Objective To explore the effect of CB-103 on pyroptosis in oral squamous cell carcinoma(OSCC)cells via the reactive oxygen species(ROS)/caspase-3/gasdermin-E(GSDME)signaling pathway.Methods The OSCC cell line SCC-7 was treated with varying concentrations of CB-103(0,20,40,60,80,and 100 μg/mL).The proliferation activity of CB-103 cells was measured using cell counting kit-8(CCK-8)assay.The cell migration was assessed using a wound-healing assay.Morphological changes in the cells were observed under an inverted microscope.Western blotting was performed to evaluate the protein expression of GSDME,GSDME-N ter-minal,and cleaved caspase-3.ATP release was measured using an ATP detection kit.The levels of intracellular high-mobility group box 1(HMGB1)and ROS were quantified by immunofluorescence.Results Compared to the control group,CB-103 inhibited the proliferation and migration of SCC-7 cells.Additionally,CB-103 increased ROS levels and upregulated the expression of cleaved caspase-3 protein.Furthermore,CB-103 promoted the cleavage of GSDME and increased the number of GSDME-N terminal fragments(all P＜0.05),thereby inducing pyroptosis in SCC-7 cells.Conclusion CB-103 promotes pyroptosis in OSCC cells by activating the ROS/caspase-3/GSDME pathway.

Objective:To preliminarily explore the relationship between intraventricular pressure gradients (IVPG) measured by ultrasound hemodynamic analysis and left ventricular cardiotoxicity after anthracycline chemotherapy.Methods:This was a retrospective cohort study. Patients with diffuse large B-cell lymphoma (DLBCL) who completed 6 cycles of R-CHOP chemotherapy at Fudan University Shanghai Cancer Center from 2014 to 2015 were included. Echocardiography was performed at baseline (T0), after 2 cycles of chemotherapy (T1), after 4 cycles of chemotherapy (T2), and after all chemotherapy cycles (T3). Left ventricular global longitudinal strain (LVGLS), left ventricular global circumferential strain (LVGCS), and left ventricular ejection fraction (LVEF) were analyzed using speckle-tracking imaging technology, and IVPG was measured using hemodynamic analysis technology, including IVPG of long-axis (IVPG-LA) and IVPG of short-axis. The change rate of each index from T0 to T2 was marked as Δ. Left ventricular cardiotoxicity was defined as a decrease in LVEF of ≥10% from the baseline level or LVEF ≤50%. Univariate logistic regression analysis was used to explore the related factors of left ventricular myocardial toxicity, and the receiver operating characteristic curve was drawn to analyze their evaluation efficiency for left ventricular myocardial toxicity.Results:A total of 55 patients were included, including 28 males (51%), aged (46.5±11.7) years. Twelve patients (22%) developed left ventricular cardiotoxicity. Compared with T0, IVPG-LA decreased at T1 ((10.73±2.51)% vs. (11.52±3.62)%, P=0.037); while LVGLS, LVGCS, and LVEF only decreased at T3 (all P<0.05). Univariate logistic regression analysis showed that ΔIVPG-LA and ΔLVGLS were related factors for left ventricular myocardial toxicity in patients with DLBCL receiving chemotherapy (all P<0.05). The receiver operating characteristic curve showed that the area under the curve of ΔLVGLS was 0.702, with an optimal cut-off value of 13.15% (sensitivity 66.7%, specificity 62.8%); the area under the curve of ΔIVPG-LA was 0.812, with an optimal cut-off value of 20.74% (sensitivity 75.0%, specificity 90.7%). Conclusions:Hemodynamic analysis technology shows promise clinical application value in evaluating subclinical changes in left ventricular function in tumor patients after anthracycline chemotherapy; the change rate of IVPG-LA could be used as an early indicator of left ventricular toxicity after anthracycline chemotherapy.

Objective:To explore the spectrum of genetic variants and phenotypes of Phenylalanine hydroxylase deficiency (PAHD) in Lianyungang area and the correlation between genotype and phenotypes among the patients.Methods:Eighty children with Hyperphenylalaninemia (HPA) diagnosed at the Lianyungang Branch of Jiangsu Provincial Newborn Screening Center between January 2015 and December 2022 were enrolled. Peripheral blood samples were collected for genetic analysis using next generation sequencing (NGS), Sanger sequencing, and multiplex ligation-dependent probe amplification (MLPA) to identify the variants of PAH gene. Clinical and phenotypic data were concurrently analyzed to investigate the correlation between the types of PAH gene variant and phenotypes. This study was approved by the Medical Ethics Committee of Lianyungang Maternal and Child Health Care Hospital (Ethics No.: XM2022041). Results:① PAH variants were identified in 93.75% (75/80) of the children, classified as PAHD cases, while 6.25% (5/80) harbored PTS variants. ② Of the 150 PAH alleles from 75 PAHD children, a total of 152 variants (55 distinct types) were detected, with a detection rate of 100%. 80.26% (122/152) were located in exons, with the main types of variants were missense variants (67.11%, 102/152). 53.29% (81/152) of coding sequence variants occurred in the PAH gene catalytic center region of PAH protein, while 19.74% (30/152) of variants involved non-coding sequences. ③The phenotypes of the 75 PAHD children were evenly distributed. The rescreening Phe concentrations and Phe/Tyr ratios of classic-phenylketonuria (CPKU) and mild-phenylketonuria (MPKU) patients were markedly higher than initial screening values ( P<0.001, P<0.001; P=0.004, P=0.016). The genotypes of the PAHD patients mostly occurred as compound heterozygotes, and different mutation positions and variant types significantly affect the phenotype ( P=0.042, P=0.045). ④APV/GPV genotype-phenotype analysis of 61 patients showed high consistency between predicted and actual phenotypes ( κ=0.755, P<0.001). Conclusion:PAH variants were detected in the most of HPA children in Lianyungang area. The location and type of PAH variants were related to the severity of the phenotype, and the non-coding sequence variants and non-missense variants may aggravate the phenotype, and the APV/GPV model predicted the phenotype was highly consistent with the actual phenotype.

Objective:To explore the changes of atlantoaxial joint spaces and pharyngeal airway after combined orthodontic-orthognathic treatment in skeletal class Ⅲ patients with mandibular deviation.Methods:A total of 34 adult skeletal class Ⅲ patients (10 males and 24 females) with mandibular deviation who received combined orthodontic-orthognathic treatment at the Department of Orthodontics and the Department of Orthognathic Surgery in the Stomatological Hospital of Chongqing Medical University from August 2014 to October 2021 were retrospectively selected. The patients were 22 (5) years old (18-33 years). Cone-beam CT data of patients taken before treatment (T0), after preoperative orthodontics (T1), and 6 to 12 months after orthognathic surgery (T2) were collected. The anterior atlanto-dental interval (ADI), variance of bilateral lateral atlanto-dental interval (VBLADI), the anterior posterior length (APL), maximum transverse width (LTW), aspect ratio (L/W), cross-sectional area (CSA) of each airway cross-section, the airway volumes, as well as the positions of the maxillofacial landmark points [subspinale (point A), supramental (point B), posterior nasal spine (point PNS), the most anterior and superior point of the hyoid bone (point H)] were measured at different time points. The correlations between airway changes, maxillofacial movements as well as the changes in the atlantoaxial joint spaces were also analyzed.Results:During the combined orthodontic-orthognathic treatment, no statistically significant differences were found in the ADI and VBLADI among different treatment time points (all P>0.05). After preoperative orthodontics, the volume of total airway increased from 20 868 (6 669) mm 3 to 21 302 (8 911) mm 3 ( P<0.05). After orthognathic surgery, there were no statistically significant differences in the APL, CSA of the PNS plane, the L/W of the uvula plane, and the nasopharyngeal airway volume compared with those after preoperative orthodontics (all P>0.05). The L/W of the PNS plane after surgery was significantly increased compared with that after preoperative orthodontics ( P<0.05), while other airway parameters were all significantly decreased compared with those after preoperative orthodontics (all P<0.05). Compared with before treatment, the nasopharyngeal airway volume after surgery [6 186 (1 707) mm3] increased significantly ( P<0.05) and the palatopharyngeal airway volume [8 145 (2 594) mm3] and the glossopharyngeal airway volume [5 605 (4 395) mm3] decreased significantly (all P<0.05). There was no statistically significant difference in the total airway volume between after surgery and before treatment ( P>0.05). Correlation analysis showed that after preoperative orthodontics, the amount of the sagittal movement of point B was moderately positively correlated with the total airway volume change ( r=0.40, P=0.022). Before and after orthognathic surgery, the amount of the sagittal movement of point PNS was moderately positively correlated with the changes in the palatopharyngeal airway volume and the total airway volume ( r=0.43, P=0.015; r=0.46, P=0.008). In addition, the change in VBLADI before and after orthognathic surgery was weakly positively correlated with the changes in the CSA of the PNS plane and the APL of the uvula plane ( r=0.35, P=0.029; r=0.38, P=0.016). Conclusions:During the combined orthodontic-orthognathic treatment, the anterior atlanto-dental interval in skeletal class Ⅲ patients with mandibular deviation remained stable among different treatment time points. The total airway volume increased after preoperative orthodontics. After orthognathic surgery, the backward movement of the mandible tended to reduce the size of the pharyngeal airway, and the morphology of the glossopharyngeal airway tended to become more flattened. The changes in the pharyngeal airway dimensions were correlated with the maxillomandibular movements and the atlantoaxial joint space changes.

OBJECTIVE: To explore the spectrum of genetic variants and phenotypes of Phenylalanine hydroxylase deficiency (PAHD) in Lianyungang area and the correlation between genotype and phenotypes among the patients. METHODS: Eighty children with Hyperphenylalaninemia (HPA) diagnosed at the Lianyungang Branch of Jiangsu Provincial Newborn Screening Center between January 2015 and December 2022 were enrolled. Peripheral blood samples were collected for genetic analysis using next generation sequencing (NGS), Sanger sequencing, and multiplex ligation-dependent probe amplification (MLPA) to identify the variants of PAH gene. Clinical and phenotypic data were concurrently analyzed to investigate the correlation between the types of PAH gene variant and phenotypes. This study was approved by the Medical Ethics Committee of Lianyungang Maternal and Child Health Care Hospital (Ethics No.: XM2022041). RESULTS: PAH gene variants were identified in 93.75% (75/80) of the children, classified as PAHD cases, while 6.25% (5/80) harbored PTS gene variants. Of the 150 PAH alleles from 75 PAHD children, a total of 152 variants (55 distinct types) were detected, with a detection rate of 100%. 80.26% (122/152) of the variants were located in exons, with the main types being missense variants (67.11%, 102/152). 53.29% (81/152) of coding sequence variants have occurred in the PAH gene's catalytic center region, while 19.74% (30/152) of the variants involved non-coding sequences. The phenotypes of the 75 PAHD children were evenly distributed. The re-screened Phe concentrations and Phe/Tyr ratios of classic-phenylketonuria (CPKU) and mild-phenylketonuria (MPKU) patients were markedly higher than initial screening values (P < 0.001, P < 0.001; P = 0.004, P = 0.016). The genotypes of the PAHD patients mostly occurred as compound heterozygotes, and different mutation positions and variant types have significantly affected the phenotypes (P = 0.042, P = 0.045). APV/GPV genotype-phenotype analysis of 61 patients showed high consistency between predicted and actual phenotypes (κ = 0.755, P < 0.001). CONCLUSION PAH gene variants were detected in most HPA children from Lianyungang area. The location and type of PAH gene variants has correlated with the severity of the phenotype, and the non-coding sequence variants and non-missense variants may aggravate the phenotype, and the APV/GPV model has predicted the phenotype with high consistency with the actual phenotype.
Humans ; Phenylalanine Hydroxylase/genetics* ; Female ; Phenylketonurias/enzymology* ; Male ; Phenotype ; Genotype ; Child ; Infant ; Infant, Newborn ; Child, Preschool ; China ; Mutation ; Alleles

Objective:To explore the changes of atlantoaxial joint spaces and pharyngeal airway after combined orthodontic-orthognathic treatment in skeletal class Ⅲ patients with mandibular deviation.Methods:A total of 34 adult skeletal class Ⅲ patients (10 males and 24 females) with mandibular deviation who received combined orthodontic-orthognathic treatment at the Department of Orthodontics and the Department of Orthognathic Surgery in the Stomatological Hospital of Chongqing Medical University from August 2014 to October 2021 were retrospectively selected. The patients were 22 (5) years old (18-33 years). Cone-beam CT data of patients taken before treatment (T0), after preoperative orthodontics (T1), and 6 to 12 months after orthognathic surgery (T2) were collected. The anterior atlanto-dental interval (ADI), variance of bilateral lateral atlanto-dental interval (VBLADI), the anterior posterior length (APL), maximum transverse width (LTW), aspect ratio (L/W), cross-sectional area (CSA) of each airway cross-section, the airway volumes, as well as the positions of the maxillofacial landmark points [subspinale (point A), supramental (point B), posterior nasal spine (point PNS), the most anterior and superior point of the hyoid bone (point H)] were measured at different time points. The correlations between airway changes, maxillofacial movements as well as the changes in the atlantoaxial joint spaces were also analyzed.Results:During the combined orthodontic-orthognathic treatment, no statistically significant differences were found in the ADI and VBLADI among different treatment time points (all P>0.05). After preoperative orthodontics, the volume of total airway increased from 20 868 (6 669) mm 3 to 21 302 (8 911) mm 3 ( P<0.05). After orthognathic surgery, there were no statistically significant differences in the APL, CSA of the PNS plane, the L/W of the uvula plane, and the nasopharyngeal airway volume compared with those after preoperative orthodontics (all P>0.05). The L/W of the PNS plane after surgery was significantly increased compared with that after preoperative orthodontics ( P<0.05), while other airway parameters were all significantly decreased compared with those after preoperative orthodontics (all P<0.05). Compared with before treatment, the nasopharyngeal airway volume after surgery [6 186 (1 707) mm3] increased significantly ( P<0.05) and the palatopharyngeal airway volume [8 145 (2 594) mm3] and the glossopharyngeal airway volume [5 605 (4 395) mm3] decreased significantly (all P<0.05). There was no statistically significant difference in the total airway volume between after surgery and before treatment ( P>0.05). Correlation analysis showed that after preoperative orthodontics, the amount of the sagittal movement of point B was moderately positively correlated with the total airway volume change ( r=0.40, P=0.022). Before and after orthognathic surgery, the amount of the sagittal movement of point PNS was moderately positively correlated with the changes in the palatopharyngeal airway volume and the total airway volume ( r=0.43, P=0.015; r=0.46, P=0.008). In addition, the change in VBLADI before and after orthognathic surgery was weakly positively correlated with the changes in the CSA of the PNS plane and the APL of the uvula plane ( r=0.35, P=0.029; r=0.38, P=0.016). Conclusions:During the combined orthodontic-orthognathic treatment, the anterior atlanto-dental interval in skeletal class Ⅲ patients with mandibular deviation remained stable among different treatment time points. The total airway volume increased after preoperative orthodontics. After orthognathic surgery, the backward movement of the mandible tended to reduce the size of the pharyngeal airway, and the morphology of the glossopharyngeal airway tended to become more flattened. The changes in the pharyngeal airway dimensions were correlated with the maxillomandibular movements and the atlantoaxial joint space changes.

Objective To explore the effect of CB-103 on pyroptosis in oral squamous cell carcinoma(OSCC)cells via the reactive oxygen species(ROS)/caspase-3/gasdermin-E(GSDME)signaling pathway.Methods The OSCC cell line SCC-7 was treated with varying concentrations of CB-103(0,20,40,60,80,and 100 μg/mL).The proliferation activity of CB-103 cells was measured using cell counting kit-8(CCK-8)assay.The cell migration was assessed using a wound-healing assay.Morphological changes in the cells were observed under an inverted microscope.Western blotting was performed to evaluate the protein expression of GSDME,GSDME-N ter-minal,and cleaved caspase-3.ATP release was measured using an ATP detection kit.The levels of intracellular high-mobility group box 1(HMGB1)and ROS were quantified by immunofluorescence.Results Compared to the control group,CB-103 inhibited the proliferation and migration of SCC-7 cells.Additionally,CB-103 increased ROS levels and upregulated the expression of cleaved caspase-3 protein.Furthermore,CB-103 promoted the cleavage of GSDME and increased the number of GSDME-N terminal fragments(all P＜0.05),thereby inducing pyroptosis in SCC-7 cells.Conclusion CB-103 promotes pyroptosis in OSCC cells by activating the ROS/caspase-3/GSDME pathway.

Objective:To explore the spectrum of genetic variants and phenotypes of Phenylalanine hydroxylase deficiency (PAHD) in Lianyungang area and the correlation between genotype and phenotypes among the patients.Methods:Eighty children with Hyperphenylalaninemia (HPA) diagnosed at the Lianyungang Branch of Jiangsu Provincial Newborn Screening Center between January 2015 and December 2022 were enrolled. Peripheral blood samples were collected for genetic analysis using next generation sequencing (NGS), Sanger sequencing, and multiplex ligation-dependent probe amplification (MLPA) to identify the variants of PAH gene. Clinical and phenotypic data were concurrently analyzed to investigate the correlation between the types of PAH gene variant and phenotypes. This study was approved by the Medical Ethics Committee of Lianyungang Maternal and Child Health Care Hospital (Ethics No.: XM2022041). Results:① PAH variants were identified in 93.75% (75/80) of the children, classified as PAHD cases, while 6.25% (5/80) harbored PTS variants. ② Of the 150 PAH alleles from 75 PAHD children, a total of 152 variants (55 distinct types) were detected, with a detection rate of 100%. 80.26% (122/152) were located in exons, with the main types of variants were missense variants (67.11%, 102/152). 53.29% (81/152) of coding sequence variants occurred in the PAH gene catalytic center region of PAH protein, while 19.74% (30/152) of variants involved non-coding sequences. ③The phenotypes of the 75 PAHD children were evenly distributed. The rescreening Phe concentrations and Phe/Tyr ratios of classic-phenylketonuria (CPKU) and mild-phenylketonuria (MPKU) patients were markedly higher than initial screening values ( P<0.001, P<0.001; P=0.004, P=0.016). The genotypes of the PAHD patients mostly occurred as compound heterozygotes, and different mutation positions and variant types significantly affect the phenotype ( P=0.042, P=0.045). ④APV/GPV genotype-phenotype analysis of 61 patients showed high consistency between predicted and actual phenotypes ( κ=0.755, P<0.001). Conclusion:PAH variants were detected in the most of HPA children in Lianyungang area. The location and type of PAH variants were related to the severity of the phenotype, and the non-coding sequence variants and non-missense variants may aggravate the phenotype, and the APV/GPV model predicted the phenotype was highly consistent with the actual phenotype.

Objective:To preliminarily explore the relationship between intraventricular pressure gradients (IVPG) measured by ultrasound hemodynamic analysis and left ventricular cardiotoxicity after anthracycline chemotherapy.Methods:This was a retrospective cohort study. Patients with diffuse large B-cell lymphoma (DLBCL) who completed 6 cycles of R-CHOP chemotherapy at Fudan University Shanghai Cancer Center from 2014 to 2015 were included. Echocardiography was performed at baseline (T0), after 2 cycles of chemotherapy (T1), after 4 cycles of chemotherapy (T2), and after all chemotherapy cycles (T3). Left ventricular global longitudinal strain (LVGLS), left ventricular global circumferential strain (LVGCS), and left ventricular ejection fraction (LVEF) were analyzed using speckle-tracking imaging technology, and IVPG was measured using hemodynamic analysis technology, including IVPG of long-axis (IVPG-LA) and IVPG of short-axis. The change rate of each index from T0 to T2 was marked as Δ. Left ventricular cardiotoxicity was defined as a decrease in LVEF of ≥10% from the baseline level or LVEF ≤50%. Univariate logistic regression analysis was used to explore the related factors of left ventricular myocardial toxicity, and the receiver operating characteristic curve was drawn to analyze their evaluation efficiency for left ventricular myocardial toxicity.Results:A total of 55 patients were included, including 28 males (51%), aged (46.5±11.7) years. Twelve patients (22%) developed left ventricular cardiotoxicity. Compared with T0, IVPG-LA decreased at T1 ((10.73±2.51)% vs. (11.52±3.62)%, P=0.037); while LVGLS, LVGCS, and LVEF only decreased at T3 (all P<0.05). Univariate logistic regression analysis showed that ΔIVPG-LA and ΔLVGLS were related factors for left ventricular myocardial toxicity in patients with DLBCL receiving chemotherapy (all P<0.05). The receiver operating characteristic curve showed that the area under the curve of ΔLVGLS was 0.702, with an optimal cut-off value of 13.15% (sensitivity 66.7%, specificity 62.8%); the area under the curve of ΔIVPG-LA was 0.812, with an optimal cut-off value of 20.74% (sensitivity 75.0%, specificity 90.7%). Conclusions:Hemodynamic analysis technology shows promise clinical application value in evaluating subclinical changes in left ventricular function in tumor patients after anthracycline chemotherapy; the change rate of IVPG-LA could be used as an early indicator of left ventricular toxicity after anthracycline chemotherapy.

Objective:To compare the efficacy of maxillary distraction osteogenesis (DO) and Le FortⅠ osteotomy (LFⅠ) in patients with complex cleft lip and palate.Methods:A retrospective study was conducted, clinical data were collected involving patients with complex cleft lip and palate who required combined orthodontic and orthognathic treatment and were treated at the Stomatological Hospital of Chongqing Medical University from January 2015 to December 2022. Patients were divided into three groups based on the surgical method used for the maxilla: total maxillary distraction (TMD, group A), anterior maxillary distraction (AMD, group B), and Le Fort Ⅰ osteotomy (LFⅠ, group C). Cone-beam CT scans and lateral cephalograms were obtained preoperatively and at 3 months postoperatively. Three-dimensional reconstructions were performed using Mimics 21.0 and Dolphin Imaging 11.9 software to evaluate changes in craniofacial morphology and airway. Data analysis was conducted using SPSS 25.0. Intragroup comparisons before and after surgery were performed using the Wilcoxon rank sum test, and intergroup comparisons among the three groups were conducted using the Kruskal-Wallis H test. Results:A total of 15 patients were included, with 5 patients in each group. The cohort comprised 8 males and 7 females, aged between 15 and 21 years. There were no statistically significant differences in the distribution of gender, age, or cleft lip and palate classification among the three groups ( P>0.05). Postoperatively, all three groups showed improvement in maxillary hypoplasia. Compared to preoperative measurements, the angle formed by the points A (subspinale), N (nasion), and B (supramentale) (ANB angle) increased in all three groups (all P<0.05). The vertical distance from point A to the nasion perpendicular (A-Nperp) increased in groups A and B ( P<0.05 for both) but not in group C ( P>0.05). The area of the alveolar gap showed an increasing trend in all three groups ( P>0.05). The mandibular plane angle (FMA) decreased postoperatively in group B but showed an increasing trend in the other two groups, though the differences were not statistically significant ( P>0.05). Postoperative airway volume increased or showed an increasing trend in groups A ( P<0.05) and B ( P>0.05) but decreased in group C ( P>0.05). Intergroup comparisons showed significant differences in the angle formed by the sella (S), nasion (N), and point A (SNA angle) and the vertical distance from the anterior nasal spine to the coronal plane (ANS-CP) ( P<0.05). Group A had significantly larger SNA angles and ANS-CP values than group B, and the ANS-CP value in group A was significantly larger than in group C (all P<0.05). There were no other statistically significant differences among the groups ( P>0.05). Conclusion:For patients with severe maxillary hypoplasia due to complex cleft lip and palate, TMD can correct sagittal discrepancies between the upper and lower jaws, increase upper airway volume, but may potentially enlarge the alveolar gap area and increase vertical height of the maxilla. AMD result in less change in maxillary position compared to TMD and is mainly used for patients with severe maxillary dental crowding, needing increased arch length, having minor sagittal discrepancies, or with preexisting velopharyngeal dysfunction. LFⅠ result in changes in maxillary position similar to AMD but less than TMD, making it suitable for patients with moderate maxillary hypoplasia and mild maxillary dental crowding. The advantage of LFⅠ lies in its precise postoperative occlusal design and accurate three-dimensional movement of the jaw.