ChangPu YuJin Tang improves Tourette disorder symptoms by modulating amino acid neurotransmitters in IDPN model rats.

INTRODUCTION: Changpu Yujin Tang(CPYJT), a Chinese herbal compound, is an effective therapeutic strategy for pediatric patients with Tourette disorder (TD). Therefore, this work aims to investigate the therapeutic mechanisms of CPYJT. METHODS: Behavioral and cellular ultrastructural evaluation of the therapeutic effects of CPYJT in TD model rats. Colorimetric methods, reverse transcription­quantitative PCR, and Western Blot were used to measure the altered levels of GLU, GABA, and the levels of VGLUT1, GLUD1, GABRA3, and GAD65 in the cortex, striatum, and thalamus of the TD model rats after 7, 14, 21, and 28 days of CPYJT administration. RESULTS: CPYJT significantly reduced stereotypic behavior and motor behavior scores in TD model rats. CPYJT ameliorates myelin structural damage in TD model rat neuronal cells. CPYJT decreased GLU content, elevated GABA content, decreased GLUD1 and VGLUT1 levels, and elevated GAD65 and GABRA3 levels in TD model rats' cortex, striatum, and thalamus. CPYJT has different regulatory time points in the cortex, striatum, and thalamus for critical factors of amino acid-based neurotransmission. CONCLUSION: CPYJT protects behavioral and structural damage of neuronal cells in multiple brain regions in TD model rats.

Elevated Risk of Adverse Prognosis in Patients with T2-3 Stage Breast Cancer Exhibiting Non-Pathological Complete Response Following Neoadjuvant Chemotherapy: Significance of Regenerating Islet-Derived Family Member 4.

Objective: In this study, we aimed to establish the role of regenerating islet-derived family member 4 (Reg IV) as an independent risk factor and prognostic predictor in patients with T2-3 stage breast cancer who exhibit a non-pathological complete response (non-pCR) following neoadjuvant chemotherapy (NACT). Additionally, we examined the potential correlation and interaction between Reg IV and epidermal growth factor receptor (EGFR). Methods: A total of 67 patients with T2-3 stage breast cancer exhibiting non-pCR after NACT between September 2019 and December 2021 were included in this study. The analysis involved Kaplan-Meier survival comparisons, pooled hazard ratios for risk quantification, Cox regression analysis to isolate the impact of Reg IV on prognosis, Riskplots for visualizing risk profiles, and SHAP analysis to assess the importance of variables in predicting outcomes. Results: The findings indicate that patients positive for Reg IV had a significantly poorer prognosis (HR: 2.62, 95% CI: 1.06-6.47). Co-expression of Reg IV and EGFR was associated with the worst outcomes compared to patients negative for both markers. Cox regression analysis confirmed the independent prognostic impact of Reg IV (HR: 2.63, 95% CI: 1.66-3.59). Riskplot analysis showed that patients positive for both Reg IV and EGFR predominantly experienced disease progression. SHAP analysis further reinforced the significant effect of Reg IV on the disease course, without substantial interaction with EGFR. Conclusion: Reg IV may serve as an independent risk factor and predictive marker for adverse outcomes in patients with T2-3 stage breast cancer who do not achieve non-pCR following NACT.

Analysis of the Dynamic Expression of the SMAD Family in the Periosteum During Guided Bone Regeneration.

OBJECTIVE: The aim of this study was to investigate the dynamic expression of the SMAD family during guided bone regeneration for the reconstruction of cranio-maxillofacial bone defects. METHODS: A swine model of guided bone regeneration was established with one side of the rib as the trauma group and the contralateral as control group. Periosteal and regenerative tissue specimens were harvested at 9 time points in the early, middle, and late phases, and were subjected to gene sequencing and tissue staining. Expression data of each SMAD family were extracted for further analysis, in which the correlation of the expression of the respective members within and between groups and at different time points was analyzed. RESULTS: The expression of individual members of the SMAD family fluctuates greatly, especially during the first month. The SMAD3 and SMAD4 genes were the most highly expressed. The foldchange value of SMAD6 was the largest and remained above 1.5 throughout the process. The dynamic expression levels of SMAD2, SMAD4, SMAD5, SMAD6, and SMAD9 showed a significant positive correlation in both groups. The expression levels of each gene showed a positive correlation with other SMAD genes. Tissue staining showed that the overall contour of the regenerated bone tissue was basically formed within the first 1 month. CONCLUSION: The first month of guided bone regeneration is a critical period for bone regeneration and is an important period for the SMAD family to play a role. The SMAD6 may play an important role in the whole process of guided bone regeneration.

High-power single-frequency continuous-wave 355 nm UV laser via a frequency-correlated dual-wavelength laser.

An all-solid-state single-frequency continuous-wave (CW) 355 nm ultraviolet (UV) laser based on a dispersion-compensated doubly resonant resonator is presented in this Letter that is achieved by employing homemade high-stability all-solid-state frequency-correlated dual-wavelength lasers at 1064 and 532 nm and a temperature-controlled type-I critical-phase-matching LiB3O5 (LBO) to act as the fundamental laser source and the nonlinear medium, respectively. The frequency-correlated dual-wavelength single-frequency CW laser supplies the fundamental frequency 1064 and 532 nm lasers with good frequency synchronization. And the temperature-controlled LBO acts as the dispersion-compensation element to realize double resonance of the 1064 and 532 nm laser. Finally, a 4.2 W high-stability 355 nm UV laser is experimentally obtained, and the corresponding total conversion efficiency is up to 20.5%. To the best of our knowledge, this is the highest power reported about single-frequency CW 355 nm UV laser. The presented method can pave a way to develop a compact single-frequency 355 nm UV laser with high output power.

Dynamic Transcriptome Analysis of SFRP Family in Guided Bone Regeneration With Occlusive Periosteum in Swine Model.

BACKGROUND: A variety of congenital or acquired conditions can cause craniomaxillofacial bone defects, resulting in a heavy financial burden and psychological stress. Guided bone self-generation with periosteum-preserved has great potential for reconstructing large bone defects. METHODS: A swine model of guided bone regeneration with occlusive periosteum was established, the rib segment was removed, and the periosteum was sutured to form a closed regeneration chamber. Hematoxylin and eosin staining, Masson's staining, and Safranine O-Fast Green staining were done. Nine-time points were chosen for collecting the periosteum and regenerated bone tissue for gene sequencing. The expression level of each secreted frizzled-related protein (SFRP) member and the correlations among them were analyzed. RESULTS: The process of bone regeneration is almost complete 1 month after surgery, and up to 1 week after surgery is an important interval for initiating the process. The expression of each SFRP family member fluctuated greatly. The highest expression level of all members ranged from 3 days to 3 months after surgery. The expression level of SFRP2 was the highest, and the difference between 2 groups was the largest. Secreted frizzled-related protein 2 and SFRP4 showed a notable positive correlation between the control and model groups. Secreted frizzled-related protein 1, SFRP2, and SFRP4 had a significant spike in fold change at 1 month postoperatively. Secreted frizzled-related protein 1 and SFRP2 had the strongest correlation. CONCLUSIONS: This study revealed the dynamic expression of the SFRP family in guided bone regeneration with occlusive periosteum in a swine model, providing a possibility to advance the clinical application of bone defect repair.

The effects of temperament type on infusion extravasation in newborns.

Infusion extravasation has an increased incidence in newborns, which can result in various adverse outcomes. This study aimed to investigate the effects of different types of temperament on infusion extravasation in newborns. A total of 209 newborns aged 4-7 days who were treated with infusion therapy were assessed for temperament type using the neonatal behavioral assessment scale score (NBAS). The 2009 Infusion Nurses Society clinical grading criteria for extravasation were used, and the clinical data of the newborns, such as gestational age and body weight, were collected. Out of 209 newborns assessed, 107 developed infusion extravasations, with an incidence rate of 51.2%. Newborns with intermediate temperament type were more prone to develop infusion extravasation. Newborns with low body weight, amniotic fluid aspiration syndrome, or meconium aspiration syndrome were prone to develop infusion extravasation. Body weight, temperament type of consolability, temperament type of peak of excitement, diseases, general temperament type, and NBAS total scores of the neonates were independent risk factors for infusion extravasation. Thus, different types of temperament can have an impact on neonatal extravasation.

Development and validation of a neoadjuvant chemotherapy pathological complete remission model based on Reg IV expression in breast cancer tissues: a clinical retrospective study.

OBJECTIVE: To develop and authenticate a neoadjuvant chemotherapy (NACT) pathological complete remission (pCR) model based on the expression of Reg IV within breast cancer tissues with the objective to provide clinical guidance for precise interventions. METHOD: Data relating to 104 patients undergoing NACT were collected. Variables derived from clinical information and pathological characteristics of patients were screened through logistic regression, random forest, and Xgboost methods to formulate predictive models. The validation and comparative assessment of these models were conducted to identify the optimal model, which was then visualized and tested. RESULT: Following the screening of variables and the establishment of multiple models based on these variables, comparative analyses were conducted using receiver operating characteristic (ROC) curves, calibration curves, as well as net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Model 2 emerged as the most optimal, incorporating variables such as HER-2, ER, T-stage, Reg IV, and Treatment, among others. The area under the ROC curve (AUC) for Model 2 in the training dataset and test dataset was 0.837 (0.734-0.941) and 0.897 (0.775-1.00), respectively. Decision curve analysis (DCA) and clinical impact curve (CIC) further underscored the potential applications of the model in guiding clinical interventions for patients. CONCLUSION: The prediction of NACT pCR efficacy based on the expression of Reg IV in breast cancer tissue appears feasible; however, it requires further validation.

Digitoxin inhibits ICC cell properties via the NF­κB/ST6GAL1 signaling pathway.

Intrahepatic cholangiocarcinoma (ICC) is a type of liver cancer associated with poor prognosis and increased mortality; the limited treatment strategy highlights the urgent need for investigation. Traditional Chinese Medicine (TCM), used alone or in combination with other treatments, can enhance therapeutic efficacy, improve life quality of patients and extend overall survival. In total, two rounds of screening of a TCM library of 2,538 active compounds were conducted using a Cell Counting Kit­8 assay and ICC cell lines. Cell proliferation and migration abilities were assessed through colony formation, 5­ethynyl­2'­deoxyuridine, would healing and Transwell assays. The impact of digitoxin (DT) on signaling pathways was initially investigated using RNA sequencing and further validated using reverse transcription­quantitative PCR, western blotting, lectin blotting and flow cytometry. ICC cells stably overexpressing ST6 ß­galactoside α­2,6­sialyltransferase 1 (ST6GAL1) were generated through lentiviral transfection. It was shown that DT emerged as a highly effective anti­ICC candidate from two rounds high­throughput library screening. DT could inhibit the proliferation and migration of ICC cells by suppressing NF­κB activation and reducing nuclear phosphorylated­NF­κB levels, along with diminishing ST6GAL1 mRNA and protein expression. The aforementioned biological effects and signal pathways of DT could be counteracted by overexpressing ST6GAL1 in ICC cells. In conclusion, DT suppressed ICC cell proliferation and migration by targeting the NF­κB/ST6GAL1 signaling axis. The findings of the present study indicated the promising therapeutic effects of DT in managing ICC, offering new avenues for treatment strategies.

Network Pharmacology Combined with Animal Models to Investigate the Mechanism of ChangPu YuJin Tang in the Treatment of Tourette Syndrome.

BACKGROUND: ChangPu YuJin Tang (CPYJT) is a Chinese herbal formula that has been shown to be an effective therapeutic strategy for pediatric patients with Tourette Syndrome (TS). Using an integrated strategy of network pharmacology and animal model, the aim of this study was to investigate the mechanism of CPYJT in the treatment of TS. METHODS: Compound libraries of CPYJT were established using databases, such as the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). The TCMSP database and Swiss Target Prediction database were used to predict the targets. The above results were constructed into a CPYJT-Drug-Component-Target network. Moreover, TS targets were predicted using GeneCards and other databases. The targets corresponding to the potential ingredients in CPYJT and the targets corresponding to TS were taken as the intersections to construct the CPYJT-TS network. The target network was analysed by PPI using the string database. GO and KEGG enrichment analyses were performed on the target network. The whole process was performed using Cytoscape 3.7.2 to make visual network diagrams of the results. CPYJT was characterised by Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry (UHPLC-MS). Transmission Electron Microscopy (TEM) was used to observe the structural changes of CPYJT on the neuronal cells of the IDPN model rats. RT-PCR and Western Blot were used to analyse the changes in the mRNA and protein expression levels of BDNF, TrkB, PI3K, and AKT in the cortex, striatum, and thalamus brain regions after CPYJT administration in IDPN model rats. RESULTS: Network pharmacology and UHPLC-MS studies revealed that CPYJT acted on the TS through multiple neurotransmitters and the BDNF/TrkB and PI3K/AKT signalling pathways. CPYJT ameliorated neurocellular structural damage in the cortex, striatum, and thalamus of TS model rats. Additionally, CPYJT up-regulated the levels of BDNF, TrkB, PI3k, and AKT in the cortex, striatum, and thalamus of TS model rats. CONCLUSION: It was found that CPYJT protected neuronal cells from structural damage in multiple brain regions and affected the expression levels of BDNF, TrkB, PI3K, and Akt in the cortex, striatum, and thalamus during TS treatment.

Effect of Special Training Method Based on Breathing Meditation Training on Negative Emotions, Job Burnout and Attention in Operating Room Nurses.

Objective: Nurses working in the operating room face high levels of work stress, leading to an increased prevalence of negative emotions and job burnout. These issues not only affect the well-being of nurses, but may also affect the quality of patient care. Therefore, this study aimed to investigate the effect of a special training method based on breathing meditation on negative emotions, job burnout, attention, and caring ability of operating room nurses. Methods: Taking special training time based on breathing meditation training for nurses in the operating room (June 2022) as the dividing point, operating room nurses with routine training from March 2022 to May 2022 were taken as a pre-training group, and operating room nurses who underwent special training of breathing meditation training from June 2022 to August 2022 were enrolled as a post-training group, special training consisted of breathing meditation training for 8 weeks, once a day, 5 days a week. The same group of nurses (n=35) were enrolled before and after training, and 53 patients in each group were included in the two intervention periods for cooperative study. The scores of nurses' negative emotions [Symptom Checklist (SCL-90), Self-Reporting Questionnaire 20 (SRQ-20)], job burnout scores (emotional consumption, depersonalization and personal accomplishment), attention scores (visual attention, auditory attention and audio-visual combination attention) and caring ability (cognition, courage and patience) before and after training and satisfaction of nursing work were compared between the two groups of patients. Results: The data analysis was performed using SPSS 22.0, with chi-squared tests for categorical data, and t-tests (LSD or paired) for continuous data. The scores of SCL-90 and SRQ-20 of nurses in the post-training group were significantly lower than those in the pre-training group (P < .05). The scores of emotional consumption, depersonalization and, personal accomplishment and total score of job burnout of nurses were significantly lower in a post-training group than those in a pre-training group (P < .05). The visual attention, auditory attention, audio-visual combination attention and total attention score of nurses in the post-training group were significantly higher compared with those in a pre-training group (P < .05). The scores of cognition, courage and patience and total score of the caring ability of nurses in the post-training group were significantly higher than those in the pre-training group (P < .05). The satisfaction of nursing work in post-training group (98.11%) was significantly higher than that in the pre-training group (84.91%) (P < .05). The results indicate that the post-training group of nurses experienced significantly lower levels of emotional distress, reduced job burnout, and improved attention and caring abilities compared to the pre-training group. Additionally, their satisfaction with nursing work significantly increased. These findings suggest that the training program had a positive impact on nurses' mental well-being, job performance, and job satisfaction, which is highly relevant for enhancing the quality of patient care in clinical practice. Conclusion: Our findings are consistent with existing literature on the benefits of meditation and mindfulness training in healthcare Settings. These results have practical implications for both operating room nurses and patient care, indicating that breathing meditation training can be used as an effective tool to improve nurses' mental health and work productivity. Although the study sample was limited, these preliminary results provide valuable directions for future research.

Multi-Instance Learning for Vocal Fold Leukoplakia Diagnosis Using White Light and Narrow-Band Imaging: A Multicenter Study.

OBJECTIVES: Vocal fold leukoplakia (VFL) is a precancerous lesion of laryngeal cancer, and its endoscopic diagnosis poses challenges. We aim to develop an artificial intelligence (AI) model using white light imaging (WLI) and narrow-band imaging (NBI) to distinguish benign from malignant VFL. METHODS: A total of 7057 images from 426 patients were used for model development and internal validation. Additionally, 1617 images from two other hospitals were used for model external validation. Modeling learning based on WLI and NBI modalities was conducted using deep learning combined with a multi-instance learning approach (MIL). Furthermore, 50 prospectively collected videos were used to evaluate real-time model performance. A human-machine comparison involving 100 patients and 12 laryngologists assessed the real-world effectiveness of the model. RESULTS: The model achieved the highest area under the receiver operating characteristic curve (AUC) values of 0.868 and 0.884 in the internal and external validation sets, respectively. AUC in the video validation set was 0.825 (95% CI: 0.704-0.946). In the human-machine comparison, AI significantly improved AUC and accuracy for all laryngologists (p < 0.05). With the assistance of AI, the diagnostic abilities and consistency of all laryngologists improved. CONCLUSIONS: Our multicenter study developed an effective AI model using MIL and fusion of WLI and NBI images for VFL diagnosis, particularly aiding junior laryngologists. However, further optimization and validation are necessary to fully assess its potential impact in clinical settings. LEVEL OF EVIDENCE: 3 Laryngoscope, 2024.

Multi-instance learning based artificial intelligence model to assist vocal fold leukoplakia diagnosis: A multicentre diagnostic study.

OBJECTIVE: To develop a multi-instance learning (MIL) based artificial intelligence (AI)-assisted diagnosis models by using laryngoscopic images to differentiate benign and malignant vocal fold leukoplakia (VFL). METHODS: The AI system was developed, trained and validated on 5362 images of 551 patients from three hospitals. Automated regions of interest (ROI) segmentation algorithm was utilized to construct image-level features. MIL was used to fusion image level results to patient level features, then the extracted features were modeled by seven machine learning algorithms. Finally, we evaluated the image level and patient level results. Additionally, 50 videos of VFL were prospectively gathered to assess the system's real-time diagnostic capabilities. A human-machine comparison database was also constructed to compare the diagnostic performance of otolaryngologists with and without AI assistance. RESULTS: In internal and external validation sets, the maximum area under the curve (AUC) for image level segmentation models was 0.775 (95 % CI 0.740-0.811) and 0.720 (95 % CI 0.684-0.756), respectively. Utilizing a MIL-based fusion strategy, the AUC at the patient level increased to 0.869 (95 % CI 0.798-0.940) and 0.851 (95 % CI 0.756-0.945). For real-time video diagnosis, the maximum AUC at the patient level reached 0.850 (95 % CI, 0.743-0.957). With AI assistance, the AUC improved from 0.720 (95 % CI 0.682-0.755) to 0.808 (95 % CI 0.775-0.839) for senior otolaryngologists and from 0.647 (95 % CI 0.608-0.686) to 0.807 (95 % CI 0.773-0.837) for junior otolaryngologists. CONCLUSIONS: The MIL based AI-assisted diagnosis system can significantly improve the diagnostic performance of otolaryngologists for VFL and help to make proper clinical decisions.

Scalp Composite Tissue Transplantation for Repairing Upper Lip Defect: A Feasible Clinical Study.

BACKGROUND: The repair of upper lip defects is difficult and can result in asymmetry. The authors have developed a postauricular scalp composite tissue for the repair of upper lip defects. Herein, the authors, present the feasibility of scalp composite tissue grafts for repairing of upper lip defects. METHODS: The authors conducted a retrospective study of 10 patients who underwent scalp composite tissue transplantation for upper lip repair. The surgical procedure consisted of the excision of skin lesions or scar tissue from the upper lip to prepare the recipient area, and then the scalp composite tissue was excised behind the ear and transplanted to the upper lip defect. The authors reviewed the photographs and clinical notes of these patients. The patients' self-reported satisfaction with the repair effect was assessed. Tissue sections and hematoxylin and eosin staining of the scalp composite tissues were performed. RESULTS: All patients successfully underwent lesion resection and scalp composite tissue transplantation to repair the wound. There was no necrosis of the scalp composite tissue in the early postoperative period. The lip wound healed completely within 2 weeks. The mean follow-up time was 16 months, ranging from 12 to 20 months. Histologic sections and hematoxylin and eosin staining showed that the scalp composite tissue had abundant capillaries and dense fibrous connective tissue. All 10 patients were satisfied with the clinical effect of the procedure. CONCLUSION: Scalp composite tissue transplantation is a viable method for repairing upper lip defects. The special histomorphological characteristics of the scalp provide the basis for clinical application. LEVEL OF EVIDENCE: IV.

XELOX (capecitabine plus oxaliplatin) plus bevacizumab (anti-VEGF-A antibody) with or without adoptive cell immunotherapy in the treatment of patients with previously untreated metastatic colorectal cancer: a multicenter, open-label, randomized, controlled, phase 3 trial.

Fluoropyrimidine-based combination chemotherapy plus targeted therapy is the standard initial treatment for unresectable metastatic colorectal cancer (mCRC), but the prognosis remains poor. This phase 3 trial (ClinicalTrials.gov: NCT03950154) assessed the efficacy and adverse events (AEs) of the combination of PD-1 blockade-activated DC-CIK (PD1-T) cells with XELOX plus bevacizumab as a first-line therapy in patients with mCRC. A total of 202 participants were enrolled and randomly assigned in a 1:1 ratio to receive either first-line XELOX plus bevacizumab (the control group, n = 102) or the same regimen plus autologous PD1-T cell immunotherapy (the immunotherapy group, n = 100) every 21 days for up to 6 cycles, followed by maintenance treatment with capecitabine and bevacizumab. The main endpoint of the trial was progression-free survival (PFS). The median follow-up was 19.5 months. Median PFS was 14.8 months (95% CI, 11.6-18.0) for the immunotherapy group compared with 9.9 months (8.0-11.8) for the control group (hazard ratio [HR], 0.60 [95% CI, 0.40-0.88]; p = 0.009). Median overall survival (OS) was not reached for the immunotherapy group and 25.6 months (95% CI, 18.3-32.8) for the control group (HR, 0.57 [95% CI, 0.33-0.98]; p = 0.043). Grade 3 or higher AEs occurred in 20.0% of patients in the immunotherapy group and 23.5% in the control groups, with no toxicity-associated deaths reported. The addition of PD1-T cells to first-line XELOX plus bevacizumab demonstrates significant clinical improvement of PFS and OS with well tolerability in patients with previously untreated mCRC.

An Innovative Preauricular Free Flap Pedicled with Retrograde Vascular (PFFPRV) for Pediatric Nasal Reconstruction.

SUMMARY: Nasal reconstruction in pediatric patient is very challenging and it requires consideration of later nasal development. Herein, we introduce an innovative preauricular free flap pedicled with retrograde vascular (PFFPRV) for pediatric nasal reconstruction. In this PFFPRV technique, the retrograde superficial temporal vessels were used as the flap pedicle. The lateral alar artery and angular vein were used as vessels of the nasal recipient zone. The flap vessels were anastomosed directly to the recipient area vessels without additional vessel transplantation. Eight pediatric patients with nasal defects underwent this operation. All patients were followed up for more than 2 years. Patients' medical history data were retrospectively analyzed. Preoperative and postoperative facial photos were compared and analyzed. The satisfaction of patient's parents with the aesthetic results was assessed. All patients were successfully operated without intraoperative complications. None of the procedures required additional blood vessel grafts. One patient developed a vascular crisis the next day after the surgery and underwent vascular exploration operation. The free flaps of all patients survived without wound infection or necrosis. The color difference of flap gradually became unobvious. The transplanted flap did not show obvious contracture or retraction, and the nose was symmetrical and developed well. The parents of all patients were satisfied with the surgical results. We think this PFFPRV technique can be a reasonable alternative strategy for reconstruction of pediatric nasal defect, with no adverse effect on nasal development and no need of vascular transplantation. LEVEL OF EVIDENCE: Level IV, therapeutic study.

High Starch Induces Hematological Variations, Metabolic Changes, Oxidative Stress, Inflammatory Responses, and Histopathological Lesions in Largemouth Bass (Micropterus salmoides).

This study evaluated effects of high starch (20%) on hematological variations, glucose and lipid metabolism, antioxidant ability, inflammatory responses, and histopathological lesions in largemouth bass. Results showed hepatic crude lipid and triacylglycerol (TAG) contents were notably increased in fish fed high starch. High starch could increase counts of neutrophils, lymphocytes, monocytes, eosinophils, and basophils and serum contents of TAG, TBA, BUN, and LEP (p < 0.05). There were increasing trends in levels of GLUT2, glycolysis, gluconeogenesis, and LDH in fish fed high starch through the AKT/PI3K signal pathway. Meanwhile, high starch not only triggered TAG and cholesterol synthesis, but mediated cholesterol accumulation by reducing ABCG5, ABCG8, and NPC1L1. Significant increases in lipid droplets and vacuolization were also shown in hepatocytes of D3-D7 groups fed high starch. In addition, high starch could decrease levels of mitochondrial Trx2, TrxR2, and Prx3, while increasing ROS contents. Moreover, high starch could notably increase amounts of inflammatory factors (IL-1ß, TNF-α, etc.) by activating NLRP3 inflammasome key molecules (GSDME, caspase 1, etc.). In conclusion, high starch could not only induce metabolic disorders via gluconeogenesis and accumulation of glycogen, TAG, and cholesterol, but could disturb redox homeostasis and cause inflammatory responses by activating the NLRP3 inflammasome in largemouth bass.

Correction of nasal tip deformity using an island flap of nasal dorsum.

Bifid nose is a rare congenital malformation, and few cases have been reported due to its low incidence. Herein, we report a new surgical procedure to treat patients with excess dorsal nasal tissue and an underfilled tip. A total of 22 patients with bifid nose deformities underwent surgery at our institution between 2012 and 2022. They were characterized by a broad nasal dorsum and a missing or underdeveloped nasal tip. We designed an innovative island flap of nasal dorsum as a new surgical method for treating this bifid nose deformity. Nasal length, tip projection, and photographs of nose morphology were obtained before and after the surgery. Outcomes, complications, indications, and patient satisfaction were analyzed and interviewed. The follow-up time ranges from 6 to 33 months (8.7 ± 5.5 months). The deformity was successfully corrected with an improved nasal appearance. Nasal length increased from initially 4.2 ± 0.3 mm to 4.6 ± 0.3 mm. Tip projection reached 19.9 ± 4.0 mm, which was 15.7 ± 2.9 mm before surgery. No severe complications were observed except poor venous reflux within postoperative 72 hours in four cases. Six patients (27.3%) got moderate healing and acceptable scars, and 14 patients (63.6%) got good healing. Most patients were very satisfied with the outcome (93.9%). The newly designed nasal dorsum island flap is a safe and effective technical approach to correct nose deformity featured by broad nasal dorsum and a missing or underdeveloped nasal tip.

Engineered Luminescent Oncolytic Vaccinia Virus Activation of Photodynamic-Immune Combination Therapy for Colorectal Cancer.

Oncolytic virus therapy is currently regarded as a promising approach in cancer immunotherapy. It has greater therapeutic advantages for colorectal cancer that is prone to distant metastasis. However, the therapeutic efficacy and clinical application of viral agents alone for colorectal cancer remain suboptimal. In this study, an engineered oncolytic vaccinia virus (OVV-Luc) that expresses the firefly luciferase gene is developed and loaded Chlorin e6 (Ce6) onto the virus surface through covalent coupling, resulting in OVV-Luc@Ce6 (OV@C). The OV@C infiltrates tumor tissue and induces endogenous luminescence through substrate catalysis, resulting in the production of reactive oxygen species. This unique system eliminates the need for an external light source, making it suitable for photodynamic therapy (PDT) in deep tissues. Moreover, this synergistic effect between PDT and viral immunotherapy enhances dendritic cell maturation, macrophage polarization, and reversal of the immunosuppressive microenvironment. This synergistic effect has the potential to convert a "cold" into a "hot" tumor, it offers valuable insights for clinical translation and application.

Nasofacial Groove Pedicled Flap for the Reconstruction of Lateral Alar Defect.

BACKGROUND: The repair of nasal alar defects is challenging for plastic surgeons, and there is currently no standard operation. Herein, the authors reported the clinical outcomes of a nasofacial groove pedicled flap for the reconstruction of alar defect. METHODS: This retrospective study included patients who underwent the nasofacial groove pedicled flap for the reconstruction of alar defect between January 2018 and June 2020. Photographs of standard facial postures were taken before and after surgery to record the surgical results of the patients. The patient's medical history was reviewed retrospectively. Self-reported satisfaction of patients on scar morphology and reconstructive effect were evaluated with a questionnaire survey. RESULTS: There were 26 eligible patients enrolled, and all patients were followed up for more than 1 year after surgery. All flaps were free of ischemia and necrosis and healed well. No patient experienced restricted nostril ventilation. Eight patients underwent reoperation to trim the flap pedicle and the scar. Eight patients (8/26) reported "very satisfied," and 17 patients (17/26) reported "satisfied" with the repair effect and scar morphology. One patient went through multiple laser treatments to improve her scars but still remained visible hyperpigmentation. She was dissatisfied with postoperative flap pigmentation but was satisfied with the correction effect. CONCLUSIONS: The clinical results indicated that the nasal groove flap was safe for the treatment of the lateral alar defect, and the patients were satisfied with the clinical results. The authors believe that this flap can be used as an alternative method for repairing the lateral alar defect. LEVEL OF EVIDENCE: Level -IV, therapeutic study.

Effects of selenoprotein extracts from Cardamine hupingshanensis on growth, selenium metabolism, antioxidant capacity, immunity and intestinal health in largemouth bass Micropterus salmoides.

This study aimed to assess the impact of dietary selenoprotein extracts from Cardamine hupingshanensis (SePCH) on the growth, hematological parameters, selenium metabolism, immune responses, antioxidant capacities, inflammatory reactions and intestinal barrier functions in juvenile largemouth bass (Micropterus salmoides). The base diet was supplemented with four different concentrations of SePCH: 0.00, 0.30, 0.60 and 1.20 g/Kg (actual selenium contents: 0.37, 0.59, 0.84 and 1.30 mg/kg). These concentrations were used to formulate four isonitrogenous and isoenergetic diets for juvenile largemouth bass during a 60-day culture period. Adequate dietary SePCH (0.60 and 1.20 g/Kg) significantly increased weight gain and daily growth rate compared to the control groups (0.00 g/Kg). Furthermore, 0.60 and 1.20 g/Kg SePCH significantly enhanced amounts of white blood cells, red blood cells, platelets, lymphocytes and monocytes, and levels of hemoglobin, mean corpuscular volume and mean corpuscular hemoglobin in the hemocytes. In addition, 0.60 and 1.20 g/Kg SePCH increased the mRNA expression levels of selenocysteine lyase, selenophosphate synthase 1, 15 kDa selenoprotein, selenoprotein T2, selenoprotein H, selenoprotein P and selenoprotein K in the fish liver and intestine compared to the controls. Adequate SePCH not only significantly elevated the activities of antioxidant enzymes (Total superoxide dismutase, catalase, glutathione reductase, glutathione peroxidase), the levels of total antioxidant capacity and glutathione, while increased mRNA transcription levels of NF-E2-related factor 2, Cu/Zn-superoxide dismutase, catalase, glutathione reductase and glutathione peroxidase. However, adequate SePCH significantly decreased levels of malondialdehyde and H2O2 and the mRNA expression levels of kelch-like ECH-associated protein 1a and kelch-like ECH-associated protein 1b in the fish liver and intestine compared to the controls. Meanwhile, adequate SePCH markedly enhanced the levels of immune factors (alkaline phosphatase, acid phosphatase, lysozyme, complement component 3, complement component 4 and immunoglobulin M) and innate immune-related genes (lysozyme, hepcidin, liver-expressed antimicrobial peptide 2, complement component 3 and complement component 4) in the fish liver and intestine compared to the controls. Adequate SePCH reduced the levels of pro-inflammatory cytokines (tumour necrosis factor-α, interleukin 8, interleukin 1ß and interferon γ), while increasing transforming growth factor ß1 levels at both transcriptional and protein levels in the liver and intestine. The mRNA expression levels of mitogen-activated protein kinase 13 (MAPK 13), MAPK14 and nuclear factor kappa B p65 were significantly reduced in the liver and intestine of fish fed with 0.60 and 1.20 g/Kg SePCH compared to the controls. Histological sections also demonstrated that 0.60 and 1.20 g/Kg SePCH significantly increased intestinal villus height and villus width compared to the controls. Furthermore, the mRNA expression levels of tight junction proteins (zonula occludens-1, zonula occludens-3, Claudin-1, Claudin-3, Claudin-5, Claudin-11, Claudin-23 and Claudin-34) and Mucin-17 were significantly upregulated in the intestinal epithelial cells of 0.60 and 1.20 g/Kg SePCH groups compared to the controls. In conclusion, these results found that 0.60 and 1.20 g/Kg dietary SePCH can not only improve growth, hematological parameters, selenium metabolism, antioxidant capacities, enhance immune responses and intestinal functions, but also alleviate inflammatory responses. This information can serve as a useful reference for formulating feeds for largemouth bass.