The use of tyrosine kinase inhibitors （TKI） has been an important advance in the systemic treatment of hepatocellular carcinoma， but their sustained anti-angiogenic therapy leads to increased tumor hypoxia， accelerates the development of a hypoxic microenvironment and promotes the expressions of hypoxia-inducible factors （HIF）， thereby inducing drug resistance of tumor patients to TKI. This paper summarizes the mechanism of action of HIF mediating TKI resistance in hepatocellular carcinoma in aspects of metabolic reprogramming， abnormal expressions of cancer and cancer-associated genes， and ferroptosis， and sorts resistance response strategies to provide reference for clinical solutions to TKI resistance issues. As results show， HIF/ glycolysis axis inhibitors （isoflavonoid genistein， simvastatin， etc.） can improve TKI resistance based on metabolic reprogramming mechanism； oncogene-targeted inhibitors combined with TKI （the combination of capsaicin and sorafenib） can improve TKI resistance based on abnormal expression of cancer and cancer-related genes； fatty acid synthase inhibitor （orlistat） can improve TKI resistance based on ferroptosis mechanism.

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.

Objective:To compare the impact of orthodontic treatment on pulp volume in adolescents and adults.Methods:Cone-beam CT data of 62 patients undergoing orthodontic treatment at the Department of Orthodontics, Stomatological Hospital of Chongqing Medical University, from January 2019 to March 2022 were collected. Patients were divided into two age groups (31 patients in each group): adolescent group (aged 13-17, 17 males and 14 females) and adult group (aged 21-25, 12 males and 19 females). Pre-and post-treatment reconstructions of the pulp and dental tissues of upper first molars (UM1) and lower central incisors (L1) were performed. Measurements included pulp volume for UM1 (UM1 P) and L1 (L1 P), pulp chamber volume (UM1 PC) and root canal volume (UM1 RC) for UM1, root length for L1 (L1 RL), and mesiobuccal root length for UM1 (UM1 RL), as well as chamber heights at specific landmarks [the lengths from the central fossa fusion site to the roof of the pulp chamber (H1), the floor of the pulp chamber (H2), the nearest point of root divergence as well as crown-root bifurcation (H3), the farthest point of root divergence (H4), and the pulp chamber height (H5)] in UM1. Changes in these indices were calculated and analyzed using paired and independent sample t-tests for within-group and between-group differences, respectively. Pearson correlation was used to assess potential associations among H5, root length, and pulp volume changes. Results:Before and after orthodontic treatment, no significant difference was observed in the adult group for L1 P ( t=-0.03, P=0.975), while significant differences were noted for UM1 P, UM1 PC, and UM1 RC ( t=9.98, P<0.001; t=9.04, P<0.001; t=6.69, P<0.001). In the adolescent group, significant differences were found for both L1 P and UM1 P ( t=2.25, P=0.029; t=6.30, P<0.001). After orthodontic treatment, the absolute value changes of UM1 P, UM1 PC, and L1 P in the adolescent group were (19.75±9.58), (15.07±7.65) and (1.89±6.29) mm 3, respectively, and in the adult group were (13.33±9.41), (9.16±7.05) and (0.02±4.66) mm 3, respectively ( t=3.77, P<0.001; t=4.48, P<0.001; t=2.34, P=0.048). There was no significant absolute difference in the amount of UM1 RC between the two groups after orthodontic treatment ( t=0.86, P=0.391). Before and after orthodontic treatment, the absolute value changes of L1 RL, H1 and H5 in the adolescent group were (0.54±0.41), (0.38±0.27) and (0.71±0.33) mm, respectively, and the absolute value changes in the adult group were (0.78±0.62), (0.26±0.20) and (0.57±0.28) mm, respectively ( t=-2.43, P=0.017; t=2.96, P=0.004; t=2.57, P=0.011). Whereas no significant differences were observed for UM1 RL, H2, H3, and H4 ( t=-0.85, P=0.400; t=0.43, P=0.669; t=-0.50, P=0.619; t=1.46, P=0.148). Additionally, significant correlations were found between changes in H5 and UM1 RL with UM1 P ( r=0.35, P<0.001; r=0.19, P=0.030), but not between Changes in L1 RL and L1 P ( r=0.11, P>0.05). Conclusions:The effect of orthodontic treatment on pulp volume in adolescents and adults were different.

Objective To analyze the changes in left ventricular deformation function in patients with diffuse large B-cell lymphoma(DLBCL)treated with different doses of anthracycline chemotherapy using 3D speckle-tracking imaging(3D-STI).Methods 66 DLBCL patients receiving anthracycline chemotherapy were enrolled.Based on the cumulative dose of anthracycline received,the patients were divided into a high-dose group(＞360 mg/m2,n=39)and a low-dose group(≤360 mg/m2,n=27).Patients underwent transthoracic echocardiography before chemotherapy and within one week after completion of the entire chemotherapy cycle.Left ventricular global longitudinal strain(LVGLS),left ventricular global circumferential strain(LVGCS),and other indices were analyzed using 3D-STI to assess changes in left ventricular deformation indices after chemotherapy and between two groups.Results Compared to baseline,DLBCL patients showed significant reductions in LVGLS,LVGCS and left atrial global longitudinal strain(LAGLS)after treatment completion(P＜0.001).When comparing the high-dose group with the low-dose group,there was a significant increase in relative LVGCS change rate at the end of chemotherapy(21.12[6.52,35.37]vs 5.49[-14.73,27.01];P=0.03).However,there were no statistically significant differences in relative left ventricular ejection fraction(LVEF),LVGLS,LVGCS,LVEF change rate,or LVGLS change rate between the two groups.Conclusions 3D-STI can be a potential method to identify the sub-clinical deterioration of left ventricular systolic function in patients received anthracycline chemotherapy,the difference of change rate of LVGCS may predict the variation of sub-clinical deterioration of left ventricular function between patients received high and low doses of 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.

Objective:To explore the correlation between structural chromosomal abnormality and clinical characteristics of a child featuring gonadal dysplasia.Methods:A 13-year-old child who was admitted to Lianyungang Maternal and Child Health Care Hospital on February 7, 2023 for primary amenorrhoea and occasional abdominal pain was selected as the study subject. Clinical data of the child was collected, and peripheral blood samples of the child and her parents were collected. G-banding chromosomal karyotyping and copy number variation sequencing (CNV-seq) were carried out. "Pseudodual centromere isochromosome X" and "psu idic(X)" were used as keywords to search the CNKI, Wanfang and PubMed databases, and the search period was set as from January 1, 2002 to June 1, 2023. Relevant literature on the structural abnormality of X chromosome was searched and analyzed retrospectively.Results:The child has a height of 153 cm and weighed 45 kg. She has no obvious facial dysmorphism. Laboratory tests showed that she had higher FSH and luteinizing hormone, and lower E2. Ultrasonography showed that she had small ovaries and rudimentary uterus. She was found to have a karyotype of 46, X, psu idic(X)(q21.3)[40]/mos 45, X[3], whilst both of her parents had a normal karyotype. CNV-seq showed that she had a 63.27 Mb deletion in Xq21.32q28 and a 91.59 Mb duplication in Xp22.33q21.32 (mosaicism rate = 74%). A total of 11 relevant literature were retrieved. Clinical phenotypes of patients with similar structural chromosomal abnormalities were diverse, which was closely related to the mosaicism rate of the 45, X karyotype and the location of the breaking point.Conclusion:46, X, psu idic(X)(q21.3)/45, X probably underlay the dysplasia of uterus and ovary and sex hormone abnormalities in this child, while her height was spared. Deletion of Xq21.32q28 is a key factor leading to Turner syndrome-like phenotype such as rudimentary uterus and ovarian dysplasia.

Objective:To explore the clinical phenotype and pathogenesis of a child with partial duplication in the long arm of chromosome 10 (10q), and conduct a review of relevant literature.Methods:A child presented at Lianyungang Maternal and Child Health Care Hospital in April 2018 for growth retardation, intellectual disability, and autism spectrum disorder (ASD) was selected as the study subject. Peripheral blood samples were collected from the child and his parents for G-banded chromosomal karyotyping analysis. Genomic DNA was also extracted for chromosomal microarray analysis (CMA). The clinical phenotype and relevant genes were searched in the Online Mendelian Inheritance in Man (OMIM) and the UK Database of Genomic Variation and Phenotype in Humans using Ensembl Resources (DECIPHER). The pathogenicity of chromosomal variation was analyzed based on guidelines from the American College of Medical Genetics and Genomics (ACMG). Relevant literature was searched from the CNKI, Wanfang Data, and PubMed databases by using keywords such as " 10q" " duplication" and " trisomy", with the time set as from the establishment of database to December 1, 2023. This study has been approved by the Medical Ethics Committee of the Lianyungang Maternal and Child Health Care Hospital (No. XM2023030).Results:The clinical phenotype of child had included growth retardation, intellectual disability, and ASD. G-banded chromosomal analysis suggested that the child has a karyotype of 46, XY, dup(10)(q23.31q24.33), whilst both of his parents were normal. CMA analysis of the child revealed that the child was arr[19]10q23.31q24.33(87603382_104948862)×3, with a 17.34 Mb duplication in the 10q23.31q24.33 region. Search of the OMIM database suggested that the duplicated segment has contained 171 genes associated with various diseases, and search of the DECIPHER database has identified cases with overlapping with the duplication. A search of the PubMed database has identified 2 publications involving 2 patients with chromosomal duplications overlapping the 10q23.31q24.33 region with a segment length of > 10 Mb. The 2 patients had mainly manifested growth retardation, intellectual disability, ASD, and facial and limb malformations. The main pathogenic genes had included PTEN, WNT8B, LZTS2, NFKB2, PAX2, KIF11, FRA10AC1, and CNNM2. No similar case was retrieved from the CNKI and Wanfang Data databases. Conclusion:The partial 10q duplication as a novel CNV involving genes such as PTEN and WNT8B probably underlay the growth retardation, intellectual disability and ASD in the child. This study has enriched the genotype-phenotype spectrum of patients with partial 10q23.31q24.33 duplications.

Thalamocortical circuitry has a substantial impact on emotion and cognition.Previous studies have demonstrated alterations in thalamocortical functional connectivity(FC),characterized by region-dependent hypo-or hyper-connectivity,among individuals with major depressive disorder(MDD).However,the dynamical reconfiguration of the thalamocortical system over time and potential abnormalities in dynamic thalamocortical connectivity associated with MDD remain unclear.Hence,we analyzed dynamic FC(dFC)between ten thalamic subregions and seven cortical subnetworks from resting-state functional magnetic resonance images of 48 patients with MDD and 57 healthy controls(HCs)to investigate time-varying changes in thalamocortical FC in patients with MDD.Moreover,dynamic laterality analysis was conducted to examine the changes in functional lateralization of the thalamocortical system over time.Correlations between the dynamic measures of thalamocortical FC and clinical assessment were also calculated.We identified four dynamic states of thalamocortical circuitry wherein patients with MDD exhibited decreased fractional time and reduced transitions within a negative connectivity state that showed strong correlations with primary cortical networks,compared with the HCs.In addition,MDD patients also exhibited increased fluctuations in functional laterality in the thalamocortical system across the scan duration.The thalamo-subnetwork analysis unveiled abnormal dFC variability involving higher-order cortical networks in the MDD cohort.Significant correlations were found between increased dFC variability with dorsal attention and default mode networks and the severity of symptoms.Our study comprehensively investigated the pattern of alteration of the thalamocortical dFC in MDD patients.The heterogeneous alterations of dFC between the thalamus and both primary and higher-order cortical networks may help characterize the deficits of sensory and cognitive processing in MDD.

Purpose To investigate the diagnostic value of multimodal imaging in cardiac lipoma.Materials and Methods The clinical symptoms,echocardiography,CT and cardiac magnetic resonance images of 14 patients with cardiac lipoma diagnosed in Xijing Hospital of Air Force Military Medical University from July 2016 to November 2022 were retrospectively analyzed.Results Five patients with lipoma had symptoms of chest tightness and shortness of breath.A total of 18 lesions were found in 14 cases with cardiac lipoma.The locations of cardiac lipomas were widely distributed in the heart,of which 9 were located under the inner lining of the ventricular lumen(6 in the left ventricle,3 in the right ventricle),5 in the myocardium(4 in the left ventricle wall,1 in the right ventricle wall),3 in the pericardium,and 1 in the right ventricle.Echocardiography of 12 cases showed strong echoic mass image,and CT of 7 cases showed uniform low-density mass image.All patients cardiac magnetic resonance showed high signal of T1WI,and the tumor signal of lipid-pressure sequence decreased significantly.T2WI showed high signal and low signal ring around the tumor,indicating a chemical shift artifact.In the film sequence of heart,the mass could be seen to wobble gently and change in the shape of spontaneous motion cycle.The first perfusion scan did not show perfusion elevation.No enhancement was observed on the delayed enhanced scan.Native T1 mapping showed that the T1 value of mass was significantly lower than that of normal myocarda[(255.9±48.4)ms vs.(994.2±66.4)ms],and the difference was statistically significant(t=-32.5,P<0.001).Conclusion Multimodal imaging can provide objective evidence for clinical diagnosis of cardiac lipoma.Lipomas with extremely low T1 values were found,which is helpful to assist in the diagnosis of cardiac lipoma,clearer observation of the lesions,accurate localization,and strong ability to detect small lesions.Therefore,when cardiac lipoma is suspected,T1 mapping can be used as a routine examination method for the diagnosis and differential diagnosis of cardiac masses.

China prospective multicenter birth cohort (Prospective Omics Health Atlas birth cohort, POHA birth cohort) study was officially launched in 2022. This study, in collaboration with 12 participating units, aims to establish a high-quality, multidimensional cohort comprising 20 000 naturally conceived families and assisted reproductive families. The study involves long-term follow-up of parents and offspring, with corresponding biological samples collected at key time points. Through multi-omics testing and analysis, the study aims to conduct multi-omics big data research across the entire maternal and infant life cycle. The goal is to identify new biomarkers for maternal and infant diseases and provide scientific evidence for risk prediction related to maternal diseases and neonatal health.