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Yanjie Yang,1,2 Shuang-Yu Lv,2 Bianfei Yu,1 Shuang Xu,1 Jianmin Shen,3 Tong Zhao,1 Haixia Zhang1 1Key Laboratory of Nonferrous Metal Chemistry and Resources Utilization of Gansu Province, Lanzhou University, Lanzhou, Gansu, 2School of Medicine, Henan University, Kaifeng, Henan, 3Institute of Biochemistry and Molecular Biology, School of Life Sciences, Lanzhou University, Lanzhou, Gansu, People’s Republic of China Abstract: Doped ZnS quantum dots (QDs) have a longer dopant emission lifetime and potentially lower cytotoxicity compared to other doped QDs. The liver is the key organ for clearance and detoxification of xenobiotics by phagocytosis and metabolism. The present study was designed to synthesize and evaluate the hepatotoxicity of Mn-doped ZnS QDs and their polyethylene glycol-coated counterparts (1 mg/kg and 5 mg/kg) in mice. The results demonstrated that daily injection of Mn-doped ZnS QDs and polyethylene glycol-coated QDs via tail vein for 7 days did not influence body weight, relative liver weight, serum aminotransferases (alanine aminotransferase and aspartate aminotransferase), the levels of antioxidant enzymes (catalase, glutathione peroxidase, and superoxide dismutase), or malondialdehyde in the liver. Analysis of hepatocyte ultrastructure showed that Mn-doped ZnS QDs and polyethylene glycol-coated QDs mainly accumulated in mitochondria at 24 hours after repeated intravenous injection. No damage to cell nuclei or mitochondria was observed with either of the QDs. Our results indicate that Mn-doped ZnS QDs did not cause obvious damage to the liver. This study will assist in the development of Mn-doped ZnS QDs-based bioimaging and biomedical applications in the future. Keywords: liver, serum aminotransferases, antioxidant enzymes, ultrastructure

Feng Gao,2 Peng Jing,2 Jian Liu,2 Yuanfei Lu,1 Peicheng Zhang,2 Wei Han,1 Guoliang Liu,1 Ning Ru,2 Guanghui Cui,2 Chenglin Sun,1 Yebing Che,1 Huaming Zhang,1 Qnglong Hu,3 Huan-you Wang,4 Yingli Wu,2 Changjiang Guan,2 Qiang Fu,1 Zhenlu Ma,2 Baofa Yu1–3 1Jinan Baofa Cancer Hospital, Jinan, People's Republic of China; 2TaiMei Baofa Cancer Hospital, Dongping, People's Republic of China; 3Beijing Baofa Cancer Hospital, Beijing, People's Republic of China; 4Department of Pathology, UCSD School of Medicine, La Jolla, CA, USAPurpose: To compare the therapeutic effects of ultra-minimum incision personalized intratumoral chemoimmunotherapy (UMIPIC) with intratumoral chemotherapy (ITCT) in the treatment of advanced hepatocellular carcinomas and to analyze the effect of hapten as an immune booster.Materials and methods: Patients with advanced hepatocellular carcinomas were treated with UMIPIC or ITCT with the same therapeutic procedure; the UMIPIC method had a proprietary regimen including an oxidant, a cytotoxic drug, and hapten, while ITCT delivered the same drug excluding hapten. Of 339 patients in total, 119 of the UMIPIC patients (n=214) had response data and 214 had survival data, and of the ITCT patients (n=125), 61 had response data and 125 had survival data. Tumor response was assessed with a computed tomography scan 6–8 weeks after the initial treatment; the survival rate was evaluated by follow-up visits. Tumor size was classified as small (10 cm); tumor sizes with liver function categorized using Child–Pugh class (A and B) were analyzed by correlation with overall survival.Results: The response rates (complete response + partial response + stable disease) were 78.68% and 81.52% in the UMIPIC and ITCT groups, respectively, with no statistically significant difference; however, the median overall survival was 7 months for UMIPIC (test) and 4 months for ITCT (control), respectively (P

Baofa Yu,1–3 Yuanfei Lu,1 Feng Gao,2 Peng Jing,2 Han Wei,1 Peicheng Zhang,2 Guoliang Liu,1 Ning Ru,2 Guanghui Cui,2 Xinhai Xu,1 Chenglin Sun,1 Changjiang Guan,2 Yebing Che,1 Yingli Wu,2 Zhenlu Ma,2 Qiang Fu,1 Jian Liu,2 Huan-You Wang4 1Jinan Baofa Cancer Hospital, Jinan, 2TaiMei Baofa Cancer Hospital, Dongping, 3Beijing Baofa Cancer Hospital, Beijing, People’s Republic of China; 4Department of Pathology, University of California, San Diego, CA, USAAim: The objective of the study reported here was to evaluate the therapeutic effects of hapten-enhanced chemoimmunotherapy in the treatment of advanced lung cancer by ultra-minimum incision personalized intratumoral chemoimmunotherapy (UMIPIC) and to analyze the effect of this immune booster.Materials and methods: A total of 97 patients with advanced lung cancer were treated with UMIPIC or intratumoral chemotherapy (ITCT). UMIPIC was delivered intratumorally in combination with a proprietary therapeutic regimen composed of three components – an oxidant, a cytotoxic drug, and hapten. ITCT applied using the same procedures and regimen, only without hapten. All data from the two groups were reviewed and analyzed. A total of 55 patients were treated with UMIPIC and 42 with ITCT. Patient responses were assessed with computed tomography scan 4–6 weeks after treatment, and all of the patients were followed until their deaths.Results: Median overall survival was 11.23 months in the UMIPIC (test) group and 5.62 months in the ITCT (control) group (P

Background: Orofacial clefts represent the most prevalent form of craniomaxillofacial deformity. Genetic factors are particularly significant in the development of orofacial clefts. This study was to investigate genetic variation in patients with orofacial clefts., Methods: This is a retrospective descriptive study. Whole-exome sequencing (WES) was conducted to identify mutated genes and mutation loci in patients with orofacial clefts. The identified mutation was validated through Sanger sequencing. Furthermore, functional analysis of the mutated gene was performed by utilizing a comprehensive database., Results: The results of WES showed IRF6 was mutated, and the variant locus was IRF6: NM_006147.4, IRF6 c.174+1delG chr1-209974583-ac-a. The variant locus was detected in the patient's mother with orofacial clefts by Sanger sequencing. The Human Gene Database for variant gene shows that the IRF6 gene may be associated with craniomaxillofacial developmental abnormalities., Conclusion: The authors identified a novel locus within the IRF6 gene in a family with orofacial clefts that has not been previously reported. Functional analysis of the mutated gene suggests that this newly discovered mutation site may be associated with the genetic etiology of orofacial clefts in these patients. The findings will provide valuable data for elucidating the molecular mechanisms underlying orofacial clefts., Level of Evidence: IV., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by Mutaz B. Habal, MD.)

Technique: Nostril "Q" deformity is a common postoperative deformity in nasal alar reduction surgery, and there are no clinical reports on its correction. Based on the traditional Z-plasty technique, we designed an asymmetric Z-plasty technique to transfer the triangular mucosal flap inside the nasal cavity to the zone of notch deformity to correct the Q deformity., Results: We included 12 patients in recent years in this study. The patient cohort included 9 females and 3 males, with a mean age of 29 years. The average surgical time for nostril correction was 40 min. The wound healed and sutures were removed normally in all patients 7 days after surgery. The postoperative results were satisfactory and there was no need for a second stage of surgery to correct the nostril morphology. During more than 12 months postoperative follow-up, the patient had good aesthetic results with no recurrence. All patients reported being satisfied with the clinical results., Conclusions: This asymmetric Z-plasty technique, which is a modification of traditional methods, can be used as an effective repair method for iatrogenic nostril "Q" malformation in Asians., Competing Interests: Declaration of competing interest The authors have no conflict of any interest relevant to this article to disclose., (Copyright © 2024 Asian Surgical Association and Taiwan Society of Coloproctology. Published by Elsevier B.V. All rights reserved.)

Objective: To validate the feasibility of an innovative nasal lining-framework complex (NLFC) for reconstructing total nasal defects., Study Design: Retrospective cohort study., Methods: This NLFC is composed of forearm flap and support framework. Twenty-four patients were followed up for a minimum of 17 months in 5 centers. Patients' medical history data were retrospectively analyzed. Visual Analog Scale (VAS) of surgeons and patients was used to evaluate the aesthetic effects and self-satisfaction. The Nasal Obstruction Symptom Evaluation (NOSE) questionnaire and Rhinoplasty Outcome Evaluation (ROE) questionnaire were used for functional assessment., Results: Reconstruction surgeries were all successfully completed. The flaps healed well in all patients, and there were no signs of ischemic necrosis. The healing time of the wound was 10 to 14 days, except for 1 case with infection. The nasal lining was reconstructed and no significant contracture was observed. The average VAS of surgeons was 4.29 ± 0.69 (range 3-5). The mean VAS score of patients was 3.75 ± 0.79 (range 2-5). There was a significant positive correlation between patients' and surgeons' VAS scores (P = .007, r = .5355). The results of the NOSE questionnaire showed that all patients had no obvious ventilation restriction, and only 3 patients mildly felt that the nasal inspirations were slightly insufficient during exercise or exertion. The mean ROE of the patients was 21 ± 1.96 (range 18-25)., Conclusion: This NLFC is suitable for total nasal reconstruction, which can provide effective support to prevent flap collapse and retraction and ensure good nasal ventilation., Level of Evidence: Level IV, therapeutic study., (© 2024 American Academy of Otolaryngology–Head and Neck Surgery Foundation.)

To investigate mRNA Expression profile and associated signaling pathways in the treatment of diabetic foot ulcer healing by tibial cortex transverse distraction. Tissue samples were collected from the wound edge before and after the surgery. After reference genome transcriptome sequencing and subsequent bioinformatics analysis, the differentially expressed genes and related pathways were explored, and functional analysis of important genes and pathways was conducted. qRT-PCR was used to verify the significantly expressed genes-HLA-DRB1, HLA-DRB5, CXCL5 and IGFL1. There were 2441 significantly up-regulated and 3904 significantly down-regulated genes in the postoperative group. The qRT-PCR results showed the expression of HLA-DRB1, HLA-DRB5 and CXCL5 was consistent with the transcriptional sequencing results. CXCL5 and CXCL6 differentially up-regulated genes are involved in the process of neovascularization, and HLA-DRB1 is involved in the improvement of the degree of diabetic peripheral nerve degeneration. Pathway analysis showed that differential genes were most significantly enriched in Adherens junction, Inflammatory mediator regulation of TRP channels and Wnt signaling pathway. Inflammatory mediator regulation of TRP channels is involved in the improvement of peripheral neurodegeneration, VEGF signaling pathway is involved in the process of neovascularization, and Wnt signaling pathway is involved in the process of bone healing. Significantly up-regulated CXCL5 and CXCL6 and enriched VEGF signaling pathway analyzed are involved in postoperative lower limb neovascularization. The HLA-DRB1 and the enriched Inflammatory mediator regulation of TRP channels may be related to the improvement of postoperative peripheral neurodegeneration. The differentially expressed genes and related pathways can provide objective basis for further mechanism study., (© 2024. The Author(s).)

Background: The external nasal alar reduction can be associated with many complications, such as nostril malformation and significant scarring. The authors proposed a 3-part analysis method for the design of nasal alar reduction surgery with the aim of improving nasal alar morphology more precisely., Methods: The 3-part analysis was based on the patient's flared nose, wide nasal base, and drooping ala, respectively. We included 20 patients who underwent this surgery between January 2021 and January 2022. The visual analog scale (VAS) and the Stony Brook Scar Evaluation Scale (SBSES) were used to assess postoperative scar outcomes. The preoperative and postoperative ratios of the interalar distance to intercanthal distance and nostril shape were analyzed. Patient-reported satisfaction with the esthetic outcome was also assessed., Results: All operations were successfully completed. There were no postoperative complications, such as wound infection or skin necrosis. Both VAS and SBSES assessment of postoperative scarring suggested keloid hyperplasia at 3 months postoperatively. At 12 months postoperatively, the scarring was insignificant and improved significantly over 3 months postoperatively. The mean ratio of the interalar distance to intercanthal distance decreased significantly from 1.15 preoperatively to 1.01 postoperatively (P<0.05). The shape of the patient's nostrils was also significantly improved after surgery compared with the preoperative period. Patient-reported satisfaction after surgery was high at long-term follow-up., Conclusions: The 3-part analysis to design an external nasal alar reduction procedure can accurately improve the morphology of nasal flaring, excessively wide nasal alar base, and nasal ptosis in Asian patients., Level of Evidence: IV., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by Mutaz B. Habal, MD.)

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., (Copyright © 2024 by Mutaz B. Habal, MD.)

Gizzerosine is a biogenic amine produced in fish meal drying process and posted higher mortality due to gizzard erosion in poultry than histamine. However, it is difficult to obtain gizzerosine and achieve sensitive practical detection due to its simple structure. Herein, a monoclonal antibody (mAb) specific to gizzerosine was generated based on the new structural design and a fluorescence immunosensor for sensitive and on-site detection of gizzerosine in feed was first established. Molecular modeling of the three-dimensional (3D) structure and surface electrostatic potential of gizzerosine indicated that the carbonyl group of gizzerosine hapten might affect the important sites of antigen-antibody interactions. The proposed structure was used to obtain the sensitive and specific mAb with IC 50 of 3.88 ng/mL in indirect competitive ELISA which was approximately 100-fold lower than that of direct competitive ELISA. Considering the practical application scenarios, a fluorescence immunosensor based on microporous dry method integrated with independent quality control line was established to improve detection stability. Under the optimum conditions, the proposed immunosensor showed a good linear relationship from 1.10 to 19.78 ng/mL and provided a low detection limit of 50 ng/g which was approximately 80-fold lower than the maximum recommended amount (0.4 mg/kg) of gizzerosine in feed. The recoveries of 6 kinds of feed ranged from 83.1 % to 114.3 %, which was in good consistence with that of UHPLC-MS/MS. Overall, this work provides a fast, cost-effective and reliable on-site tool for rapid screening of gizzerosine residues in feed samples., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

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., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by Mutaz B. Habal, MD.)

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., Competing Interests: Conflict of Interest: The authors have no conflict of any interest relevant to this article to disclose., (Copyright © 2024 by the American Society of Plastic Surgeons.)

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., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by Mutaz B. Habal, MD.)

Background: Restricted ventilation is common after rhinoplasty with an endogenous extension stent. The authors proposed an exogenous extension stent concept for Asian rhinoplasty patients to avoid this problem. Herein, we introduce an innovative stent in rhinoplasty for Asians, which is an application of this concept., Methods: An L-shaped expanded polytetrafluoroethylene is hand-carved, and the long arm is placed at the nose back to improve the flatness of the nose, while the short arm supports the nasal column to raise the nose tip. The prosthesis does not occupy nasal volume and therefore theoretically does not affect nasal ventilation. The fan-shaped ear cartilage was placed at the nasal tip to prevent visualization of the nasal tip. The safety and effectiveness of this method were verified through 20 years of clinical practice. The difficulty of learning and popularizing the method was tested through the course of rhinoplasty among 22 plastic surgeons., Results: After 20 years of clinical practice, it was found that this stent could not only effectively improve the nasal dorsum and tip morphology, but also did not actually affect the nasal volume and thus did not affect the nasal ventilation of patients. Among the trainees in plastic surgery, we found that it was not difficult to learn this method of rhinoplasty and the trainees could complete the prosthesis carving well after standardized training., Conclusion: This stent consisting of expanded polytetrafluoroethylene and ear cartilage is suitable in rhinoplasty for Asians with significant advantages, one of which is that it has no risk of resulting in restricted nasal ventilation., Level of Evidence: Level IV., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 by Mutaz B. Habal, MD.)

Background: Current strategies for correcting alar retraction mainly include cartilage grafting and composite grafting, which are relatively complicated and may produce injury to the donor site. Herein, we introduce a simple and effective external Z-plasty technique for correcting alar retraction in Asian patients with poor skin malleability., Methods: Twenty-three patients were presented with alar retraction and poor skin malleability, and they were very concerned about the shape of the nose. These patients undergoing external Z-plasty surgery were analyzed retrospectively. In this surgery, no grafts were needed, and the location of the Z-plasty was according to the highest point of the retracted alar rim. We reviewed the clinical medical notes and photographs. During the postoperative follow-up period, patients' reported satisfaction with aesthetic outcome were also evaluated., Results: The alar retraction of all the patients was successfully corrected. The postoperative mean follow-up period was 8 months (range: 5-28 mo). No incidents of flap loss, recurrence of alar retraction, or nasal obstruction were observed during postoperative follow-up. Within postoperative 3-8 weeks, minor red scarring was visible at the operative incisions in most patients. However, these scars turned unobvious after postoperative 6 months. There were 15 cases (15/23) being very satisfied with the aesthetic outcome of this procedure. Seven patients (7/23) were satisfied with the effect and the invisible scar of this operation. Only one patient was dissatisfied with the scar, but she was satisfied with the correction effect of the retraction., Conclusion: This external Z-plasty technique can be an alternative method for correction of alar retraction with no need of cartilage grafting, and the scar can be unobvious with fine surgical suture. However, the indications should be limited in patients with severe alar retraction and poor skin malleability, who should not particularly care about the scars., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 by Mutaz B. Habal, MD.)

Objective: Nasal tip hypertrophy is common in Asians, and its reshaping is very critical in rhinoplasty. For patients who refuse any implant placed in the nose, there are limited options for tip reshaping. Herein, we introduce a new procedure of nasal tip and alar groove plasty through external nasal cutting in Asians., Methods: A total of 20 patients who had hypertrophic nasal tip and refused to have any implants were included in this study. They were performed this procedure of nasal tip and alar groove plasty through external nasal cutting. The authors carefully reviewed the patients' medical records and preoperative and postoperative photographs. Self-reported satisfactions of patients with the scar morphology and correction effect were assessed at postoperative every follow-up using a questionnaire survey., Results: All of the patients' procedures were completely successful, and the hypertrophic nasal tip was improved. In the long-term postoperative follow-up, the patients' wound showed no abnormalities such as scar contracture deformity, scar bumps, and nasal deformation. In 1 patient, the nasal wound developed significant scarring, and we performed reoperation to remove the superficial scar tissue. Surgical scars in the remaining patients were not obvious. Eight patients (8/20) reported "very satisfied" with scar shape and nasal tip shape improvement results, and 10 patients (10/20) reported "satisfied" with the outcomes., Conclusions: This procedure of nasal tip and alar groove plasty could be an alternative for making the nasal tip more refined. However, the surgical indications for this procedure need to be strictly limited to specific patients., Level of Evidence: Level IV., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 by Mutaz B. Habal, MD.)

Background: Pseudomonas aeruginosa is an opportunistic pathogen, and because of its specificity, its treatments appear tricky in postrhinoplasty infections with internal implants. This study summarizes the clinical characteristics and treatment of this type of infections to provide some reference for clinical work., Methods: We retrospectively analyzed 10 patients who were diagnosed with a nasal infection of P. aeruginosa after implant nasal augmentation. The results of the bacterial culture and drug sensitivity test of the patients' wound secretions were summarized and analyzed. We summarized the characteristics of the patients' infection and the treatments, and we also summarized the patients' prognosis., Results: In these 10 cases, their implants included rib cartilage and ear cartilage alone, as well as their own cartilage combined with expanded polytetrafluoroethylene and silicone. All patients developed wound infections within 1 month after rhinoplasty, with bacterial cultures of P. aeruginosa . Prolonged use of sensitive antibiotics, as well as wound dressing changes, failed to keep the infection well under control. Patients whose implant was removed and thoroughly debrided within 1 week of infection did not experience any serious complications. In patients who were infected for >1 week before surgery to remove the implants, complications such as nasal column necrosis and nasal contracture occurred, and later the nasal repair was performed after multiple surgeries., Conclusions: For bacterial infections in postrhinoplasty wounds with implants, we recommend early bacterial culture. If the infection is clearly P. aeruginosa , the implant should be removed and thoroughly debrided as soon as possible to avoid serious complications., Level of Evidence: Level IV., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 by Mutaz B. Habal, MD.)

Isolated congenital alar rim defects are extremely rare, and there has been no standard technique for the reconstruction of remarkable aesthetic deformity. Herein, we introduce a trifoliate flap for the correction of isolated congenital alar rim defects in pediatric patients. Fifteen cases undergoing nasal alar sulcus rotation flap surgery were analyzed retrospectively. This rotation flap including 3 triangles was a modified flap based on prior studies. Clinical medical notes and photographs were reviewed. Patients' (or their parents) reported satisfactions with aesthetic outcome were also evaluated during the post-operative follow-up period. In all patients, the isolated congenital alar rim defects were successfully reconstructed. The rotation flap survived and the wound healed primarily. The follow-up period ranged from 6 to 22 months (average 11 months). There were no incidents of flap loss, step-off deformities, nasal obstruction, or alar retraction. At follow-up of post-operative 3 months, pale red scars were observed in the operative area in few patients (2/15). However, these scars gradually became invisible at post-operative 6 months. All patients (or their parents) were satisfied with the aesthetic outcome of this operation. This newly designed trifoliate flap can be an alternative method for the reconstruction of isolated congenital alar rim defects in pediatric patients. The scars of this procedure can be unobvious with fine surgical suture., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© 2021 The Author(s).)

Background: Guided bone self-generation with periosteum-preserved has successfully regenerated mandibular, temporomandibular and interphalangeal joint. The aim of this study was to investigate the dynamic changes of gene expression of periosteum which was involved in the guided bone self-generation., Methods: Rib defects of critical size were created in mature swine with periosteum-preserved. The periosteum was sutured into a sealed sheath that closed the bone defect. The periosteum of trauma and control sites were harvested at postoperative 9 time points, and total RNA was extracted. Microarray analysis was conducted to identify the differences in the transcriptome of different time points between two groups., Results: The differentially expressed genes (DEGs) between control and trauma group were different at postoperative different time points. The dynamic changes of the number of DEGs fluctuated a lot. There were 3 volatility peaks, and we chose 3 time points of DEG number peak (1 week, 5 weeks and 6 months) to study the functions of DEGs. Oxidoreductase activity, oxidation-reduction process and mitochondrion are the most enriched terms of Go analysis. The major signaling pathways of DEGs enrichment include oxidative phosphorylation, PI3K-Akt signaling pathway, osteoclast differentiation pathway and Wnt signaling., Conclusions: The oxidoreductase reaction was activated during this bone regeneration process. The oxidative phosphorylation, PI3K-Akt signaling pathway, osteoclast differentiation pathway and Wnt signaling may play important roles in the guided bone self-generation with periosteum-preserved. This study can provide a reference for how to improve the application of this concept of bone regeneration., (© 2023. The Author(s).)

Parry-Romberg syndrome is a rare craniofacial disorder which is characterized by progressive facial atrophy. The etiology and pathogenesis of the disease are not known. Herein, we report the genetic variants in patient with this disease. A 25-year-old woman was diagnosed with Parry-Romberg syndrome according to her clinical manifestation, which presented with typical progressive unilateral facial soft tissue atrophy. Using peripheral blood samples, Whole exome sequencing (WES) was conducted on this patient and her parents. Variant loci of the genes were validated by Sanger sequencing in her twin sister who had no Parry-Romberg syndrome. Subsequently, we searched the GeneCards ® : the Human Gene Database for variant genes, annotated them and analyzed their functions. The results of WES showed that 2 genes (MTOR, DHX37) were mutated, and the variant loci were MTOR: NM&#95;004958.4: exon31: c.4487A>T: p.Q1496L and DHX37: NM&#95;032656.4: exon17: c.2180C>T: p.T727M, respectively. However, the variant loci were also detected in her twin sister by Sanger sequencing. The Human Gene Database for variant genes shows that the two genes may be associated with craniomaxillofacial developmental abnormalities. Although MTOR and DHX37 genes were tested and found to have mutations in patient with Parry-Romberg syndrome, these variants may not directly determine the clinical phenotype. When studying clinical etiology, other factors, such as the environment, should also be taken into account., (© 2023. The Author(s).)

Background: Chronic refractory wounds were common and the treatments were complicated for burn and plastic surgeons. This study was to investigate the bacterial distribution characteristics and bacterial drug resistance of chronic refractory wound secretions., Methods: The authors retrospectively analyzed 425 patients with chronic refractory wound infection. The results of bacterial culture of wound secretions and drug sensitivity test were retrospectively analyzed. Further, the location area of the wound was divided into 4 regions, and the difference of the bacterial culture results between different regions was analyzed., Results: The wound secretions were cultured into 401 bacterial strains, including 206 gram-positive bacteria strains, accounting for 51.4%, with the highest detection rate of Staphylococcus aureus at 26.2% (105/401). There were 195 gram-negative bacteria strains, accounting for 48.6%, with the highest detection rate of Pseudomonas aeruginosa at 14.2% (57/401). There were 6 fungal strains. The proportion of gram-negative bacteria in the III region of the wound zone was significantly greater than that in the other 3 regions., Conclusions: The detection rate of gram-positive bacteria and gram-negative bacteria of chronic refractory wound secretions is not much different. However, in the area close to the perineum (III region), gram-negative bacteria is significantly higher, which has a certain reference value for the use of antibiotics in clinical practice., Level of Evidence: Level 4., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 by Mutaz B. Habal, MD.)

Downregulated DSC2 involved in the metastasis of cancers. Unfortunately, its role on the development of gastric cancer (GC) and the potential mechanisms remain unclear. Bioinformatics analysis, Western blot, qRT-PCR, and immunohistochemistry were performed to detect the DSC2 levels of human GC and normal stomach tissues. The role of DSC2 and the downstream signaling in gastric carcinogenesis were explored by using GC specimens, GC cells with different DSC2 expression, inhibitors, and mouse metastasis models. We found that the level of DSC2 decreased significantly in GC tissues and cells. Recovered DSC2 inhibited the invasion and migration of GC cells both in culture and in xenografts. Mechanistically, DSC2 could not only decrease Snail level and nuclear BRD4 level by forming DSC2/BRD4, but also inhibit nuclear translocation of β -catenin. We concluded that DSC2 inhibited the metastasis of GC, and the underlying mechanisms were closely related to the regulation on nuclear translocation of BRD4 and β -catenin. Our results suggest that DSC2 may serve as a novel therapeutic target for GC., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Chao Sun et al.)

Lung adenocarcinoma (LUAD) is the most challenging neoplasm to treat in clinical practice. Ankyrin repeat domain 49 protein (ANKRD49) is highly expressed in several carcinomas; however, its pattern of expression and role in LUAD are not known. Tissue microarrays, immunohistochemistry, χ 2 test, Spearman correlation analysis, Kaplan-Meier, log-rank test, and Cox's proportional hazard model were used to analyse the clinical cases. The effect of ANKRD49 on the LUAD was investigated using CCK-8, clonal formation, would healing, transwell assays, and nude mice experiment. Expressions of ANKRD49 and its associated downstream protein molecules were verified by real-time PCR, Western blot, immunohistochemistry, and/or immunofluorescence analyses. ANKRD49 expression was highly elevated in LUAD. The survival rate and Cox's modelling analysis indicated that there may be an independent prognostic indicator for LUAD patients. We also found that ANKRD49 promoted the invasion and migration in both in in vitro and in vivo assays, through upregulating matrix metalloproteinase (MMP)-2 and MMP-9 activities via the P38/ATF-2 signalling pathway Our findings suggest that ANKRD49 is a latent biomarker for evaluating LUAD prognosis and promotes the metastasis of A549 cells via upregulation of MMP-2 and MMP-9 in a P38/ATF-2 pathway-dependent manner., (© 2022 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Objective: To investigate the dynamic expression of NFAT family of periosteum in guided bone regeneration process., Material and Methods: The swine ribs on one side were used as the trauma group and the contralateral side as the control group. After rib segment was removed, periosteum was sutured to form a closed cavity mimicking guided bone regeneration. The periosteum and regenerated bone tissue were collected at nine time points for gene sequencing and hematoxylin-eosin staining. The expression data of each member were extracted for analysis. Expression correlations among various members were analyzed., Results: Staining showed the guided bone regeneration was almost completed 1 month after the operation with later stage for bone remodeling. The expression levels of each member in both groups changed greatly, especially within postoperative 1.5 months. The expression of NFATc1 and NFATC2IP in trauma group was significantly correlated with those of control group. The foldchange of each member also had large fluctuations especially within 1.5 months. In the trauma group, NFATc2 and NFATc4 were significantly upregulated, and there was a significant aggregation correlation of NFAT family expression between the various time points within one month, similar to the "pattern-block" phenomenon., Conclusion: This study revealed the dynamic expression of NFAT family in guided bone regeneration, and provided a reference for the specific mechanism. The first 1.5 months is a critical period and should be paid attention to. The significant high-expression of NFATc2 and NFATc4 may role importantly in this process, which needs further research to verify it., (© 2022. The Author(s).)

Lung squamous cell carcinoma (LUSC) is associated with poor clinical outcomes and identifying novel biomarkers that are involved in the progression of LUSC is important for prognosis and targeted treatment. Herein, ankyrin repeat domain 49 (ANKRD49) protein in LUSC versus paired noncancerous lung tissues was tested and its clinical significance was evaluated through χ 2 test, log-rank test, and Cox proportional hazards model. The results showed the ANKRD49 protein in LUSC was elevated and correlated with the tumor-node-metastasis stage, lymph node metastasis, distal metastasis, and differentiation. Patients with higher ANKRD49 had lower overall survival rate and higher ANKRD49 expression in lung tissues may be used as an independent prognostic marker for LUSC patients., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

In this paper, we developed an amplified fluorescence biosensor for acetylcholinesterase (AChE) activity detection by taking advantage of the mercury ion-mediated Mgzyme (Mg 2+ -dependent DNAzyme) activity. The catalytic activity of Mgzyme can be inhibited by the formation of T-Hg 2+ -T base pairs between the Mgzyme and mercury ions. Therefore, the Mgzyme-Hg 2+ complex has no activity on a molecular beacon (MB) substrate, which afforded a very weak fluorescence background for this biosensor. After the addition of acetylcholinesterase (AChE), the substrate acetylthiocholine could be hydrolyzed to thiocholine, which has a stronger binding power with mercury ions than T-Hg 2+ -T base pairs. Therefore, the Mgzyme activity was recovered. The activated Mgzyme could hybridize with the MB substrate and undergo many cleavage cycles, resulting in a significant increase of fluorescence intensity. This biosensor displayed high sensitivity with the detection limit as low as 0.01 mU mL -1 . Moreover, this design did not require complex composition and sequence design; thus it is simple and convenient. This biosensor was also applied for the determination of AChE in human blood and showed satisfactory results.

Large eyelid defect after excision of malignancies or trauma is difficult to reconstruct due to special structure and function of the eyelid. In this study, we aimed to present the outcomes of subcutaneous pedicled propeller flap for reconstructing the large eyelid defect after excision of malignancies or trauma. A retrospective review of patients diagnosed with eyelid defect due to excision of malignancies or trauma, and undergoing subcutaneous pedicled propeller flap for reconstructing the large eyelid defect, was conducted at our hospital. The clinical data were collected and analyzed. A total of 15 patients were included in the cases series. Nine patients were diagnosed with basal cell carcinoma, 3 patients with epidermoid carcinoma, and 3 patients with trauma. All the defects were successfully covered with this designed flap. There was no flap necrosis in all the cases. No functional problems were observed in all of the cases. At long-term postoperative follow-up, the average score of patients' satisfaction was good. This subcutaneous pedicled propeller flap is a feasible alternative technique for reconstructing the large eyelid defect after excision of malignancies or trauma. This flap option could avoid the use of free flaps for large defect., (© 2022. The Author(s).)

Background: According to Tessier classification, number 1 and number 2 craniofacial clefts involve the nasal ala. Congenital nasal cleft is not common and is difficult for reconstruction. Notches in the medial one-third of either nasal ala are typical manifestations in these patients. Herein, we introduce a alar rim triangular flap, which is indeed a local flap, for the treatment of isolated nasal cleft due to congenital deformities in pediatric patients., Methods: The authors conducted a retrospective cohort study including 10 consecutive pediatric patients undergoing this surgery. This alar rim triangular flap including 2 triangles was existing nasal tissue near the cleft. The alar rim defect was covered through local tissue re-arrangement. The authors reviewed the photographs and clinical medical notes of these patients carefully. Self-reported satisfactions of patients (or children's parents) with the scar morphology and correction effect of this procedure were evaluated as well at postoperative every follow-up., Results: All the cases were followed up regularly, and the average follow-up time was 22 months (ranged from 13-38 months). All the nasal clefts were reconstructed successfully. The alar rim triangular flap survived with no flap loss. The wound created by this procedure healed primarily. No alar retraction, nasal obstruction or step-off deformities were observed during postoperative follow-up. There were no patients unsatisfied with the outcome of the scar morphology and correction effect of this operation., Conclusions: The newly designed alar rim triangular flap in this study can be an alternative treatment for correcting isolated congenital nasal cleft with optimal clinical outcome., Level of Evidence: Level 4., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 by Mutaz B. Habal, MD.)

Background: Obvious scar and deformities are commonly observed with incision anterior to the alar-facial groove in alar excision surgery. The authors explored modified sill and alar excision to correct wide alar base and flare synchronously and decreased incident of unacceptable scar and deformities in Asian patients., Methods: The authors conducted a retrospective cohort study including 52 consecutive patients undergoing this surgery. Contrary to previous studies, the incision for alar excision was located in the alar-facial groove and was closed by intracutaneous suture. Scars were assessed with visual analog scale and the Stony Brook Scar Evaluation Scale. Ratio of the interalar distance to intercanthal distance, nostril shape, and nostril symmetry was recorded., Results: The mean follow-up time was 18 months. Visual analog scale results showed 50 patients (96.2%) reported unnoticeable scar and 2 noticeable but acceptable scar. Stony Brook Scar Evaluation Scale results indicated 49 patients (94.2%) with good scar outcomes and 3 (5.8%) with moderate scar outcomes. The mean ratio of interalar distance to intercanthal distance reduced significantly from preoperative 1.10 to postoperative 1.02. The frequency of horizon-shaped nostrils changed from preoperative 16 cases (30.8%) to postoperative 2 cases (3.8%). The frequency of the pear-shaped (preferred shape) nostrils improved from preoperative 15 cases (28.8%) to postoperative 26 cases (50.0%). The frequency of symmetrical nostril shape improved from preoperative 36 patients (69.2%) to 42 (80.8%). There were no patients with complications like alar deformities, and patients' dissatisfaction., Conclusions: When performing sill and alar excision in Asian patients, the authors recommended a modified approach with the incision for alar excision being placed in the alar-facial groove and closed by intracutaneous suture, which can avoid obvious scar and deformities in Asian patients.Level of evidence: Level 4., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 by Mutaz B. Habal, MD.)

Despite extensive research, the exact mechanisms involved in colorectal cancer (CRC) etiology and pathogenesis remain unclear. This study aimed to examine the correlation between tumor-associated alternative splicing (AS) events and tumor immune infiltration (TII) in CRC. We analyzed transcriptome profiling and clinical CRC data from The Cancer Genome Atlas (TCGA) database and lists of AS-related and immune-related signatures from the SpliceSeq and Innate databases, respectively to develop and validate a risk model of differential AS events and subsequently a TII risk model. We then conducted a two-factor survival analysis to study the association between TII and AS risk and evaluated the associations between immune signatures and six types of immune cells based on the TIMER database. Subsequently, we studied the distribution of six types of TII cells in high- and low-risk groups for seven AS events and in total. We obtained the profiles of AS events/genes for 484 patients, which included 473 CRC tumor samples and 41 corresponding normal samples, and detected 22581 AS events in 8122 genes. Exon Skip (ES) (8446) and Mutually Exclusive Exons (ME) (74) exhibited the most and fewest AS events, respectively. We then classified the 433 patients with CRC into low-risk (n = 217) and high-risk (n = 216) groups based on the median risk score in different AS events. Compared with patients with low-risk scores (mortality = 11.8%), patients with high-risk scores were associated with poor overall survival (mortality = 27.6%). The risk score, cancer stage, and pathological stage (T, M, and N) were closely correlated with prognosis in patients with CRC ( P < 0.001). We identified 6479 differentially expressed genes from the transcriptome profiles of CRC and intersected 468 differential immune-related signatures. High-AS-risk and high-TII-risk predicted a poor prognosis in CRC. Different AS types were associated with different TII risk characteristics. Alternate Acceptor site (AA) and Alternate Promoter (AP) events directly affected the concentration of CD4T cells, and the level of CD8T cells was closely correlated with Alternate Terminator (AT) and Exon Skip (ES) events. Thus, the concentration of CD4T and CD8T cells in the CRC immune microenvironment was not specifically modulated by AS. However, B cell, dendritic cell, macrophage, and neutrophilic cell levels were strongly correlated with AS events. These results indicate adverse associations between AS event risk levels and immune cell infiltration density. Taken together, our findings show a clear association between tumor-associated alternative splicing and immune cell infiltration events and patient outcome and could form a basis for the identification of novel markers and therapeutic targets for CRC and other cancers in the future., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Shi, Bi, Yu, Wang, Teng and Wu.)

Objective: To assess the effect and complications of tibial cortex transverse distraction (TCTD) in treating diabetic foot ulcers and draw attention to the concerning issues of this procedure., Methods: This case series included 30 patients with diabetic foot ulcers from four centers. The ulcers had not healed after >6 months. The patients then underwent TCTD combined with other procedures (debridement, vacuum sealing drainage, and others). All patients were followed up for >12 months postoperatively., Results: Three patients underwent amputation because of aggravated infections. Tibial fractures occurred in two patients after surgery, and the fractures healed after 3 months of plaster fixation. Pin-site infections occurred in five patients, and the infected pin site healed after the patients underwent pin removal and dressing changes for 3.3 ± 2.1 weeks. The ulcers of the other 27 patients healed by 13.5 ± 8.2 weeks postoperatively, and the postoperative visual analog scale score was significantly lower than the preoperative score., Conclusions: Although TCTD can be performed as an adjuvant treatment for diabetic foot ulcers, the effect should not be exaggerated and the complications should not be ignored. Further research is needed to propose a standard operative procedure and avoid postoperative complications such as tibial fractures.

Objective: To evaluate the feasibility of locked intramedullary nailing, rather than locking plate fixation combined with fibular allograft augmentation, for initial varus proximal humeral fractures., Methods: This prospective pilot study enrolled patients with initial varus proximal humeral fractures that were treated with a locking intramedullary nail. Radiography was performed to evaluate fracture healing. Data about the visual analogue scale (VAS) pain score, Constant Shoulder Score (CSS), Disabilities of the Arm, Shoulder and Hand (DASH) score, American Shoulder and Elbow Surgeons (ASES) score and shoulder range of motion (ROM) were recorded., Results: Twenty patients, including eight with Neer two-part and 12 with three-part fractures, were followed-up, with a mean time of 12.3 months. All patients sustained fractures that healed without re-varus. During the last follow-up, the shoulder function of the patients had recovered well, with a mean VAS pain score of 1.4, a mean CSS of 83.1, a mean DASH score of 80.8, a mean ASES score of 84.0 and a satisfactory ROM. In one patient, the proximal locking screw came out and was removed via a second surgery., Conclusions: The use of a locking intramedullary nail alone for initial varus proximal humeral two-/three-part fractures was feasible. This treatment has advantages, such as preventing re-varus and causing milder surgical trauma, than that seen with a locking plate.

Purpose: The study was to explore whether the 3-dimensional printing guiding plate system could facilitate the modified procedure for arthroscopic treatment of nondisplaced scaphoid nonunion., Methods: Patients, diagnosed with scaphoid nonunion without displacement, were randomly assigned into two groups. In Group A, the 3-dimensional printing guiding plate system was used for guiding fixation during the surgery. In Group B, fixation was performed with intra-operative fluoroscopy. The bone operation time was recorded during the surgery. The patients were evaluated before surgery and followed-up after six post-operative months, including motion ratio, strength ratio, Visual Analogue Scale, modified Mayo Scores, Patient Rated Wrist Evaluation scores, plain radiography and CT scan., Results: Sixteen patients were recruited for the study. The average bone operation time in Group A was statistically shorter than that in Group B., Conclusions: 3-dimensional printing technique-assisted arthroscopic bone graft and fixation of scaphoid nonunion constitute an effective and accurate clinical treatment option., The Translational Potential of This Article: The concept and technique of 3D printing assisted percutaneous fixation introduced in this paper have the potential to be applied in a variety of operations requiring accurate percutaneous fixation, especially for the joint injuries., Competing Interests: The authors have no conflicts of interest to disclose in relation to this article., (© 2020 The Authors.)

The ulnar-sided approach for arthroscopic peripheral triangular fibrocartilage complex (TFCC) repair may be associated with injury to the dorsal branch of the ulnar nerve (DBUN). The goal of this study was to develop a small incision to help minimize DBUN injury. Ten cadaveric upper limbs were used to measure the anatomic parameters of the DBUN. Based on these measured anatomical relationships, a 20 mm longitudinal incision with the ulnar styloid process as the midpoint was designed to explore and protect the DBUN. Three additional cadaveric upper limbs were used to test the feasibility of this method. Then this method was applied in 15 patients with TFCC injury (IB type). In 10 cadavers, the DBUN was located volar to the ulnar styloid process. The mean linear distance between the DBUN and the ulnar styloid process was 8.04 mm (range: 7.02-8.82mm) in the transverse-volar direction and 13.78 mm (range: 11.06-16.02mm) in the longitudinal-distal volar direction. In three additional cadavers, the DBUN was successfully explored and retracted with this incision, creating a safer space for passing sutures and tying knots. This modified method was used successfully in 15 patients, and the DBUN was protected during surgery. There were no complications, and most importantly, no injuries to the DBUN at the 6-month follow-up visit. Therefore, we recommend that a 20 mm longitudinal incision with the ulnar styloid process as the midpoint be made prior to passing sutures during the arthroscopic repair of TFCC tears to avoid injuring the various branches of the DBUN., (Copyright © 2019 SFCM. Published by Elsevier Masson SAS. All rights reserved.)

Introduction: We previously reported transferring seventh cervical (C7) nerve from unaffected side to affected side in patients with spastic hemiplegia due to chronic cerebral injury, to improve function and reduce spasticity of paralyzed upper limb. In the clinics, some patients also reported changes of spasticity in their lower limb, which could not be detected by routine physical examinations. Pennation angle of muscle can indirectly reflect the condition of spasticity. The purpose of this study was to evaluate whether this upper limb procedure may affect spasticity of lower limb, using ultrasonography to detect changes of muscle pennation angle (PA)., Methods: Twelve spastic hemiplegia patients due to cerebral injury including stroke, cerebral palsy, and traumatic brain injury, who underwent C7 nerve transfer procedure, participated in this study. B-mode ultrasonography was used to measure PA of the gastrocnemius medialis (GM) muscle at rest preoperatively and postoperatively. The plantar load distribution of the lower limbs was evaluated using a Zebris FDM platform preoperatively and postoperatively., Results: The PA of the GM was significantly smaller on the affected side than that of unaffected side before surgery. On the affected side, the postoperative PA was significantly larger than preoperative PA. On the unaffected side, the postoperative PA was not significantly different compared to preoperative PA. The postoperative plantar load distribution of the affected forefoot was significantly smaller than preoperative load distribution, which was consistent with ultrasonography results., Conclusions: This study indicates that C7 nerve transfer surgery for improving upper limb function can also affect muscle properties of lower limb in spastic hemiplegia patients, which reveals a link between the upper and lower limbs. The interlimb interactions should be considered in rehabilitation physiotherapy, and the regular pattern and mechanism need to be further studied., (© 2019 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.)

Background: Endogenous α-synuclein (α-Syn) is involved in many pathophysiological processes in the secondary injury stage after acute spinal cord injury (SCI), and the mechanism governing these functions has not been thoroughly elucidated to date. This research aims to characterize the effect of α-Syn knockdown on transcriptional levels after SCI and to determine the mechanisms underlying α-Syn activity based on RNA-seq., Result: The establishment of a rat model of lentiviral vector-mediated knockdown of α-Syn in Sprague-Dawley rats with T3 spinal cord contusion (LV&#95;SCI group). The results of the RNA-seq analysis showed that there were 337 differentially expressed genes (DEGs) between the SCI group and the LV&#95;SCI group, and 153 DEGs specific to LV&#95;SCI between the (SCI vs LV&#95;SCI) and (SCI vs CON) comparisons. The top 20 biological transition terms were identified by Gene ontology (GO) analysis. The Kyoto Gene and Genomic Encyclopedia (KEGG) analysis showed that the LV&#95;SCI group significantly upregulated the cholinergic synaptic & nicotine addiction and the neuroactive ligand receptor interaction signaling pathway. Enriched chord analysis analyzes key genes. Further cluster analysis, gene and protein interaction network analysis and RT-qPCR results showed that Chrm2 and Chrnb2 together significantly in both pathways. The proliferation of muscarinic cholinergic receptor subtype 2 (Chrm2) and nicotinic cholinergic receptor subtype β2 (Chrnb2), and the neurogenesis were elevated in the injury site of LV&#95;SCI group by immunofluorescence. Further by subcellular localization, the LV&#95;SCI group enhanced the expression of Chrnb2 at the cell membrane., Conclusion: Knockdown of α-Syn after SCI enhance motor function and promote neurogenesis probably through enhancing cholinergic signaling pathways and neuroreceptor interactions. This study not only further clarifies the understanding of the mechanism of knockdown of α-Syn on SCI but also helps to guide the treatment strategy for SCI.

Background: Flap transplantation is often needed for soft tissue defects of the fingers that cannot be closed directly. Sensory reconstruction of the fingers is important for patients to recover feelings. In this study, we report clinical outcomes of using free neurovascular transverse wrist crease flap for repairing finger defects from multiple centers., Methods: This case series includes 72 consecutive patients with finger defects between June 2013 and June 2016 from multiple centers. A neurovascular transverse free radial artery superficial palmar branch flap, named transverse wrist crease flap, was designed to reconstruct soft tissue defects of the fingers with microvascular anastomosis. When there were soft tissue defects of the fingers with digital nerve defect, end-to-end neurorrhaphy between the median palmar cutaneous branch and the digital nerves was also performed. The donor incision was sutured directly. All the patients were followed-up for more than 24 months., Results: The soft tissue defects of the fingers were all completely covered with this free neurovascular transverse wrist crease flap, and the flaps in 71 patients survived completely without ischemia. Vascular crisis appeared in one case, and the wound healed gradually after changing wound dressing for nearly 1 month. Slight infections of wounds appeared in eight cases. There were no complications in the donor site, like infection and poor wound healing. At the last follow-up, the mean static two-point discrimination was 9.6 ± 2.4 mm on the injured finger and 4.5 ± 0.8 on the contralateral corresponding finger. The motion range of the distal interphalangeal joint and proximal interphalangeal joint on the injured finger were 72.5 ± 23.3% and 78.7 ± 32.5% of the contralateral corresponding finger, respectively. Patient self-evaluations were good in 53 cases and fair in 19 cases., Conclusions: The results indicate that the free neurovascular transverse wrist crease flap is a good choice for repairing soft tissue defects of the fingers., Level of Evidence: Therapeutic IV.

Spermatogenesis is a complicated process that is tightly regulated by the well-coordinated expression of a series of genes in the testes. Ankyrin repeat domain-containing protein 49 (ANKRD49), an evolutionarily conserved protein highly expressed in the testes, is mainly found in spermatogonia, spermatocytes, and round spermatids. However, the exact function of ANKRD49 in spermatogenesis has remained elusive. In this study, we sought to investigate the role of ANKRD49 in apoptosis and determine the mechanism underlying this process in male germ cell-derived GC-1 cells. Nuclear staining with Hoechst 33258 and annexin V-FITC/PI, as well as analysis of caspase 3 activity, mitochondrial membrane potential, and apoptotic protein expression, showed that etoposide-induced apoptosis was attenuated by ANKRD49 overexpression but promoted by RNA interference-induced ANKRD49 knockdown. Furthermore, assessment of the levels of caspase 9, caspase 8, and proteins of the Bcl-2 family revealed ANKRD49 to be involved in an intrinsic apoptosis pathway. Examination of the subcellular distribution of the NF-κB p65 subunit after treatment with an NF-κB signaling inhibitor or p65 small interfering RNA demonstrated that ANKRD49 modulated etoposide-induced GC-1 cell apoptosis via the NF-κB pathway. Taken together, these results suggest that ANKRD49 plays an important role in reducing intrinsic apoptosis of GC-1 cells by modulating the NF-κB signaling pathway.

Objective: To report the methods and clinical outcomes of microscopic minimally invasive keyhole technique for surgical resection of thoracic spinal meningiomas. Methods: Thirty-nine patients with thoracic spinal meningiomas received keyhole surgery from May 2013 to June 2017 in the Department of Spine Surgery, Fujian Provincial Hospital. A working channel with a diameter of 1.8 cm was inserted percutaneously about 2.0 to 3.5 cm away from the mid-line. Dorsally attached tumors were resected with hemilaminectomy fenestration; for the spinal meningiomas located in the lateral side of the spinal cord, hemilaminectomy combined with partial facetectomy were used; hemilaminectomy combined with hemifacetectomy fenestration were used for spinal meningiomas located ventrally. No internal fixation was performed in all cases. Clinical outcome was assessed using the visual analog scale (VAS) for pain relief and the American Spinal Injury Association (ASIA) scale for evaluation of the function of the spinal cord after surgery. The pre-and post-operative data were compared by paired t test. Results: Among the 39 patients, the tumors in 36 cases located in the thoracic spine and 3 in the cervicothoracic junction. Complete resection was achieved in all patients. Mean operative time was (148±21) min (range, 120-185 min). Mean blood loss during surgery was (101±27) ml (range, 50-200 ml). No infection or aggravation of spinal cord injury occurred after operation, except for 3 patients who had postoperative cerebrospinal fluid leakage that recovered after conservative treatment. The mean hospital stay was (6.1±0.8) days (range, 5-9 days). Patients were followed-up for a period of 9 to 57 months, with a mean follow-up time of (29±13) months. At the last follow-up, all patients had a reduced level of pain as suggested by an average VAS score that improved from (7.38±1.71) to (0.31±0.63), the ASIA grade improved in all patients except for 2 cases (5.1%), 24 cases (61.5%) improved by 1 grade, 9 cases (23.1%) improved by 2 grades, and 4 cases (10.3%) improved by 3 grades. No evidence of tumor recurrence or secondary spinal instability was observed in any patients during the postoperative follow-up. Conclusion: Microscopic minimally invasive keyhole technique can be used to completely resect the thoracic spinal meningiomas; such surgical procedures convey reliable clinical outcomes and good postoperative spinal stability.

Objective: LncRNA downregulated in liver cancer stem cells (lnc-DILC) has been implicated as a tumor suppressor in colorectal cancer (CRC). However, the clinical significance of lnc-DILC in CRC patients has not been investigated. In this study, we aimed to explore the diagnostic and prognostic value of lnc-DILC in CRC patients., Patients and Methods: The expression of lnc-DILC was measured in 174 paired CRC tissues and adjacent normal tissues using Real Time-Polymerase Chain Reaction (RT-PCR). The correlation of lnc-DILC expression with clinicopathological factors was statistically analyzed by the Chi-square test. Besides, overall survival analysis was carried out with the Kaplan-Meier curve with the log-rank test. Univariate and multivariate analyses were performed to explore the prognostic significance of lnc-DILC expression., Results: We found that lnc-DILC expression was downregulated in CRC tissues compared to their adjacent normal tissues (p<0.01). ROC analyses showed that lnc-DILC levels were reliable in distinguishing patients with CRC from normal colorectal tissues. Then, down-regulation of lnc-DILC was positively associated with aggressive clinical characteristics, including depth of invasion (p=0.018) and advanced TNM stage (p=0.009). Moreover, the Kaplan-Meier analysis demonstrated that overexpression of lnc-DILC was associated with poorer overall survival (p=0.0205) and disease-free survival (p<0.001). Finally, multivariate analyses confirmed that expression of lnc-DILC was an independent prognostic factor in CRC., Conclusions: Our results firstly suggested that lnc-DILC could be a favorable indicator of prognosis in CRC.

Earthworms are useful indicator organisms of soil health and Eisenia fetida have been extensively used as test organisms in ecotoxicological studies. In order to gain insight into the gene expression profiles associated with physiological functions of earthworms, a full‑length enriched cDNA library of the Eisenia fetida genome was successfully constructed using Switching Mechanism at 5'End of RNA Template technology. Construction of a cDNA library and analysis of Expressed Sequence Tags (ESTs) are efficient approaches for collecting genomic information and identifying genes important for a given biological process. Furthermore, analysis of the expression abundance of ESTs was performed with the aim of providing genetic and transcriptomic information on the development and regenerative process of earthworms. Phrep and Crossmatch were used to process EST data and a total of 1,140 high‑quality EST sequences were determined by sequencing random cDNA clones from the library. Clustering analysis of sequences revealed a total of 593 unique sequences including 225 contiguous and 368 singleton sequences. Basic Local Alignment Search Tool analysis against the Kyoto Encyclopedia of Genes and Genomes database resulted in 593 significant hits (P‑value <1x10‑8), of which 168 were annotated through Gene Ontology analysis. The STRING database was used to determine relationships among the 168 ESTs, identifying associated genes involved in protein‑protein interactions and gene expression regulation. Based on nucleic acid and protein sequence homology, the mutual relationships between 287 genes could be obtained, which identified a portion of the ESTs as known genes. The present study reports on the construction of a high‑quality cDNA library representative of adult earthworms, on a preliminary analysis of ESTs and on a putative functional analysis of ESTs. The present study is expected to enhance our understanding of the molecular basis underlying the biological development of earthworms.

Objective: The aim of this study was to evaluate the safety and efficacy of the microscopic minimally invasive keyhole technique for surgical resection of thoracic spinal meningiomas., Methods: Seventeen consecutive patients with thoracic spinal meningiomas were included in the series from May 2015 to August 2017. All patients were treated using a microscopic keyhole technique through a tubular retractor system. The demographic data and perioperative variables were recorded. At last follow-up, clinical outcome was assessed using the visual analog scale for pain and the American Spinal Injury Association scale for motor and sensory outcome., Results: All patients underwent microscopic keyhole surgery and complete resection was achieved. Mean operative time was 153.2 minutes (range 115-300 minutes). Mean blood loss during surgery was 110.3 mL (range 50-175 mL). No infection or aggravation of spinal cord injury occurred after operation, except for 2 patients who had postoperative cerebrospinal fluid leakage that recovered after conservative treatment. The mean duration of hospital stay was 6.8 days (range 5-10 days). At the last follow-up, all patients had a reduced level of pain as suggested by an average visual analog scale score that improved from 7.6 to 0.2. The American Spinal Injury Association grade improved or remained normal in all patients except 1. No evidence of tumor recurrence or secondary spinal deformity was observed in any patients during the postoperative follow-up period, and spinal stabilities were found to be satisfactory., Conclusions: Based on our results, the microscopic minimally invasive keyhole technique can be used safely and effectively for resection of thoracic spinal meningiomas., (Copyright © 2019 Elsevier Inc. All rights reserved.)

In this paper, by taking advantage of the fact that silver ions could mediate the Mg2+-dependent DNAzyme (Mgzyme) activity, we for the first time developed a turn-on fluorescent biosensor for amplified cysteine (Cys) detection. Because Mgzyme can interact with the silver ion and form cytosine-Ag+-cytosine (C-Ag+-C) base pairs, the conformation of its catalytic core was changed. As a result, the catalytic activity of Mgzyme was suppressed and the Mgzyme-Ag+ complex could not initiate the cleavage reaction. Therefore, the background fluorescence of the biosensor was very low. In the presence of Cys, Cys can bind tightly to the silver ion and disrupt the C-Ag+-C base pairs in the Mgzyme-Ag+ complex, leading to the restoration of Mgzyme activity. The activated Mgzyme could hybridize with the MB substrate and undergo many cleavage cycles, resulting in a significant increase of fluorescence intensity. This designed strategy provided amplified fluorescence detection of cysteine, with a detection limit of 2 nM. Moreover, the strong binding between Cys and Ag+ ensured that the biosensor had a desirable selectivity for Cys. This sensing system was also used to detect Cys in human urine samples and displayed satisfying results.

Background: Spasticity and muscle weakness are common severe neurologic sequelae after stroke. Contralateral peripheral neurotization has been applied successfully to promote motor function of the hemiplegic upper extremity in patients with central neurological injury. To our knowledge, we present the first report of contralateral lumbar to sacral nerve transfer for the lower extremities in hemiplegic patients after stroke., Case Description: Two patients were enrolled in the study. The first patient is a 57-year-old man who experienced permanent muscle weakness in his left leg after a right cerebral infarction. The second patient is a 42-year-old man who had spasticity and hemiplegia in both upper and lower limbs on the right side 32 months after a left cerebral hemorrhage. Both patients underwent contralateral lumbar-to-sacral nerve rerouting to improve lower-limb motor function. Twenty months after surgery, both patients experienced significant improvement in ambulatory status., Conclusions: Although long-term follow-up and a randomized controlled trial are required, this study demonstrates the safety and possible benefits of contralateral lumbar-to-sacral nerve transfer for hemiplegic patients after stroke. This novel surgical approach could provide a new means for lower-limb motor functional recovery., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Club cell protein (CC16) is expressed primarily by club cells possesses anti‑inflammatory properties and is located in the bronchiolar epithelium. Previous studies have demonstrated that CC16 deficiency is associated with the progression of chronic obstructive pulmonary disease (COPD). In the present study, the therapeutic effects of recombinant rat CC16 protein in mice with COPD were examined and the underlying mechanisms investigated. A total of 30 adult male C57/BL6 mice were randomly divided into three groups (10 mice/group). A mouse COPD model was generated by exposing 20 mice to cigarette smoke (CS) for 24 weeks. A total of 10 mice were treated intranasally with rCC16 (2.5 µg/g body weight) and control mice were exposed to normal room air. Results indicated that rCC16 treatment ameliorated pathological damage in the lungs and reduced the production of tumor necrosis factor (TNF)‑α, interleukin (IL)‑6 and IL‑8, which were induced by CS exposure. After rCC16 administration, endogenous CC16 was upregulated and the body weight of COPD mice was increased, whereas the opposite was observed in CS‑exposed mice. Additionally, rCC16 treatment inhibited the DNA binding of NF‑κB/p65 in lung tissues and reduced nuclear translocation of NF‑κB/p65 in BALF and epithelial cells. Moreover, rCC16 treatment lead to a decrease in the total number of BALF cells, including macrophages, which was elevated in COPD mice. In conclusion, the present results demonstrate that rCC16 has therapeutic effects on COPD by downregulating pro‑inflammatory factors via the NF‑κB pathway.

Background: The medicinal plant, Catharanthus roseus (C. roseus), accumulates a wide range of terpenoid indole alkaloids (TIAs). Ethylene (ET) and methyl-jasmonate (MeJA) were previously reported as effective elicitors for the production of various valuable secondary metabolites of C. roseus, while a few ET or MeJA induced transcriptomic research is yet reported on this species. In this study, the de-novo transcriptome assembly of C. roseus is performed by using the next-generation sequencing technology., Results: The result shows that phenolic biosynthesis genes respond specifically to ET in leaves, monoterpenoid biosynthesis genes respond specifically to MeJA in roots. By screening the database, 23 ATP-binding cassette (ABC) transporter partial sequences are identified in C. roseus. On this basis, more than 80 key genes that encode key enzymes (namely TIA pathway, transcriptional factor (TF) and candidate ABC transporter) of alkaloid synthesis in TIA biosynthetic pathways are chosen to explore the integrative responses to ET and MeJA at the transcriptional level. Our data indicated that TIA accumulation is strictly regulated by the TF ethylene responsive factor (ERF) and bHLH iridoid synthesis 1 (BIS1). The heatmap, combined with principal component analysis (PCA) of C. roseus, shows that ERF co-expression with ABC2 and ABC8 specific expression in roots affect the root-specific accumulation of vinblastine in C. roseus. On the contrast, BIS1 activities follow a similar pattern of ABC3 and CrTPT2 specific expression in leaves, which affects the leaf-specific accumulation of vindoline in C. roseus., Conclusions: Results presented above illustrate that ethylene has a stronger effect than MeJA on TIA induction at both transcriptional and metabolite level. Furthermore, meta-analysis reveals that ERF and BIS1 form a positive feedback loop connecting two ABC transporters respectively and are actively involved in TIAs responding to ET and MeJA in C. roseus.