AIM:To investigate the effect of protopanaxatriol(PPT)on the drug resistance of paclitaxel(PTX)-resistant human breast cancer MDA-MB-231 cells(MB231-PR cells).METHODS:The MB231-PR cells were constructed as cell models.They were treated with PPT,and incubated for a certain period of time according to the experi-mental settings.CellTiter-Glo was used to determine the viability of MB231-PR cells and MDA-MB-231 parental cells(MB231-PT cells).The change of sub-G1 phase was detected by flow cytometry.Western blot was used to evaluate the apoptosis-related proteins,such as cleaved caspase-3,cleaved poly(ADP-ribose)polymerase(PARP),B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax)and survivin.The activity of nuclear factor-κB(NF-κB)was detected by lu-ciferase reporter assay and immunofluorescence assay.The mRNA expression levels of interleukin-6(IL-6),IL-8,chemo-kine CXC motif ligand 1(CXCL1),chemokine CC motif ligand 2(CCL2),CD44,NANOG,octamer-binding transcrip-tion factor 4(OCT4),sex-determining region Y-box 2(SOX2)and aldehyde dehydrogenase 1(ALDH1)were detected by qPCR.The protein levels of IL-6 and IL-8 were measured by ELISA.Tumor sphere formation assay was used to evaluate the characteristics of stem cells.RESULTS:(1)The viability of MB231-PR cells was suppressed by PPT treatment in a dose-dependent manner compared with MB231-PT cells(P<0.01).Besides,the viability of MB231-PR cells was de-creased after combined treatment with PPT and PTX(P<0.01),the accumulation of sub-G1 phase was induced(P<0.01),the ratio of Bax/Bcl-2 was elevated(P<0.01),and the protein levels of survivin,cleaved PARP and cleaved cas-pase-3 were increased(P<0.05).(2)After PPT treatment combined with PTX,the mRNA expression of inflammatory cy-tokines(IL-6,IL-8,CXCL1 and CCL2)and cancer stem cell-related markers(OCT4,SOX2,NANOG,ALDH1 and CD44)was reduced(P<0.05),and the protein levels of IL-6 and IL-8 were decreased(P<0.01).The activity of NF-κB in MB231-PR cells was suppressed(P<0.05),and the growth of tumor spheres from MB231-PR cells was damaged(P<0.05).(3)Immunofluorescence assay showed that PTX induced nuclear p-p65 expression,but this effect was attenuated by PPT.CONCLUSION:Combined treatment with PPT and PTX could attenuate PTX resistance of MB231-PR cells by inhibiting inflammatory cytokines and cancer stem cells.

Eclipta prostrata L.has been used in traditional medicine and known for its liver-protective properties for centuries.Wedelolactone(WEL)and demethylwedelolactone(DWEL)are the major coumarins found in E.prostrata L.However,the comprehensive characterization of these two compounds on non-alcoholic fatty liver disease(NAFLD)still remains to be explored.Utilizing a well-established zebrafish model of thioacetamide(TAA)-induced liver injury,the present study sought to investigate the impacts and mechanisms of WEL and DWEL on NAFLD through integrative spatial metabolomics with liver-specific transcriptomics analysis.Our results showed that WEL and DWEL significantly improved liver function and reduced the accumulation of fat in the liver.The biodistributions and metabolism of these two compounds in whole-body zebrafish were successfully mapped,and the discriminatory endogenous metabolites reversely regulated by WEL and DWEL treatments were also characterized.Based on spatial metabolomics and transcriptomics,we identified that steroid biosynthesis and fatty acid metabolism are mainly involved in the hepatoprotective effects of WEL instead of DWEL.Our study unveils the distinct mechanism of WEL and DWEL in ameliorating NAFLD,and presents a"multi-omics"platform of spatial metabolomics and liver-specific transcriptomics to develop highly effective compounds for further improved therapy.

OBJECTIVE: To investigate the clinical features and genetic variant of a child with X-linked dominant Alport syndrome (XLAS). METHODS: A child who had presented at the First Affiliated Hospital of Zhengzhou University in May 2019 was selected as the study subject. Clinical data of the child was collected. Next generation sequencing (NGS) was carried out for the child. Candidate variants were validated by Sanger sequencing of his family members. RESULTS: The child, a 12-year-old boy, had mainly manifested gross hematuria, proteinuria, nephrotic syndrome, and progressive renal impairment in conjunct with hearing loss. Kidney biopsy has revealed uneven glomerular basement membrane thickness. DNA sequencing revealed that the child and his mother have both carried a heterozygous c.2632G>A (p.G878R) variant of the COL4A5 gene, for which his father and brother were of the wild type. This variant was unreported previously. Based on the guidelines from the American College of Medical Genetics and Genomics, the variant was classified as pathogenic (PS1+PM1+PM2_Supporting+PP3). CONCLUSION The maternally derived hemizygous c.2632G>A (p.G878R) variant of the COL4A5 gene probably underlay the XLAS in this child. Above finding has enriched the mutational spectrum of the COL4A5 gene.
Male ; Female ; Humans ; Child ; Nephritis, Hereditary/genetics* ; Deafness ; Kidney Glomerulus ; Genomics ; Mothers

Objective The intervention effect of Huoxue Jiedu Huayu Recipe on the pyroptosis of vascular smooth muscle cells(VSMC)on the contralateral renal vessel of 6-month unilateral ureteral obstruction(UUO)rat model was observed,and part of the treatment mechanism of Huoxue Jiedu Huayu Recipe on chronic kidney disease(CKD)was investigated.Methods Forty male wistar rats were randomly divided into 4 groups:the sham operation(Sham)group,the unilateral ureteral obstruction(UUO)group,the eplerenone treatment(EPL)group and the Huoxue Jiedu Huayu Recipe intervention(HJHR)group,10 rats in each group.The EPL group was given eplerenone and the HJHR group was given traditional Chinese medicine.The right kidney was collected after 6 months.Pathological changes were assessed by HE staining and Masson staining.The expressions of Cysteinyl aspartate specific proteinase1(Caspase-1),Interleukin-1β(IL-1β),Serum and glucocorticoid-induced kinase 1(SGK1)and nuclear factor κappa-B(NF-κB)were detected by immunohistochemistry.The DNA damage in renal VSMC was examined by TUNEL staining.Rat VSMCs were used for in vitro experiments.The cells were divided into 4 groups using the random number method:the control(CON)group,the aldosterone(ALD)group,the aldosterone plus eplerenone treatment(EPL)group and the aldosterone plus Huoxue Jiedu Huayu Recipe treatment(HJHR)group.The ALD group was given aldosterone stimulation for 24 h.The EPL group and the HJHR group were given eplerenone and rat serum containing 10%Huoxue Jiedu Huayu Recipe pretreatment before aldosterone stimulation,respectively.The apoptosis rate was detected by flow cytometry.Perforation of gasdermin D(GSDMD)and nuclear translocation of NR3C2(Encode MR)in cell membranes were examined by immunofluorescence.The protein expression of inflammation and pyroptosis-related signaling molecules were examined by western blotting.The mRNA expression of pyroptosis signaling pathway were detected by qRT-PCR.Results Compared with the Sham group,DNA damage of renal blood vessels and VSMCs was increased in UUO group,and expressions of Caspase-1,IL-1β,SGK1 and NF-κB were increased.Compared with the UUO group,the DNA damage of renal blood vessels and VSMCs in EPL and HJHR groups was reduced,and the expressions of Caspase-1,IL-1β,SGK1 and NF-κB were decreased.Compared with the CON group,the ALD group showed pyroptosis and DNA damage of rat VSMC.The expression of NR3C2,NLRP3,Caspase-1,GSDMD,IL-1β,SGK1 and NF-κB was up-regulated.Compared with the ALD group,the pyroptosis and DNA damage were alleviated,and the expression of NR3C2,NLRP3,Caspase-1,GSDMD,IL-1β,SGK1 and NF-κB was decreased in EPL and HJHR groups.Conclusion Huoxue Jiedu Huayu Recipe reduce the vascular damage of the contralateral kidneys of UUO by inhibiting the activation of the MR/NLRP3 inflammasome pathway and inhibiting the pyroptosis of VSMC.

Objective:To explore the relationship between parental rearing style and mental health of community correction offenders, as well as the mediating role of personality and coping styles in it.Methods:A questionnaire survey was conducted on 385 community correction offenders by the Egma Minnen av Bardndosna uppforstran(EMBU), symptom checklist-90 (SCL-90), NEO five-factor inventory(NEO-FFI) and simplified coping style questionnaire(SCSQ) from February to July 2022.SPSS 27.0 software was used for correlation analysis and regression analysis.AMOS 26.0 was used for the construction of structural equation, and Bootstrap was used for mediating effect analysis.Results:In parental rearing styles, the dimension of parents' severe punishment(19.09±5.32, 12.93±4.77), father's preference for subjects(9.29±3.30), father's excessive protection(10.40±2.19), mother's excessive interference and protection(33.81±6.06)and parents' refusal and denial (9.08±3.03, 12.17±4.25) were significantly positively correlated with the total score of SCL-90 (140.63±44.28)( r=0.114, 0.168, 0.121, 0.144, 0.224, 0.187, 0.220 respectively, all P<0.05). Parents' emotional warmth and understanding, parents' severe punishment and parents' refusal and denial were significantly correlated with coping styles ( r=0.420, 0.420, -0.189, -0.190, -0.174, -0.163 respectively, P<0.05). Neuroticism, extraversion, conformity, rigor in personality were significantly correlated with the total score of SCL-90 ( r=0.542, -0.442, -0.204, -0.202 respectively, P<0.05). Coping style was significantly negatively correlated with the total score of SCL-90 ( r=-0.352, P<0.05). The father's refusal and denial, the mother's emotional warmth and understanding, the mother's excessive interference and protection in the parental rearing styles could predict the mental health of community correction offenders ( β=0.191, -0.163, 0.233 respectively, P<0.05). Coping styles had a negative predictive effect on mental health ( β=-0.352, P<0.05). Neuroticism, preciseness and extra-version in personality could predict mental health ( β=0.461, 0.183, -0.281 respectively, P<0.05). The pathway coefficient of parental rearing styles → mental health was 0.261 ( P<0.001), and the direct effect was significant. The confidence intervals of parental rearing styles → personality traits → mental health path, parental rearing styles → coping tendency → mental health path did not include 0, indicating that partial mediating effect of personality traits and coping tendency were significant. Conclusion:Personality traits and coping styles play a mediating role in the influence of parental rearing style on mental health of community correction offenders.

Objective:To investigate the expression level of β-catenin and its relationship with clinicopathology and prognosis of patients with pancreatic ductal adenocarcinoma (PDAC).Methods:Real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression of β-catenin mRNA in primary pancreatic cancer cell line and pancreatic ductal epithelial cell line HPDE6-C7 of the healthy. The data of 45 patients with PDAC confirmed by pathology at Xinjiang Medical University Cancer Hospital from June 2012 to December 2013 were retrospectively analyzed. Immunohistochemical method was used to detect the expression level of β-catenin in cancer tissues and adjacent tissues, and the correlation of β-catenin with pathological characteristics of patients with PDAC was analyzed. Cox proportional hazard model was performed to make univariate and multivariate analysis on the influencing factors of overall survival (OS).Results:The relative expression of β-catenin mRNA in primary pancreatic cancer cells was higher than that in HPDE6-C7 cell line [(3.83±0.83) vs. (1.00±0.03)], and the difference was statistically significant ( t = 3.45, P = 0.003). The high expression rate of β-catenin protein in PDAC tissues was higher than that in para-cancer tissues [68.9% (31/45) vs. 28.9% (14/45)], and the difference was statistically significant ( χ2 = 7.50, P = 0.005). The high expression rate of β-catenin protein in PDAC patients with different tumor diameter and TNM staging had statistically significant differences ( P = 0.026, P = 0.036). The median OS time of 45 patients was 22.5 months, and that of high expression of β-catenin protein group in 31 patients was 19 months, that of low expression of β-catenin group in 14 patients was 29 months, and the difference was statistically significant ( P = 0.009). Univariate Cox analysis showed that preoperative carbohydrate antigen199 (CA199) level, tumor diameter, tumor differentiation degree and the expression level of β-catenin protein were influencing factors of OS of patients with PDAC. Multivariate Cox analysis showed that preoperative CA199 ( OR = 9.883, 95% CI 2.815-34.689, P < 0.001), tumor diameter ( OR = 6.117, 95% CI 1.578-24.179, P = 0.009), tumor differentiation degree ( OR = 3.834, 95% CI 1.158-12.697, P = 0.028), the expression level of β-catenin protein ( OR = 0.139, 95% CI 0.045-0.430, P = 0.001) were independent affecting factors of OS of patients with PADC. Conclusions:β-catenin is abnormally highly expressed in PDAC which is correlated with the disease progression of patients and may be a new indicator and therapeutic target of prognosis for PDAC patients.

Objective:To investigate the effect of Suhuang Zhike Capsule on airway inflammation in patients with acute episode of allergic rhinitis and asthma syndrome.Methods:Eighty patients with allergic rhinitis and asthma syndrome were admitted to North China University of Science and Technology Affiliated Hospital from June 2016 to September 2017.A prospective cohort study was carried out and randomly divided into treatment group and control group with 40 patients in each group.The control group was treated with conventional anti-inflammatory, expectorant and antiasthmatic therapy, while the treatment group was treated with Suhuang Zhike Capsule.The changes of nasal symptoms and asthma clinical symptoms in the two groups were compared before and after treatment, and the changes of nitric oxide in exhaled air, eosinophils in blood and induced sputum were measured.Results:Compared with the control group, there was no significant difference in the number of eosinophils in the exhaled nitric oxide, eosinophil count in blood and induced sputum before treatment in the treatment group ((161.45±4.67)×10 -9 vs.(163.12±4.56)×10 -9, (1.59±0.53)×10 9/L vs.(1.60±0.51)×10 9/L, (1.11±0.06)×10 9/L vs.(1.18±0.09)×10 9/L; t values were 0.10, 0.44, 1.75, respectively, all P>0.05). After treatment, the exhaled nitric oxide, eosinophil count in blood and induced sputum in the treatment group were significantly lower than those before treatment((30.86±5.54)×10 -9 vs. (161.45±4.67)×10 -9; (0.32±0.05)×10 9/L vs. (1.59±0.53)×10 9/L; (0.06±0.02)×10 9/L vs. (1.11±0.06)×10 9/L, t values were 91.32, 41.63, 51.77, respectively, all P<0.01). In the treatment group, the effective rate of nasal symptom control was 85.0% (34/40) significantly higher than 62.5% (25/40) in the control group (χ 2=5.23, P<0.05), and the effective rate of asthma clinical symptom control was significantly higher than that in the control group(90.0%(36/40), 72.5%(29/40), χ 2=4.02, P<0.05). Conclusion:Suhuang Zhike capsule can obviously improve the airway inflammatory response of patients with allergic rhinitis asthma syndrome in the acute attack stage, and the combination of conventional treatment plan is helpful to improve the curative effect.

Objective: To investigate the level of human blood basic fibroblast growth factor (FGF2) among children with autism spectrum disorder (ASD) and its correlation with behavioral phenotypes, to provide a reference for etiological research of ASD. Methods: ASD Children were selected to get rehabitation training in reseach center of children development behavior in Harbin Medical University and the rehabitation constitution for ASD disabilities in Heilongjiang, 40 children were induded as ASD group, 41 healthy children in Harbin kindergarten was classified as control group. The Autism Behavior Checklist (ABC), Childhood Autism Rating Scale (CARS) and Peabody Picture Vocabulary Test (PPVT) were used to assess the severity and intelligence of ASD children, respectively. Results: No difference was found in FGF2 level between ASD children (4.95 pg/mL) and normal children(8.51 pg/mL)（P>0.05). However, difference in FGF2 level between the two groups were found in 4-year-old group(P<0.05). The level of FGF2 differed across different severity and intelligence of ASD children(P<0.05). Conclusion Abnormal levels of FGF2 in ASD children may correlate with severity of autistic traits and intelligence of children.

Objective: To investigate the impact of informal care satisfaction on quality of life on the elderly by establishing a structural equation model between them and introducing two mediating variables of frailty and depressive factors. Methods: A total of 210 elderly over 60 years old from 6 communities of 2 urban areas in Qingdao were surveyed by general information questionnaire, the informal care satisfaction scale, frailty phenotype, depression scale and the SF-36 brief health scale. Results: There was a direct effect on quality of life of daily life care dimension in informal nursing satisfaction (β=0.160, P<0.01) and an indirect effect of debilitating as intermediary (β=0.055, P<0.01). There was a direct effect on quality of life (β=0.130, P<0.01) and an indirect effect mediated by depression (β=0.132, P<0.01). There was a direct effect on quality of life (β=0.150, P<0.01) and an indirect effect mediated by debilitating and depression (β=0.147, P<0.01). Conclusions We should pay more attention to the impact of informal care on the quality of life on the elderly. Taking corresponding measures to promote the use of informal nursing and improving the quality of informal care is of great significance to improve the quality of life of the elderly and promote healthy aging.

Objective To observe the effect of edaravone (ED) on cognition function and expression of Nogo-A in prefrontal cortex neuron of rats with serious intermittent hypoxia.Methods Ninety-six adult male Wistar rats were randomly divided into normal control group, chronic intermittent hypoxia (CIH) model group and ED group, 32 rats in each group. The rat model of CIH was reproduced in a low oxygen box at 08:00-15:00 every day: alternatively, different flow rates of nitrogen and compressed air were given, 120 seconds being one cycle, maintaining the oxygen concentration at 5%-21% in the low oxygen chamber; the normalcontrol group was continuously under the circumstance fulfilled with compressed air. The rat in ED group was given intravenous injection of 3 mg/kg ED in a tail vein at 07:00 daily. After modeling for 7, 14, 21, 28 days, the learning and memory functions of rats were assessed with the Morris water maze test, and the reactive oxygen species (ROS) content in the rat prefrontal lobe tissue was detected; the level of Nogo-A protein expression in the rat prefrontal cortex was examined by immunohistochemical method .Results ① Rat learning results: in CIH model group, with the time prolongation escaping latency period was gradually longer, since 14 days after the modeling, the difference was statistically significant compared with that in normal control group, while the learning time in ED group was obviously shorter than that in the CIH model group (seconds: 14 days was 26.97±3.35 vs. 34.95±3.36, 21 days was 32.78±4.59 vs. 46.72±4.11, 28 days was 41.39±3.84 vs. 57.35±3.72, allP < 0.05). ② Rat memory results: the rats in CIH model group, with the time prolongation crossing the target quadrant time was gradually shorter, since 14 days after the modeling, the difference was statistically significant compared with that of the normal control group, while the memory time in the ED group was obviously longer than that of the model group (seconds: 14 days was 42.72±3.35 vs. 39.88±3.56, 21 days was 40.48±4.62 vs. 28.72±3.93, 28 days was 31.13±3.46 vs. 22.79±3.24, allP < 0.05). ③ ROS content: with the time prolongation, ROS content was gradually increased in CIH model group, but the ROS content in ED group was significantly lower than that in CIH model group at various time points (MU/L: 7 days was 13.27±0.23 vs. 17.68±0.51, 14 days was 15.51±0.28 vs. 20.41±0.65, 21 days was 20.29±0.44 vs. 23.86±0.35, 28 days was 24.46±0.53 vs. 30.43±0.85, allP < 0.05). ④ Protein expression of Nogo-A: with the time prolongation, the protein expression of Nogo-A was gradually increased in CIH model group, they reached the peak on the 14th day, the expression of Nogo-A [absorbance (A) value] in ED group were significantly lower than that in CIH model group at each time point (×103: 7 days was 4.80±0.70 vs. 5.99±0.62, 14 days was 5.89±0.90 vs. 7.42±0.66, 21 days was 4.92±0.64 vs. 5.90±0.37, 28 days was 3.59±0.59 vs. 4.27±0.40, allP < 0.05).Conclusions The mechanism of ED has a valid therapeutic effect on the cognitive dysfunction induced by serious intermittent hypoxia in rats, ED can remove oxygen free radicals and inhibit the protein expression of Nogo-A in the prefrontal cortex, so ED can alleviate the damage of cognitive function in rats with CIH.