Targeting ENPP1 depletion may be a promising therapeutic strategy for treating oral squamous cell carcinoma via cytotoxic autophagy-related apoptosis.

ENPP1 depletion closely related with modulation immunotherapy of several types of cancer. However, the role of ENPP1 correlation with autophagy in oral squamous cell carcinoma (OSCC) pathogenesis remain unknown. In this study, effects of ENPP1 on OSCC cells in vitro were examined by cell proliferation assay, transwell chamber assay, flow cytometry analysis and shRNA technique. Cellular key proteins related to cell autophagy and apoptosis were evaluated by Western blot and immunofluorescent staining. Moreover, functions of ENPP1 on OSCC process were observed in nude mouse model. We reported that overexpression of ENPP1 promote the growth of OSCC cell xenografts in nude mouse model. In contrast, ENPP1 downregulation significantly inhibits OSCC cancer growth and induces apoptosis both in vitro and in vivo, which are preceded by cytotoxic autophagy. ENPP1downregulation induces a robust accumulation of autophagosomes, increases LC3B-II and decreases SQSTM1/p62 in ENPP1-shRNA-treated cells and xenografts. Mechanistic studies show that ENPP1 downregulation increases PRKAA1 phosphorylation leading to ULK1 activation. AMPK-inhibition abrogates ENPP1 downregulation-induced ULK1-activation, LC3B-turnover and SQSTM1/p62-degradation while AMPK-activation potentiates it's effects. Collectively, these data uncover that ENPP1 downregulation induces autophagic cell death in OSCC cancer, which may provide a potential therapeutic target for the treatment of OSCC.

[Effect of Neodymium-Doped Yttrium Aluminum Garnet Laser Combined With Desensitizing Toothpaste on Dentinal Tubule Occlusion Against Acid Challenge].

Objective To assess the effects of different application sequences of neodymium-doped yttrium aluminum garnet(Nd∶YAG)laser and the desensitizing toothpaste containing stannous fluoride on dentinal tubule occlusion.Methods Twelve intact third molars freshly extracted from human were selected and prepared into dentin slices with a thickness of 0.8 mm.Each dentin slice was subdivided into four small slices,three of which were etched with 6% citric acid and randomly assigned to the following three groups(n=12):(1)control group:no treatment;(2)Nd∶YAG+toothbrushing(TB)group:first irradiated with Nd∶YAG laser and then brushed with desensitizing toothpaste;(3)TB+Nd∶YAG group:first brushed with desensitizing toothpaste and then irradiated with Nd∶YAG laser.The Nd∶YAG laser irradiation were carried out at 1 W,15 pulses/s,and the pulse width of 150 µs for 10 s(for a total of 6 cycles).After the above treatment,the 12 dentin slices from the Nd∶YAG+TB and TB+Nd∶YAG groups were randomly assigned to four subgroups(n=3)and subjected to acid etching in the Coca-Cola solution for 0,5,10,and 15 min.A scanning electron microscope was used to observe and photograph the dentin slices in each group,and eight single-blinded examiners scored the slices according to uniform criteria.The analysis of variance was carried out to compared the scores between groups.Results Before acid etching,the dentin tubule occlusion scores of the Nd∶YAG+TB and TB+Nd∶YAG groups were(4.83±0.09) scores and(3.85±0.66) scores,respectively,which had no significant difference between each other(P=0.0590)and were higher than that[(0.10±0.07)scores]of the control group(both P<0.0001).The dentin tubule occlusion scores of the Nd∶YAG+TB group after acid etching for 5,10,and 15 min were(4.33±0.60)scores,(4.27±0.24)scores,and(3.63±0.07)scores,respectively,which were not significantly different from those[(4.04±0.10)scores,(3.76±0.59)scores,and(3.17±0.29)scores,respectively]of the TB+Nd∶YAG group(all P>0.05).In the Nd∶YAG+TB subgroup,the dentin tubule occlusion score after acid etching for 15 min was significantly lower than that before acid etching(P=0.0011).In the TB+Nd∶YAG group,there was no statistically significant difference in the score between before and after acid etching(P>0.05).Conclusions Nd∶YAG laser irradiation with appropriate parameters combined with the use of desensitizing toothpaste could produce an excellent occluding effect on dentinal tubules regardless of the sequence.However,brushing with desensitizing toothpaste followed by Nd∶YAG laser irradiation produced more consistent dentin sealing after acid etching.

The Use of 810 and 1064 nm Lasers on Dental Implants: In Vitro Analysis of Temperature, Surface Alterations, and Biological Behavior in Human Gingival Fibroblasts.

Objective: The primary objective of this study was to evaluate the safety of 810 and 1064 nm laser treatment on dental implants. Background: Peri-implantitis is a challenge for clinicians and researchers. Methods: A pig mandible model was used to evaluate temperature increases during laser irradiation. Surface alterations on processed pure titanium discs were analyzed via scanning electron microscopy and measurement of surface contact angles. Processed titanium discs were cocultured in vitro with human gingival fibroblasts; subsequently, cell proliferation was measured. Results: The maximum temperature and time to reach each threshold were comparable. No surface alterations were detected after 810 nm laser irradiation, whereas surface cracks were observed after 1064 nm laser irradiation under the parameter setting of 31.84 W/cm2. Compared with unaltered processed pure titanium discs, the proliferation of human gingival fibroblasts was significantly greater on altered processed pure titanium discs. Conclusions: The use of either 810 or 1064 nm laser treatments may increase the risk of thermal damage in terms of increased temperature if the parameter setting is not warranted. In addition, the use of 1064 nm laser treatment could lead to changes in pure titanium discs that do not negatively affect cell proliferation. Further investigations of laser-assisted therapy are necessary to improve guidelines concerning the treatment of peri-implantitis. Clinical trial registration number: 2021-P2-098-01.

Impact of a Modified Restoration of Tensor Veli Palatini on Hearing and Middle Ear Function in Cleft Palate Children-a Retrospective Study.

BACKGROUND: Many children with cleft palate also exhibit hearing loss and middle ear dysfunction, which could last for years. There are still arguments on how to treat this problem. This study aimed to evaluate the impact of a modified restoration of tensor veli palatine (TVP) on hearing and middle ear function in the cleft palate children. METHODS: This retrospective study was completed using records of the cleft palate children who received surgery in Peking Union Medical College Hospital from May 2013 to December 2020. They were divided into 2 groups: Group 1: children who received cleft palate surgery without specific restoration of TVP; Group 2: children who received palate surgery with a specific TVP restoration technique. Perioperative information was collected. The conductive auditory brainstem response and the 226-Hz tympanometry before and after the cleft surgery were compared intragroup and intergroup. RESULTS: Totally 42 children were included in this study, 21 children in each group. There were no significant differences considering clinical characteristics between the 2 groups. The modified TVP restoration didn't increase operation time or complication compared with no TVP restoration. Statistically, neither the auditory brainstem response air conduction hearing thresholds nor the 226-Hz tympanometry results had significant differences between the 2 groups after the surgery. CONCLUSIONS: This modified restoration of TVP was not time-consuming and did not increase complications. The beneficial effect of the modified TVP restoration on the hearing or the middle ear function of cleft palate children was uncertain around 6 months after surgery compared with no restoration.

Effectiveness of case-based learning in Chinese dental education: a systematic review and meta-analysis.

OBJECTIVE: The application of case-based learning (CBL) pedagogy has been emerging as an improved and more practical learning method across the Chinese dental education system. This article provides a critical overview of CBL pedagogy and further assesses the effectiveness of this teaching model in Chinese dental education. DESIGN: A systematic review and meta-analysis. METHODS: Studies published up to December 2019 were searched in the following electronic databases: China National Knowledge Infrastructure, China Science Periodical Database, Chinese Biomedical documental database, Wanfang data, PubMed, EMBASE and Cochrane Central Register of Control Trials. All randomised controlled trials (RCTs) that compared the effectiveness of the CBL teaching model and the traditional lecture-based learning (LBL) model in all dental disciplines were included. The assessment of methodological quality was based on the guidelines described in the Cochrane Handbook for Systematic Reviews, and the meta-analysis was performed using the software RevMan V.5.3 RESULTS: A total of 30 RCTs were finally included, with a total sample size of 2356 dental students. The CBL pedagogy significantly increased knowledge scores (standardised mean difference (SMD)=1.58, 95% CI: 0.95 to 2.20, p<0.0001), skill scores (SMD=1.22, 95% CI: 0.34 to 2.11, p<0.0001), comprehensive ability scores (SMD=1.91, 95% CI: 1.74 to 4.07, p<0.0001) and teaching satisfaction (risk ratio=1.38; 95% CI: 1.15 to 1.65; p=0.01) compared with the LBL teaching model among the dental students. Additionally, a subgroup analysis showed significant differences in the effects of CBL on knowledge scores, skill scores and comprehensive ability scores when comparing theoretical and practical courses. CONCLUSIONS: The meta-analysis and systematic review of the eligible literature showed that the CBL pedagogy in Chinese dental education is an effective way to increase knowledge scores, skill scores, comprehensive ability scores and teaching satisfaction. Successful adaptation of this teaching model could solve the scarcity of highly skilled and professional dentists in dental schools and hospitals across China.

Radiomics-based comparison of MRI and CT for differentiating pleomorphic adenomas and Warthin tumors of the parotid gland: a retrospective study.

OBJECTIVE: The objective of this study was to compare the diagnostic performance of magnetic resonance imaging (MRI) and computed tomography (CT) in differentiating pleomorphic adenomas from Warthin tumors using radiomics. STUDY DESIGN: We retrospectively reviewed 626 patients who underwent preoperative MRI or CT for parotid tumor diagnosis. Patient groups were balanced by propensity score matching (PSM) and 123 radiomic features were extracted from tumor images. Radiomic signatures (rad-scores) were generated using a least absolute shrinkage and selection operator logistic regression model. The Canny edge detector was used to define tumor borders (border index). The diagnostic performance of rad-score and border index before and after PSM was evaluated with area under the receiver operating characteristic curve analysis. RESULTS: For differentiation of pleomorphic adenomas and Warthin tumors, rad-score and border index areas under the curve for MRI after PSM were 0.911 (95% confidence interval [CI], 0.871-0.951) and 0.716 (95% CI, 0.646-0.787), respectively; those for CT were 0.876 (95% CI, 0.829-0.923) and 0.608 (95% CI, 0.527-0.690), respectively. Tumor border index on MRI, but not CT, had superior diagnostic performance (P < .05); MRI- and CT-based rad-scores showed similar performance (P >.05). CONCLUSIONS: MRI is superior to CT for tumor margin examination; however, the radiomics features of both modalities showed no difference.

Magnetic resonance image biomarkers improve differentiation of benign and malignant parotid tumors through diagnostic model analysis.

OBJECTIVES: To explore the effectiveness of magnetic resonance image (MRI)-based biomarkers for identifying benign and malignant parotid tumors via diagnostic model analysis. METHODS: This retrospective study included 109 patients (development cohort and validation cohort) who underwent MRI preoperatively, including T1- and T2-weighted images. Parameters based on 2D or 3D texture analysis were extracted from tumor lesions by MaZda software, fisher discriminant and bootstrap method were used to perform parameter reduction, diagnostic models with the selected biomarkers were established along with clinical data, model performance (discrimination and calibration) was furtherly evaluated by internal and external validation, decision curve analysis was applied to measure the improvement of clinical benefits. RESULTS: S(5,5) Entrop, S(0,1) ASM, WavEnHH (s-4), S(1,1,0) Entropy and Perc.10% were significantly associated with the pathological diagnosis of parotid tumor (benign versus malignancy), when adding these biomarkers to the regression analysis, model performance significantly improved in the development cohort (likelihood-ratio-test; p < 0.05, with an increase of AUC from 0.72 (reference model) to 0.85), and these results were maintained in a small external validation cohort. Decision curve analysis indicated that clinical benefit was greater with the application of MRI-based biomarkers. CONCLUSIONS: MRI-based texture analysis is proven to be an effective tool in differentiating benign and malignant parotid tumors, preoperative diagnosis was improved with the selected biomarkers compared to the reference model.

lncRNA SNHG5 promotes cell proliferation, migration and invasion in oral squamous cell carcinoma by sponging miR-655-3p/FZD4 axis.

Recently, previous studies have shown that long non-coding RNA (lncRNA) can act as a tumor promoter or inhibitor in the pathogenesis of oral squamous cell carcinoma (OSCC). However, the regulatory mechanism of lncRNA SNHG5 is unknown in OSCC. Therefore, the functional mechanism of lncRNA SNHG5 in OSCC was initially revealed in this study. Here, RT-qPCR and western blot analysis were used to assess mRNA and protein expression. The functional mechanism of SNHG5 was investigated by MTT, Transwell and luciferase reporter assays. The results showed that SNHG5 expression was upregulated in OSCC and promoted the viability, migration and invasion of OSCC cells. In addition, SNHG5 is the sponge of miR-655-3p in OSCC. And miR-655-3p was found to play an inhibitory effect in OSCC by interacting with SNHG5. Moreover, miR-655-3p directly targets FZD4 and negatively regulates its expression in OSCC. Functionally, FZD4 promoted the progression of OSCC by interacting with the SNHG5/miR-655-3p axis. In conclusion, lncRNA SNHG5 promotes cell proliferation, migration and invasion in OSCC by regulating miR-655-3p/FZD4 axis.

Erratum: Author Correction: Identification of novel genetic variants predisposing to familial oral squamous cell carcinomas.

[This corrects the article DOI: 10.1038/s41421-019-0126-6.].

Hsa_circ_0079662 induces the resistance mechanism of the chemotherapy drug oxaliplatin through the TNF-α pathway in human colon cancer.

The aim of the study was to research the biological functions of circRNA (hsa_circ_0079662) and its underlying mechanism in colorectal cancer. Drug-resistant cell lines (HT29-LOHP, HCT116-LOHP, HCT8-LOHP) were separately dealt with oxaliplatin concentration gradient (0.1-10 µmol/L). Real-time PCR, Western blotting, dual-luciferase assay, miRNA pull-down assay, coimmunoprecipitation and ELASA were performed to explore the mechanism of chemotherapy drug oxaliplatin resistance in CRC. The results showed that the expression of hsa_circ_0079662 was increased in drug-resistant cell lines by RT-PCR. The expression of HOXA9, TRIP6, Vcam-1, VEGFC, MMP3, MMP9 and MMP14 was higher by Western blotting. Interaction between HOXA9 and TRIP6 in CO-IP detection. Additionally, the cytokines TNF-α, IL-1 and IL-6 were also found. In conclusion, hsa_circ_0079662, as a ceRNA binding with hsa-mir-324-5p, can regulate target gene HOXA9 and induced the mechanism of chemotherapy drug oxaliplatin resistance in CRC through the TNF-α pathway in human colon cancer.

Follicular dendritic cell sarcoma of the parotid gland: A case report.

Follicular dendritic cell sarcoma (FDCS) is an exceedingly rare malignant neoplasm. The management of this tumor is fully challenging due to its rarity and lack of documentations. We share a case with primary parotid FDCS. This case report depicts the clinicopathological features of FDCS, which intends to serve as a reference to clinicians in its correct identification.

Identification of novel genetic variants predisposing to familial oral squamous cell carcinomas.

Oral squamous cell carcinoma (OSCC) is a common subtype of head and neck squamous cell carcinoma (HNSCC), but the pathogenesis underlying familial OSCCs is unknown. Here, we analyzed whole-genome sequences of a family with autosomal dominant expression of oral tongue cancer and identified proto-oncogenes VAV2 and IQGAP1 as the primary factors responsible for oral cancer in the family. These two genes are also frequently mutated in sporadic OSCCs and HNSCCs. Functional analysis revealed that the detrimental variants target tumorigenesis-associated pathways, thus confirming that these novel genetic variants help to establish a predisposition to familial OSCC.

Transverse facial cleft (macrostomia) repair: Modification of a traditional technique.

OBJECTIVE: Outcomes from surgical repair of transverse facial cleft (macrostomia) may not be very satisfactory when conventional methods are used to position the oral commissure to be repaired. To improve patient outcomes, we developed a modified oral commissure positioning and reconstruction method for transverse facial cleft repair. METHOD: In the modified positioning method, the oral commissure at the abnormal side was positioned precisely and reconstructed by a combination of two conventional methods, namely, the distance measurement method and the anatomical charateristics method. The function of the orbicularis oris muscle was preserved. Postoperative surgical scar score and oral commissure symmetry score were determined and compared between patients and healthy controls. The scores ranged from one to five, with one representing the best and five indicating the worst results. RESULTS: Nine patients aged 4-31 months (7 girls) underwent the modified transverse facial cleft repair surgery. All the patients had unilateral transverse facial cleft with or without microsomia and/or complete cleft lip. The patients were followed up for one to five years. Although average surgical scar scores of patients (close-mouth: 1.8 ± 0.8, range: 1.0-2.8; open-mouth: 1.8 ± 0.9, range 1.0-3.6) remained significantly higher (P < 0.05) than those of the healthy controls (N = 8, close-mouth 1.1 ± 0.4, range: 1.0-1.4, open-mouth: 1.1 ± 0.3, range: 1.0-1.2) 6 months after the surgery, their average close-mouth oral commissure symmetry score (1.9 ± 0.7, range: 1.6-2.8) was similar (P = 0.381) to those of the healthy controls (1.8 ± 0.8, range: 1.0-2.6). CONCLUSIONS: The modified procedure appears to lead to promising long-term benefit on restoring oral commissure symmetry.

Combined overexpression of cadherin 6, cadherin 11 and cluster of differentiation 44 is associated with lymph node metastasis and poor prognosis in oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is a highly invasive lesion that frequently metastasizes to the cervical lymph nodes and is associated with a poor prognosis. Several adhesion factors, including cadherin 6 (CDH6), cadherin 11 (CDH11) and cluster of differentiation 44 (CD44), have been reported to be involved in the invasion and metastasis of multiple types of cancer. Therefore, the aim of the present study was to determine the expression of CDH6, CDH11 and CD44 in tumor tissues from patients with OSCC, and whether this was associated with the metastasis and survival of OSCC. The mRNA expression of the human tumor metastasis-related cytokines was examined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) in OSCC tumors with or without lymph node metastasis (n=10/group). The expression of CDH6, CDH11 and CD44 in 101 OSCC and 10 normal oral mucosa samples was examined by immunohistochemical staining. The association between overall and disease-specific survival times of patients with OSCC and the expression of these three proteins was evaluated using Kaplan-Meier curves and the log-rank test. RT-qPCR results indicated that the mRNA expression of CDH6, CDH11 and CD44 was increased in OSCC patients with lymph node metastasis (2.93-, 2.01- and 1.92-fold; P<0.05). Overexpression of CDH6, CDH11 and CD44 was observed in 31/35 (89%), 25/35 (71%) and 31/35 (89%) patients, respectively. The number of OSCC patients with lymph node metastasis exhibiting CDH6, CDH11 and CD44 overexpression was significantly higher than the number of patients without lymph node metastasis exhibiting overexpression of these proteins (P=0.017, P=0.038 and P=0.007, respectively). OSCC patients with high co-expression of CDH6, CDH11 and CD44 exhibited lower disease-specific survival times (P=0.047; χ2=3.933) when compared with OSCC patients with low co-expression of these adhesion factors. CDH6, CDH11 and CD44 serve important roles in OSCC metastasis and the combined use of these factors as biomarkers may improve the accuracy of the prediction of cancer metastases and prognosis.

Determination of temperature and residual laser energy on film fiber-optic thermal converter for diode laser surgery.

BACKGROUND: The diode laser was utilized in soft tissue incision of oral surgery based on the photothermic effect. The contradiction between the ablation efficiency and the thermal damage has always been in diode laser surgery, due to low absorption of its radiation in the near infrared region by biological tissues. Fiber-optic thermal converters (FOTCs) were used to improve efficiency for diode laser surgery. The purpose of this study was to determine the photothermic effect by the temperature and residual laser energy on film FOTCs. METHODS: The film FOTC was made by a distal end of optical fiber impacting on paper. The external surface of the converter is covered by a film contained amorphous carbon. The diode laser with 810 nm worked at the different rated power of 1.0 W, 1.5 W, 2.0 W, 3.0 W, 4.0 W, 5.0 W, 6.0 W, 7.0 W, 8.0 W in continuous wave (CW)and pulse mode. The temperature of the distal end of optical fiber was recorded and the power of the residual laser energy from the film FOTC was measured synchronously. The temperature, residual power and the output power were analyzed by linear or exponential regression model and Pearson correlations analysis. RESULTS: The residual power has good linearity versus output power in CW and pulse modes (R2 = 0.963, P < 0.01 for both). The temperature on film FOTCs increases exponentially with adjusted R2 = 0.959 in continuous wave mode, while in pulsed mode with adjusted R2 = 0.934. The temperature was elevated up to about 210 °C and eventually to be a stable state. Film FOTCs centralized approximately 50% of laser energy on the fiber tip both in CW and pulsed mode while limiting the ability of the laser light to interact directly with target tissue. CONCLUSIONS: Film FOTCs can concentrate part of laser energy transferred to heat on distal end of optical fiber, which have the feasibility of improving efficiency and reducing thermal damage of deep tissue.

Mesenchymal chondrosarcoma of the right buccal region: A case report and review of the literature.

Extraskeletal mesenchymal chondrosarcoma (EMCS) is a rare malignant cartilaginous tumor arising from the soft tissues. The most common areas of extraskeletal origin are the lower extremities, the orbits and the central nervous system, among others. In this study, the case of primary EMCS arising from the right buccal region in a 26-year old female is presented. Histological and immunohistochemical analysis confirmed the diagnosis of EMCS. Subseqently, the patient was treated with radical surgery, but declined chemotherapy or radiotherapy, which was recommended. One year after surgery, no recurrence had been identified in the patient. To the best of our knowledge, only one case of primary EMCS of the buccal region has been reported previously. In the current study, a case of primary EMCS of the buccal region is presented.

Application of a peripheral nerve block technique in laser treatment of the entire facial skin and evaluation of its analgesic effect.

BACKGROUND: The aim was to develop a technique for peripheral nerve block anesthesia (PNB) for the skin of the entire face and neck, considering the nerves anesthetized, injection sites, use of an injection method assisted by computer-controlled local anesthetic delivery (CCLAD), and to evaluate the analgesic effects of the PNB technique. METHODS: 50 patients who suffered from large nevus of Ota lesions or port-wine stains on their facial and neck skin and who required laser treatment were included. This study was designed as a non-randomized self-control trial. All the patients received the laser treatment under topical anesthesia in the first phase and three to six months later, they received the same treatment under the PNB using CCLAD. The differences in scores from the visual analogue scale of pain for the two phases were analyzed by the t-test. P values <0.05 were considered to be statistically significant. RESULTS: The peripheral nerve block technique was simple to execute and easy to learn, the anesthetic injection site was generally located at a subcutaneous depth of 0.5-1.0 cm. The analgesic effect of PNB was significant, the mean pain score (2.8 ± 2.2) was significantly lower than that with topical anesthesia (P<0.0001). Patients during the PNB phase did not experience injection pain following CCLAD. CONCLUSION: The peripheral nerve block technique can greatly ease the pain that occurs during laser treatment, especially for patients with larger lesions. CCLAD will allow PNB to be broadly applied in laser treatments.

[The application of free tissue flap in simultaneous reconstruction of defects after tongue cancer].

OBJECTIVE: To discuss the feasibility of using free tissue flap for simultaneous tongue reconstruction after tongue cancer resection. METHOD: Radial forearm flaps and anterolateral thigh flaps were used for simultaneous reconstruction of different defects after tongue cancer resection in 47 cases. The functional evaluation was assessed during the follow-up period of 3 months to 9 years. RESULTS: Only one flap failed,giving a success rate of 97.7%. The 36 patient available for postoperative follow-up were all able to communicate in basic languages and eat normally. Among them, normal speech was found in 34, while slurred speech was found in two. 31 patients could eat normal diet ,while eight could eat soft diet and two could eat liquid diet. CONCLUSIONS: Simultaneous tongue reconstruction with free tissue flap is a reliable method with high successful rate. Flaps selection based on different tongue defects is the key point to achieve good functional and cosmetic results for the reconstruction tongue.

An extraoral nasoalveolar molding technique in complete unilateral cleft lip and palate.

SUMMARY: Although nasoalveolar molding is commonly performed before cleft lip surgery, customized palatal plate availability is limited for patients far from a hospital. This case report describes a preformed extraoral nasoalveolar molding (PENAM) appliance and treatment approach for presurgical nasoalveolar molding in newborns with complete unilateral cleft lip and palate. A 12-day-old boy presented with complete unilateral cleft lip and palate. The PENAM device was supported by an adhesive-taped upper lip, which consisted of a lip nasal stent made from a 0.5-mm stainless steel wire. The spring was activated monthly. The shape of the cartilaginous septum, alar cartilage tip, medial crus, lateral crus, and alveolar segments was molded to resemble the normal shape of these structures. The 9.3-mm alveolar gaps were reduced and approximated. The approximation mostly came from the major alveolus segment with approximately 6.4-mm movement. Cleft side nostril height increased 5.5 mm and deviation of the columella was corrected by 42°. PENAM can be helpful in infants with unilateral cleft lip and palate because it has benefits for long-term forced delivery, requires less frequent activations, and is suitable for patients who live far from a hospital.