Objective:To investigate the therapeutic efficacy and safety of conditioning regimen with oral melphalan in tandem autologous hematopoieticstem cell transplantation (ASCT) for patients with malignant plasma cell diseases.Methods:A retrospective case series study was conducted. The clinical data of 13 patients with malignant plasma cell diseases who underwent tandem ASCT between October 2019 and March 2024 in the First Affiliated Hospital of Xi'an Jiaotong University were collected. Compared with the use of intravenous melphalan as conditioning regimen for the first ASCT, hematopoietic reconstruction after transplantation, the therapeutic effects, adverse reactions after drug usage and survival of conditioning regimen with oral melphalan after tandem ASCT were analyzed.Results:Among the 13 patients, there were 10 males and 3 females, with a median age [ M ( Q1, Q3)] of 53 (48, 61) years; 11 cases were multiple myeloma and 2 cases were plasma cell leukemia. Before the first ASCT, tandem ASCT was performed 2-6 months later. The median reconstruction time of neutrophils after the first and second ASCT were both 9 (9, 10) d, and the median reconstruction time of platelets after the first and second ASCT were both 10 (9, 11) d, and there were no statistically significant differences in reconstruction rate of granulocytes on day 9 [69.2% (9/13) vs. 61.5% (8/13)] and platelets on day 10 [46.2% (6/13) vs. 53.8% (7/13)] between the first and second transplantation (all P > 0.05). There were 4 cases of strict complete remission (sCR), 3 cases of complete remission (CR), 4 cases of very good partial remission (VGPR), and 2 cases of partial remission (PR) before the first ASCT. After the first ASCT 1 month later, 1 case achieved VGPR, 1 case achieved PR, 11 cases achieved sCR; all 13 patients achieved sCR at 6 months after second ASCT. Compared with conditioning regimen of intravenous melphalan for the first ASCT, the non-hematological adverse reactions such as nausea (7 cases vs. 9 cases), vomiting (4 cases vs. 13 cases), diarrhea (4 cases vs. 13 cases) and oral mucositis (2 cases vs. 9 cases) in the conditioning regimen of oral melphalan after the second ASCT was reduced, and the differences were statistically significant (all P < 0.01). After the 2 transplantation conditioning regimen with melphalan, Ⅳ degree myelosuppression occurred in 13 cases. After the second ASCT, the median follow-up time was 14 (10, 22) months, 7 patients received maintenance therapy containing lenalidomide, 3 patients received maintenance therapy containing bortezomib, 2 patients received pomalidomide maintenance therapy, and 1 patient received maintenance therapy containing CD38 monoclonal antibody. At the last follow-up, all patients survived, among which 6 multiple myeloma patients relapsed; and the median recurrence time was 13 (10, 22) months after the second ASCT. The estimated 5-year progression-free survival rate was 28.6%. Conclusions:Conditioning regimen with oral melphalan for the second ASCT is safe and well tolerated, and it may further improve the efficacy of the first transplantation.

Objective To study the clinical efficacy of Xiaoqinglong decoction combined with the conventional protocol of western medicine in the treatment of acute exacerbation of chronic obstructive pulmonary disease(AECOPD)presenting with exterior cold and interior fluid retention syndrome,and to evaluate its effect on the short-term prognosis of patients.Methods A total of 124 AECOPD patients presenting exterior cold and interior fluid retention syndrome were divided into an observation group(62 cases)and a control group(62 cases)using a random number table.Patients in the control and observation groups were managed with conventional western medicine treatment protocols consisting of bronchodilators,glucocorticoids,and antibacterial drugs.In addition,patients in the observation group were also given Xiaoqinglong decoction at one dose per day for 10 days in succession.The primary outcome indicators included the total effective treatment rate and the main traditional Chinese medicine(TCM)syndrome scores before treatment and after 10 days of Xiaoqinglong decoction treatment.The secondary outcome indicators included infection and inflammatory indicators,including white blood cell count(WBC),procalcitonin(PCT),interleukin(IL)-6,C-reactive protein(CRP),and arterial blood gas indicators,including arterial partial pressure of oxygen(PaO2),arterial partial pressure of carbon dioxide(PaCO2),and arterial oxygen saturation(SaO2),measured before treatment and after 10 days of treatment,adverse drug reactions during treatment,and the severity of dyspnea assessed by the modified Medical Research Council(mMRC)dyspnea scale at the 1-month follow-up after discharge.Results Compared with baseline findings for the same group before treatment,the main TCM syndrome scores and the total score were reduced in both groups after treatment(P<0.05).After treatment,compared with those of the control group,the syndrome scores for cough,aversion to cold,nasal congestion,and runny nose,and the total score in the observation group were lower(P<0.05).The total effective treatment rate in the observation group(94.91%)was significantly higher than that in the control group(82.76%)(P<0.05).After 10 days of treatment,the levels of PaCO2,WBC,PCT,IL-6,and CRP in both groups were significantly reduced compared with those before treatment(P<0.05).After treatment,the levels of PaCO2,WBC,PCT,IL-6,and CRP in the observation group were lower than those in the control group(P<0.05).Compared with those before treatment,PaO2 and SaO2 levels in both groups increased significantly after 10 days of treatment(P<0.05).During the course of treatment,no severe adverse reactions,such as liver or kidney dysfunction,occurred in either group.No adverse reactions associated with Xiaoqinglong decoction were observed.No patients in either group reached mMRC grade 4 at the 1-month follow-up after discharge.The mMRC grades in both groups declined at the 1-month follow-up after discharge compared to those before treatment(P<0.05).At the 1-month follow-up after discharge,the mMRC grades of patients in the observation group were lower than those of the control group(P<0.05).Conclusion Xiaoqinglong decoction combined with the conventional protocol of western medicine deminstrates good clinical efficacy in treating patients with AECOPD of exterior cold and interior fluid retention syndrome,and can effectively improve the TCM syndromes,relieve the symptoms of dyspnea,reduce the inflammatory response,promote the resolution of infection,delay disease progression,improve short-term prognosis,and shows better safety.

Objective To observe the safety and efficacy of levosimendan in the perioperative pe-riod for patients with pulmonary hypertension associated with valvular heart disease undergoing heart valve replacement surgery.Methods A total of 90 patients with pulmonary hypertension associated with valvular heart disease who underwent valve replacement surgery from April 2023 to May 2024 were enrolled.Based on the use of levosimendan,patients were divided into low-dose group,high-dose group,and control group,with 30 patients in each group.The control group received conventional drug therapy;the low-dose group received one dose of levosimendan from 3 days before surgery to 3 days after surgery combined with conventional drug therapy;the high-dose group received two doses of levosimendan from 3 days before surgery to 3 days after surgery combined with conventional drug therapy.Data on brain natriuretic peptide(BNP),left ventricular ejection fraction(LVEF),left ventricular end-diastolic diameter(LVEDD),creatinine(Cr),mean pulmonary artery pressure(mPAP),PH related to left heart disease(PH-LHD)status,postoperative ICU stay,postoperative hospital stay,and cardiac function classification were collected and recorded at admission and before discharge.Results There were no statistically significant differences in gender,age,and body mass among the control group,low-dose group,and high-dose group(P＞0.05).There was no sta-tistically significant difference in the increase in Cr among the three groups(P＞0.05).There were statistically significant differences in postoperative ICU stay between the control group and the high-dose group,and between the control group and the low-dose group(P=0.017,0.028).However,there was no statistically significant difference in postoperative ICU stay between the low-dose group and the high-dose group(P=0.839).There were statistically significant differences in postopera-tive hospital stay between the control group and the high-dose group,and between the control group and the low-dose group(P=0.001,0.009),but no statistically significant difference was found between the low-dose group and the high-dose group(P=0.463).No serious complications oc-curred in any of three groups,and no patients withdrew from the study.Only one patient in the high-dose group experienced hypotension during the postoperative use of levosimendan,which nor-malized after fluid replacement.There was no statistically significant difference in the decrease in mPAP among the three groups(P＞0.05).There was a statistically significant difference in the de-crease in BNP between the control group and the high-dose group(P=0.025);however,there were no statistically significant differences in the decrease in BNP between the control group and the low-dose group,or between the low-dose group and the high-dose group(P=0.068,0.970).There was a statistically significant difference in the increase in LVEF between the control group and the high-dose group(P=0.019);however,there were no statistically significant differences in the increase in LVEF between the control group and the low-dose group,or between the low-dose group and the high-dose group(P=0.055,0.652).There were statistically significant differences in the decrease in LVEDD between the control group and the low-dose group,and between the control group and the high-dose group(P=0.019,0.033);however,there was no statistically significant difference between the low-dose group and the high-dose group(P=0.829).In the control group,18 patients(60.0％)had clinically effective treatment,22 patients(73.3％)in the low-dose group,and 24 patients(80.0％)in the high-dose group.There was no statistically significant differ-ence in clinical efficacy among the three groups(P=0.220).Conclusion Levosimendan is safe and effective in the perioperative period for patients with pulmonary hypertension associated with valvular heart disease,and high-dose use can more significantly improve LVEF and reduce BNP levels.

Objective To analyze the single nucleotide polymorphism (SNP) and copy number variation (CNV) of cardiac myxoma to find the SNP sites and CNV events that may play important roles in the occurrence of tumors. Methods The patients with myxoma admitted to our hospital from 2015 to 2019 were randomly selected. The SNP analysis and the CNV test in gene level were performed through whole exome sequencing (WES). The samples were divided into two groups according to the mean size of the tumor: a diameter≤5.7 cm group and a diameter>5.7 cm group. The analysis results were compared between the two groups. Results A total of 14 patients were enrolled, including 8 females and 6 males with a mean age of 61.4 (41-79) years. Thirty-seven cancer-genes with SNP were detected, among which 18 mutated sites had a mutation rate of>10%; and TP53, EP300 and CREBBP played a core binding role in protein-protein interaction-network. The GO enrichment results showed significant differences in the regulation of cell secretion of the mutated genes, and the KEGG enrichment results showed significant differences in the PI3K-AKT and JAK-STAT signaling pathways in the occurrence of myxoma. In addition, 17 new mutation sites of tumor genes with high mutation effect were found in SNP detection. The WES results of 14 samples showed that the CNV events were detected in 120 tumor genes of the samples, 10 of which were included in two tumor databases. The GO enrichment results showed significant differences in the tube development and regulation of cell proliferation, and the KEGG enrichment results showed significant differences in the comprehensive tumor signaling pathway. Statistical differences of ERCC6L and INTS6L in CNV test were found (P=0.030). Conclusion There may be multiple tumor gene site mutations in the process of tumor generation, among which there are multiple core tumor genes such as TP53, EP300 and CREBBP, regulating tumor cells through PI3K-AKT and JAK-STAT signaling pathways and playing an important role in tumor generation. The CNV of ERCC6L and INTS6L genes may be related to tumor growth.

Objective:To investigate the effects of exosome derived from miR-133a-3p engineered human umbilical cord blood mesenchymal stem cells (ucMSC) on myocardial repair after acute myocardial infarction (AMI) in rats.Methods:UcMSC was amplified and cultured in vitro. Lentiviral carrying miR-133a-3p and negative control vectors were transfected into ucMSC. Exosomes secreted by the transfected ucMSC were named miR-133a-3p-Exo and miR-NC-Exo, respectively. The AMI model of rats was established by ligation of the left anterior descending coronary artery. MiR-133a-3p-Exo or miR-NC-Exo were then injected into the border zone of the infarct area. Cardiac function was assessed by echocardiography after twenty-eight days of intervention, and Masson staining was used to evaluate the area of myocardial fibrosis post-AMI. The myocardial apoptosis after infarction was evaluated by TUNEL staining and the angiogenesis after infarction was evaluated by immunofluorescence staining in the current study. Results:Compared with the miR-NC-Exo group, the left ventricular ejection fraction in the miR-133a-3p-Exo group was significantly increased ((47.4%±9.8%) vs. (64.2%±8.9%), P<0.05). While the myocardial fibrosis area ((31.2%±7.3%) vs. (18.0%±1.5%), P<0.01) and the percentage of apoptotic cardiomyocytes ((25.6%±3.6%) vs. (15.1%±4.4%), P<0.05) was significantly reduced in the miR-133a-Exo group. Besides, the expression of CD31 and α-smooth muscle actin (α-SMA) were also increased significantly in the miR-133a-3p-Exo group compared to the miR-NC-Exo group (CD31: (2.9±0.9) vs. (13.9±2.0), P<0.000 1, α-SMA: (3.5±0.9) vs. (11.0±1.6), P<0.000 1). Conclusion:Exosome derived from miR-133a-3p engineered ucMSC effectively inhibited myocardial apoptosis and promoted angiogenesis, thus improving the cardiac function after myocardial infarction in rats.

BACKGROUND: In China, lung cancer remains the cancer with the highest incidence and mortality rate. Among early-stage lung adenocarcinomas (LUAD), the micropapillary (MPP) component is prevalent and typically exhibits high aggressiveness, significantly correlating with early metastasis, lymphatic infiltration, and reduced five-year survival rates. Therefore, the study is to explore the similarities and differences between MPP and non-micropapillary (non-MPP) components in malignant pulmonary nodules characterized by GGOs in early-stage LUAD, identify unique mutational features of the MPP component and analyze the relationship between the ZNF469 gene, a member of the zinc-finger protein family, and the prognosis of early-stage LUAD, as well as its correlation with immune infiltration. METHODS: A total of 31 malignant pulmonary nodules of LUAD were collected and dissected into paired MPP and non-MPP components using microdissection. Whole-exome sequencing (WES) was performed on the components of early-stage malignant pulmonary nodules. Mutational signatures analysis was conducted using R packages such as maftools, Nonnegative Matrix Factorization (NMF), and Sigminer to unveil the genomic mutational characteristics unique to MPP components in invasive LUAD compared to other tumor tissues. Furthermore, we explored the expression of the ZNF469 gene in LUAD using The Cancer Genome Atlas (TCGA) database to investigate its potential association with the prognosis. We also investigated gene interaction networks and signaling pathways related to ZNF469 in LUAD using the GeneMANIA database and conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Lastly, we analyzed the correlation between ZNF469 gene expression and levels of immune cell infiltration in LUAD using the TIMER and TISIDB databases. RESULTS: MPP components exhibited a higher number of genomic variations, particularly the 13th COSMIC (Catalogue of Somatic Mutations in Cancer) mutational signature characterized by the activity of the cytidine deaminase APOBEC family, which was unique to MPP components compared to non-MPP components in tumor tissues. This suggests the potential involvement of APOBEC in the progression of MPP components in early-stage LUAD. Additionally, MPP samples with high similarity to APOBEC signature displayed a higher tumor mutational burden (TMB), indicating that these patients may be more likely to benefit from immunotherapy. The expression of ZNF469 was significantly upregulated in LUAD compared to normal tissue, and was associated with poor prognosis in LUAD patients (P<0.05). Gene interaction network analysis and GO/KEGG enrichment analysis revealed that COL6A1, COL1A1, COL1A2, TGFB2, MMP2, COL8A2 and C2CD4C interacted with ZNF469 and were mainly involved in encoding collagen proteins and participating in the constitution of extracellular matrix. ZNF469 expression was positively correlated with immune cell infiltration in LUAD (P<0.05). CONCLUSIONS The study has unveiled distinctive mutational signatures in the MPP components of early-stage invasive LUAD in the Asian population. Furthermore, we have identified that the elevated expression of mutated ZNF469 impacts the prognosis and immune infiltration in LUAD, suggesting its potential as a diagnostic and prognostic biomarker in LUAD.
Humans ; Lung Neoplasms/genetics* ; Adenocarcinoma of Lung/genetics* ; China ; Prognosis ; Transcription Factors

BACKGROUND:Peroxisome proliferators-activated receptor gamma co-activator 1α(PGC-1α)is closely related to aging and plays an important regulatory role in exercise anti-aging.However,there is a lack of comprehensive reviews on the role of PGC-1α in exercise anti-aging from the perspective of different tissues and organs. OBJECTIVE:To provide a detailed overview of the role of PGC-1α in exercise anti-aging and discuss its regulation from the perspective of different tissues and organs. METHODS:A literature search was conducted from May 1,2023 to July 1,2023.The search covered self-built databases up to July 2023,as well as databases such as Web of Science,PubMed,China National Knowledge Infrastructure(CNKI),WanFang,and VIP.The Chinese search terms included"PGC-1α,peroxisome proliferators-activated receptor gamma co-activator 1α,PPARGC1A,aging,exercise,older adults".The English search terms were"PGC-1α,aging,exercise,exercise training,older adults".Boolean logical operators were used to connect the search terms,and corresponding search strategies were developed.Based on inclusion and exclusion criteria,83 articles were included in the review. RESULTS AND CONCLUSION:(1)PGC-1α is an important transcriptional coactivator that plays a key regulatory role in maintaining mitochondrial function,regulating energy metabolism,and adapting to different metabolic demands.(2)PGC-1α has a significant regulatory role in mitochondrial aging and various functions in multiple cell types,and is associated with inflammatory pathways,redox control,protein modifications,and epigenetic changes.(3)The expression level of PGC-1α can be increased by exercise training,and it exerts positive effects through regulating mitochondrial biogenesis,energy metabolism,and anti-oxidative stress pathways.It plays an important role in exercise-induced improvement of adipose tissue aging,cardiovascular aging,neurosystem aging,renal aging,skeletal muscle aging,and liver aging.(4)The expert group recommends future research directions including exploring the regulatory effects of different types,intensities,and durations of exercise on PGC-1α expression,studying the regulatory mechanisms of protein modifications and epigenetic changes in PGC-1α, and strengthening the research on the mechanisms of PGC-1α in different aging-related diseases.

Objective The reliability and validity of the SGGC-Net-based motion capture system(SGGC-Net system)and SIMI system for parsing walking gait were compared using a three-dimensional(3D)motion capture system(Vicon)with marker points as a reference standard.Methods Thirty healthy college students were recruited,and their gait characteristics while walking on a treadmill were analyzed.Kinematic data were collected using the Vicon system,and video data were collected synchronously using four cameras to obtain the right shoulder,elbow,hip,knee,and ankle joint angles.Reliability was assessed using intraclass correlation coefficients(ICCs)with 95％confidence intervals and standard error of measurement(SEM).Validity was assessed using multiple correlation coefficients(MCCs)and root mean square errors(RMSEs).Results The ICCs of the maximum and minimum 3D coordinate angles of the upper and lower limb joints of the SGGC-Net system ranged from 0.798-0.990 with an SEM of 0.04°-0.95°,and the ICCs of the SIMI system ranged from 0.650-0.967,with an SEM of 0.31°-1.24°.The ICCs of the SGGC-Net system were higher than those of the SIMI system for all joint angles except for the minimum hip and maximum knee angles.Compared to the joint angle curves derived from the SIMI system,the MCCs of the curves derived from the SGGC-Net system ranged from 0.945-0.996,with RMSEs of 1.44°-4.65°,and the multiple correlation coefficients of the SIMI system ranged from 0.815-0.986,with RMSEs of 2.56°-9.99°.The MCCs of the SGGC-Net system were greater than those of the SIMI system at all angles except for the ankle joint.The RMSEs of the SGGC-Net system were smaller than those of the SIMI system at all angles except for the ankle joints.Conclusions The SGGC-Net system has better reliability and validity than the SIMI system in most of the variables,and it has better repeatability and accuracy in analyzing walking gait.It can be applied to motion capture environments without marker points,such as technical analysis of athletes'movements and clinical gait analysis of special populations.

More than 70%of tumor patients require radiotherapy.Medical electron linear accelerators are important high-end radiotherapy equipment for tumor radiotherapy.With the application of artificial intelligence technology in medical electron linear accelerator,radiotherapy has evolved from ordinary radiotherapy to today's intelligent radiotherapy.This study introduces the development history,working principles and system composition of medical electron linear accelerators.It outlines the key technologies for improving the performance of medical linear electron accelerators,including beam control,multi-leaf collimator,guiding technology and dose evaluation.It also looks forward to the development trend of major radiotherapy technologies,such as biological guided radiotherapy,FLASH radiotherapy and intelligent radiotherapy,which provides references for the development of medical electron linear accelerators.