainstream treatment for superficial lesions but is limited by its low penetrable properties. We aimed to develop a superior skin permeation drug while maintaining the therapeutic properties of timolol. We predict that this drug will promote the involution of thick and deep IH lesions and avoid sequelae. We chemically modified drug structure to prepare butyryl timolol maleate (BT) prodrug and conducted in vitro and in vivo toxicity evaluations of BT with rat dorsal skin and normal skin cells. Skin permeation and absorption comparisons of TM and BT were conducted using rat and porcine skin models. Conversion efficiency of BT to timolol was also tested on human skin ex vivo. BT did not cause skin irritation on rat dorsal skin and exhibited low cytotoxicity overall. BT exhibited superior skin permeation ability compared with that of TM, whilst maintaining a low systemic absorbance. Further, BT was converted to timolol in human skin in a time-dependent manner. Noticeably, timolol accumulation in the skin from BT was higher than that from TM. Finally, BT demonstrated similar biocompatibility with TM in the IH tumor. BT enhances local delivery of timolol and its skin permeation. Using BT, we could eliminate thicker IH lesions that are prone to leave sequelae, and potentially help young children avoid dermal sequelae, disfigurement, and concomitant therapy.

16.
Ann Plast Surg ; 88(6): 631-634, 2022 06 01.
Article En | MEDLINE | ID: mdl-35502945

BACKGROUND: Vermilion deformities after intralesional bleomycin A5 injections for hemangiomas of the upper lip have not been rare during the past 2 decades in China. In this article, we summarized our 10 years of experience using a lower to upper axial cross-lip musculomucosal flap with bipedicle lower labial coronary arteries for 1-stage reconstruction of large upper vermillion defects. Based on several years of experience, we also created some modified approaches to achieve satisfactory cosmetic outcomes. PATIENTS AND METHODS: From July 2006 to July 2016, a total of 25 patients with moderate and severe vermilion defects of the upper lip were treated with this method at the Department of Plastic and Reconstructive Surgery in Shanghai Ninth People's Hospital. The cosmetic outcomes and complications were reviewed. RESULTS: The overall mean follow-up time was 14.9 months. No patients had infection or hematoma. All the flaps survived, and all the patients were satisfied with the postoperative appearance. CONCLUSIONS: Our experience has proven that a lower to upper axial cross-lip musculomucosal flap with bipedicle lower labial coronary arteries is a safe and effective approach for correcting large upper vermillion defects. It is a 1-stage operation for the overall length of upper vermillion reconstruction. This method could improve upper-lip aesthetics and achieve reconstructive goals while avoiding lower-lip deformities.


Lip , Plastic Surgery Procedures , China , Humans , Mouth Mucosa , Surgical Flaps
17.
Ann Plast Surg ; 89(2): 214-217, 2022 08 01.
Article En | MEDLINE | ID: mdl-35502973

BACKGROUND: Oral propranolol can effectively activate and accelerate infantile hemangioma (IH) involution; however, could the final outcome of oral propranolol treatment for IHs commensurate that of spontaneous involution? OBJECTIVE: This study aimed to investigate the long-term therapeutic effect of oral propranolol for IHs. METHODS: We present an individual matching comparative study with (1) oral propranolol therapy for mixed and deep IHs on the lips, nose, and parotid and (2) lesion type- and lesion location-matched untreated IHs as controls. Patients' follow-up photographs were assessed by 3 surgeons blinded of their treatment. Outcome measures were the quantification of the degree of sequelae ranging from 1 to 4 and the age at which IH achieved involution arrest. RESULTS: Ten groups of oral propranolol and untreated patients with matched lesions were assessed. Average age at which lesions stabilized and reached no change in appearance was 1.7 years old and 6.3 years old for propranolol group and untreated group ( t = 5.663, P < 0.001). There was no significant difference in the quantified degree of sequelae for oral propranolol group and untreated group upon follow-up (1.60 vs 1.40, respectively; t = 1.259, P = 0.240). CONCLUSIONS: Oral propranolol therapy accelerates IH involution but does not have a superior effect than spontaneous involution on the overall outcome of problematic IHs.


Hemangioma, Capillary , Hemangioma , Skin Neoplasms , Administration, Oral , Adrenergic beta-Antagonists/therapeutic use , Disease Progression , Hemangioma/drug therapy , Hemangioma, Capillary/drug therapy , Humans , Infant , Propranolol/therapeutic use , Retrospective Studies , Skin Neoplasms/complications , Treatment Outcome
19.
Invest New Drugs ; 40(3): 469-477, 2022 06.
Article En | MEDLINE | ID: mdl-34985594

Our previous studies have revealed the important roles of the nonseed regions of microRNAs (miRNAs) in gene regulation, which provided novel insight into the development of miRNA analogs for cancer therapy. Here, we altered each nucleotide in the nonseed region of miR-34a and obtained novel synthetic miRNA analogs. Among them, AM22, with a base alteration from G to C at the 17th nucleotide of miR-34a, showed extensive antiproliferative activity against several colorectal tumor cell lines and achieved effective inhibition of core binding factor subunit ß (CBFB) expression. Subsequent investigations demonstrated that AM22 directly targeted CBFB by binding to its 3'-untranslated region (3'-UTR). Inhibition of CBFB showed obvious antiproliferative activity on HCT-116 and SW620 cells. Furthermore, the antiproliferative effects of AM22 on these cells were also measured in xenograft mouse models. In conclusion, this study identified AM22 as a potential antitumor miRNA by targeting CBFB and provided a new design approach for miRNA-based cancer treatment by changing the nonseed region of miRNA.


Colorectal Neoplasms , MicroRNAs , Animals , Cell Line, Tumor , Cell Proliferation/genetics , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Core Binding Factor beta Subunit/genetics , Core Binding Factor beta Subunit/metabolism , Gene Expression Regulation, Neoplastic , Humans , Mice , MicroRNAs/genetics , MicroRNAs/metabolism , Nucleotides
20.
Aesthet Surg J ; 42(5): NP265-NP272, 2022 04 12.
Article En | MEDLINE | ID: mdl-34850808

BACKGROUND: Postsurgical scar management significantly affects patient satisfaction. However, reliable skin support options are limited. OBJECTIVES: The present study aimed to determine the efficacy and safety of using tissue adhesive zippers in postsurgical scar prevention among patients undergoing surgical excision of the face. The primary outcome was a reduction in scar width, which was evaluated 1, 3, 6, and 12 months postoperatively. Scar width at Month 12 was considered the final outcome. METHODS: This was a prospective, randomized, controlled, rater-blinded trial. Sixty-four patients were randomly assigned to 2 groups (the zip group, defined as those using a tissue adhesive zipper for 3 months after surgery, and the control group). Outcomes were evaluated 1, 3, 6, and 12 months postoperatively based on scar width and Patient Observer Scar Assessment Scale score. Skin irritation was monitored during the first 3 months after surgery. The incidence of hypertrophic scar formation was recorded at a 12-month follow-up. RESULTS: Scar width differed significantly between the zip (mean [standard deviation], 1.68 [0.45] mm) and control groups (2.15 [0.64] mm). The scars spread rapidly in the first month after surgery but slowed down and stabilized after 6 months. The Patient Observer Scar Assessment Scale scores of the zip group were significantly lower than those of the control group. Neither group experienced significant complications. CONCLUSIONS: Prolonged use of tissue adhesive zippers immediately after surgery reduced scar width and improved scar appearance without obvious side effects.


Cicatrix, Hypertrophic , Tissue Adhesives , Cicatrix/etiology , Cicatrix/prevention & control , Cicatrix, Hypertrophic/etiology , Face/surgery , Humans , Prospective Studies , Tissue Adhesives/therapeutic use , Treatment Outcome
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