Objective:To observe the effects of sorafenib on the lesions and vascular growth factors in the mouse model of hepatic alveolar echinococcosis.Methods:One hundred healthy female Kunming mice weighing (20±4) g were used to establish a model of alveolar echinococcosis infection by intraperitoneal injection of alveolar echinococcosis protoscoleces. After 6 weeks of feeding, the rats were divided into 5 groups, 15 rats in each group, which were given warm saline, albendazole (100 mg/kg), and sorafenib at high-dose (100 mg/kg), middle-dose (50 mg/kg) and low-dose (30 mg/kg) by gavage for 6 weeks, respectively. Eyeball blood and hepatic alveolar echinococcosis tissue were collected from the mice after the last administration, and the body weight of the mice and the lesion weight were weighed. The concentrations and expression levels of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor-A (VEGF-A) and vascular endothelial growth factor receptor-2 (VEGFR-2) in serum and lesion tissues were detected by enzyme-linked immunosorbent assay (ELISA) and Western blotting.Results:There was no statistically significant difference in the body weight of mice among the saline group, albendazole group and low-dose, medium-dose and high-dose sorafenib groups ( F=0.43, P=0.784). The ratios of lesion weight to body weight in the above groups were (0.057±0.009), (0.031±0.005), (0.033±0.005), (0.031±0.005), and (0.031±0.005), respectively. The saline group had a higher ratio than the other four groups, and the differences were statistically significant (all P<0.05). The relative expression levels of HIF-1α, VEGF-A, VEGFR-2, CD31 and CD34 detected by Western blotting in the saline group were all higher than those in the albendazole group and the high-dose, medium-dose and low-dose sorafenib groups, and the differences were statistically significant (all P<0.05). The relative expression levels of the above proteins in the medium-dose and high-dose sorafenib groups were lower than those in the albendazole group, and the relative expression levels of the above proteins in the high-dose sorafenib group were also lower than those in the medium-dose sorafenib group, and the differences were statistically significant (all P<0.05). The concentration levels of HIF-1α, VEGF-A and VEGFR-2 in serum of mice in each group detected by ELISA were consistent with those detected by Western blotting. Conclusion:Sorafenib inhibits the proliferation of alveolar echinococcosis in mice by suppressing the expression of angiogenic factors in alveolar echinococcosis lesions.

Local anesthetics (LAs), such as articaine (AT), exhibit limited efficacy in inflammatory environments, which constitutes a significant limitation in their clinical application within oral medicine. In our prior research, we developed AT-17, which demonstrated effective properties in chronic inflammatory conditions and appears to function as a novel oral LA that could address this challenge. In the present study, we further elucidated the beneficial effects of AT-17 in acute inflammation, particularly in oral acute inflammation, where mitochondrial-related apoptosis played a crucial role. Our findings indicated that AT-17 effectively inhibited lipopolysaccharide (LPS)-induced nerve cell apoptosis by ameliorating mitochondrial dysfunction in vitro. This process involved the inhibition of mitochondrial reactive oxygen species (mtROS) production and the subsequent activation of the NRF2 pathway. Most notably, improvements in mitochondria-related apoptosis were key contributors to AT-17's inhibition of voltage-gated sodium channels. Additionally, AT-17 was shown to reduce mtROS production in nerve cells through the Na⁺/NCLX/ETC signaling axis. In conclusion, we have developed a novel local anesthetic that exhibits pronounced anesthetic functionality under inflammatory conditions by enhancing mitochondria-related apoptosis. This advancement holds considerable promise for future drug development and deepening our understanding of the underlying mechanisms of action.

OBJECTIVE: To explore the genetic etiology for a child presenting with motor retardation, language delay, intellectual disability, and dysmorphic features. METHODS: A child presented at Linyi People's Hospital in June 2022 was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples were obtained from the child and her parents. Following extraction of genomic DNA, whole-exome sequencing (WES) was carried out. Candidate variant was validated by Sanger sequencing. Amniotic fluid samples were obtained from the mother's subsequent pregnancies for prenatal diagnosis. This study has been reviewed and approved by the Medical Ethics Committee of Linyi People's Hospital (Ethics No.: 2019-134). RESULTS: The proband was a 2-year-old girl showing developmental delays in motor, language, and intellectual domains, strabismus, hypertelorism, hearing impairment, obesity, and brachymesophalangy of the fifth finger. Magnetic resonance imaging revealed abnormalities of the white matter. Chromosomal microarray analysis (CMA) identified a 15q26.3 duplication (chr15:101562020_102060896 × 3) inherited from her mother. WES has uncovered a heterozygous c.1931A>G (p.Tyr644Cys) variant in the FBXO11 gene. Sanger sequencing confirmed the variant to be de novo in origin. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as likely pathogenic. Prenatal diagnosis revealed that the fetuses from the mother's second and third pregnancies did not harbor the same variant. CONCLUSION The c.1931A>G (p.Tyr644Cys) variant of the FBXO11 gene probably underlay the abnormal phenotype in the child. Based on its genotype and phenotype, the proband was diagnosed with Intellectual developmental disorder with dysmorphic facies and behavioral abnormalities.
Humans ; Female ; Intellectual Disability/genetics* ; Child, Preschool ; F-Box Proteins/genetics* ; Protein-Arginine N-Methyltransferases/genetics* ; Exome Sequencing

Objective:To explore the genetic etiology for a child presenting with motor retardation, language delay, intellectual disability, and dysmorphic features.Methods:A child presented at Linyi People′s Hospital in June 2022 was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples were obtained from the child and her parents. Following extraction of genomic DNA, whole-exome sequencing (WES) was carried out. Candidate variant was validated by Sanger sequencing. Amniotic fluid samples were obtained from the mother′s subsequent pregnancies for prenatal diagnosis. This study has been reviewed and approved by the Medical Ethics Committee of Linyi People′s Hospital (Ethics No.: 202402-H-034).Results:The proband was a 2-year-old girl showing developmental delays in motor, language, and intellectual domains, strabismus, hypertelorism, hearing impairment, obesity, and brachymesophalangy of the fifth finger. Magnetic resonance imaging revealed abnormalities of the white matter. Chromosomal microarray analysis (CMA) identified a 15q26.3 duplication (chr15: 101562020_102060896×3) inherited from her mother. WES has uncovered a heterozygous c. 1931A>G (p.Tyr644Cys) variant in the FBXO11 gene. Sanger sequencing confirmed the variant to be de novo in origin. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as likely pathogenic. Prenatal diagnosis revealed that the fetuses from the mother′s second and third pregnancies did not harbor the same variant. Conclusion:The c. 1931A>G (p.Tyr644Cys) variant of the FBXO11 gene probably underlay the abnormal phenotype in the child. Based on its genotype and phenotype, the proband was diagnosed with Intellectual developmental disorder with dysmorphic facies and behavioral abnormalities.

Lens injury is an important etiological factor in the reduction of visual function following ocular trauma.Currently, there are no clear standards for the classification of lens injury, and comprehensive diagnostic tools are lacking.This deficiency leads to numerous controversies and challenges in critical areas, such as diagnosis and preoperative evalution, timing of surgery, surgical strategy, and assessment of postoperative prognosis.Tomographic imaging technology, such as computed tomography, magnetic resonance imaging, optical coherence tomography, has introduced a new dimension to the evaluation of lens injury, which is crucial for assessing the transparency, texture, location, morphology, and integrity of the lens, as well as the zonules and nearby intraocular structures.However, the use of tomographic imaging technology is somewhat limited due to the limitations of relying on a single method.With the ongoing advancement of imaging technologies and the rapid development of big data and artificial intelligence, tomographic imaging will become an increasingly essential tool in the future management of lens injury.Our expert group reviewed the epidemiological characteristics and classification of lens injury and the major challenges currently faced in the diagnosis and treatment of lens injury, and provided expert recommendations mainly focusing on the application, shortcomings and limitations of current tomographic imaging technology in the diagnosis and treatment of lens injury, and future development directions.

Lens injury is an important etiological factor in the reduction of visual function following ocular trauma.Currently, there are no clear standards for the classification of lens injury, and comprehensive diagnostic tools are lacking.This deficiency leads to numerous controversies and challenges in critical areas, such as diagnosis and preoperative evalution, timing of surgery, surgical strategy, and assessment of postoperative prognosis.Tomographic imaging technology, such as computed tomography, magnetic resonance imaging, optical coherence tomography, has introduced a new dimension to the evaluation of lens injury, which is crucial for assessing the transparency, texture, location, morphology, and integrity of the lens, as well as the zonules and nearby intraocular structures.However, the use of tomographic imaging technology is somewhat limited due to the limitations of relying on a single method.With the ongoing advancement of imaging technologies and the rapid development of big data and artificial intelligence, tomographic imaging will become an increasingly essential tool in the future management of lens injury.Our expert group reviewed the epidemiological characteristics and classification of lens injury and the major challenges currently faced in the diagnosis and treatment of lens injury, and provided expert recommendations mainly focusing on the application, shortcomings and limitations of current tomographic imaging technology in the diagnosis and treatment of lens injury, and future development directions.

Objective:To observe the effects of sorafenib on the lesions and vascular growth factors in the mouse model of hepatic alveolar echinococcosis.Methods:One hundred healthy female Kunming mice weighing (20±4) g were used to establish a model of alveolar echinococcosis infection by intraperitoneal injection of alveolar echinococcosis protoscoleces. After 6 weeks of feeding, the rats were divided into 5 groups, 15 rats in each group, which were given warm saline, albendazole (100 mg/kg), and sorafenib at high-dose (100 mg/kg), middle-dose (50 mg/kg) and low-dose (30 mg/kg) by gavage for 6 weeks, respectively. Eyeball blood and hepatic alveolar echinococcosis tissue were collected from the mice after the last administration, and the body weight of the mice and the lesion weight were weighed. The concentrations and expression levels of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor-A (VEGF-A) and vascular endothelial growth factor receptor-2 (VEGFR-2) in serum and lesion tissues were detected by enzyme-linked immunosorbent assay (ELISA) and Western blotting.Results:There was no statistically significant difference in the body weight of mice among the saline group, albendazole group and low-dose, medium-dose and high-dose sorafenib groups ( F=0.43, P=0.784). The ratios of lesion weight to body weight in the above groups were (0.057±0.009), (0.031±0.005), (0.033±0.005), (0.031±0.005), and (0.031±0.005), respectively. The saline group had a higher ratio than the other four groups, and the differences were statistically significant (all P<0.05). The relative expression levels of HIF-1α, VEGF-A, VEGFR-2, CD31 and CD34 detected by Western blotting in the saline group were all higher than those in the albendazole group and the high-dose, medium-dose and low-dose sorafenib groups, and the differences were statistically significant (all P<0.05). The relative expression levels of the above proteins in the medium-dose and high-dose sorafenib groups were lower than those in the albendazole group, and the relative expression levels of the above proteins in the high-dose sorafenib group were also lower than those in the medium-dose sorafenib group, and the differences were statistically significant (all P<0.05). The concentration levels of HIF-1α, VEGF-A and VEGFR-2 in serum of mice in each group detected by ELISA were consistent with those detected by Western blotting. Conclusion:Sorafenib inhibits the proliferation of alveolar echinococcosis in mice by suppressing the expression of angiogenic factors in alveolar echinococcosis lesions.

Objective:To explore the genetic etiology for a child presenting with motor retardation, language delay, intellectual disability, and dysmorphic features.Methods:A child presented at Linyi People′s Hospital in June 2022 was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples were obtained from the child and her parents. Following extraction of genomic DNA, whole-exome sequencing (WES) was carried out. Candidate variant was validated by Sanger sequencing. Amniotic fluid samples were obtained from the mother′s subsequent pregnancies for prenatal diagnosis. This study has been reviewed and approved by the Medical Ethics Committee of Linyi People′s Hospital (Ethics No.: 202402-H-034).Results:The proband was a 2-year-old girl showing developmental delays in motor, language, and intellectual domains, strabismus, hypertelorism, hearing impairment, obesity, and brachymesophalangy of the fifth finger. Magnetic resonance imaging revealed abnormalities of the white matter. Chromosomal microarray analysis (CMA) identified a 15q26.3 duplication (chr15: 101562020_102060896×3) inherited from her mother. WES has uncovered a heterozygous c. 1931A>G (p.Tyr644Cys) variant in the FBXO11 gene. Sanger sequencing confirmed the variant to be de novo in origin. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as likely pathogenic. Prenatal diagnosis revealed that the fetuses from the mother′s second and third pregnancies did not harbor the same variant. Conclusion:The c. 1931A>G (p.Tyr644Cys) variant of the FBXO11 gene probably underlay the abnormal phenotype in the child. Based on its genotype and phenotype, the proband was diagnosed with Intellectual developmental disorder with dysmorphic facies and behavioral abnormalities.

Objective To investigate the effect of type 2 diabetes mellitus(T2DM)on the expression of human leukocyte antigen-DR(HLA-DR)on the peripheral blood monocytes in patients with sepsis.Methods From March 2021 to February 2022,65 cases of sepsis with T2DM(sepsis with T2DM group),67 cases of sepsis without T2DM(sepsis group),and 60 cases of T2DM patients(T2DM group)admitted to Beijing Chaoyang Hospital of Capital Medical University were selected as the research objects.A total of 45 healthy volunteers who underwent physical examination during the same period were enrolled as the healthy control group.Gender,age,past medical history,glycated hemoglobin(HbA1c),blood glucose at admission,white blood cell count(WBC),lymphocyte count(LYM),hypersensitivity C-reactive protein(hs-CRP)and major infection sites were collected,sequential organ failure assessment(SOFA)score was performed within 24 hours after admission.The levels of HLA-DR+CD14+ in peripheral blood were detected by flow cytometry,expressed as a percentage and mean fluorescence intensity(MFI).The patients were followed up for 28 days.The effect of T2DM on the prognosis of sepsis patients at 28 days was observed,and the difference of HLA-DR+CD14+ levels between the survivor group and the non-survivor group was compared.Results The percentage and MFI of HLA-DR+CD14+ expressions in T2DM group were significantly lower than those in the healthy control group[the percentage of HLA-DR+CD14+ expression:87.72%(76.18%,93.64%)vs.94.86%(92.91%,95.70%),HLA-DR+CD14+ MFI:10.80(8.45,14.45)vs.12.40(1.45,15.28)],the sepsis with T2DM group and sepsis group were further reduced than those in healthy control group and T2DM group[the percentage of HLA-DR+CD14+ expression:70.78%(42.22%,84.73%),68.95%(44.95%,87.00%)vs.94.86%(92.91%,95.70%),87.72%(76.18%,93.64%),MFI of HLA-DR+CD14+:5.50(3.81,9.20),5.29(3.35,9.59)vs.12.40(1.45,15.28),10.80(8.45,14.45),all P<0.05].There was no significant difference in the percentage and MFI of HLA-DR+CD14+ expressions,SOFA score,and 28-day mortality between sepsis group and sepsis with T2DM group(P>0.05).The age of the non-survivor group of sepsis patients with and without T2DM was significantly higher than that of the survivor group[years:sepsis group was 68(60,74)vs.61(52,69),sepsis with T2DM group was 66(64,73)vs.60(53,68),both P<0.05],and SOFA score was significantly higher than that of the survivor group[sepsis group:14(11,16)vs.8(5,11),sepsis with T2DM group:12(9,16)vs.8(6,11),both P<0.05],the percentage of HLA-DR+CD14+ and HLA-DR+CD14+ MFI in the non-survivor group were significantly lower than those in the survivor group[the percentage of HLA-DR+CD14+was 44.94%(28.01%,64.45%)vs.77.14%(47.41%,88.35%)in sepsis group and 40.68%(34.83%,66.64%)vs.73.46%(58.44%,85.31%)in sepsis with T2DM group,the MFI of HLA-DR+CD14+ was 3.92(2.30,5.44)vs.7.07(3.39,10.55)in sepsis group and 3.90(3.34,6.04)vs.6.81(4.41,9.32)in sepsis with T2DM group,all P<0.05].Correlation analysis showed that the percentage of HLA-DR+CD14+ in T2DM group,sepsis group,and sepsis with T2DM group was negatively correlated with hs-CRP(r values were-0.448,-0.628 and-0.457,all P<0.001),MFI was also negatively associated with hs-CRP(rvalues were-0.289,-0.540,-0.323,all P<0.05).The percentage of HLA-DR+CD14+ in sepsis group and sepsis with T2DM group was negatively correlated with SOFA score(r values were-0.520 and-0.558,all P<0.001),and MFI was also negatively correlated with SOFA score(r values were-0.327 and-0.482,all P<0.01).Conclusion The levels of HLA-DR+CD14+ decreased in both T2DM and sepsis patients,however,there was no further decrease in those patients with sepsis who also had T2DM.

ObjectiveTo establish the fingerprint of seven commercially available Yangyin Qingfei preparations， to quantitatively analyze the index components， to evaluate their quality uniformity with multivariate statistical analysis， and to explore the quality differences among different dosage forms. MethodA total of 33 batches of commercially available 7 kinds of Yangyin Qingfei preparations were analyzed by high performance liquid chromatography（HPLC）， the fingerprints were established and the common peaks were identified. Paeoniflorin， verbascoside， harpagoside， glycyrrhizic acid and paeonol were selected as the indicators of quality attributes to quantitatively analyze 33 batches of preparations. Based on the administration methods of Yangyin Qingfei preparations， the daily intake was calculated and the radar charts were poltted， and cluster analysis and principal component analysis were used to explore the quality differences of 7 kinds of Yangyin Qingfei preparations and the quality uniformity among different batches of the same dosage form. ResultThe similarity of fingerprints of 7 dosage forms was 0.248-0.956， suggesting that there were significant differences among different dosage forms of Yangyin Qingfei preparations， and a total of 15 common peaks were calibrated， of which peak 7， peak 8， peak 11， peak 13 and peak 15 were paeoniflorin， verbascoside， harpagoside， glycyrrhizic acid and paeonol， respectively. The radar plots showed that the average total daily intake of large honeyed pills and water honeyed pills was the highest， and the uniformity of pill components was better. The quality of 33 batches of samples was divided into poor quality and high quality by cluster analysis. Principal component analysis showed that the uniformity and dosage form of different dosage forms were significantly different， the oral liquid had the best quality homogeneity with the minimum dispersion. And the content of paeonol in different dosage forms was significantly different， which was the key component of quality control of Yangyin Qingfei preparations. ConclusionYangyin Qingfei large honeyed pills and water honeyed pills show high content and good uniformity， which are relatively preferred dosage forms. Different preparation processes have a great influence on the content of paeonol， and its quality control should be emphasized during production. This study provides a scientific method for the comparison of product quality of different dosage forms of traditional Chinese medicine prescriptions， which is helpful for the development of preferred dosage forms of different prescriptions， and provides a reference for efficient use of medication in the clinical practice.