Eugenol-loaded polyurethane gelatin dressing for efficient angiogenesis and antibacterial effects in refractory diabetic wound defect healing.

The amelioration of refractory diabetic ulcers presents a formidable conundrum on a global scale, attributable to the elevated peril of contagion and protracted convalescence durations. Within the purlieus of this reparative epoch, the deployment of efficacious wound coverings endowed with both angiogenesis and antibacterial attributes is of paramount significance. Hydrogel wound dressings are distinguished by their elevated biocompatibility, adhesive tenacity, and innate regenerative capacity. Eugenol, a substance distilled from the blossoms of the lilac, serves as a precursor to metformin and is known to impede the genesis of reactive oxygen species. Although its antibacterial effects have been extensively chronicled, the angiogenic ramifications of eugenol within the context of wound remediation remain under-investigated. This research aimed to evaluate the effectiveness of eugenol-infused hydrogel as a wound dressing material. In this context, polyurethane gelatin (PG) was combined with eugenol at concentrations of 0.5% and 1%, creating PG-eugenol hydrogel mixtures with specific mass ratios for both in vivo and in vitro assessments. The in vivo studies indicated that hydrogels infused with eugenol expedited diabetic wound healing by fostering angiogenesis. Enhanced healing was noted, attributed to improved antibacterial and angiogenic properties, increased cell proliferation, tissue regeneration, and re-epithelialization. The in vitro analyses revealed that eugenol-enriched hydrogels stimulated the growth of fibroblasts (HFF-1) and human umbilical vein endothelial cells (HUVECs) and exhibited antibacterial characteristics. This investigation confirms the potential of eugenol-laden hydrogels in effectively treating diabetic wound defects.

Central Channelopathies in Obesity.

As obesity has raised heightening awareness, researchers have attempted to identify potential targets that can be treated for therapeutic intervention. Focusing on the central nervous system (CNS), the key organ in maintaining energy balance, a plethora of ion channels that are expressed in the CNS have been inspected and determined through manipulation in different hypothalamic neural subpopulations for their roles in fine-tuning neuronal activity on energy state alterations, possibly acting as metabolic sensors. However, a remaining gap persists between human clinical investigations and mouse studies. Despite having delineated the pathways and mechanisms of how the mouse study-identified ion channels modulate energy homeostasis, only a few targets overlap with the obesity-related risk genes extracted from human genome-wide association studies. Here, we present the most recently discovered CNS-specific metabolism-correlated ion channels using reverse and forward genetics approaches in mice and humans, respectively, in the hope of illuminating the prospects for future therapeutic development.

Force Balance Reconstruction of the Orbicularis Oris in Secondary Unilateral Cleft Lip Deformity.

BACKGROUND: Secondary unilateral cleft lip deformities are commonly observed in patients with cleft lip and traditional surgical methods can't completely tackle this problem. The purpose of this study was to evaluate the outcomes of a novel surgical technique using force balance reconstruction of the orbicularis oris. METHODS: 53 patients with secondary unilateral cleft lip deformity were included in this study, in which the orbicularis oris muscle was reconstructed symmetrically to achieve optimal force balance. Photometric 2d indexes were employed to evaluate the outcome of 27 patients, and 3d indexes for the remaining 26 patients. Aesthetic evaluation and parent-patient satisfaction surveys were also recorded. RESULTS: Significant differences were found in the following: (1) LH (the lip height), LW (the lip width), D1(the vertical distance from the white roll to the vermilion bottom at the christa philtra points) and D2(the vertical distance from the christa philtra points to the facial midline) when comparing preoperative and postoperative 2D images; (2) LH, LW, D1 and D2 when comparing preoperative and follow-up 2D images; (3) RMS (root mean of square) when comparing preoperative and postoperative 3D images. Aesthetic evaluation in the follow-up period was a mean of 4.29, while parent-patient satisfaction of the overall appearance was a mean of 4.41. CONCLUSIONS: The results suggest this new muscle reconstruction technique can significantly improve the surgical outcome of secondary unilateral cleft lip deformities. 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 ."

Pd(II)-Catalyzed Desymmetrizing gem-Dimethyl C(sp3)-H Alkenylation/Aza-Wacker Cyclization Directed by PIP Auxiliary.

Desymmetrization of gem-dimethyl groups has been developed as an efficient pathway to achieve asymmetric C(sp3)-H functionalization. Herein, we described a Pd(II)-catalyzed desymmetrizing gem-dimethyl C(sp3)-H alkenylation/aza-Wacker cyclization directed by a bidentate 2-pyridinylisopropyl auxiliary. Chiral α-methyl γ-lactams were obtained in good yields (up to 82%) and high enantioselectivities (up to 91.5% ee).

Cobalt-Catalyzed Domino Transformations via Enantioselective C-H Activation/Nucleophilic [3 + 2] Annulation toward Chiral Bridged Bicycles.

Selective synthesis of chiral bridged (hetero)bicyclic scaffolds via asymmetric C-H activation constitutes substantial challenges due to the multiple reactivities of strained bicyclic structures. Herein, we develop the domino transformations through an unprecedented cobalt-catalyzed enantioselective C-H activation/nucleophilic [3 + 2] annulation with symmetrical bicyclic alkenes. The methods offer straightforward access to a wide range of chiral molecules bearing [2.2.1]-bridged bicyclic cores with four and five consecutive stereocenters in a single step. Two elaborate salicyloxazoline (Salox) ligands were synthesized based on the rational design and mechanistic understanding. The well-defined chiral pockets generated from asymmetric coordination around the trivalent cobalt catalyst direct the orientation of bicyclic alkenes, leading to excellent enantioselectivity.

Neuronal population activity in the olivocerebellum encodes the frequency of essential tremor in mice and patients.

Essential tremor (ET) is the most prevalent movement disorder, characterized primarily by action tremor, an involuntary rhythmic movement with a specific frequency. However, the neuronal mechanism underlying the coding of tremor frequency remains unexplored. Here, we used in vivo electrophysiology, optogenetics, and simultaneous motion tracking in the Grid2dupE3 mouse model to investigate whether and how neuronal activity in the olivocerebellum determines the frequency of essential tremor. We report that tremor frequency was encoded by the temporal coherence of population neuronal firing within the olivocerebellums of these mice, leading to frequency-dependent cerebellar oscillations and tremors. This mechanism was precise and generalizable, enabling us to use optogenetic stimulation of the deep cerebellar nuclei to induce frequency-specific tremors in wild-type mice or alter tremor frequencies in tremor mice. In patients with ET, we showed that deep brain stimulation of the thalamus suppressed tremor symptoms but did not eliminate cerebellar oscillations measured by electroencephalgraphy, indicating that tremor-related oscillations in the cerebellum do not require the reciprocal interactions with the thalamus. Frequency-disrupting transcranial alternating current stimulation of the cerebellum could suppress tremor amplitudes, confirming the frequency modulatory role of the cerebellum in patients with ET. These findings offer a neurodynamic basis for the frequency-dependent stimulation of the cerebellum to treat essential tremor.

Acupuncture and related acupoint therapies for smoking cessation: An umbrella review and updated meta-analysis.

INTRODUCTION: Acupuncture and related acupoint therapies have been widely used for smoking cessation. Some relevant systematic reviews (SRs) have been published. There is a need to summarize and update the evidence to inform practice and decision-making. METHODS: Eight databases were searched from their inception to December 2023. SRs, any randomized controlled trials (RCTs) comparing acupuncture therapies with sham acupuncture, pharmacotherapy, behavioral therapy, or no treatment, were included. The primary outcome was the abstinence rate. AMSTAR-2 was employed to assess the quality of SRs. An updated meta-analysis was conducted based on SRs and RCTs. Data were synthesized using risk ratios (RR) with 95% confidence intervals (CIs). The GRADE approach was employed to assess the certainty of the updated evidence. RESULTS: Thirteen SRs and 20 RCTs outside of the SRs were identified. The SRs were of low or very low quality by AMSTAR-2. Sixteen (80%) RCTs were at high risk of performance bias. Eight acupuncture and related acupoint therapies were involved. The short-term (≤6 months) abstinence rate outcome was summarized as follows. Most SRs suggested that filiform needle acupuncture or acupressure had a better effect than sham acupuncture, but the findings were inconsistent. The updated meta-analysis also suggested that filiform needle acupuncture was more effective than sham acupuncture (RR=1.44; 95% CI: 1.02-2.02; I2 = 66%; low certainty; 9 RCTs, n=1358). Filiform needle acupuncture combined with acupressure was comparable to nicotine patches (RR=0.99; 95% CI: 0.74-1.32; low certainty; 6 RCTs, n= 524). Acupressure was superior to counseling (RR=1.46; 95% CI: 1.14-1.87; I2=5%; low certainty; 8 RCTs, n=595). No serious adverse events were reported in these SRs or RCTs. CONCLUSIONS: Low certainty evidence suggests that filiform needle acupuncture and auricular acupressure appear to be safe and effective in achieving short-term smoking cessation. However, long-term follow-up data are needed.

Examining the relationship between self-efficacy, career development, and subjective wellbeing in physical education students.

We investigated the relationship between self-efficacy and career development via subjective well-being of students majoring in physical education. Life satisfaction, positive affect, and negative affect were the componennts of subjective well-being. Participants were the 1381 adolescents with major in physical education with an age range of 18-22 years (Mage = 19.5 ± 1; females = 34.76%). Hayes PROCESS model was used to develop a multiple mediation model. The results suggest that higher self-efficacy leads to better career development. Further, a significant mediating role was played by negative and positive affect in case of the relationship between self-efficacy and career exploration, but life-satisfaction is not significant mediator. Conversely, life satisfaction and positive affect are significant mediators between self-efficacy and career adaptability but negative affect is not. The findings suggest that self-efficacy and subjective well-being benefit career development of adolescents in the physical education field.

Surgical Management of Airway Obstruction Following Posterior Pharyngeal Flap.

BACKGROUND: Posterior pharyngeal flap (PPF) is effective in managing velopharyngeal insufficiency (VPI) but is of airway obstruction risk. This study compared the effectiveness and complications of two PPF revision procedures and screened potential prognostic factors to postoperative hypernasality and persistent obstruction. METHODS: Patients who received flap division (FD) or port enlargement (PE) for airway obstruction following PPF were reviewed. Ventilation status was assessed using the nasal obstruction symptom evaluation (NOSE) scale, and velopharyngeal closure was assessed using subjective speech evaluation and nasopharyngoscopy. The effectiveness of ventilation relief and complication rate (hypernasality and persistent obstruction) of the two techniques were compared. A comprehensive panel of factors, including age, velopharyngeal mobility, obstruction laterality, body mass index, jaw relationship, and adenoid hypertrophy, were evaluated for correlation with complications. RESULTS: 79 patients were enrolled, with 51 receiving FD and 28 PE. Both techniques significantly improved ventilation dysfunction and hyponasality. Mild hypernasality occurred among 10 cases in the FD group and 3 in the PE group. Age at surgery was significantly associated with persistent obstruction after PPF revision. The occurrence of persistent obstruction was significantly higher among patients below 12 years than those above. Obstruction laterality was suggested in significant correlation with hypernasality post-PPF revision. Among patients with unilateral port obstruction, the occurrence of hypernasality after FD was significantly higher than after PE. CONCLUSION: Both flap division and port enlargement are effective revision procedures to relieve airway obstruction after PPF. Patients below 12 years are more likely to experience persistent ventilation problem after PPF revision.

Evaluation of Secondary Alveolar Bone Grafting for Unilateral Complete Cleft Alveolus: A Retrospective Cone Beam Computed Tomography-Based Study.

Background: In patients with cleft lip and palate (CLP), secondary alveolar bone grafting (SABG) with particulate cancellous bone marrow (PCBM) is recommended. Objective: To compare bone graft outcomes in patients with unilateral CLP, when SABG is completed before or after canine tooth eruption (ACE or BCE), as measured by cone beam computed tomography (CBCT). Methods: Patients were allocated into two cohorts, ACE and BCE. The outcomes were evaluated using CBCT, followed by univariate and multifactorial analyses. Results: A total of 468 patients (age 11.61 ± 4.03 years; male/female 288/180) were analyzed, including 282 in the BCE group (9.41 ± 1.59 years, 175/107) and 186 in the ACE group (14.95 ± 4.31 years, 113/73). Although 5-level assessment revealed no significant difference in clinical success rate (>4 points) between the BCE and ACE groups (53.90% vs. 47.85%, p = 0.20), BCE group showed significantly higher rate of bone bridges formation (73.05% vs. 62.90%, p = 0.02), which can be attributed to variations in orthodontic participation and follow-up time. Independent predictors of graft failure were wide cleft, severe oronasal fistula, no palatal bone wall, and insufficient PCBM filling (p < 0.01). Conclusions: SABG should be performed before canine eruption with more aggressive PCBM filling and oral fistula management.

Lithium chloride promotes mesenchymal-epithelial transition in murine cutaneous wound healing via inhibiting CXCL9 and IGF2.

Cutaneous wound healing is a challenge in plastic and reconstructive surgery. In theory, cells undergoing mesenchymal transition will achieve re-epithelialization through mesenchymal-epithelial transition at the end of wound healing. But in fact, some pathological stimuli will inhibit this biological process and result in scar formation. If mesenchymal-epithelial transition can be activated at the corresponding stage, the ideal wound healing may be accomplished. Two in vivo skin defect mouse models and dermal-derived mesenchymal cells were used to evaluate the effect of lithium chloride in wound healing. The mesenchymal-epithelial transition was detected by immunohistochemistry staining. In vivo, differentially expressed genes were analysed by transcriptome analyses and the subsequent testing was carried out. We found that lithium chloride could promote murine cutaneous wound healing and facilitate mesenchymal-epithelial transition in vivo and in vitro. In lithium chloride group, scar area was smaller and the collagen fibres are also orderly arranged. The genes related to mesenchyme were downregulated and epithelial mark genes were activated after intervention. Moreover, transcriptome analyses suggested that this effect might be related to the inhibition of CXCL9 and IGF2, subsequent assays demonstrated it. Lithium chloride can promote mesenchymal-epithelial transition via downregulating CXCL9 and IGF2 in murine cutaneous wound healing, the expression of IGF2 is regulated by ß-catenin. It may be a potential promising therapeutic drug for alleviating postoperative scar and promoting re-epithelialization in future.

Correlating Jaw Bone Growth and Nasal Morphology Among Adult Patients With Cleft Lip and Palate: A Retrospective Cephalometric Study.

This retrospective cross-sectional study reviewed adult patients with operated cleft lip and/or palate (CL/P) and normal control, and performed comprehensive craniofacial and nasal morphological analyses based on lateral cephalometric radiographs. Pearson or Spearman correlation coefficient assessed intraclass correlation. Seven hundred fifty-seven operated patients with CL/P, and 165 noncleft normal controls were enrolled. Among the normal and CL/P groups, S-N-A angle registered positive correlations with nasal base prominence (S-N'-Sn, degrees). Upper facial height (N-ANS, mm) had positive correlations with nasal dorsum length (N'-Prn, mm) and nasal bone length (N-Na, mm). Although in patients with bilateral cleft lip and palate, there were moderate negative correlations (r=-0.541, P<0.05) with soft tissue facial profile angle (FH-N'Pog', degree) and nasolabial angle (Cm-Sn-ULA, degree). Correlation exists between the morphology of jaw bones and external nose among patients with CL/P. Maxillary sagittal insufficiency is associated with concave nasal profile, and maxilla height is associated with nasal length.

Identification of agricultural surface source pollution in plain river network areas based on 3D-EEMs and convolutional neural networks.

Agricultural non-point sources, as major sources of organic pollution, continue to flow into the river network area of the Jiangnan Plain, posing a serious threat to the quality of water bodies, the ecological environment, and human health. Therefore, there is an urgent need for a method that can accurately identify various types of agricultural organic pollution to prevent the water ecosystems in the region from significant organic pollution. In this study, a network model called RA-GoogLeNet is proposed for accurately identifying agricultural organic pollution in the river network area of the Jiangnan Plain. RA-GoogLeNet uses fluorescence spectral data of agricultural non-point source water quality in Changzhou Changdang Lake Basin, based on GoogLeNet architecture, and adds an efficient channel attention (ECA) mechanism to its A-Inception module, which enables the model to automatically learn the importance of independent channel features. ResNet are used to connect each A-Reception module. The experimental results show that RA-GoogLeNet performs well in fluorescence spectral classification of water quality, with an accuracy of 96.3%, which is 1.2% higher than the baseline model, and has good recall and F1 score. This study provides powerful technical support for the traceability of agricultural organic pollution.

[Clinical Characteristics Analysis of 1051 Cases of Cleft Lip With/Without Cleft Palate in the Ethnic Tibetan Population]. / 1051ä¾‹è—æ—å”‡è ­è£‚æ‚£è€ ä¸´åºŠç‰¹å¾åˆ†æž.

Objective: To examine the characteristics of the prevalence of congenital cleft lip with/without cleft palate in the ethnic Tibetan population and to provide support for the precise prevention and treatment of cleft lip with/without cleft palate in the Tibetan population. Methods: The clinical data of Tibetan patients with cleft lip with/without cleft palate were collected and the clinical characteristics of the patients were analyzed. The patients' age ranged from 2 months to 51 years old. All the subjects were admitted to West China Stomatology Hospital, Sichuan University for the treatment of cleft lip with/without cleft palate between January 2016 and August 2023. Most of the subjects came from Sichuan Province and the Tibet Autonomous Region. Results: A total of 1051 patients were enrolled and children aged under 12 months (460 cases) accounted for the largest proportion. Among the subjects, 383 had cleft lip only (36.44%), 140 had cleft palate only (13.32%), and 528 had cleft lip with cleft palate (50.24%). The male-to-female ratios of patients with cleft lip only (0.99∶1), cleft palate only (0.54∶1), and cleft lip with cleft palate (1.67∶1) exhibited significant differences (P<0.001). However, there was no significant difference in the male-to-female ratio in patients with cleft lip only or those with cleft lip with cleft palate when the subjects were divided into two groups according to whether they had unilateral or bilateral cleft lip with/without cleft palate. Most of the patients with bilateral cleft lip were female, while most of the patients with unilateral cleft lip and unilateral or bilateral cleft lip with cleft palate were male. The unilateral cleft lip with/without cleft palate was located predominantly on the left side. Syndromic cleft lip with/without cleft palate accounted for 3.43% of all the cases and the most common concomitant deformity was congenital heart disease. 3.81% (40 cases) of the patients had a family history. In the patients with cleft lip only and those with cleft palate only, the proportion of patients having parents with corresponding phenotypes was higher than those of other phenotypes of cleft lip with/without cleft palate. Regarding the birth time distribution of the children with cleft lip with/without cleft palate, Spring saw the highest number of births of these children (311 cases, 29.59%), while Winter saw the lowest number of births (231 cases, 21.98%). Conclusion: The cases of cleft lip with/without cleft palate in the ethnic Tibetan population are predominantly cleft lip and palate. Unilateral cleft lip only or cleft lip with palate is predominantly located on the left side. Lip disease phenotypes may be more heritable.

Embosphere microspheres size for bronchial artery embolization in patients with hemoptysis caused by bronchiectasis: a retrospective comparative analysis of 500-750 versus 700-900 µm microspheres.

BACKGROUND: Bronchial arterial embolization (BAE) has been accepted as an effective treatment for bronchiectasis-related hemoptysis. However, rare clinical trials compare different sizes of specific embolic agents. This study aims to evaluate whether different Embosphere microsphere sizes change the outcome of BAE. METHODS: A retrospective review was conducted on consecutive patients with bronchiectatic hemoptysis who were scheduled to undergo BAE treatment during a period from January 2018 to December 2022. The patients received BAE using microspheres of different sizes: group A patients were treated with 500-750 µm microspheres, and group B patients were treated with 700-900 µm microspheres. The cost of embolic microspheres (Chinese Yuan, CNY), duration of hospitalization, complications, and hemoptysis-free survival were compared between patients in group A and those in group B. A Cox proportional hazards regression model was used to identify predictors of recurrent hemoptysis. RESULTS: Median follow-up was 30.2 months (range, 20.3-56.5 months). The final analysis included a total of 112 patients (49-77 years of age; 45 men). The patients were divided into two groups: group A (N = 68), which received 500-750 µm Embosphere microspheres, and group B (N = 44), which received 700-900 µm Embosphere microspheres. Except for the cost of embolic microspheres(group A,5314.8 + 1301.5 CNY; group B, 3644.5 + 1192.3 CNY; p = 0.042), there were no statistically significant differences in duration of hospitalization (group A,7.2 + 1.4 days; group B, 8 + 2.4days; p = 0.550), hemoptysis-free survival (group A, 1-year, 2-year, 3-year, 85.9%, 75.8%, 62.9%; group B, 1-year, 2-year, 3-year, 88.4%, 81.2%,59.4%;P = 0.060), and complications(group A,26.5%; group B, 38.6%; p = 0.175) between the two groups. No major complications were observed. The multivariate analysis results revealed that the presence of cystic bronchiectasis (OR 1.61, 95% CI 1.12-2.83; P = 0.001) and systemic arterial-pulmonary shunts (SPSs) (OR 1.52, 95% CI 1.10-2.72; P = 0.028) were independent risk factors for recurrent bleeding. CONCLUSIONS: For the treatment of BAE in patients with bronchiectasis-related hemoptysis, 500-750 µm diameter Embosphere microspheres have a similar efficacy and safety profile compared to 700-900 µm diameter Embosphere microspheres, especially for those without SPSs or cystic bronchiectasis. Furthermore, the utilization of large-sized (700-900 µm) Embosphere microspheres is associated with the reduced cost of an embolic agent.

Integrative Salt Selection and Formulation Optimization: Perspectives of Disproportionation and Microenvironmental pH Modulation.

We report a novel utilization of a pH modifier as a disproportionation retardant in a tablet formulation. The drug molecule of interest has significant bioavailability challenges that require solubility enhancement. In addition to limited salt/cocrystal options, disproportionation of the potential salt(s) was identified as a substantial risk. Using a combination of Raman spectroscopy with chemometrics and quantitative X-ray diffraction in specially designed stress testing, we investigated the disproportionation phenomena. The learnings and insight drawn from crystallography drove the selection of the maleate form as the target API. Inspired by the fumarate form's unique stability and solubility characteristics, we used fumaric acid as the microenvironmental pH modulator. Proof-of-concept experiments with high-risk (HCl) and moderate-risk (maleate) scenarios confirmed the synergistic advantage of fumaric acid, which interacts with the freebase released by disproportionation to form a more soluble species. The resultant hemifumarate helps maintain the solubility at an elevated level. This work demonstrates an innovative technique to mediate the solubility drop during the "parachute" phase of drug absorption using compendial excipients, and this approach can potentially serve as an effective risk-mitigating strategy for salt disproportionation.

Analysis of Risk Factors for Velopharyngeal Insufficiency and Palatal Fistula After Sommerlad-Furlow Palatoplasty.

This study aimed to introduce a surgery technique-Sommerlad-Furlow palatoplasty (SFP) and analyze the risk factors of velopharyngeal insufficiency (VPI) and palatal fistula after SFP. Cases after SFP under the age of 5 between 2011 and 2021 were reviewed, and the cases with complete follow-up information were included. Univariate and multivariate logistic regression were used to evaluate the effects of surgical age, surgery technique, surgeon's experience, and cleft type on velopharyngeal function and the occurrence of palatal fistula. SFP is a safe and effective procedure to increase the palatal length and reconstruct the levator veli palatini sling. The speech outcome after SFP was associated with cleft type and age at operation. Age = 1.285 years is the best cutoff value. The fistula occurrence was associated with cleft type only.

Preliminary study on reliability and validity of the Chinese version of the Asher-McDade aesthetic index.

OBJECTIVES: This study aims to test the reliability and validity of the Chinese version of the Asher-McDade aesthetic index and clarify its feasibility for the postoperative outcome evaluation of cleft lip in China. METHODS: The Chinese version of the Asher-McDade aesthetic index was established through translation, back translation, debugging, and pre-survey. Eighty postoperative photographs of patients with cleft lip admitted to the West China Hospital of Stomatology, Sichuan University were included. Ten healthcare professionals, including surgeons, nurses, and students, in the department of cleft lip and palate surgery finished the index to test its reliability and validity. RESULTS: The Cronbach's alpha coefficient and retest reliability of this index are 0.804 and 0.895, respectively. The item-level content validity index (I-CVI) and scale-level content validity index ave-rage (S-CVI/ave) of the index are 1.000 and 0.95, respectively. For this index, the Kaiser-Meyer-Olkin (KMO) test score is 0.706, the χ2 value of Bartlett's test for the consistency of the index is 962.260 (P<0.01), and the cumulative variance contribution rate is 63.095%. CONCLUSIONS: The Chinese version of the Asher-McDade aesthe-tic index has good reliability and validity and is applicable to the professional evaluation of the effect of postoperative photographs in Chinese patients with cleft lip.

Review on the Role of IRF6 in the Pathogenesis of Non-syndromic Orofacial Clefts.

Non-syndromic orofacial clefts (NSOCs) are the most common craniofacial malformation. In the complex aetiology and pathogenesis of NSOCs, genetic factors play a crucial role and IRF6, located at chromosome 1q32.2, is the best documented NSOC susceptibility gene. IRF6 is a key factor in oral maxillofacial development and known to contribute the most in NSOCs. It is essential to conduct a complete review of the existing results on IRF6 to further understand its role in the pathogenesis of NSOCs. Thus, the present authors summarised the research progress on the mechanism of IRF6 in NSOCs from both genetic and functional perspectives in this review.

Tumor-targeted delivery of copper-manganese biomineralized oncolytic adenovirus for colorectal cancer immunotherapy.

Oncolytic viral therapy (OVT) is a novel anti-tumor immunotherapy approach, specifically replicating within tumor cells. Currently, oncolytic viruses are mainly administered by intratumoral injection. However, achieving good results for distant metastatic tumors is challenging. In this study, a multifunctional oncolytic adenovirus, OA@CuMnCs, was developed using bimetallic ions copper and manganese. These metal cations form a biomineralized coating on the virus's surface, reducing immune clearance. It is known that viruses upregulate the expression of PD-L1. Copper ions in OA@CuMnCs can decrease the PD-L1 expression of tumor cells, thereby promoting immune cell-related factor release. This process involves antigen presentation and the combination of immature dendritic cells, transforming them into mature dendritic cells. It changes "cold" tumors into "hot" tumors, further inducing immunogenic cell death. While oncolytic virus replication requires oxygen, manganese ions in OA@CuMnCs can react with endogenous hydrogen peroxide. This reaction produces oxygen, enhancing the virus's replication ability and the tumor lysis effect. Thus, this multifunctionally coated OA@CuMnCs demonstrates potent amplification in immunotherapy efficacy, and shows great potential for further clinical OVT. STATEMENT OF SIGNIFICANCE: Oncolytic virus therapy (OVs) is a new anti-tumor immunotherapy method that can specifically replicate in tumor cells. Although the oncolytic virus can achieve a therapeutic effect on some non-metastatic tumors through direct intratumoral injection, there are still three major defects in the treatment of metastatic tumors: immune response, hypoxia effect, and administration route. Various studies have shown that the immune response in vivo can be overcome by modifying or wrapping the surface protein of the oncolytic virus. In this paper, a multifunctional coating of copper and manganese was prepared by combining the advantages of copper and manganese ions. The coating has a simple preparation method and mild conditions, and can effectively enhance tumor immunotherapy.