Objective To investigate the protective effect of AKAP12/PCK6 signaling pathway on podocyte autophagy in diabetic kidney disease(DKD).Methods A total of 40 C57/B6 AKAP12 KO(AKAP12-/-)mice and wild-type(WT)littermates were randomly divided into four groups,with 10 mice in each group:Ctrl+WT group,Ctrl+AKAP12-/-group,DKD+WT group and DKD+AKAP12-/-group.Primary podocytes were obtained from AKAP12-/-mice and WT mice,and exposed to high glucose(HG,30 mmol/L)or mannitol for 24 h to investigate the mitosis and autophagy of podocytes.The primary podocytes were divided into Mannitol+WT,G+WT,Mannitol+AKAP12-/-and HG+AKAP12-/-.In addition,AKAP12-/-podocytes were transfected with sh-PCSK6 to knockdown the expression of PCK6.Mito-Tracker staining was used to analyze the morphology of mitochondria in podocytes.The expressions of mitotic proteins(FIS1 and DRP1),mitochondrial autophagy(PINK1 and Parkin)and autophagy-related proteins(LC3 and p62)were analyzed by Western blot.Results Compared with HG+WT group,the number of single mitochondria and the expression of FIS1,DRP1,PINK1,Parkin,LC3Ⅱ and p62 proteins increased,while the average branch length of mitochondria decreased in HG+AKAP12-/-group(P＜0.05).Compared with HG+sh-NC group,the number of single mitochondria and the expression of FIS1,DRP1,PINK1,Parkin and LC3Ⅱ proteins decreased significantly in HG+sh-PCSK6 group(P＜0.05 or P＜0.01),while the average branch length of mitochondria increased significantly(P＜0.05).Conclusions AKAP12/PCSK6 signaling pathway mediates the regulation of mitochondrion division and mitochondrion autophagy in podocytes under HG environment.

ObjectiveTo investigate the tumor-suppressing effect of Shenqi Yiliu prescription combined with cisplatin in hepatoma H22-bearing mice based on the phosphatase and tensin homolog deleted on chromosome ten （PTEN）/phosphatidylinositol-3-kinase （PI3K）/protein kinase B （Akt） pathway. MethodH22-bearing mice were prepared and randomized into model group， cisplatin group， and cisplatin combined with high-， medium-， and low-dose Shenqi Yiliu prescription groups， with 10 mice in each group. Another 10 healthy mice were randomly selected as normal group. Shenqi Yiliu prescription was given by gavage with the high， medium， low dose of 54.06， 27.03， 13.515 g·kg^-1·d^-1， respectively， and cisplatin （2.5 mg·kg^-1） was administered by intraperitoneal injection， twice a week. Normal group and model group received normal saline. After 13 days of treatment， mice were killed and the tumor inhibition rate was calculated. The pathomorphological changes of tumor were observed based on hematoxylin-eosin （HE） staining， and enzyme-linked immunosorbent assay （ELISA） and immunofluorescence method were used to detect the content of cyclin-dependent kinase inhibitor 1A （p21） and cyclin-dependent kinase inhibitor 1B （p27） in tumor tissue of mice. The levels of PTEN， PI3K and phosphorylated protein kinase B （p-Akt） in tumor tissue were measured by Western blot. ResultCompared with the model group， cisplatin alone and cisplatin in combination with the high-， medium-， and low-dose Shenqi Yiliu prescription decreased tumor mass （P<0.05）， particularly the cisplatin in combination with the high-dose Shenqi Yiliu prescription. Necrosis of the tumor tissue was observed in each group， especially the cisplatin combined with high-dose Shenqi Yiliu prescription group. As compared with the model group， cisplatin alone and cisplatin in combination with the high-， medium-， and low-dose Shenqi Yiliu prescription raised the expression of p21， p27， and PTEN （P<0.05） and lowered the expression of PI3K and p-Akt （P<0.05）， particularly the cisplatin in combination with high-dose Shenqi Yiliu prescription. ConclusionShenqi Yiliu prescription may regulate the expression of key molecules in PTEN/PI3K/Akt signaling pathway， thereby upregulating the expression of downstream proliferation inhibitors p21 and p27， further suppressing the tumor in H22-bearing mice， and enhancing the effect of chemotherapy.

Objective:The nasal swell body（NSB） consists of the nasal septal cartilage, nasal bone, and swollen soft tissue, all of which are visible during endoscopic and imaging examinations. Although the function of the NSB remains uncertain, there is evidence to suggest that it plays a vital role in regulating nasal airflow and filtering inhaled air. Based on anatomical and histological evidence, it is hypothesized that the NSB is indispensable in these processes. This study aims to investigate the impact of NSB on nasal aerodynamics and the deposition of allergen particles under physiological conditions. Methods:The three-dimensional （3D） nasal models were reconstructed from computed tomography （CT） scans of the paranasal sinus and nasal cavity in 30 healthy adult volunteers from Northwest China, providing basis for the construction of models without NSB following virtual NSB-removal surgery. To analyze the distribution of airflow in the nasal cavity, nasal resistance, heating and humidification efficiency, and pollen particle deposition rate at various anatomical sites, we employed the computed fluid dynamics（CFD） method for numerical simulation and quantitative analysis. In addition, we created fully transparent segmented nasal cavity models through 3D printing, which were used to conduct bionic experiments to measure nasal resistance and allergen particle deposition. Results:①The average width and length of the NSB in healthy adults in Northwest China were （12.85±1.74） mm and （28.30±1.92） mm, respectively. ②After NSB removal, there was no significant change in total nasal resistance, and cross-sectional airflow velocity remained essentially unaltered except for a decrease in topical airflow velocity in the NSB plane. ③There was no discernible difference in the nasal heating and humidification function following the removal of the NSB; ④After NSB removal, the deposition fraction（DF） of Artemisia pollen in the nasal septum decreased, and the DFs post-and pre-NSB removal were（22.79±6.61）% vs （30.70±12.27）%, respectively; the DF in the lower airway increased, and the DFs post-and pre-NSB removal were（24.12±6.59）% vs （17.00±5.57）%, respectively. Conclusion:This study is the first to explore the effects of NSB on nasal airflow, heating and humidification, and allergen particle deposition in a healthy population. After NSB removal from the healthy nasal cavities: ①nasal airflow distribution was mildly altered while nasal resistance showed no significantly changed; ②nasal heating and humidification were not significantly changed; ③the nasal septum's ability to filter out Artemisia pollen was diminished, which could lead to increased deposition of Artemisia pollen in the lower airway.
Adult ; Humans ; Cross-Sectional Studies ; Nasal Cavity/surgery* ; Allergens ; Pollen ; Artemisia ; Hydrodynamics

OBJECTIVE: To assess the association of 7 single nucleotide polymorphisms (SNPs) including rs13278062 (TNFRSF10A), rs3750846 (ARMS2-HTRA1), rs429358 (APOE), rs5817082 (CEPT), rs2043085 (LIPC), rs1626340 (TGFBR1), and rs8135665 (SLC16A8) identified through genome-wide association study (GWAS) with age-related macular degeneration (AMD) among ethnic Han Chinese from Sichuan, China. METHODS: A cohort of 576 AMD patients and 572 healthy controls were enrolled in a case-control study. The SNPs were genotyped by a Mass array MALDI-TOF System. On the premise that the genotype distribution of each SNP locus in both groups satisfied Hardy-Weinberg equilibrium, the genetic pattern was analyzed and the scores of allele and genotype frequencies ware compared. RESULTS: There was a significant association between TNFRSF10A rs13278062 and AMD under the heterozygous model (P = 0.000, OR = 1.529, 95%CI = 1.196-1.954) and the dominant model (P = 0.002, OR = 1.459, 95%CI = 1.154-1.865), suggesting that subjects carrying rs13278062GT and rs13278062TT + GT are more likely to develop the AMD, whereas no significant difference was observed for rs13278062 under other models. No association was detected with the other six SNPs and AMD under various genetic models. CONCLUSION This case-control association study has indicated that TNFRSF10A rs13278062 is associated with AMD under the heterozygous and dominant models, suggesting that the TNFRSF10A variant may be involved in the development of AMD among ethnic Han Chinese population.
Case-Control Studies ; Gene Frequency ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Genotype ; High-Temperature Requirement A Serine Peptidase 1/genetics* ; Humans ; Macular Degeneration/genetics* ; Polymorphism, Single Nucleotide

Objective:To explore the molecular mechanisms of a Chinese pedigree with hereditary factor Ⅺ (FⅪ) deficiency.Methods:All of the 15 exons, flanking sequences of the FⅪ gene and the corresponding mutation sites of family members were analyzed by the Sanger sequencing, followed by the extraction of the peripheral blood genomic DNA. And all the results were verified by the reverse sequencing. The conservation of the mutated sites was analyzed by the ClustalX-2.1-win. Three online bioinformatics software tools, including Mutation Taster, PolyPhen2 and the PROVEAN, were used to assess the possible impact of the mutations. Swiss-pdbviewer software was used to analyze the effects of mutant amino acids on protein structure.Results:Genetic analysis revealed that the proband had compound heterozygous mutations including a nonsense mutation of c. 1107C>A (Tyr369stop) in exon 10 and missense mutation of c. 1562A>G (Tyr521Cys) in exon 13. The same c. 1107C>A (Tyr369stop) was present in her father, the same c. 1562A>G (Tyr521Cys) was present in both her mother and daughter. Conservation analysis indicated that Tyr521 was a highly conserved site during evolution. The prediction of pathogenicity showed that both c. 1107C>A and c. 1562A>G were pathogenic mutations. Protein structure prediction showed that in the wild type FⅪ protein structure, Tyr521 formed a hydrogen bond with the Lys572 and Ile388, respectively. When Tyr521 was replaced by Cys521, the original benzene ring structure disappeared, and side chains of Lys572 added a hydrogen bond with the Cys521, which may chang protein catalytic domain structure. When Tyr369 was mutated to a stop codon, resulting in the truncated protein.Conclusion:The compound heterozygous mutations including the c. 1107C>A heterozygous missense variant in exon 10 and the c. 1562A>G heterozygous nonsense mutation in exon 13 may be responsible for the hereditary factor Ⅺ deficiency in this Chinese pedigree.

Objective: The study was designed to analyze the clinicopanthologic characteristics, treatments and outcomes of a series of patients with primary angiosarcoma. Methods: The clinical, surgical and pathological data and treatment of 68 patients with pathologically confirmed angiosarcoma admitted to Peking Union Medical College Hospital from January 1990 to June 2017 was retrospectively analyzed. Kaplan-Meier method and Log rank test were used for univariate survival analysis and Cox regression model was used for multivariate survival analysis. Results: A total of 68 patients were enrolled, 38 were male, 30 were female. The median age at diagnosis was 50.5 years. The time from symptom onset to diagnosis was (7.5±7.5) months. The primary sites included face and scalp, breast, chest wall, lung, heart, liver, spleen, extremities, bones and so on. At diagnosis, the mean size of tumors were (7.4±7.3) cm, 28 patients (41.2%) had localized disease (stage Ⅰ+ Ⅱ) and 40 patients had metastatic disease (stage Ⅲ+ Ⅳ). There were 37 patients treated with surgery alone, three receiving radiotherapy alone, five receiving chemotherapy alone and sixteen receiving comprehensive treatment with 5 underwent surgery plus radiotherapy, three treated by surgery plus chemotherapy, four had surgery plus interventional therapy, two had chemoradiotherapy, one had radiotherapy and interventional therapy and 1 had surgery plus chemoradiotherapy and targeted therapy. Five patients received only palliative treatment, and 2 patients lost follow-up after diagnosed. Fifty patients were followed up with a median overall survival time of 8.5 months. The median survival time of patients with metastatic angiosarcoma was 6.6 months, significantly shorter than that of patients with localized disease (15.0 months, P=0.020). The median survival time of patients with cardiac angiosarcoma was 3.0 months, significantly shorter than that of patients with angiosarcoma at other sites (11.5 months, P=0.010). The median survival time of patients receiving comprehensive treatment was 31.0 months, significantly longer than that of patients without comprehensive treatment (5.6 months, P=0.007). Multivariate analysis showed that staging, heart occurrence and comprehensive treatment were independent factors for the prognosis of primary angiosarcoma (all P<0.05). Conclusions Angiosarcoma is a rare malignancy, and patients with metastatic disease or cardiac occurence have poor prognosis. Comprehensive treatment can improve the prognosis of patients with angiosarcoma.

Objective To analyze whether studying abroad has any influence on clinicians′scientific research ability, and study the rationality of the indicators reflecting the scientific research ability. Methods A total of 36 clinicians who studied abroad more than 3 months between 2008 and 2010 were selected as the abroad group, and the control group of 36 clinicians was selected from the clinician information database of the hospital by the method of Propensity Score Match.A comparison and analysis were made regarding the number of papers(SCI), grants and scientific and technological achievements between the two groups. Meanwhile, covariance analysis was used to compare the difference in the number of scientific research achievements between the two groups.Logistic regression analysis was used to compare the changes in scientific research achievements of clinicians before and after their abroad study. Results The number of articles( SCI) published and grants obtained in the 3 years after going abroad was significantly higher than that of the control group, and the number of grants obtained in the 4-6 years after going abroad was also significantly higher than that in the control group.The number of papers(SCI)published in the three years after going abroad was more than that in the 3 years before going abroad.The number of grants obtained in the 4-6 years after going abroad was more than that in the 3 years before going abroad.These differences were statistically significant. Conclusions Studying abroad has a beneficial effect on the improvement of clinicians′ scientific research ability. It is reasonable and practical to take the number of SCI articles published as the indicator of short-term changes and the number of funds obtained as the indicator of long-term changes in scientific research ability.

Objective The study was designed to analyze the clinicopanthologic characteristics, treatments and outcomes of a series of patients with primary angiosarcoma. Methods The clinical, surgical and pathological data and treatment of 68 patients with pathologically confirmed angiosarcoma admitted to Peking Union Medical College Hospital from January 1990 to June 2017 was retrospectively analyzed. Kaplan?Meier method and Log rank test were used for univariate survival analysis and Cox regression model was used for multivariate survival analysis. Results A total of 68 patients were enrolled, 38 were male, 30 were female. The median age at diagnosis was 50.5 years. The time from symptom onset to diagnosis was (7.5±7.5) months. The primary sites included face and scalp, breast, chest wall, lung, heart, liver, spleen, extremities, bones and so on. At diagnosis, the mean size of tumors were ( 7.4 ± 7.3) cm, 28 patients (41.2%) had localized disease (stage Ⅰ+Ⅱ) and 40 patients had metastatic disease ( stage Ⅲ+ Ⅳ). There were 37 patients treated with surgery alone, three receiving radiotherapy alone, five receiving chemotherapy alone and sixteen receiving comprehensive treatment with 5 underwent surgery plus radiotherapy, three treated by surgery plus chemotherapy, four had surgery plus interventional therapy, two had chemoradiotherapy, one had radiotherapy and interventional therapy and 1 had surgery plus chemoradiotherapy and targeted therapy. Five patients received only palliative treatment, and 2 patients lost follow?up after diagnosed. Fifty patients were followed up with a median overall survival time of 8.5 months. The median survival time of patients with metastatic angiosarcoma was 6.6 months, significantly shorter than that of patients with localized disease (15.0 months, P＝0.020). The median survival time of patients with cardiac angiosarcoma was 3.0 months, significantly shorter than that of patients with angiosarcoma at other sites (11.5 months, P＝0.010). The median survival time of patients receiving comprehensive treatment was 31.0 months, significantly longer than that of patients without comprehensive treatment ( 5.6 months, P＝0.007). Multivariate analysis showed that staging, heart occurrence and comprehensive treatment were independent factors for the prognosis of primary angiosarcoma (all P＜0.05). Conclusions Angiosarcoma is a rare malignancy, and patients with metastatic disease or cardiac occurence have poor prognosis. Comprehensive treatment can improve the prognosis of patients with angiosarcoma.

Objective The study was designed to analyze the clinicopanthologic characteristics, treatments and outcomes of a series of patients with primary angiosarcoma. Methods The clinical, surgical and pathological data and treatment of 68 patients with pathologically confirmed angiosarcoma admitted to Peking Union Medical College Hospital from January 1990 to June 2017 was retrospectively analyzed. Kaplan?Meier method and Log rank test were used for univariate survival analysis and Cox regression model was used for multivariate survival analysis. Results A total of 68 patients were enrolled, 38 were male, 30 were female. The median age at diagnosis was 50.5 years. The time from symptom onset to diagnosis was (7.5±7.5) months. The primary sites included face and scalp, breast, chest wall, lung, heart, liver, spleen, extremities, bones and so on. At diagnosis, the mean size of tumors were ( 7.4 ± 7.3) cm, 28 patients (41.2%) had localized disease (stage Ⅰ+Ⅱ) and 40 patients had metastatic disease ( stage Ⅲ+ Ⅳ). There were 37 patients treated with surgery alone, three receiving radiotherapy alone, five receiving chemotherapy alone and sixteen receiving comprehensive treatment with 5 underwent surgery plus radiotherapy, three treated by surgery plus chemotherapy, four had surgery plus interventional therapy, two had chemoradiotherapy, one had radiotherapy and interventional therapy and 1 had surgery plus chemoradiotherapy and targeted therapy. Five patients received only palliative treatment, and 2 patients lost follow?up after diagnosed. Fifty patients were followed up with a median overall survival time of 8.5 months. The median survival time of patients with metastatic angiosarcoma was 6.6 months, significantly shorter than that of patients with localized disease (15.0 months, P＝0.020). The median survival time of patients with cardiac angiosarcoma was 3.0 months, significantly shorter than that of patients with angiosarcoma at other sites (11.5 months, P＝0.010). The median survival time of patients receiving comprehensive treatment was 31.0 months, significantly longer than that of patients without comprehensive treatment ( 5.6 months, P＝0.007). Multivariate analysis showed that staging, heart occurrence and comprehensive treatment were independent factors for the prognosis of primary angiosarcoma (all P＜0.05). Conclusions Angiosarcoma is a rare malignancy, and patients with metastatic disease or cardiac occurence have poor prognosis. Comprehensive treatment can improve the prognosis of patients with angiosarcoma.

Objective To study the qualitative and quantitative standard of Shengui anti-pruritic mixture. Mehtods Sophorae Flavescentis Radix, Cnidii Fructus, Polygoni Multiflori Radix, Astragali Radix, Paeoniae Radix Alba and Glycyrrhizae Radix Et Rhizoma were identified by TLC.The contents of matrine and ferulic acid were determined by HPLC. Results The TLC showed the obvious characteristics with the spots clear and well-separated with no interference by negative control. Matrine showed a good linear relationship at 0.062 5- 2.500 0 μg (r=0.999 9) with a good meeting of adding sample recovery test. Ferulic acid showed a good linear relationship at 0.021 0-0.840 0 μg (r=0.999 9) with a good meeting of adding sample recovery test. Conclusions The method is easy-operated and accurate which showed a good specificity for the quality control of Shengui anti-pruritic mixture.