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AIM: To elucidate the relationship between childhood asthma susceptibility and clinical efficacy of inhaled glucocorticoids (ICS) in children with different genotypes of asthma by exploring rs776746 and rs15524 single nucleotide polymorphisms (SNPs) of cytochrome P450 enzyme 3A5 (CYP3A5) gene in asthmatic children and healthy children. METHODS: The CYP3A5 gene rs776746 and rs15524 polymorphic sites were detected in 79 children (Case group) with asthma of Han nationality and 100 healthy children (Control group) who met the inclusion criteria admitted to the Northern Theater General Hospital in Northeast China from October 2016 to October 2020, and genotype, allele and linkage analysis were performed. The case group was given inhaled glucocorticoids by nebulised inhalation for 3 months, and lung function and exhaled breath nitric oxide (FeNO) were measured at entry and after treatment, and asthma control score C-ACT/ACT was done after treatment, so as to compare the prevalence of different genotypes and the differences in the above test index scores. RESULTS: There was complete linkage disequilibrium at rs776746 and rs15524 loci. There were three genotypes of T/T, T/C and C/C at rs776746 locus of CYP3A5 gene. There were significant differences in the frequency of different genotypes between the case group and the control group (χ
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Objective:To explore the causes of postoperative mortality within 3 months after lobar lung transplantation and summarize the institutional experiences of diagnosis and treatment so as to improve its early survival rate.Methods:From January 2016 to December 2022, 7 adults underwent lobar lung transplantation and died within 3 months post-lung transplantation at First Affiliated Hospital of Guangzhou Medical University.Age, gender, preoperative status, reasons of lobar lung transplantation, surgical approaches, postoperative managements and major causes of death were summarized.Results:The 3-month postoperative mortality rate was 15.6%.Seven of them died within 3 months.There were 5 males and 2 females with a mean age of 63(49-72)year.Preoperatively 5 recipients stayed in a stable condition and 2 cases were critical with mechanical ventilation.Single lobar LT plus contralateral lung transplantation(4 cases), bilateral lobar LT(2 cases)and unilateral lobar lung transplantation(1 case)were performed.Lobar resection was due to pneumonia of donor lung(5 cases)and size mismatch(2 cases). Cause of mortality was pneumonia(3 cases), bronchial stump fistula(2 cases), kidney failure(1 case) and cardiac failure(1 case).Conclusions:Early 3 months mortality remains high after adult lobar lung transplantation.All risk factors should be comprehensively considered for lowering early mortality.
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OBJECTIVE To explore the effects of ADRB2 gene regulatory region polymorphism on the efficacy of short-acting beta 2 receptor agonists (SABA) in the treatment of acute asthma attack in children. METHODS A total of 127 children with acute mild to moderate bronchial asthma who received SABA treatment for 7 days in the General Hospital of Northern Theater Command from October 2016 to October 2020 were selected to detect their genotype distribution and compare the improvement of pulmonary functional indicators and curative effect among different genotypes. The effect of the high-order interaction of gene polymorphism on therapeutic effect was investigated. RESULTS Among 127 children, there were 80, 44 and 3 cases of TT, TA and AA types at locus rs2895795, 93, 32 and 2 cases of CC, CG and GG types at locus rs11168070, and 41, 64 and 22 cases of GG, GA and AA types at locus rs12654778, respectively, in accordance with Hardy-Weinberg equilibrium (P>0.05). After treatment, the improvement rate of the peak expiratory flow in percent predicted value (PEF%pred) and the improvement rate of the forced expiratory flow at 75% vital capacity in percent predicted value (FEF75%pred) in children with TA type were significantly lower than that of TT type at locus rs2895795 (P<0.05); the improvement rates of PEF%pred and FEF75%pred in children with CG type were significantly lower than that of CC type at locus rs11168070 (P<0.05); the improvement rates of PEF%pred in children with GA and AA type were significantly lower than that of GG type at locus rs12654778 (P<0.05). The differences in fractional exhaled nitric oxide before and after treatment were not statistically significant among different genotypes at each locus (P>0.05). The proportion of remarkable improvement of children with TT type at locus rs2895795 was 2.358 times that of children with TA+ AA type (P<0.05), and there was no significant effect of higher-order interaction of ADRB2 polymorphism on the efficacy in children with asthma (P>0.05). CONCLUSIONS Polymorphisms in the regulatory region of the ADRB2 gene in children with bronchial asthma are associated with the efficacy of SABA in the treatment of acute asthma attack in children. At locus rs2895795, rs11168070 and rs12654778, the improvement of lung function of children with wild-type is more obvious, and the efficacy of SABA treatment on children with TT type is better at locus rs2895795.
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@#Objective To analyze the pathological manifestations and imaging characteristics of bronchiolar adenoma (BA). Methods The clinical data of 11 patients with BA who received surgeries in our hospital from January 2019 to September 2020 were retrospectively analyzed, including 5 males and 6 females aged 40-73 (62.40±10.50) years. The intraoperative rapid freezing pathological diagnosis, postoperative pathological classification, cell growth pattern, nuclear proliferation index Ki-67 and other immunohistochemical staining combined with preoperative chest CT imaging characteristics were analyzed. Results The average preoperative observation time was 381.10±278.28 d. The maximum diameter of imaging lesions was 5-27 (10.27±6.34) mm. Eight (72.7%) patients presented with irregular morphology of heterogeneous ground-glass lesions, and 3 (27.3%) patients presented with pure ground-glass lesions. There were 10 (90.9%) patients with vascular signs, 8 (72.7%) patients with vacuolar signs, 1 (9.1%) patient with bronchus sign, 3 (27.3%) patients with pleural traction and 9 (81.8%) patients with burr/lobular sign. The surgical methods included sub-lobectomy in 10 patients and lobectomy in 1 patient. Five (45.5%) patients were reported BA by intraoperative frozen pathology. The postoperative pathological classification included 8 patients with distal-type and 3 patients with proximal-type, and the maximum diameter of the lesions was 4-20 (8.18±5.06) mm. Eight (72.7%) patients showed characteristic bilayer cell structure under microscope, and 10 (90.9%) patients showed thyroid transcription factor 1 expression in pathological tissues. The expression of NapsinA in intracavity cells was found in 9 (81.8%) patients. The Ki-67 index of the lesion tissue was 1%-5% (3.22%±1.72%). Conclusion The pathological features and imaging findings of BA confirm the premise that BA is a neoplastic lesion. However, to identify BA as a benign or inert tumor needs more clinical data and evidence of molecular pathological studies.
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Objective:To explore the mutational loci associated with the occurrence of dilated cardiomyopathy (DCM).Methods:Six children with DCM and 3 healthy children were recruited through the " Children DCM Susceptibility Gene Research Project" for a prospective study from December 2019 to June 2021.Six patients were aged from 4 months to 14 years, including 5 girls and 1 boy.Three healthy children were aged between 3-13 years, including 2 girls and 1 boy.Whole exome sequencing was performed on the research subjects, and the pathogenic genes were identified by bioinformatics methods.At the same time, the venous blood of the first-degree relatives of the corresponding children was collected, and the region with gene mutations was subjected to next-generation sequencing.Results:A total of 4 mutational loci that might be related to DCM were identified.Case 1 was found to have a c. 2011-3C>G mutation in the jounctophiilin-2 ( JPH2) gene.The c.2011-3C>G mutation was homozygous (GG) in the child, but heterozygous (CG) in the parents.This child also had a c.G49415A mutation in the titin ( TTN) gene.This c.G49415A mutation was homozygous (AA) in the child, but heterozygous (GA) in the parents.Case 4 was found to have a c.G23033A mutation in the TTN gene.The c.G23033A mutation was heterozygous (GA) in both the subject and the father, but a wild type (GG) in the mother.Case 5 was found to have a c.16975_16978del mutation in the TTN gene.The c.16975_16978del mutation was heterozygous (TCTTC/T) in the child and the father, but a wild type (TCTTC/TCTTC) in the mother. Conclusions:A total of 4 pathogenic gene loci related to the pathogenesis of DCM are identified in this study.The finding enriches the DCM disease gene spectrum and provides targets for the implementation of precision medicine.
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OBJECTIVES@#To systematically evaluate the efficacy and safety of bosentan in the treatment of persistent pulmonary hypertension of the newborn (PPHN).@*METHODS@#Chinese Journal Full-text Database, Weipu Database, Wanfang Data, China Biology Medicine disc, PubMed, Web of Science, Embase, and Cochrane Library were searched for literature on bosentan in the treatment of PPHN published up to August 31, 2021.@*RESULTS@#A total of 8 randomized controlled trials were included for Meta analysis. The results of the Meta analysis showed that compared with the control group, the bosentan treatment group had a significantly lower treatment failure rate (RR=0.23, P<0.001), a significantly greater reduction in pulmonary artery pressure [mean difference (MD)=-11.79, P<0.001)], significantly greater increases in oxygen partial pressure (MD=10.21, P=0.006) and blood oxygen saturation (MD=8.30, P<0.001), and a significantly shorter length of hospital stay (MD=-1.35, P<0.001). The descriptive analysis showed that the bosentan treatment group had a lower degree of tricuspid regurgitation than the control group after treatment. The main adverse reactions of bosentan treatment included abnormal liver function, anemia and edema. The results of subgroup analysis based on treatment regimen, research area, and drug dose were consistent with those before stratification.@*CONCLUSIONS@#Bosentan is effective in the treatment of PPHN. However, when using bosentan, attention should be paid to adverse reactions such as abnormal liver function.
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Humanos , Recién Nacido , Bosentán/uso terapéutico , China , Hipertensión Pulmonar/tratamiento farmacológico , Insuficiencia del TratamientoRESUMEN
Neutrophils have always been considered as a short-lived and homogeneous cell type in the innate immune system, which have limited pro-inflammatory or anti-inflammatory effects. However, in recent 10 years, the understanding of neutrophils has been undergoing some kind of revival as researches progressed. The researches on the heterogeneity of neutrophils and the mechanism of their interaction with other immune cells have promoted the researchers to re-understand the physiological and pathophysiological roles of neutrophils. In the following decades, with the development of single-cell sequencing technology, spatial transcriptome sequencing technology, and multi-omics combined sequencing technology, researchers will have a better understanding of the biological behaviors of neutrophils. This paper briefly reviews the biological behaviors of neutrophils and their roles in various diseases in recent years.
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NeutrófilosRESUMEN
Objective: To investigate the changes of heparin-binding protein (HBP) in severe burn patients during shock stage and its effects on human umbilical vein endothelial cells (HUVECs) and neutrophils in vitro. Methods: Prospective observational and experimental research methods were used. Twenty severe burn patients who met the inclusion criteria and were admitted to the Department of Burns and Plastic Surgery of Affiliated Suzhou Hospital of Nanjing Medical University from August to November 2020 were included in severe burn group (12 males and 8 females, aged 44.5 (31.0, 58.0) years). During the same period, 20 healthy volunteers with normal physical examination results in the unit's Physical Examination Center were recruited into healthy control group (13 males and 7 females, aged 39.5 (26.0, 53.0) years). Enzyme-linked immunosorbent assay (ELISA) method was used to detect the protein expression levels of HBP and tissue inhibitor of metalloproteinase 1 (TIMP-1) in plasma of patients within 48 hours after injury in severe burn group and in plasma of volunteers in healthy control group. The correlation between protein expression of HBP and that of TIMP-1 in the plasma in the two groups was analyzed by Pearson correlation analysis. The fourth passage of HUVECs in logarithmic growth phase were used for the experiment. The HUVECs were divided into normal control group with routine culture (the same treatment below) and recombinant HBP (rHBP)-treated 12 h group, rHBP-treated 24 h group, and rHBP-treated 48 h group with corresponding treatment according to the random number table (the same grouping method below), and the mRNA expression of TIMP-1 in cells was detected by real-time fluorescence quantitative reverse transcription polymerase chain reaction. The HUVECs were divided into normal control group and rHBP-treated 48 h group with corresponding treatment, and the protein expression of TIMP-1 in the cells was detected by Western blotting. The HUVECs were divided into normal control group, rHBP alone group, aprotinin alone group, and rHBP+aprotinin group treated with the corresponding reagents (with the final molarity of rHBP being 200 nmol/L and the final concentration of aprotinin being 20 μg/mL, respectively), cultured for 48 h, and ELISA was used to detect the protein expression of TIMP-1 in the culture supernatant of cells. The neutrophils were isolated from the peripheral venous blood of the aforementioned 10 healthy volunteers by immunomagnetic bead sorting, and the cells were divided into normal control group, recombinant TIMP-1 (rTIMP-1) alone group, phorbol acetate (PMA) alone group, and rTIMP-1+PMA group treated with corresponding reagents (with the final concentration of rTIMP-1 being 500 ng/mL and the final molarity of PMA being 10 nmol/L, respectively). After being cultured for 1 h, the expression of CD63 protein in cells was detected by immunofluorescence method, the positive expression rate of CD63 protein in cells was detected by flow cytometry, and the protein expression levels of HBP and myeloperoxidase (MPO) in the culture supernatant of cells were detected by ELISA. The normal control group underwent the above-mentioned related tests at appropriate time points. The number of samples was 3 in each group of cell experiment. Data were statistically analyzed with chi-square test, Mann-Whitney U test, Kruskal-Wallis H test, and Tamhane's T2 test. Results: The protein expression levels of HBP and TIMP-1 in the plasma of patients in severe burn group were 404.9 (283.1, 653.2) and 262.1 (240.6, 317.4) ng/mL, respectively, which were both significantly higher than 61.6 (45.0, 68.9) and 81.0 (66.3, 90.0) ng/mL of volunteers in healthy control group (with Z values of -5.41 and -5.21, respectively, P<0.01). The correlation between the protein expression of HBP and that of TIMP-1 in the plasma of volunteers in healthy control group was not strong (P>0.05). The protein expression of HBP was significantly positively correlated with that of TIMP-1 in the plasma of patients in severe burn group (r=0.64, P<0.01). Compared with that in normal control group, the mRNA expression of TIMP-1 in HUVECs was significantly increased in rHBP-treated 12 h group, rHBP-treated 24 h group, and rHBP-treated 48 h group (with t values of -3.58, -2.25, and -1.26, respectively, P<0.05). Western blotting detection showed that compared with that in normal control group, the protein expression of TIMP-1 in HUVECs in rHBP-treated 48 h group was significantly enhanced. After 48 h of culture, compared with that in normal control group, the protein expression level of TIMP-1 in the culture supernatant of HUVECs in rHBP alone group was significantly increased (t=9.43, P<0.05), while the protein expression level of TIMP-1 in the culture supernatant of HUVECs didn't change significantly in aprotinin alone group or rHBP+aprotinin group (P>0.05); compared with that in rHBP alone group, the protein expression level of TIMP-1 in the culture supernatant of HUVECs in rHBP+aprotinin group was significantly decreased (t=4.76, P<0.01). After 1 h of culture, the trend of CD63 protein expression in neutrophils detected by immunofluorescence method and that by flow cytometry were consistent in each group. After 1 h of culture, compared with that in normal control group, the positive expression rate of CD63 protein in the neutrophils and the protein expression levels of HBP and MPO in the culture supernatant of cells in rTIMP-1 alone group all had no significant changes (P>0.05), while the positive expression rate of CD63 protein in the neutrophils and the protein expression levels of HBP and MPO in the culture supernatant of cells were all significantly increased in PMA alone group and rTIMP-1+PMA group (with t values of 2.41, 3.82, 5.73, 1.05, 4.16, and 1.08, respectively, P<0.05 or P<0.01); compared with that in PMA alone group, the positive expression rate of CD63 protein in the neutrophils and the protein expression levels of HBP and MPO in the culture supernatant of cells in rTIMP-1+PMA group were all significantly decreased (with t values of 5.26, 2.83, and 1.26, respectively, P<0.05 or P<0.01). Conclusions: The expression level of HBP in the plasma of severe burn patients is increased during shock stage. HBP can induce HUVECs to secrete TIMP-1 in vitro, and TIMP-1 can reduce the expression of CD63 molecule in human neutrophils.
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Adulto , Femenino , Humanos , Masculino , Péptidos Catiónicos Antimicrobianos , Proteínas Sanguíneas , Quemaduras , Células Endoteliales de la Vena Umbilical Humana , Neutrófilos , Inhibidor Tisular de Metaloproteinasa-1RESUMEN
Objective To analyze the dynamic changes and the influencing factors of T lymphocyte subsets in recipients with stable graft status within 1 year after lung transplantation. Methods Clinical data of 41 recipients with stable graft status after allogeneic lung transplantation were analyzed. The absolute value and ratio of T lymphocyte subsets in peripheral blood from recipients were measured by flow cytometry before operation, 2 weeks and each month (within 1 year) after operation, respectively. The effects of age, gender, body mass index (BMI), surgical method, incidence of primary graft dysfunction (PGD) after operation, and primary disease upon the absolute values of T lymphocytes were evaluated. Results Within 1 year after lung transplantation, the absolute values of CD3+, CD3+CD4+, CD3+CD8+T lymphocytes and CD4+/CD8+ ratio were changed over time (all P < 0.001). Compared with preoperative values, there was no statistical significance in the absolute values of CD3+ and CD3+CD4+T lymphocytes at 12 months after operation (P=0.659, 0.109), whereas the absolute value of CD3+CD8+T lymphocytes was increased (P=0.02) and the CD4+/CD8+ ratio was decreased (P < 0.001). Age, gender, BMI, surgical method and incidence of PGD after operation exerted no significant effect on the dynamic changes of absolute values of CD3+CD4+ and CD3+CD8+T lymphocytes (all P > 0.05). Primary disease before lung transplantation exerted no effect on the changes of CD3+CD4+T lymphocytes, whereas the postoperative absolute value of CD3+CD8+T lymphocytes was higher in recipients with infectious lung diseases (P < 0.05). Conclusions The absolute values of CD3+, CD3+CD4+, CD3+CD8+T lymphocytes in recipients with stable graft status after lung transplantation are relatively low in the early stage after lung transplantation, then gradually restore, and stabilize at 6 months after operation. Dynamic changes are not associated with age, gender, BMI, surgical method and incidence of PGD after operation of recipients.
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Purpose@#Resveratrol (REV), a natural compound found in red wine, exhibits antitumor activity in various cancers, including ovarian cancer (OC). However, its potential anti-tumor mechanisms in OC are not well characterized. Here, we tried to elucidate the underlying mechanisms of REV in OC cells. @*Materials and Methods@#The anti-proliferative effects of REV against OC cells were measured using CCK-8 assay. Apoptosis was measured using an Annexin V-FITC/PI apoptosis detection kit. The anti-metastasis effects of REV were evaluated by invasion assay and wound healing assay. The miRNA profiles in REV-treated cells were determined by microarray assay. @*Results@#Our results showed that REV treatment suppresses the proliferation, induces the apoptosis, and inhibits the invasion and migration of OV-90 and SKOV-3 cells. miR-34a was selected for further study due to its tumor suppressive roles in various human cancers. We found miR-34a overexpression enhanced the inhibitory effects of REV on OC cells, whereas miR-34a inhibition had the opposite effect in OC cells. In addition, we verified that BCL2, an anti-apoptotic gene, was found directly targeted by miR-34a.We also found that REV reduced the expression of Bcl-2 in OC cells. Further investigations revealed that overexpression of Bcl-2 significantly abolished the anti-tumor effects of REV on OC cells. @*Conclusion@#Overall, these results demonstrated that REV exerts anti-cancer effects on OC cells through an miR-34a/Bcl-2 axis, highlighting the therapeutic potential of REV for treatment of OC.
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Purpose@#Resveratrol (REV), a natural compound found in red wine, exhibits antitumor activity in various cancers, including ovarian cancer (OC). However, its potential anti-tumor mechanisms in OC are not well characterized. Here, we tried to elucidate the underlying mechanisms of REV in OC cells. @*Materials and Methods@#The anti-proliferative effects of REV against OC cells were measured using CCK-8 assay. Apoptosis was measured using an Annexin V-FITC/PI apoptosis detection kit. The anti-metastasis effects of REV were evaluated by invasion assay and wound healing assay. The miRNA profiles in REV-treated cells were determined by microarray assay. @*Results@#Our results showed that REV treatment suppresses the proliferation, induces the apoptosis, and inhibits the invasion and migration of OV-90 and SKOV-3 cells. miR-34a was selected for further study due to its tumor suppressive roles in various human cancers. We found miR-34a overexpression enhanced the inhibitory effects of REV on OC cells, whereas miR-34a inhibition had the opposite effect in OC cells. In addition, we verified that BCL2, an anti-apoptotic gene, was found directly targeted by miR-34a.We also found that REV reduced the expression of Bcl-2 in OC cells. Further investigations revealed that overexpression of Bcl-2 significantly abolished the anti-tumor effects of REV on OC cells. @*Conclusion@#Overall, these results demonstrated that REV exerts anti-cancer effects on OC cells through an miR-34a/Bcl-2 axis, highlighting the therapeutic potential of REV for treatment of OC.
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Objective:To investigate the relationship between rs2075748 and rs542269 single nucleotide polymorphisms of cholinergic muscarinic receptor 1 (CHRM1)gene and susceptibility of childhood asthma, as well as the differences of pulmonary function and serum acetylcholine(Ach)levels among different genotypes.Methods:A total of 156 asthmatic children who were treated in the outpatient or hospitalized in the General Hospital of the Northern Theater Command from September 2018 to September 2020 were selected as the case group, while 134 non-asthmatic children who had a healthy physical examination were selected as the control group.The SNaPshot SNP typing technique was used to analyze the genotype of the CHRM1 gene rs2075748 and rs542269 of the study subjects.Serum Ach level was detected by double antibody sandwich method, and the pulmonary function of the case group was detected.Results:After analyzing the CHRM1 gene polymorphism, it was found that the CC, CT, and TT genotype frequencies at rs2075748 were 65.4%, 28.8%, 5.8% in the case group, and 62.8%, 32.4%, 4.8% in the control group.The C and T allele frequencies were 79.8% and 20.2% in the case group, 74.3% and 25.7% in the control group.There were no significant difference in the genotype and allele frequency distribution between the two group ( χ2=2.688, 2.530, both P>0.05), and there were no significant difference in the recessive and dominant modes between the two groups ( χ2=0.338, 2.686, both P>0.05). The TT and CT genotype frequencies at rs542269 locus were 72.4% and 27.6% in the case group, 62.7% and 37.3% in the control group.The T and C allele frequency were 86.2% and 13.8% in the case group, 81.3% and 18.7% in the control group.The genotype and allele frequency distribution were not obvious different between the two group ( χ2=3.145, 2.544, both P>0.05). The risk of asthma with variant CT and TT at rs2075748 locus of CHRM1 gene were not statistically different from that of wild-type CC (both P>0.05), and the risk of asthma with variant CT at rs542269 locus was no different from that of wild-type TT ( P>0.05). The difference in FEF50% Pred and FEF75% Pred of different genotypes at rs2075748 were statistically significant( F=3.118, 4.808, both P<0.05), wild-type CC was lower than variant CT(both P<0.05). There were no statistically significant difference in pulmonary function among different genotypes at rs542269 (both P>0.05). There was significant difference in serum Ach level between different genotypes of rs2075748 ( F=4.716, P<0.05), variant CT was lower than wild-type CC ( P<0.05), variant TT was lower than wild-type CC ( P<0.05), while no significant difference was find between variant CT and TT ( P>0.05). There was no significant difference in serum Ach level between different genotypes of rs542269 ( P>0.05). Conclusion:The rs2075748 locus of CHRM1 gene is not susceptible to asthma, but it may be related to the small airway function of asthmatic children, besides there are differences in serum Ach levels with different genotypes, and the variant serum Ach level is lower.The rs542269 locus is not a susceptibility site for asthma, and there are no difference in pulmonary function and serum Ach levels in asthmatic children with different genotypes.
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Objective:To investigate the short-term therapeutic effect and long-term survival of multiple myeloma patients with extramedullary disease (EMD) in the new drug era.Methods:The data of 74 patients with multiple myeloma diagnosed and treated in Anhui Wanbei Coal and Electricity Group General Hospital from January 2015 to January 2020 were retrospectively analyzed, including 17 patients with soft tissue infiltration (EM-S), 9 patients with bone infiltration (EM-B), and 48 patients without EMD (No-EMD). The short-term efficacy, the 4-year progression-free survival (PFS) rate and overall survival (OS) rate, and their influencing factors in three groups of patients after receiving bortezomib regimen were analyzed.Results:After 3-4 courses of early induction therapy of bortezomib regimen, the overall response rate of patients in the EM-S group was lower than that in the No-EMD group and the EM-B group [58.8% (10/17) vs. 85.4% (41/48), 100.0% (9/9)], and the differences were statistically significant ( χ2 = 13.7, P = 0.036; χ2 = 26.5, P = 0.003), while the difference between No-EMD group and EM-B group was not statistically significant ( χ2 = 12.7, P = 0.211). Survival analysis showed that the 4-year PFS rate of No-EMD group was higher than that of the EM-S group and EM-B group (41.0% vs. 7.6%, 0), and the differences were statistically significant ( χ2 = 10.835, P < 0.01; χ2 = 8.276, P = 0.004). Meanwhile, the 4-year OS rate of EM-S group was lower than that of the No-EMD group and EM-B group (16.5% vs. 54.3%, 59.3%), and the differences were statistically significant ( χ2 = 9.146, P = 0.002; χ2 = 4.066, P = 0.044). Conclusion:The early treatment effect of bortezomib regimen, PFS and OS in multiple myeloma patients with EM-S are poor, while the EM-B has no effect on OS.
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Objective:To investigate the therapeutic effect and signaling pathway of ginsenoside Rb1 on myocardial injury in mice with Kawasaki disease.Methods:BALB/C mice aged 5-6 weeks were randomly divided into control group, model group, aspirin group, ginsenoside Rb1 low dose group(50 mg/kg) and high dose group(100 mg/kg), with 12 mice in each group.Except the control group, other groups were treated with intermittent intraperitoneal injection of 10% bovine serum albumin saline solution to induce Kawasaki disease myocardial injury pathological model with a total of 6 days(twice a day); aspirin group, Rb1 low and high-dose group were given corresponding drugs by gavage for 20 days after modeling.The pathological changes of myocardial tissue were observed by hematoxylin eosin staining.The levels of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), interleukin-6(IL-6) and cardiac troponin I(cTnI) in serum and myocardial tissue were detected by ELISA.The activities of creatine kinase(CK), creatine kinase isoenzyme(CK-MB), lactate dehydrogenase(LDH), α-hydroxybutyrate dehydrogenase(α-HBDH) and aspartate aminotransferase(AST) in serum were detected by enzyme coupling method.The expression levels of janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT3) signaling pathway related proteins in myocardial tissue were detected by Western blot.Results:High dose of Rb1 significantly improved myocardial fiber rupture and tear, inflammatory infiltration and necrosis induced by myocardial injury in model group.ELISA results showed that, compared with the model group, high-dose Rb1 could significantly inhibit the high expression of tumor necrosis factor-α, interleukin-1β, interleukin-6, which were restored to the level of the control group, and there was a dose-dependent relationship between the low and high-dose groups( P<0.05). The results of enzyme coupling method showed that creatine kinase, creatine kinase isoenzyme-MB, lactate dehydrogenase, α-hydroxybutyrate dehydrogenase, and aspartate aminotrasferase in Rb1 high-dose group were restored to the level in control group, and there was a dose-dependent relationship between low and high-dose group( P<0.05). At the same time, compared with model group, Rb1 high-dose group significantly down regulated the expression level of cardiac troponin I( P<0.05). Western blot results showed that, compared with the model group, Rb1 significantly increased the relative expression levels of p-JAK2/JAK2, p-STAT3/STAT3 and B-cell lymphoma-2(Bcl-2)/β-actin, and significantly decreased the expression levels of Cleaved caspase-3/β-actin in a dose-dependent manner( P<0.05). Conclusion:Ginsenoside Rb1 can effectively reduce the myocardial injury induced by Kawasaki disease mice.The high-dose group of Rb1 can recover to the level of the control group, and the curative effect is related to the dosage of Rb1.Ginsenoside Rb1 may activate JAK2/STAT3/Bcl-2 signaling pathway, thus down regulate the expression of Cleaved caspase-3, and inhibit cardiomyocyte apoptosis and inflammation.
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Objective:To explore the clinical manifestations and imaging features of nocardia infection (NI) after lung transplantation and boost the diagnosis and treatment of NI.Methods:From January 2018 to December 2019, basic profiles, clinical manifestations, laboratory examinations, imaging features and treatment outcomes of 5 lung transplant recipients with a diagnosis of NF were retrospectively analyzed and summarized with the relevant literatures. There were 4 males and 1 female with a median age of 66(26-69) years. 3 patients were single-lung transplantation, 2 patients were bilateral-lung transplantation. The median time from an initial diagnosis of NI to lung transplant surgery was 6(5-19) months. Common symptoms included fever, cough with yellow phlegm and shortness of breath. Laboratory findings showed lymphopenia, significantly high C-reactive protein levels, a slight elevation of procalcitonin, hypoproteinemia and anemia. The major manifestations of high-resolution computed tomography (CT) included multiple nodules, consolidation, cavitation and pleural effusion.Results:Five strains of N. farcinica were identified from bloodstream infection ( n=2) and pulmonary infection ( n=3). After with a combined therapy of two sensitive agents, all patients improved and were discharged from hospital. During follow-ups, one patient died and the remainders were cured. Conclusions:Nocardia infection occurs in lung transplant recipients mostly within 1 year post-operation. There are non-specific symptoms and imaging features of multiple nodules and consolidation. Combination therapy of sensitive agents is indicated for lung transplant recipients with NI.
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Objective:To explore the incidence, clinical characteristics and prognosis of invasive pulmonary fungal infection(IPFI)in recipients of lung transplantation(LT)in southern China.Methods:From January 2003 to August 2019, retrospective analysis was performed for 300 recipients of lung transplantation at three hospitals in southern China. There were 254 males and 46 females with an average age of (54.98±14.2)years. Clinical data were collected from medical records, including symptoms and signs, imaging studies, bronchoscopy examination, pathogen separation and culture from deep sputum and bronchoalveolar lavage fluid(BALF), fungal-related laboratory tests and tissue pathology.Results:Among 300 cases, 93(31.0%)had at least one episode of IPFI. The most common pathogen was aspergillosis(60.2%), followed by candida(15 cases, 16.1%)and Pneumocystis jeroveci (13 cases, 14.0%). Kaplan Meier analysis indicated that all-cause mortality was significantly higher in IPFI group than that in non-IPFI(nIPFI)group with one-year mortality of 45.2% vs. 26.7% in IPFI and nIPFI groups respectively( P<0.05). Conclusions:IPFI is prevalent after LT in southern China. And aspergillosis is the most common pathogen and Candida comes the next. The median occurring time for aspergillosis is 6 months after LT. Candida infection occurs earlier at airway anastomosis. A higher incidence of invasive fungal disease(IFD)associated with a lower survival indicates that IPFI has a substantial mortality among recipients after LT. Prophylactic agents should be optimized based upon an epidemiologically likely pathogen.
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Objective: To observe the effects of acupoint thread-embedding therapy and low-carbohydrate diet therapy on obese patients with food addiction. Methods: Sixty-five eligible patients were randomized into a thread-embedding group of 33 cases and a diet group of 32 cases to respectively receive 12-week treatment. Before treatment, after treatment and at 6-month follow-up, the two groups were observed and compared in terms of body mass (BM), waist circumference (WC), hip circumference (HC), waist-to-hip ratio (WHR), body mass index (BMI), body fat rate (BFR), basal metabolic rate (BMR) and Yale food addiction scale version 2.0 (YFAS 2.0). Results: At the end of treatment, there were no significant differences in the general efficacy, and the improvements in BM, BMI, WC, HC, WHR and BFR between the thread-embedding group and diet group (all P>0.05). At follow-up, the thread-embedding group showed more significant improvements in all the aforementioned indicators compared with the diet group except HC (all P<0.05). At the end of treatment and follow-up, BMR and YFSA 2.0 had more significant improvements in the thread-embedding group than in the diet group (all P<0.05). Conclusion: Acupoint thread-embedding therapy can produce significant efficacy in treating obese patients with food addiction; it can improve the food addiction state and work better in maintaining the efficacy compared with low-carbohydrate diet therapy.
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Objective:To investigate the correlation between single nucleotide polymorphism of corticosteroids receptor gene(NR3C1)and children with asthma and to analyze the efficacy of inhaled corticosteroid(ICS)treatment.Methods:The study included a control group(100 healthy children)who participated in the physical examination and an asthma group(101 children with bronchial asthma)who were hospitalized in the General Hospital of the Northern Theater Command from October 2018 to October 2020.Genomic DNA was extracted from peripheral blood samples of all enrolled subjects and then the polymorphism of the glucocorticoid receptor gene locus of NR3C1 was analyzed using SNaPshot SNP gene detection technology.The comparisons of allele frequency in rs41423247、rs7701443 between two groups were performed and the treatment effects of ICS in the asthma group were evaluated at the 12th week of treatment.Results:The frequencies of GG, GC, and CC genotypes of rs41423247 locus of NR3C1 were 75.2%, 21.8%, and 3.0% in the asthma group and 72.0%, 24.0%, and 4.0% in the control group, respectively, and there were no statistically significant differences between the two groups( χ2=0.333, P>0.05). The frequencies of GG, GA, and AA genotypes of rs7701443 locus of NR3C1 were 45.5%, 39.6%, and 14.9% in the asthma group and 56.0%, 31.0%, and 13.0% in the control group, respectively, and there were no statistically significant differences between the two groups( χ2=2.259, P>0.05). After ICS treatment, the C-ACT/ACT scores were not significantly improved in children with CC genotypes at rs41423247 locus( P>0.05), while children with GG and GC genotypes were obviously improved( P<0.05). The scores of C-ACT/ACT showed obvious differences among three genotypes of rs41423247 locus after treatment with ICS( P<0.05). The C-ACT/ACT scores of all were significantly improved in children with GG, GA, or AA genotypes at rs7701443 locus after treatment with ICS( P<0.05), while there was no significant difference among those three genotypes( P>0.05). Significantly improved pulmonary function following ICS treatment in children with asthma was observed in GG and GC genotypes of rs41423247 locus of NR3C1( P<0.05), while only MMEF was improved in CC genotype( P<0.05). Meanwhile, those pulmonary function indexes were improved in all genotypes of rs7701443 after treatment with ICS( P<0.05). Conclusion:Both rs41423247 and rs7701443 locus at NR3C1 gene have polymorphisms.But there were no significant differences in the polymorphism of rs41423247 and rs7701443 locus of NR3C1 between the asthma group and the control group.Different genotype frequencies of rs41423247 and rs7701443 at NR3C1 locus in children with asthma have different effects on ICS treatment.
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Although there is guidance from different regulatory agencies, there are opportunities to bring greater consistency and stronger applicability to address the practical issues of establishing and operating a data monitoring committee (DMC) for clinical studies of Chinese medicine. We names it as a Chinese Medicine Data Monitoring Committee (CMDMC). A panel composed of clinical and statistical experts shared their experience and thoughts on the important aspects of CMDMCs. Subsequently, a community standard on CMDMCs (T/CACM 1323-2019) was issued by the China Association of Chinese Medicine on September 12, 2019. This paper summarizes the key content of this standard to help the sponsors of clinical studies establish and operate CMDMCs, which will further develop the scientific integrity and quality of clinical studies.
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OBJECTIVES@#To study the association of β2-drenergic receptor (@*METHODS@#A total of 143 children with asthma who attended the hospital from October 2016 to October 2020 were enrolled as the asthma group, among whom 61 children had mild symptoms (mild group) and 82 children had moderate-to-severe symptoms (moderate-to-severe group). A total of 137 healthy children were enrolled as the control group. Peripheral venous blood samples were collected from the two groups. The SNaPshot SNP technique was used to analyze the SNP and haplotypes of the @*RESULTS@#Polymorphisms were observed in the @*CONCLUSIONS@#SNP/haplotype of the