The attitudes of nonpsychiatric nurses towards mental disorders in China.

Background: Few studies have explored the associated factors of attitudes of nonpsychiatric nurses towards mental disorders. Therefore, this study is aimed to evaluate the attitudes of nonpsychiatric nurses towards mental disorders and especially explore the association between psychiatric clinical practice and these attitudes. Methods: A total of 1324 nonpsychiatric nurses and students majoring in nursing were recruited through an online questionnaire from December 2021 to March 2022 in Sichuan Province, China. Demographic information, personal care experience, psychiatric nursing education and the Community Attitudes towards the Mentally Ill (CAMI) were collected. A higher score indicates a stigmatizing attitude in the authoritarianism and social restrictiveness (SR) subscales and a positive attitude in the benevolence and community mental health ideology (CMHI) subscales. Multivariate linear regression was employed to analyze associated factors of attitudes towards mental disorders, and hierarchical linear regression was used to analyze the association between psychiatric clinical practice and the attitudes towards mental disorders. Results: Under the control of confounders, high education level, long residence in urban and personal care experience were positively correlated with score of authoritarianism and SR (p < 0.05), and negatively correlated with score of benevolence (p < 0.05). Long residence in urban and personal care experience were negatively correlated with score of CMHI (p < 0.05). Hierarchical linear regression analysis showed that after adjusting for demographic information, psychiatric clinical practice was associated with lower score of benevolence (B = -0.09, 95%CI = -0.17 ~ -0.003, p = 0.043) and CMHI (B = -0.09, 95%CI = -0.17 ~ -0.01, p = 0.027), but the initial associations between psychiatric clinical practice and authoritarianism, SR disappeared. Conclusions: High education level, long residence in urban, personal care experience and the psychiatric clinical practice were associated with the discrimination of nonpsychiatric nurses towards mental disorders. Further exploring practical strategies to optimize the psychiatric clinical practice experience of nonpsychiatric nurses could help improve their attitudes towards mental disorders.

Delineation of the phenotypes and genotypes of PIK3CA-related overgrowth spectrum in East asians.

PIK3CA-related overgrowth spectrum (PROS) is an umbrella term to describe a diverse range of developmental disorders. Research to date has predominantly emerged from Europe and North America, resulting in a notable scarcity of studies focusing on East Asian populations. Currently, the prevalence and distribution of PIK3CA variants across various genetic loci and their correlation with distinct phenotypes in East Asian populations remain unclear. This study aims to elucidate the phenotype-genotype correlations of PROS in East Asian populations. We presented the phenotypes and genotypes of 82 Chinese patients. Among our cohort, 67 individuals carried PIK3CA variants, including missense, frameshift, and splice variants. Six patients presented with both PIK3CA and an additional variant. Seven PIK3CA-negative patients exhibited overlapping PROS manifestations with variants in GNAQ, AKT1, PTEN, MAP3K3, GNA11, or KRAS. An integrative review of the literature pertaining to East Asian populations revealed that specific variants are uniquely associated with certain PROS phenotypes. Some rare variants were exclusively identified in cases of megalencephaly and diffuse capillary malformation with overgrowth. Non-hotspot variants with undefined oncogenicity were more common in CNS phenotypes. Diseases with vascular malformation were more likely to have variants in the helical domain, whereas phenotypes involving adipose/muscle overgrowth without vascular abnormalities predominantly presented variants in the C2 domain. Our findings underscore the unique phenotype-genotype patterns within the East Asian PROS population, highlighting the necessity for an expanded cohort to further elucidate these correlations. Such endeavors would significantly facilitate the development of PI3Kα selective inhibitors tailored for the East Asian population in the future.

One-carbon metabolism shapes T cell immunity in cancer.

One-carbon metabolism (1CM), comprising folate metabolism and methionine metabolism, serves as an important mechanism for cellular energy provision and the production of vital signaling molecules, including single-carbon moieties. Its regulation is instrumental in sustaining the proliferation of cancer cells and facilitating metastasis; in addition, recent research has shed light on its impact on the efficacy of T cell-mediated immunotherapy. In this review, we consolidate current insights into how 1CM affects T cell activation, differentiation, and functionality. Furthermore, we delve into the strategies for modulating 1CM in both T cells and tumor cells to enhance the efficacy of adoptively transferred T cells, overcome metabolic challenges in the tumor microenvironment (TME), and maximize the benefits of T cell-mediated immunotherapy.

Aesthetic Reconstruction of the Sequelae of Large Facial Involuted Infantile Hemangioma with Tissue Expanders.

BACKGROUND: Large involuted infantile hemangioma remains a challenge in facial reconstruction. The characteristic fibrofatty residuum and multiple subunits/tissues involvement contribute significantly to the difficulty of surgical management. Tissue expander plays an important role in facial reconstruction, allowing plastic surgeons to repair skin damaged by both congenital and acquired defects. METHODS: Between 2009 and 2021, 30 patients who underwent tissue expansion surgery were reviewed in a single hospital. The demographic data, lesion characteristics, surgical approaches, complication rate, and aesthetic outcomes were analyzed. RESULTS: Thirty patients (5 men and 25 women) with a mean age of 14.03 ± 7.25 years (range, 4-33 years) were included. The mean follow-up is 35.92 months, ranging from 9 to 75 months. Tissue expansion-related complications include closed infection, 2/30 (6.67%); skin ischemia, 2/30 (6.67%); hematoma, 1/30 (3.33%); flap necrosis, 1/30 (3.33%). CONCLUSION: Large facial involuted infantile hemangiomas have variable patterns of presentation and necessitate tailored therapy. Tissue expansion is a reproducible approach to achieving aesthetic reconstruction. 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 .

Practical surgical technique using the SMISS approach for lip reduction in involuted lip infantile hemangiomas.

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.

Suppression of the METTL3-m6A-integrin ß1 axis by extracellular acidification impairs T cell infiltration and antitumor activity.

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.

Clinical characteristics and surgical management of facial infiltrating lipomatosis: a single center experience.

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.

The Ram Graft: Using One Complete Piece of Conchal Cartilage for Nasal Tip Reconstruction in East Asians.

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.

Intralesional betamethasone versus oral propranolol for localized infantile hemangiomas of the lip.

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.

Delineation of the phenotypes and genotypes of facial infiltrating lipomatosis associated with PIK3CA mutations.

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.

CD146+ mural cells from infantile hemangioma display proangiogenic ability and adipogenesis potential in vitro and in xenograft models.

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.

Prognostic value of fibrinogen-to-albumin ratio combined with coronary calcification score in patients with suspected coronary artery disease.

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.

Distribution of problematic localized facial infantile haemangiomas and their response to propranolol: a retrospective cohort study.

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.

Extracellular acidosis restricts one-carbon metabolism and preserves T cell stemness.

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.

Optimal Timing of Laser Hair Removal in Expanded Forehead Flap in the Reconstruction of Facial Defects: During or After Tissue Expansion?

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.

Coronary artery calcium and cystatin C for risk stratification of MACCEs and all-cause death in symptomatic patients.

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.

Apelin Receptor Can Act as a Specific Marker and Promising Therapeutic Target for Infantile Hemangioma.

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.

Prognostic value of the PDW/HDL-C ratio in patients with chest pain symptoms and coronary artery calcification.

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.

Evaluation of Transdermal Transport and Concurrent Cutaneous Hydrolysis of Timolol Prodrug for the Treatment of Infantile Hemangiomas.

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.

One-Stage Reconstruction of Large Upper Vermillion Defects Using a Lower to Upper Bipedicle Axial Cross-Lip Vermillion Flap.

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.