Objective:To explore the correlation between serum ferritin(SF)levels and the efficacy of platelet transfusion in patients with malignant hematological diseases.Methods:Patients with malignant hematological diseases who received repeated transfusions of apheresis platelets in Department of Hematology of Aerospace Center Hospital in 2023 were selected.The platelet corrected count increment(CCI)was used to evaluate the efficacy of platelet transfusion.The correlations between sex,age,disease type,transplantation history,red blood cell transfusion history,and SF level and the efficacy of platelet transfusion were analyzed.Results:A total of 87 patients were included,with a cumulative 326 person-times platelet transfusions.As suggested by one-way analysis of variance,compared with the patients in the age groups of 24-45 years old and 46-66 years old,the patients in the age group of 2-23 years old had a better efficacy of platelet transfusion(P=0.004,P=0.004).There was no significant difference in the efficacy of platelet transfusion between the patients in the age group of 24-45 years old and those in the age group of 46-66 years old(P=0.876).Compared with the patients who had a history of red blood cell transfusion within 3 days,the patients without a history of red blood cell transfusion within 3 days had a better efficacy of platelet transfusion(P＜0.001).Compared with the groups with SF levels of 1.44-2.78 ng/L and＞2.78 ng/L,the group with SF levels＜1.44 ng/L had a better efficacy of platelet transfusion(P=0.028,P＜0.001).Compared with the group with SF levels＞2.78 ng/L,the group with SF levels of 1.44-2.78 ng/L had a better efficacy of platelet transfusion(P=0.001).After adjusting for age and the history of red blood cell transfusion,the transfusion efficacy of the group with SF levels＜1.44 ng/L was better than that of the groups with SF levels of 1.44-2.78 ng/L and＞2.78 ng/L(P=0.021,P＜0.001);Compared with the group with SF levels＞2.78 ng/L,the group with SF levels of 1.44-2.78 ng/L had a better efficacy of platelet transfusion(P=0.001).Both univariate and multivariate linear regression models showed that SF levels were negatively correlated with the efficacy of platelet transfusion(P＜0.001).Conclusion:There is a negative correlation between SF levels and the efficacy of platelet transfusion in patients with malignant hematological diseases.Detection of SF levels may provide guidance for predicting the efficacy of platelet transfusion.

Objective:To explore the correlation between serum ferritin(SF)levels and the efficacy of platelet transfusion in patients with malignant hematological diseases.Methods:Patients with malignant hematological diseases who received repeated transfusions of apheresis platelets in Department of Hematology of Aerospace Center Hospital in 2023 were selected.The platelet corrected count increment(CCI)was used to evaluate the efficacy of platelet transfusion.The correlations between sex,age,disease type,transplantation history,red blood cell transfusion history,and SF level and the efficacy of platelet transfusion were analyzed.Results:A total of 87 patients were included,with a cumulative 326 person-times platelet transfusions.As suggested by one-way analysis of variance,compared with the patients in the age groups of 24-45 years old and 46-66 years old,the patients in the age group of 2-23 years old had a better efficacy of platelet transfusion(P=0.004,P=0.004).There was no significant difference in the efficacy of platelet transfusion between the patients in the age group of 24-45 years old and those in the age group of 46-66 years old(P=0.876).Compared with the patients who had a history of red blood cell transfusion within 3 days,the patients without a history of red blood cell transfusion within 3 days had a better efficacy of platelet transfusion(P＜0.001).Compared with the groups with SF levels of 1.44-2.78 ng/L and＞2.78 ng/L,the group with SF levels＜1.44 ng/L had a better efficacy of platelet transfusion(P=0.028,P＜0.001).Compared with the group with SF levels＞2.78 ng/L,the group with SF levels of 1.44-2.78 ng/L had a better efficacy of platelet transfusion(P=0.001).After adjusting for age and the history of red blood cell transfusion,the transfusion efficacy of the group with SF levels＜1.44 ng/L was better than that of the groups with SF levels of 1.44-2.78 ng/L and＞2.78 ng/L(P=0.021,P＜0.001);Compared with the group with SF levels＞2.78 ng/L,the group with SF levels of 1.44-2.78 ng/L had a better efficacy of platelet transfusion(P=0.001).Both univariate and multivariate linear regression models showed that SF levels were negatively correlated with the efficacy of platelet transfusion(P＜0.001).Conclusion:There is a negative correlation between SF levels and the efficacy of platelet transfusion in patients with malignant hematological diseases.Detection of SF levels may provide guidance for predicting the efficacy of platelet transfusion.

Activation of nuclear factor erythroid 2-related factor 2(Nrf2)by Kelch-like ECH-associated protein 1(Keap1)alkylation plays a central role in anti-inflammatory therapy.However,activators of Nrf2 through alkylation of Keap1-Kelch domain have not been identified.Deoxynyboquinone(DNQ)is a natural small molecule discovered from marine actinomycetes.The current study was designed to investigate the anti-inflammatory effects and molecular mechanisms of DNQ via alkylation of Keap1.DNQ exhibited signif-icant anti-inflammatory properties both in vitro and in vivo.The pharmacophore responsible for the anti-inflammatory properties of DNQ was determined to be the α,β-unsaturated amides moieties by a chemical reaction between DNQ and N-acetylcysteine.DNQ exerted anti-inflammatory effects through activation of Nrf2/ARE pathway.Keap1 was demonstrated to be the direct target of DNQ and bound with DNQ through conjugate addition reaction involving alkylation.The specific alkylation site of DNQ on Keap1 for Nrf2 activation was elucidated with a synthesized probe in conjunction with liquid chromatography-tandem mass spectrometry.DNQ triggered the ubiquitination and subsequent degra-dation of Keap1 by alkylation of the cysteine residue 489(Cys489)on Keap1-Kelch domain,ultimately enabling the activation of Nrf2.Our findings revealed that DNQ exhibited potent anti-inflammatory capacity through α,β-unsaturated amides moieties active group which specifically activated Nrf2 signal pathway via alkylation/ubiquitination of Keap1-Kelch domain,suggesting the potential values of targeting Cys489 on Keap1-Kelch domain by DNQ-like small molecules in inflammatory therapies.

Objective:To establish a brain metastasis (BM) prediction model for limited-stage small cell lung cancer (LS-SCLC) patients who achieved complete response (CR) or partial response (PR) after thoracic chemoradiotherapy, and to explore the value of prophylactic cranial irradiation (PCI) in different risk groups.Methods:Clinical data of 274 patients with LS-SCLC who achieved CR/PR after thoracic chemoradiotherapy in Tianjin Medical University Cancer Institute & Hospital from January 2010 to December 2021 were retrospectively analyzed, including 144 cases in the PCI group and 130 in the non-PCI group. The nomogram was developed based on variables determined by univariate and multivariate analyses in the non-PCI group. The bootstrap method, receiver operating characteristics (ROC) curve, calibration curve and decision curve analysis (DCA) were employed to evaluate the predictive power and clinical benefits of the model. Patients were stratified into high- and low-risk groups based on risk scores. The brain metastases-free survival (BMFS), progression-free survival (PFS), extracranial progression-free survival (ePFS) and overall survival (OS) were compared between patients with and without PCI in different risk-stratified populations using the log-rank test.Results:The nomogram included five variables: systemic immune inflammation index (SII), lymphocyte-to-monocyte ratio (LMR), pro-gastrin-releasing peptide precursor (ProGRP), neuron-specific enolase (NSE), and blood calcium. The area under the ROC curve (AUC) of the nomogram in predicting 1- and 2-year BMFS was 0.761 and 0.822. In the low-risk group, there was no significant difference in the BMFS ( P=0.374), PFS ( P=0.551), ePFS ( P=0.508) and OS ( P=0.767) between the PCI and non-PCI groups. In the high-risk group, PCI could significantly increase the BMFS ( P<0.001) and PFS ( P=0.022), while there was no significant difference in the ePFS ( P=0.963) and OS ( P=0.632). And propensity score-matching (PSM) analysis showed similar results. Conclusions:PCI does not improve OS in LS-SCLC patients regardless of high or low risk of BM. However, PCI significantly prolong the BMFS and PFS in patients at a high risk of BM.

Objective To explore the regulatory role of transient receptor potential channel 6(TRPC6)on podocyte autophagy under the influence of homocysteine(Hcy)in mouse kidney.Methods Mouse renal podocytes were divided into control group and Hcy groups(stimulated by Hcy at 40,60,80 and 100 μmol/L for 48 h).The level of TRPC6 mRNA was assessed using quantitative reverse transcription polymerase chain reaction(qRT-PCR)to identify the optimal Hcy concentration for subsequent experiments.Western blotting was employed to evaluate the expression levels of autophagy-related proteins LC3 Ⅱ and p62,as well as the expression levels of podocyte structural proteins Nephrin and Podocin.The expression levels of TRPC6 mRNA and protein in both groups were determined using qRT-PCR,Western blotting and immunofluorescence.Transfections of cells with TRPC6 overexpression or interference were set as follows:(1)control group(untreated),negative control group of TRPC6 overexpression,and TRPC6 overexpression group;(2)control group(untreated),negative control group of TRPC6 interference,and TRPC6 interference group(si-1,si-2,si-3).The expression level of TRPC6 was detected using qRT-PCR.The cells after overexpressing or interfering of TRPC6 were further set as follows:(1)control group(untreated),Hcy group(80 μmol/L Hcy added),TRPC6 overexpression control+Hcy group,TRPC6 overexpression+Hcy group;(2)control group(untreated),Hcy group,TRPC6 interference control+Hcy group,and TRPC6 interference+Hcy group.The expression levels of p62,LC3 Ⅱ,and TRPC6 proteins were detected using Western blotting.Results qRT-PCR detection results showed that compared with control group,the expression level of TRPC6 mRNA in Hcy group increased with the increase of Hcy concentration,with the highest expression level observed at 80 μmol/L Hcy.Therefore,80 μmol/L Hcy was selected as the optimal concentration for intervention.At this time,the expression level of autophagy-related protein LC3 Ⅱ increased,and the expression level of p62 decreased(P<0.05).Western blotting results showed that compared with control group,the expression levels of podocyte-related proteins Nephrin and Podocin in Hcy group were significantly decreased(P<0.05).qRT-PCR results showed that compared with control group,the expression level of TRPC6 mRNA in Hcy group was significantly increased(P<0.05).Compared with negative control group for TRPC6 overexpression,both mRNA and protein expression levels of TRPC6 in TRPC6 overexpression group were significantly higher(P<0.05).Compared with negative control group for TRPC6 interference,both mRNA and protein expression levels of TRPC6 in TRPC6 interference group were significantly decreased(P<0.05).Western blotting results showed that compared with negative control group for TRPC6 overexpression,the expression level of autophagy-related protein LC3 Ⅱ in TRPC6 overexpression+Hcy group was significantly increased,and the expression level of p62 was significantly decreased(P<0.05).Compared with TRPC6 negative control+Hcy group for TRPC6 interference+Hcy,the expression level of autophagy-related protein LC3 Ⅱ in TRPC6 interference+Hcy group was significantly decreased,and the expression level of p62 was significantly increased(P<0.05).Conclusion Hcy can induce autophagy of renal podocytes.Inhibiting the expression of TRPC6 can significantly reduce the autophagy damage to podocytes.

Animals ; Rats ; Explosions ; Proteomics ; Autophagy

Objective This study used high-throughput sequencing technology to detect the regulation of JianPiHuaTan Prescription(JPHT)on the ApoE-/-mouse miRNA related to vascular smooth muscle cells proliferation and migration,verify the expression of related proteins,and explore the therapeutic effect of JPHT on atherosclerosis.Methods Ten of C57BL/6J mice were used as control group,and 30 ApoE-/-mice were randomly divided into model group,western medicine group and JPHT group.Sequencing technology was performed on aortic sample to select the differentially expressed miRNA.We screened out the tagetted miRNA related to VSMCs proliferation and migration.RT-qPCR and Western blot technology were used to test the differentially expressed miRNA and tagetted protein.Results Compared with model group,a total of 9 miRNAs were changed in JPHT group,among which 7 were up-regulated and 2 were down-regulated.The expression of miRNA-34a was up-regulated in JPHT group.The miRNA-34a and α-SMA protein expression in aorta of JPHT group were significantly different with model group by RT-qPCR and Western blot experiment(P<0.01).Conclusion Jianpi Huatan Prescription may improve ApoE-/-mice atherosclerosis through inhibitting the proliferation of vascular smooth muscle cells by regulating miRNA-34a.

Objective To explore the overall level,distribution characteristics,and differences in household fine particulate matter (PM_2.5) pollution caused by fuel burning in urban and rural areas in China. Methods The relevant articles published from 1991 to 2021 were retrieved and included in this study.The data including the average concentration of household PM_2.5 and urban and rural areas were extracted,and the stoves and fuel types were reclassified.The average concentration of PM_2.5 in different areas was calculated and analyzed by nonparametric test. Results The average household PM_2.5 concentration in China was (178.81±249.91) μg/m³.The mean household PM_2.5 concentration was higher in rural areas than in urban areas[(206.08±279.40) μg/m³ vs. (110.63±131.16) μg/m³;Z=-5.45,P<0.001] and higher in northern areas than in southern areas[(224.27±301.66) μg/m³ vs.(130.11±140.61) μg/m³;Z=-2.38,P=0.017].The north-south difference in household PM_2.5 concentration was more significant in rural areas than in urban areas[(324.19±367.94) μg/m³ vs.(141.20±151.05) μg/m³,χ²=-5.06,P<0.001].The PM_2.5 pollution level showed differences between urban and rural households using different fuel types (χ²=92.85,P<0.001),stove types (χ²=74.42,P<0.001),and whether they were heating (Z=-4.43,P<0.001).Specifically,rural households mainly used solid fuels (manure,charcoal,coal) and traditional or improved stoves,while urban households mainly used clean fuels (gas) and clean stoves.The PM_2.5 concentrations in heated households were higher than those in non-heated households in both rural and urban areas (Z=-4.43,P<0.001). Conclusions The household PM_2.5 pollution caused by fuel combustion in China remains a high level.The PM_2.5 concentration shows a significant difference between urban and rural households,and the PM_2.5 pollution is more serious in rural households.The difference in the household PM_2.5 concentration between urban and rural areas is more significant in northern China.PM_2.5 pollution in the households using solid fuel,traditional stoves,and heating is serious,and thus targeted measures should be taken to control PM_2.5 pollution in these households.
Humans ; Particulate Matter/analysis* ; Air Pollution, Indoor/analysis* ; Cooking ; Environmental Exposure/analysis* ; China ; Rural Population

Objective: To explore the clinical manifestations and genetic characteristics of patients with epilepsy and episodic ataxia caused by SCN2A gene variation. Methods: The clinical data of seizure manifestation, imaging examination and genetic results of 5 patients with epilepsy and (or) episodic ataxia because of SCN2A gene variation admitted to the Department of Pediatrics, the Third Affiliated Hospital of Zhengzhou University from July 2017 to January 2021 were analyzed retrospectively. Results: Among 5 patients, 4 were female and 1 was male. The onset age of epilepsy ranged from 4 days to 8 months. There were 2 cases of benign neonatal or infantile epilepsy and 3 cases of epileptic encephalopathy, in whom 1 case had development retardation,1 case transformed from West syndrome to infantile spasm and another one transformed from infantile spasm to Lennox-Gastaut syndrome. One case of benign neonatal-infantile epilepsy was characterized by neonatal onset seizures and episodic ataxia developed at the age of 78 months. Electroencephalograms at first visit of 5 cases showed that 2 cases were normal, 1 case had focal epileptic discharge, and 2 cases had multi-focal abnormal discharge with peak arrhythmia. The brain magnetic resonance imaging (MRI) of 3 cases were nomal, 1 case was abnormal (brain atrophy with decreased white matter) and the results of 1 case was unknown. The follow-up time ranged from 17 months to 89 months. Four cases of epilepsy were controlled and 1 case died at 2 years of age. Two cases had normal intelligence and motor development, 2 had moderate to severe intelligence retardation and motor critical state, and 1 had moderate to severe intelligence and motor development retardation. SCN2A gene variations were identified in all cases. There were 4 missense variations and 1 frameshift variation. Three variations had not been reported so far, including c.4906A>G,c.3643G>T,c.638delT. Conclusions: Variations in SCN2A gene can cause benign neonatal or infantile epilepsy and epileptic encephalopathy. Some children develop episodic ataxia with growing age. The variation of SCN2A gene is mainly missense variation.
Ataxia/genetics* ; Child ; Electroencephalography ; Epilepsy/genetics* ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Mutation ; NAV1.2 Voltage-Gated Sodium Channel/genetics* ; Retrospective Studies ; Spasms, Infantile/genetics*

Objective: To explore the heterogeneity and correlation of clinical phenotypes and genotypes in children with disorders of sex development (DSD). Methods: A retrospective study of 1 235 patients with clinically proposed DSD in 36 pediatric medical institutions across the country from January 2017 to May 2021. After capturing 277 DSD-related candidate genes, second-generation sequencing was performed to analyzed the heterogeneity and correlation combined with clinical phenotypes. Results: Among 1 235 children with clinically proposed DSD, 980 were males and 255 were females of social gender at the time of initial diagnosis with the age ranged from 1 day of age to 17.92 years. A total of 443 children with pathogenic variants were detected through molecular genetic studies, with a positive detection rate of 35.9%. The most common clinical phenotypes were micropenis (455 cases), hypospadias (321 cases), and cryptorchidism (172 cases) and common mutations detected were in SRD5A2 gene (80 cases), AR gene (53 cases) and CYP21A2 gene (44 cases). Among them, the SRD5A2 mutation is the most common in children with simple micropenis and simple hypospadias, while the AMH mutation is the most common in children with simple cryptorchidism. Conclusions: The SRD5A2 mutation is the most common genetic variant in Chinese children with DSD, and micropenis, cryptorchidism, and hypospadias are the most common clinical phenotypes. Molecular diagnosis can provide clues about the biological basis of DSD, and can also guide clinicians to perform specific clinical examinations. Target sequence capture probes and next-generation sequencing technology can provide effective and economical genetic diagnosis for children with DSD.
3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics* ; Child ; China/epidemiology* ; Cryptorchidism/genetics* ; Disorders of Sex Development/genetics* ; Female ; Genital Diseases, Male ; Genotype ; Humans ; Hypospadias/genetics* ; Male ; Membrane Proteins/genetics* ; Penis/abnormalities* ; Phenotype ; Retrospective Studies ; Steroid 21-Hydroxylase/genetics*