ABSTRACT
One previously undescribed xanthanolide sesquiterpene dimer pungiolide P (1), possessing an unprecedented scaffold with a 5/7/5/7/5 ring system skeleton and its intermediate pungiolide Q (2), ten xanthanolide sesquiterpenes (3-12), two eudesmene sesquiterpene derivatives (13-14), one phenylpropionic acid derivative (15), together with eleven known compounds (16-26) were obtained from the fruits of Xanthium italicum Moretti. A possible biosynthetic pathway for pungiolide P (1) was also proposed, which was supported by its bio-synthetic intermediate (2). Compounds 1, 4-5, 18-21, and 25 exhibited cytotoxic activity against a variety of human cancer cell lines. Furthermore, compounds 1, 4-5, could cause blockage of the cell cycle in the G2/M phase and induce apoptosis in H460 cells. Notably, pungiolide P (1) exhibited significantly superior cytotoxicity compared to previously reported compounds, providing valuable insights for natural anti-tumor sources.
Subject(s)
Antineoplastic Agents, Phytogenic , Apoptosis , Drug Screening Assays, Antitumor , Fruit , Sesquiterpenes , Xanthium , Xanthium/chemistry , Humans , Sesquiterpenes/chemistry , Sesquiterpenes/pharmacology , Sesquiterpenes/isolation & purification , Fruit/chemistry , Antineoplastic Agents, Phytogenic/pharmacology , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/isolation & purification , Cell Line, Tumor , Apoptosis/drug effects , Molecular Structure , Structure-Activity Relationship , Cell Proliferation/drug effectsABSTRACT
Triterpenoids are a type of specialized metabolites that exhibit a wide range of biological activities. However, the availability of some minor triterpenoids in nature is limited, which has hindered our understanding of their pharmacological potential. To overcome this limitation, heterologous biosynthesis of triterpenoids in yeast has emerged as a promising and time-efficient production platform for obtaining these minor compounds. In this study, we analyzed the transcriptomic data of Enkianthus chinensis to identify one oxidosqualene cyclase (EcOSC) gene and four CYP716s. Through heterologous expression of these genes in yeast, nine natural pentacyclic triterpenoids, including three skeleton products (1-3) produced by one multifunctional OSC and six minor oxidation products (4-9) catalyzed by CYP716s, were obtained. Of note, we discovered that CYP716E60 could oxidize ursane-type and oleanane-type triterpenoids to produce 6ß-OH derivatives, marking the first confirmed C-6ß hydroxylation in an ursuane-type triterpenoid. Compound 9 showed moderate inhibitory activity against NO production and dose-dependently reduced IL-1ß and IL-6 production at the transcriptional and protein levels. Compounds 1, 2, 8, and 9 exhibited moderate hepatoprotective activity with the survival rates of HepG2 cells from 61% to 68% at 10 µM.
Subject(s)
Anti-Inflammatory Agents , Cytochrome P-450 Enzyme System , Intramolecular Transferases , Triterpenes , Triterpenes/pharmacology , Triterpenes/chemistry , Humans , Cytochrome P-450 Enzyme System/metabolism , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemistry , Molecular Structure , Saccharomyces cerevisiae , Hydroxylation , Hep G2 Cells , Interleukin-1beta/metabolism , Interleukin-6/metabolism , Protective Agents/pharmacology , Protective Agents/chemistryABSTRACT
Sesquiterpene synthases (STPSs) catalyze carbocation-driven cyclization reactions that can generate structurally diverse hydrocarbons. The deprotonation-reprotonation process is widely used in STPSs to promote structural diversity, largely attributable to the distinct regio/stereoselective reprotonations. However, the molecular basis for reprotonation regioselectivity remains largely understudied. Herein, we analyzed two highly paralogous STPSs, Artabotrys hexapetalus (-)-cyperene synthase (AhCS) and ishwarane synthase (AhIS), which catalyze reactions that are distinct from the regioselective protonation of germacrene A (GA), resulting in distinct skeletons of 5/5/6 tricyclic (-)-cyperene and 6/6/5/3 tetracyclic ishwarane, respectively. Isotopic labeling experiments demonstrated that these protonations occur at C3 and C6 of GA in AhCS and AhIS, respectively. The cryo-electron microscopy-derived AhCS complex structure provided the structural basis for identifying different key active site residues that may govern their functional disparity. The structure-guided mutagenesis of these residues resulted in successful functional interconversion between AhCS and AhIS, thus targeting the three active site residues [L311-S419-C458]/[M311-V419-A458] that may act as a C3/C6 reprotonation switch for GA. These findings facilitate the rational design or directed evolution of STPSs with structurally diverse skeletons.
Subject(s)
Alkyl and Aryl Transferases , Sesquiterpenes , Cryoelectron Microscopy , Sesquiterpenes/chemistry , Catalysis , Catalytic Domain , Alkyl and Aryl Transferases/geneticsABSTRACT
Three new cadinane sesquiterpenes (1-3) and three known sesquiterpenes were isolated from the stems and branches of Illicium ternstroemioides A. C. Smith. The structures of the new compounds were elucidated by extensive analysis of spectroscopic and HRESIMS data. The structures of illiternins A-C (1-3) were confirmed by single crystal X-ray diffraction, allowing for the determination of their absolute configurations. Compounds 3 and 6 exhibited antiviral activity against Coxsackievirus B3 with IC50 values of 33.3 and 57.7 µM, respectively.
Subject(s)
Illicium , Sesquiterpenes , Illicium/chemistry , Molecular Structure , Polycyclic Sesquiterpenes , Sesquiterpenes/chemistryABSTRACT
Six previously undescribed prenylated C6-C3 derivatives (1-6) were isolated from the root of Illicium ternstroemioides A. C. Smith. Their structures were elucidated based on extensive spectroscopic analyses (UV, IR, 1D and 2D NMR, and HRESIMS). The absolute configurations of 1-3 were determined using electronic circular dichroism (ECD), and Mo2(OAc)4 induced circular dichroism (ICD). Compound 3 exhibited weak activity against Coxsackievirus B3 with an IC50 value of 33.3 µM, and compound 5 exhibited more potent activity against Coxsackievirus B3 with an IC50 value of 6.4 µM.
Subject(s)
Illicium , Illicium/chemistry , Molecular Structure , Magnetic Resonance Spectroscopy , Circular Dichroism , Antiviral Agents/pharmacologyABSTRACT
Fifteen unreported prenylated C6-C3 derivatives (1-15) were isolated from the stems and branches of Illicium ternstroemioides A. C. Smith, including one bis-prenylated C6-C3 derivative (1), three prenylated C6-C3 derivative-shikimic acid ester hybrids (2-4) and 11 prenylated C6-C3 monomers (5-15). The structures of compounds 1-15 were elucidated by spectroscopic analysis (UV, IR, 1D and 2D NMR, and HRESIMS). The absolute configurations of the compounds were determined using electronic circular dichroism (ECD), induced circular dichroism (ICD), and the modified Mosher's method. Among the isolates, compounds 11, 12, and 15 exhibited significant anti-inflammatory activities by inhibiting the nitric oxide with IC50 values ranging from 1.89 to 24.83 µM in lipopolysaccharide-stimulated murine RAW 264.7 macrophages and murine BV2 microglial cells; compounds 2, 3, and 7 exhibited antiviral activitives against Coxsackievirus B3 with an IC50 value of 33.3, 25.9, and 27.8 µM, respectively.
Subject(s)
Illicium , Mice , Animals , Illicium/chemistry , Molecular Structure , Anti-Inflammatory Agents , Macrophages , Circular DichroismABSTRACT
The present study investigated the chemical constituents from the leaves of Craibiodendron yunnanense. The compounds were isolated and purified from the leaves of C. yunnanense by a combination of various chromatographic techniques including column chromatography over polyamide, silica gel, Sephadex LH-20, and reversed-phase HPLC. Their structures were identified by extensive spectroscopic analyses including MS and NMR data. As a result, 10 compounds, including melionoside F(1), meliosmaionol D(2), naringenin(3), quercetin-3-O-α-L-arabinopyranoside(4), epicatechin(5), quercetin-3'-glucoside(6), corbulain Ib(7), loliolide(8), asiatic acid(9), and ursolic acid(10), were isolated. Compounds 1 and 2 were two new compounds, and compound 7 was isolated from this genus for the first time. All compounds showed no significant cytotoxic activity by MTT assay.
Subject(s)
Catechin , Ericaceae , Quercetin , Plant Leaves , Chromatography, High Pressure LiquidABSTRACT
Eight undescribed ß-bergamotene-type sesquiterpene oliganins A-H (1-8) and one known α-bergamotene-type sesquiterpene (9) were isolated from the leaves and twigs of Illicium oligandrum Merr. & Chun. The structures of compounds 1-8 were elucidated by extensive spectroscopic data, and the absolute configurations were determined by using a modified Mosher's method and electronic circular dichroism calculations. The isolates were further evaluated in terms of their anti-inflammatory potential on nitric oxide (NO) generation in lipopolysaccharide-stimulated RAW264.7 and BV2 cells. Compounds 2 and 8 exhibited potent inhibitory effects on the production of NO with IC50 values ranging from 21.65 to 49.28 µM, which were greater than or comparable to those of dexamethasone (positive control).
Subject(s)
Illicium , Sesquiterpenes , Illicium/chemistry , Molecular Structure , Sesquiterpenes/pharmacology , Sesquiterpenes/chemistry , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemistry , Circular Dichroism , Nitric OxideABSTRACT
Chemical investigation of an alcohol extract from the twigs and leaves of Illicium henryi Diels resulted in the isolation of two new acorane-related seco-sesquiterpenes (1 and 3), two new acorane-related seco-norsesquiterpenes (2 and 4), one new 2-epi-cedrane sesquiterpene (5), eight new acorane-type sesquiterpenes (6-13), and a known major constituent of acorenone B (14). Their structures were established by interpreting extensive spectroscopic data, including HRESIMS, NMR (1H and 13C NMR, 1H-1H COSY, HSQC, and HMBC), and NOE difference spectra analysis. The absolute configurations of 1, 2, 4-7, 9, 10, and 14 were determined by X-ray crystallography, while chemical transformation methods were performed with compound 14 as the starting material to elegantly solve the absolute configuration issue of compounds 8 and 11-13. Notably, 1 and 2 are seco-sesquiterpenes that are related to acorane and possess an unusual ketal-linked hemiacetal in a 6,8-dioxabicyclo[3.2.1]octan-7-ol scaffold ring system. Plausible biosynthetic pathways for compounds 1-14, which were derived from the acorane skeleton, were proposed. All the isolated compounds (1-14) were evaluated for their antiviral and cytotoxic activities.
Subject(s)
Antiviral Agents , Illicium , Sesquiterpenes , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Illicium/chemistry , Magnetic Resonance Spectroscopy , Molecular Structure , Plant Leaves/chemistry , Sesquiterpenes/chemistry , Sesquiterpenes/pharmacologyABSTRACT
One new taraxastane-type triterpenoid, three new grayanane-type diterpenoids (2 - 4), and 12 known compounds (5 - 16) were isolated from the leaves of Craiobiodendron yunnanens W. W. Smith. The structures of these compounds were elucidated on the basis of their spectroscopic data and chemical evidence. Compounds 1 and 8 exhibited partly anti-inflammatory activity based on the inhibition of NF-κB activity in SW480 cells at 10 µM with inhibition ratios of 60.53 and 59.20%, respectively. Compounds 10 and 13 showed excellent cytotoxicity against human leukemia cell (MV4-11) at 10 µM with inhibition ratios of 43.02 and 49.11%, respectively.
Subject(s)
Diterpenes , Ericaceae , Humans , Terpenes/pharmacology , Molecular Structure , Ericaceae/chemistry , Plant Leaves/chemistry , Diterpenes/pharmacology , Diterpenes/chemistryABSTRACT
STUDY DESIGN: Cross-sectional study. OBJECTIVE: Recently, there has been a rise in children and adolescents developing low back pain and/or sciatica. Degenerative lumbar spine MRI phenotypes can occur in this population but reports have been sporadic and the true incidence of such spine changes remains debatable. As such, the study aimed to address the epidemiology of MRI phenotypes of the lumbar spine in this young population. METHODS: 597 children and adolescents with lumbar MRIs were included in the study. T1- and T2-weighted lumbar images from L1/2 to L5/S1 were analyzed in axial and sagittal planes. Global phenotype assessment was performed of each level and based on established nomenclature protocols. RESULTS: The cohort consisted of 57.3% (342) boys and 42.7% (255) girls, with a mean age of 10.75 ± 5.25 years (range: 0 to 18 years). The prevalence of imaging findings of lumbar disc degeneration (LDD) and lumbar disc herniation (LDH) were 2.2% (95% CI: 0.93-3.43) and 5.8% (95%CI: 2.58-8.99), respectively. There was significant difference between each disc segment from L1/2 to L5/S1 for both LDD and LDH. Schmorl's nodes were noted in 16 cases (2.7%, youngest case as 15 years), with 11 boys (68.8%) and most frequent segment as L3/4. Modic changes and high-intensity zones were absent in this cohort. CONCLUSIONS: LDD can emerge as early as the first decade of life with Schmorl's nodes, without additional specific phenotypes, including Modic changes and high-intensity zones. The study provides valuable information of a unique age group that is often under-represented but equally important as adults.
ABSTRACT
BACKGROUND: There is still uncertainty on whether ionizing radiation from CT scans can increase the risks of cancer. This study aimed to identify the association of cumulative ionizing radiation from CT scans with pertaining cancer risks in adults. METHODS: Five databases were searched from their inception to November 15, 2020. Observational studies reporting cancer risks from CT scans in adults were included. The main outcome included quantified cancer risks as cancer case numbers in exposed/unexposed adult participants with unified converted measures to odds ratio (OR) for relative risk, hazard ratio. Global background radiation (2.4 mSv per year) was used as control for lifetime attribution risk (LAR), with the same period from incubation after exposure until survival to 100 years. RESULTS: 25 studies were included with a sum of 111,649,943 participants (mean age: 45.37 years, 83.4% women), comprising 2,049,943 actual participants from 6 studies with an average follow-up period as 30.1 years (range, 5 to 80 years); 109,600,000 participants from 19 studies using LAR. The cancer risks for adults following CT scans were inordinately increased (LAR adults, OR, 10.00 [95% CI, 5.87 to 17.05]; actual adults, OR, 1.17 [95%CI, 0.89 to 1.55]; combined, OR, 5.89 [95%CI, 3.46 to 10.35]). Moreover, cancer risks elevated with increase of radiation dose (OR, 33.31 [95% CI, 21.33 to 52.02]), and multiple CT scan sites (OR, 14.08 [95% CI, 6.60 to 30.05]). The risk of solid malignancy was higher than leukemia. Notably, there were no significant differences for age, gender, country, continent, study quality and studying time phrases. CONCLUSIONS: Based on 111.6 million adult participants from 3 continents (Asia, Europe and America), this meta-analysis identifies an inordinately increase in cancer risks from CT scans for adults. Moreover, the cancer risks were positively correlated with radiation dose and CT sites. The meta-analysis highlights the awareness of potential cancer risks of CT scans as well as more reasonable methodology to quantify cancer risks in terms of life expectancy as 100 years for LAR. PROSPERO TRIAL REGISTRATION NUMBER: CRD42019133487.
Subject(s)
Leukemia , Neoplasms , Adult , Female , Humans , Middle Aged , Male , Tomography, X-Ray Computed/adverse effects , Neoplasms/diagnostic imaging , Neoplasms/epidemiology , Neoplasms/etiology , Radiation, Ionizing , Odds RatioABSTRACT
Four new germacrane-type sesquiterpenoids (1-4) and two new guaiane-type sesquiterpenoids (5-6) were isolated from the fruits of Xanthium italicum Moretti. The structures of the new compounds were elucidated on the basis of spectroscopic analysis and X-ray diffraction experiment. Compounds 1, 2 and 6 showed the anti-inflammatory effects against the activation of NF-κB induced by lipopolysaccharide (LPS) with IC50 values of 20.12, 22.89 and 68.66 µM, respectively.
Subject(s)
Sesquiterpenes , Xanthium , Xanthium/chemistry , Fruit/chemistry , Molecular Structure , Sesquiterpenes/pharmacology , Sesquiterpenes/chemistry , Lipopolysaccharides/pharmacologyABSTRACT
Four minor undescribed terpenoids, including a monoterpenoid (1) and three triterpenoids (3, 6 and 7), together with 26 known terpenoids were isolated from the stems and twigs of Rhododendron Ovatum. Their structures were identified by extensive spectroscopic analyses and electronic circular dichroism (ECD) techniques. Compound 10 showed excellent cytotoxicity against human colon cancer cell (HCT-116) with IC50 value of 2.56 µM. Compounds 9 and 19 exhibited partly inhibitory effects on nitric oxide production stimulated by lipopolysaccharide-induced neuroinflammation in microglia cells at 10 µM with inhibition ratios of 39.70% and 28.08%, respectively.
Subject(s)
Rhododendron , Triterpenes , Lipopolysaccharides/pharmacology , Molecular Structure , Nitric Oxide , Rhododendron/chemistry , Terpenes/chemistry , Terpenes/pharmacology , Triterpenes/chemistryABSTRACT
A pair of new lignans [(+)- 1 and (-)- 1] and three new compounds (2-4), together with a known compound 5, were isolated from the fruits of Xanthium italicum Moretti. The structures of these compounds were determined on the basis of spectroscopic analysis, particularly HR-ESI-MS and 1 D and 2 D NMR. Compounds 2 and 3 showed antinociceptive effects in an acetic acid-induced writhing test in mice with the writhe inhibition rates of 80.50% and 67.89% at the dose of 20 mg/kg, respectively.
Subject(s)
Diterpenes , Lignans , Xanthium , Animals , Fruit/chemistry , Glycosides/chemistry , Lignans/analysis , Lignans/pharmacology , Mice , Molecular Structure , Xanthium/chemistryABSTRACT
BACKGROUND: Chronic non-specific low back pain (NLBP) affects people of all ages and pose a serious threat to human health. Fu's subcutaneous needling (FSN) has been reported to be effective in treating such disorders, but the control group is lacking. The aim of this randomized parallel study is to compare the long-term efficiency of FSN therapy with massage therapy for treatment of NLBP. METHODS: A total of 60 chronic NLBP patients recruited from Yongchuan Hospital of Chongqing Medical University were randomly assigned to the FSN therapy group or massage therapy group. The main prognostic indicators included pain intensity measured on the visual analog scale (VAS), functional outcomes assessed by the Japanese Orthopedic Association (JOA) scoring system, functional disability estimated using Oswestry Disability Index (ODI), and quality of life evaluated by Short Form Health Survey Questionnaire (SF-36). These indicators were evaluated at baseline, post-treatment, 3 months after treatment, and 12 months after treatment. RESULTS: After 12 months of follow-up, we found that the 2 treatment regimens exhibited similarly favorable results in terms of all prognostic indicators in comparison with their respective baseline data (all P<0.01). However, compared with the massage group, the FSN group showed more significant improvements in VAS, JOA, and ODI at all follow-up time points, as well as SF-36 at post-treatment and 12 months after treatment (all P<0.05). CONCLUSIONS: Our findings suggest that FSN therapy is significantly more effective than massage therapy in the improvement of pain intensity, functional outcomes, functional disability, and quality of life in a long-term follow-up. However, future studies with larger sample sizes are needed to corroborate the long-term efficiency of FSN therapy for chronic NLBP. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100050866.
Subject(s)
Low Back Pain , Humans , Low Back Pain/therapy , Massage , Pain Measurement , Quality of Life , Treatment OutcomeABSTRACT
The mechanism of sex determination remains poorly understood in hemimetabolous insects. Here, in the brown planthopper (BPH), Nilaparvata lugens, a hemipteran rice pest, we identified a feminizing switch or a female determiner (Nlfmd) that encodes a serine/arginine-rich protein. Knockdown of Nlfmd in female nymphs resulted in masculinization of both the somatic morphology and doublesex splicing. The female-specific isoform of Nlfmd, Nlfmd-F, is maternally deposited and zygotically transcribed. Depletion of Nlfmd by maternal RNAi or CRISPR-Cas9 resulted in female-specific embryonic lethality. Knockdown of an hnRNP40 family gene named female determiner 2 (Nlfmd2) also conferred masculinization. In vitro experiments showed that an Nlfmd2 isoform, NlFMD2340, bound the RAAGAA repeat motif in the Nldsx pre-mRNA and formed a protein complex with NlFMD-F to modulate Nldsx splicing, suggesting that NlFMD2 may function as an RNA binding partner of the feminizing switch NlFMD. Our results provide novel insights into the diverse mechanisms of insect sex determination.
ABSTRACT
Thirteen compounds were isolated from the lipid-soluble extracts of Illicium ternstroemioides A. C. Smith, including eleven previously undescribed prenylated C6-C3 compounds, a previously undescribed prenylated C6-C3 derivative-abscisic acid ester hybrid, and a known compound (4S)-illicinone I. Their structures and configurations were mainly elucidated by spectroscopic analyses, CD experiments and X-ray crystallography. (2S,4R,11S)-4-O-methyl-12-chloroillifunone C, (2S,4R,11R)-2,3-dihydro-4-O-methyl illioliganfunone D, and illiternfunol A were found to exhibit weak activity against Coxsackievirus B3, with IC50 values ranging from 27.8 to 33.3 µM. Illiternone B exhibited more potent activities against Coxsackievirus B3 and influenza virus A than did its geometric isomer illiternone A, with IC50 values of 7.7 µM and 2.5 µM, respectively. None of these compounds displayed cytotoxic activities.
Subject(s)
Illicium , Antiviral Agents/pharmacology , Crystallography, X-Ray , Molecular StructureABSTRACT
Lumbar spinal stenosis (LSS), which often occurs concurrently with degenerative spondylolisthesis (DS), is a common disease in the elderly population, affecting the quality of life of aged people significantly. Notwithstanding the frequently good effect of conservative therapy on LSS, a minority of the patients ultimately require surgery. Surgery for LSS aims to decompress the narrowed spinal canals with preservation of spinal stability. Traditional open surgery, either pure decompression or decompression with fusion, was considered effective for the treatment of LSS with or without DS. However, the long-term clinical outcomes of traditional open surgery are still unclear. Moreover, the disadvantages of conventional open surgery are extensive, examples including tissue injuries or secondary instability, with limited outcomes and significant reoperation rates. With the development and improvement of surgical tools, various minimally invasive spine surgery (MISS) methods, including indirect decompression techniques of interspinous process devices (IPDs) and direct decompression techniques such as microscopic spine surgery or endoscopic spine surgery (ESS), have been updated with enhancement. IPDs, such as Superion devices, were reported to behave with comparable physical function, disability, and symptoms outcomes to laminectomy decompression. As an emerging technique of MISS, ESS has beneficial hallmarks including minimal tissue injuries, reduced complication rates, and shortened recovery periods, thus gaining popularity in recent years. ESS can be classified in terms of endoscopic hallmarks and approaches. Predictably, with the continuous development and gradual maturity, MISS is expected to replace traditional open surgery widely in the surgical treatment of LSS associated with DS in the future.
ABSTRACT
BACKGROUND: Congenital pseudoarthrosis of the clavicle (CPC) is an uncommon entity. Owing to its scarce presentation, treatment of this disorder has not been well established. This study aimed (1) to compare surgical treatment methods that included excision of pseudoarthrosis and iliac crest bone graft and fixate with either the elastic stable intramedullary nail (ESIN) or K-wires or plate and screws, and (2) to assess the clinical outcomes of two different surgical methods. METHODS: A multi-central retrospective study was performed between 2013 and 2017 in four tertiary teaching hospitals. Fifteen clavicles of 11 children were identified as CPC. All patients underwent pseudarthrosis resection and iliac crest bone autograft. They were divided into two groups as per the surgical treatment they underwent-plate stabilization as group A and elastic stable intramedullary nailing (ESIN) or K-wires as group B. Nine clavicles in 6 patients in group A and 6 clavicles in 5 patients in group B, were included. The Quick Disabilities of the Arm and Shoulder (QuickDASH) score was used to assess patients' satisfaction and function following treatment at each follow-up. RESULTS: There were eight boys and three girls, with an average age of 4.7 years. All patients, except one with intellectual impairments, had radiological healing. Implant removal time was significantly shorter in group B compared to group A. No statistically significant differences existed in terms of age at surgery, time of radiological healing, complication, and clinical outcome between different groups. CONCLUSION: Surgical resection of pseudoarthrosis with an iliac crest bone graft was an effective means of surgical treatment in CPC. However, ESIN or K-wires can achieve shorter union time compared to the plate. Hence, surgical treatment is recommended for congenital pseudarthrosis of clavicular in pediatric patients. LEVEL OF EVIDENCE: Retrospective comparative study; Level III.