Neutrophil lncRNA ZNF100-6:2 is a potential diagnostic marker for active pulmonary tuberculosis.

Active pulmonary tuberculosis (PTB) poses challenges in rapid diagnosis within complex clinical conditions. Given the close association between neutrophils and tuberculosis, we explored differentially expressed long non-coding RNAs (lncRNAs) in neutrophils as potential molecular markers for diagnosing active PTB. We employed a gene microarray to screen for lncRNA alterations in neutrophil samples from three patients with active PTB and three healthy controls. The results revealed differential expression of 1457 lncRNAs between the two groups, with 916 lncRNAs upregulated and 541 lncRNAs down-regulated in tuberculosis patients. Subsequent validation tests demonstrated down-regulation of lncRNA ZNF100-6:2 in patients with active PTB, which was restored following anti-tuberculosis treatment. Our findings further indicated a high diagnostic potential for lncRNA ZNF100-6:2, as evidenced by an area under the receiver operating characteristic (ROC) curve of 0.9796 (95% confidence interval: 0.9479 to 1.000; P < 0.0001). This study proposes lncRNA ZNF100-6:2 as a promising and novel diagnostic biomarker for active PTB.

Hydrogen sulfide protects cardiomyocytes from doxorubicin-induced ferroptosis through the SLC7A11/GSH/GPx4 pathway by Keap1 S-sulfhydration and Nrf2 activation.

Recent studies have demonstrated that ferroptosis, a novel form of nonapoptotic regulated cell death plays an important role in doxorubicin (DOX)-induced cardiotoxicity (DoIC). Hydrogen sulfide (H2S) is emerging as the third important gaseous mediator in cardiovascular system. However, whether H2S has an effect on DOX-induced ferroptosis remains unknown. Here, we found that DOX not only triggered cardiomyocyte ferroptosis but also significantly inhibited the synthesis of endogenous H2S in the murine model of chronic DoIC. Application of NaHS, an H2S donor obviously activated the SLC7A11/GSH/GPx4 antioxidant pathway and thus alleviated DOX-induced ferroptosis and cardiac injury in mice. In contrast, cardiac-specific knockout of cystathionine γ-lyase gene (Cse) in mice (Csef/f/Cre+) to abolish the cardiac synthesis of endogenous H2S evidently exacerbated DOX-induced ferroptosis and cardiac dysfunction. A further suppression of SLC7A11/GSH/GPx4 pathway was obtained in Csef/f/Cre+ mice with DoIC, as compared to Csef/f/Cre- mice with DoIC. The aggravation caused by cardiac-specific Cse deficiency was remarkably rescued by exogenous supplementation of NaHS. Moreover, in DOX-stimulated H9c2 cardiomyocytes, pretreatment with NaHS dose-dependently enhanced the activity of SLC7A11/GSH/GPx4 pathway and subsequently mitigated ferroptosis and mitochondrial impairment. On the contrary, transfection with Cse siRNA in DOX-stimulated H9c2 cardiomyocytes markedly inhibited SLC7A11/GSH/GPx4 pathway, thus leading to aggravated ferroptosis and more damage to mitochondrial structure and function. In addition, the protective effect of NaHS on DOX-induced ferroptosis was closely related to the S-sulfhydrated Keap1, which in turn promoted nuclear translocation of Nrf2 and the transcription of SLC7A11 and GPx4. In conclusion, our findings suggest that H2S may exert protective effect on DoIC by inhibiting DOX-induced ferroptosis via Keap1/Nrf2-dependent SLC7A11/GSH/GPx4 antioxidant pathway.

Dynamic Prognostic Score to Predict Survival in East Asian Elderly Populations with Dysphagia.

INTRODUCTION: Dysphagia is a common disorder in older adults, leading to severe complications, including aspiration pneumonia, dehydration, malnutrition, weight loss, and even death. However, no prognostic model has been developed to predict the prognosis of older adults with dysphagia. METHODS: Data from patients with dysphagia at a single center were retrospectively reviewed between 2014 and 2017. All data were obtained from the Dryad Digital Repository. The least absolute shrinkage and selection operator regression model was used to select potentially relevant features. Multiple Cox proportional hazard analysis was used to develop a model based on the training set. RESULTS: The nomogram comprised age, sex, percutaneous endoscopic gastrostomy, chronic heart failure, total lymphocyte count, daily calorie intake, and severe pneumonia, which provided favorable calibration and discrimination in the training dataset, with AUCs for the 1-year, 2-year, and 3-year survival predictions of 0.833, 0.871, and 0.886, respectively. Furthermore, it showed acceptable discrimination in the validation cohort, with AUCs for the 1-year, 2-year, and 3-year survival predictions of 0.884, 0.834, and 0.782, respectively. Moreover, the decision curve analysis results revealed that the nomogram was clinically beneficial. CONCLUSION: A nomogram, combining seven demographic and clinical factors, provided an excellent preoperative prediction of survival probability in older individuals with dysphagia. This predictive model can be used as a reference to assist clinicians in making clinical decisions.

Hydrogen sulfide alleviates heart failure with preserved ejection fraction in mice by targeting mitochondrial abnormalities via PGC-1α.

AIM: Increasing evidence has proposed that mitochondrial abnormalities may be an important factor contributing to the development of heart failure with preserved ejection fraction (HFpEF). Hydrogen sulfide (H2S) has been suggested to play a pivotal role in regulating mitochondrial function. Therefore, the present study was designed to explore the protective effect of H2S on mitochondrial dysfunction in a multifactorial mouse model of HFpEF. METHODS: Wild type, 8-week-old, male C57BL/6J mice or cardiomyocyte specific-Cse (Cystathionine γ-lyase, a major H2S-producing enzyme) knockout mice (CSEcko) were given high-fat diet (HFD) and l-NAME (an inhibitor of constitutive nitric oxide synthases) or standardized chow. After 4 weeks, mice were randomly administered with NaHS (a conventional H2S donor), ZLN005 (a potent transcriptional activator of PGC-1α) or vehicle. After additional 4 weeks, echocardiogram and mitochondrial function were evaluated. Expression of PGC-1α, NRF1 and TFAM in cardiomyocytes was assayed by Western blot. RESULTS: Challenging with HFD and l-NAME in mice not only caused HFpEF but also inhibited the production of endogenous H2S in a time-dependent manner. Meanwhile the expression of PGC-1α and mitochondrial function in cardiomyocytes were impaired. Supplementation with NaHS not only upregulated the expression of PGC-1α, NRF1 and TFAM in cardiomyocytes but also restored mitochondrial function and ultrastructure, conferring an obvious improvement in cardiac diastolic function. In contrast, cardiac deletion of CSE gene aggravated the inhibition of PGC-1α-NRF1-TFAM pathway, mitochondrial abnormalities and diastolic dysfunction. The deleterious effect observed in CSEcko HFpEF mice was partially counteracted by pre-treatment with ZLN005 or supplementation with NaHS. CONCLUSION: Our findings have demonstrated that H2S ameliorates left ventricular diastolic dysfunction by restoring mitochondrial abnormalities via upregulating PGC-1α and its downstream targets NRF1 and TFAM, suggesting the therapeutic potential of H2S supplementation in multifactorial HFpEF.

Tyrosine kinase inhibitors as potential sensitizers of adoptive T cell therapy for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a high-incidence malignant tumor worldwide and lacks effective treatment options. Targeted drugs are the preferred recommendations for the systemic treatment of hepatocellular carcinoma. Immunotherapy is a breakthrough in the systemic treatment of malignant tumors, including HCC. However, either targeted therapy or immunotherapy alone is inefficient and has limited survival benefits on part of HCC patients. Investigations have proved that tyrosine kinase inhibitors (TKIs) have regulatory effects on the tumor microenvironment and immune response, which are potential sensitizers for immunotherapy. Herein, a combination therapy using TKIs and immunotherapy has been explored and demonstrated to improve the effectiveness of treatment. As an effective immunotherapy, adoptive T cell therapy in solid tumors is required to improve tumor infiltration and killing activity which can be possibly achieved by combination with TKIs.

The Imbalance of p53-Park7 Signaling Axis Induces Iron Homeostasis Dysfunction in Doxorubicin-Challenged Cardiomyocytes.

Doxorubicin (DOX)-induced cardiotoxicity (DoIC) is a major side effect for cancer patients. Recently, ferroptosis, triggered by iron overload, is demonstrated to play a role in DoIC. How iron homeostasis is dysregulated in DoIC remains to be elucidated. Here, the authors demonstrate that DOX challenge exhibits reduced contractile function and induction of ferroptosis-related phenotype in cardiomyocytes, evidenced by iron overload, lipid peroxide accumulation, and mitochondrial dysfunction. Compared to Ferric ammonium citrate (FAC) induced secondary iron overload, DOX-challenged cardiomyocytes show a dysfunction of iron homeostasis, with decreased cytoplasmic and mitochondrial iron-sulfur (FeS) cluster-mediated aconitase activity and abnormal expression of iron homeostasis-related proteins. Mechanistically, mass spectrometry analysis identified DOX-treatment induces p53-dependent degradation of Parkinsonism associated deglycase (Park7) which results in iron homeostasis dysregulation. Park7 counteracts iron overload by regulating iron regulatory protein family transcription while blocking mitochondrial iron uptake. Knockout of p53 or overexpression of Park7 in cardiomyocytes remarkably restores the activity of FeS cluster and iron homeostasis, inhibits ferroptosis, and rescues cardiac function in DOX treated animals. These results demonstrate that the iron homeostasis plays a key role in DoIC ferroptosis. Targeting of the newly identified p53-Park7 signaling axis may provide a new approach to prevent DoIC.

The risk factors for Group B Streptococcus colonization during pregnancy and influences of intrapartum antibiotic prophylaxis on maternal and neonatal outcomes.

BACKGROUND: Group B Streptococcus (GBS), also referred as Streptococcus agalactiae, is one of the leading causes of life-threatening invasive diseases such as bacteremia, meningitis, pneumonia and urinary tract infection in pregnant women and neonates. Rates of GBS colonization vary by regions, but large-sample studies on maternal GBS status are limited in southern China. As a result, the prevalence of GBS among pregnant women and its associated risk factors and the efficacy of intrapartum antibiotic prophylaxis (IAP) intervention in preventing adverse pregnancy and neonatal outcomes remain poorly understood in southern China. METHODS: To fill this gap, we retrospectively analyzed demographic and obstetrical data of pregnant women who have undergone GBS screening and delivered between 2016 and 2018 in Xiamen, China. A total of 43,822 pregnant women were enrolled and only a few GBS-positive women did not receive IAP administration. Possible risk factors for GBS colonization were assayed by univariate and multivariate logistic regression analysis. Generalized linear regression model was applicated to analyze whether IAP is one of the impact factors of the hospital length of stay of the target women. RESULTS: The overall GBS colonization rate was 13.47% (5902/43,822). Although women > 35 years old (P = 0.0363) and women with diabetes mellitus (DM, P = 0.001) had a higher prevalence of GBS colonization, the interaction between ages and GBS colonization was not statistically significant in Logistic Regression analysis (adjusted OR = 1.0014; 95% CI, 0.9950, 1.0077). The rate of multiple births was significantly dropped in GBS-positive group than that of GBS-negative group (P = 0.0145), with no significant difference in the rate of fetal reduction (P = 0.3304). Additionally, the modes of delivery and the incidences of abortion, premature delivery, premature rupture of membranes, abnormal amniotic fluid and puerperal infection were not significantly different between the two groups. The hospitalization stays of the subjects were not influenced by GBS infection. As for neonatal outcomes, the cases of fetal death in maternal GBS-positive group did not statistically differ from that in maternal GBS-negative group. CONCLUSION: Our data identified that pregnant women with DM are at high risk of GBS infection and IAP is highly effective in prevention of adverse pregnancy and neonatal outcomes. This stressed the necessity of universal screening of maternal GBS status and IAP administration to the target population in China, and women with DM should be considered as priorities.

Oxytocin treatments or activation of the paraventricular nucleus-the shell of nucleus accumbens pathway reduce adverse effects of chronic social defeat stress on emotional and social behaviors in Mandarin voles.

Chronic social stress can cause psychological disease. Although oxytocin (OT) has been showed to modulate effects of chronic social defeat stress (CSDS) on emotional and social behaviors, however, how OT circuits mediate effects of CSDS on emotional and social abnormalities remains unclear. Here, we found that repeated intraperitoneal OT administration in the process of CSDS buffered adverse effects of CSDS on emotional and social behaviors in mandarin voles (Microtus mandarinus) of both sexes except no effect on depression-like behavior of males. Repeated OT treatments during CSDS prevented decrease of oxytocin receptors in nucleus accumbens (NAc) in females, but produced no effects on males. Furthermore, using designer receptors exclusively activated by designer drugs (DREADDs)-based chemogenetic tools, we determined that the activation of the paraventricular nucleus (PVN)-the shell of NAc (NAcs) projections before social defeat during CSDS process significantly prevented the increase of the anxiety-like behaviors and social avoidance induced by CSDS in both sexes, and reversed the depressive-like behaviors induced by CSDS only in females. Besides, optogenetic activation of PVN-NAcs projections after CSDS reduced anxiety-like behaviors and increased levels of sociality. Collectively, we suggest that PVN-NAcs projections modulate emotional and social behaviors during or after the process of CSDS sex-specifically, although AAV viruses did not specifically infect OT neurons. These findings offer potential targets for preventing or treating emotional and social disorders induced by chronic stress.

A functional role of meningeal lymphatics in sex difference of stress susceptibility in mice.

Major depressive disorder is one of the most common mental health conditions. Meningeal lymphatics are essential for drainage of molecules in the cerebrospinal fluid to the peripheral immune system. Their potential role in depression-like behaviour has not been investigated. Here, we show in mice, sub-chronic variable stress as a model of depression-like behaviour impairs meningeal lymphatics in females but not in males. Manipulations of meningeal lymphatics regulate the sex difference in the susceptibility to stress-induced depression- and anxiety-like behaviors in mice, as well as alterations of the medial prefrontal cortex and the ventral tegmental area, brain regions critical for emotional regulation. Together, our findings suggest meningeal lymphatic impairment contributes to susceptibility to stress in mice, and that restoration of the meningeal lymphatics might have potential for modulation of depression-like behaviour.

Sex-Specific Transcriptomic Signatures in Brain Regions Critical for Neuropathic Pain-Induced Depression.

Neuropathic pain is a chronic debilitating condition with a high comorbidity with depression. Clinical reports and animal studies have suggested that both the medial prefrontal cortex (mPFC) and the anterior cingulate cortex (ACC) are critically implicated in regulating the affective symptoms of neuropathic pain. Neuropathic pain induces differential long-term structural, functional, and biochemical changes in both regions, which are thought to be regulated by multiple waves of gene transcription. However, the differences in the transcriptomic profiles changed by neuropathic pain between these regions are largely unknown. Furthermore, women are more susceptible to pain and depression than men. The molecular mechanisms underlying this sexual dimorphism remain to be explored. Here, we performed RNA sequencing and analyzed the transcriptomic profiles of the mPFC and ACC of female and male mice at 2 weeks after spared nerve injury (SNI), an early time point when the mice began to show mild depressive symptoms. Our results showed that the SNI-induced transcriptomic changes in female and male mice were largely distinct. Interestingly, the female mice exhibited more robust transcriptomic changes in the ACC than male, whereas the opposite pattern occurred in the mPFC. Cell type enrichment analyses revealed that the differentially expressed genes involved genes enriched in neurons, various types of glia and endothelial cells. We further performed gene set enrichment analysis (GSEA), which revealed significant de-enrichment of myelin sheath development in both female and male mPFC after SNI. In the female ACC, gene sets for synaptic organization were enriched, and gene sets for extracellular matrix were de-enriched after SNI, while such signatures were absent in male ACC. Collectively, these findings revealed region-specific and sexual dimorphism at the transcriptional levels induced by neuropathic pain, and provided novel therapeutic targets for chronic pain and its associated affective disorders.

p53-Dependent Mitochondrial Compensation in Heart Failure With Preserved Ejection Fraction.

Background Heart failure with preserved ejection fraction (HFpEF) accounts for 50% of patients with heart failure. Clinically, HFpEF prevalence shows age and gender biases. Although the majority of patients with HFpEF are elderly, there is an emergence of young patients with HFpEF. A better understanding of the underlying pathogenic mechanism is urgently needed. Here, we aimed to determine the role of aging in the pathogenesis of HFpEF. Methods and Results HFpEF dietary regimen (high-fat diet + Nω-Nitro-L-arginine methyl ester hydrochloride) was used to induce HFpEF in wild type and telomerase RNA knockout mice (second-generation and third-generation telomerase RNA component knockout), an aging murine model. First, both male and female animals develop HFpEF equally. Second, cardiac wall thickening preceded diastolic dysfunction in all HFpEF animals. Third, accelerated HFpEF onset was observed in second-generation telomerase RNA component knockout (at 6 weeks) and third-generation telomerase RNA component knockout (at 4 weeks) compared with wild type (8 weeks). Fourth, we demonstrate that mitochondrial respiration transitioned from compensatory state (normal basal yet loss of maximal respiratory capacity) to dysfunction (loss of both basal and maximal respiratory capacity) in a p53 dosage dependent manner. Last, using myocardial-specific p53 knockout animals, we demonstrate that loss of p53 activation delays the development of HFpEF. Conclusions Here we demonstrate that p53 activation plays a role in the pathogenesis of HFpEF. We show that short telomere animals exhibit a basal level of p53 activation, mitochondria upregulate mtDNA encoded genes as a mean to compensate for blocked mitochondrial biogenesis, and loss of myocardial p53 delays HFpEF onset in high fat diet + Nω-Nitro-L-arginine methyl ester hydrochloride challenged murine model.

Genome-Wide Identification of Petunia HSF Genes and Potential Function of PhHSF19 in Benzenoid/Phenylpropanoid Biosynthesis.

Volatile benzenoids/phenylpropanoids are the main flower scent compounds in petunia (Petunia hybrida). Heat shock factors (HSFs), well known as the main regulator of heat stress response, have been found to be involved in the biosynthesis of benzenoid/phenylpropanoid and other secondary metabolites. In order to figure out the potential function of HSFs in the regulation of floral scent in petunia, we systematically identified the genome-wide petunia HSF genes and analyzed their expression and then the interaction between the key petunia HSF gene with target gene involved in benzenoid/phenylpropanoid biosynthesis. The results revealed that 34 HSF gene family members were obtained in petunia, and most petunia HSFs contained one intron. The phylogenetic analysis showed that 23 petunia HSFs were grouped into the largest subfamily HSFA, while only two petunia HSFs were in HSFC subfamily. The DBD domain and NLS motif were well conserved in most petunia HSFs. Most petunia HSF genes' promoters contained STRE motifs, the highest number of cis-acting element. PhHSF19 is highly expressed in petal tubes, followed by peduncles and petal limbs. During flower development, the expression level of PhHSF19 was dramatically higher at earlier flower opening stages than that at the bud stage, suggesting that PhHSF19 may have potential roles in regulating benzenoid/phenylpropanoid biosynthesis. The expression pattern of PhHSF19 is positively related with PhPAL2, which catalyzes the first committed step in the phenylpropanoid pathway. In addition, there are three STRE elements in the promoter of PhPAL2. PhHSF19 was proven to positively regulate the expression of PhPAL2 according to the yeast one hybrid and dual luciferase assays. These results lay a theoretical foundation for further studies of the regulation of HSFs on plant flower scent biosynthesis.

Clinical effectiveness of the Eruption Guidance Appliances in treating malocclusion in the mixed dentition: A systematic review and meta-analysis.

AIM: To evaluate the clinical effectiveness of the eruption guidance appliances (EGAs) in treating malocclusion in the early mixed dentition. DESIGN: Electronic databases were comprehensively searched for the eligibility literature of the EGA treatment for a period spanning from the earliest available date in each database up to July 2021. Randomized controlled trials, controlled clinical trials, and prospective and retrospective cohort studies were included in the present review. The quality of clinical trials was assessed according to the Cochrane Collaboration's tools (RoB2.0 and ROBINS-I), whereas cohort studies were based on the Newcastle-Ottawa Scale (NOS). The data were gathered and synthesized with the Stata software (version 12). RESULTS: The screen yielded 436 articles, of which 17 papers were potentially eligible, and 7 articles from 3 studies (1 RCT, 1 CCT, and 1 PCS) were qualified for the final review and analysis. The meta-analysis showed both favorable dentoalveolar and skeletal changes in short term. Both overjet and overbite had a significant decrease after treatment (MD = -2.38 mm, 95% CI: -2.82 to -1.94, p < .001, and MD = -2.43 mm, 95% CI: -3.52 to -1.35, p < .001, respectively), and SNB increased significantly by 0.73 degrees (95% CI: 0.17-1.28, p = .01). After the retention period, however, overbite had a significant increase of 0.88mm, which indicated the occurrence of a relapse (95% CI: 0.60-1.16, p < .001). CONCLUSIONS: According to the existing evidence, the EGA treatment is effectively correcting overjet and overbite in the early mixed dentition in short term; furthermore, high-quality and long-term studies are warranted to determine its long-term effectiveness.

Macrophage-Mimic Hollow Mesoporous Fe-Based Nanocatalysts for Self-Amplified Chemodynamic Therapy and Metastasis Inhibition via Tumor Microenvironment Remodeling.

Fe-based nanomaterials with Fenton reaction activity are promising for tumor-specific chemodynamic therapy (CDT). However, most of the nanomaterials suffer from low catalytic efficiency due to its insufficient active site exposure and the relatively high tumor intracellular pH, which greatly impede its clinical application. Herein, macrophage membrane-camouflaged carbonic anhydrase IX inhibitor (CAI)-loaded hollow mesoporous ferric oxide (HMFe) nanocatalysts are designed to remodel the tumor microenvironment with decreased intracellular pH for self-amplified CDT. The HMFe not only serves as a Fenton agent with high active-atom exposure to enhance CDT but also provides hollow cavity for CAI loading. Meanwhile, the macrophage membrane-camouflaging endows the nanocatalysts with immune evading capability and improves tumoritropic accumulation by recognizing tumor endothelium and cancer cells through α4/VCAM-1 interaction. Once internalized by tumor cells, the CAI could be specifically released, which can not only inhibit CA IX to induce intracellular H+ accumulation for accelerating the Fenton reaction but also could prevent tumor metastasis because of the insufficient H+ formation outside cells for tumor extracellular matrix degradation. In addition, the HMFe can be employed to highly efficient magnetic resonance imaging to real-time monitor the agents' bio-distribution and treatment progress. Both in vitro and in vivo results well demonstrated that the nanocatalysts could realize self-amplified CDT and breast cancer metastasis inhibition via tumor microenvironment remodeling, which also provides a promising paradigm for improving CDT and antimetastatic treatment.

A Unified Pansharpening Model Based on Band-Adaptive Gradient and Detail Correction.

Pansharpening is used to fuse a panchromatic (PAN) image with a multispectral (MS) image to obtain a high-spatial-resolution multispectral (HRMS) image. Traditional pansharpening methods face difficulties in obtaining accurate details and have low computational efficiency. In this study, a unified pansharpening model based on the band-adaptive gradient and detail correction is proposed. First, a spectral fidelity constraint is designed by keeping each band of the HRMS image consistent with that of the MS image. Then, a band-adaptive gradient correction model is constructed by exploring the gradient relationship between a PAN image and each band of the MS image, so as to adaptively obtain an accurate spatial structure for the estimated HRMS image. To refine the spatial details, a detail correction constraint is defined based on the parameter transfer by designing a reduced-scale parameter acquisition model. Finally, a unified model is constructed based on the gradient and detail corrections, which is then solved by an alternating direction multiplier method. Both reduced-scale and full-scale experiments are conducted on several datasets. Compared with state-of-the-art pansharpening methods, the proposed method can achieve the best results in terms of fusion quality and has high efficiency. Specifically, our method improves the SAM and ERGAS metrics by 17.6% and 21.2% respectively compared to the traditional approach with the best average values, and improves these two metrics by 4.3% and 10.3% respectively compared to the learning-based approach with the best average values.

Unilateral Scissor Bite Managed with Prefabricated Functional Appliances in Primary Dentition-A New Interceptive Orthodontic Protocol.

A unilateral scissor bite is a type of severe malocclusion in primary dentition that can influence the development of the mandible and face. The present case report describes an interceptive treatment on a 4-year-old girl with a unilateral scissor bite combined with an anterior crossbite, increased reverse overjet, and overbite on a skeletal Class III base. The patient was treated with a new Prefabricated Functional Appliance (PFA) which was modified from a Frankel-III appliance to induce a mandible to move backwards and relieve an occlusion discrepancy of the dental arch, and a functional dental rehabilitation with resin and myofunctional exercises with a PFA which was modified from an oral screen appliance were performed during the treatment. The total treatment time was 11 months and a satisfactory improvement of occlusion and facial esthetics was achieved. This case report presents a new PFA system and treatment protocol in primary dentition which results in a favorable outcome, and the clinical effectiveness of this appliance system warrants further investigation.