Category: Statistics

Zhonghua Xue Ye Xue Za Zhi. 2022 May 14;43(5):400-407. doi: 10.3760/cma.j.issn.0253-2727.2022.05.009.

ABSTRACT

Objective: To explore the differences in the biological effects of different expansion systems on natural killer (NK) cells, as well as the safety and preliminary clinical efficacy in the treatment of patients with recurrence after allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: Peripheral blood cells from healthy donors were stimulated with either CD3 combined with CD52 or K562 feeder cells loaded with IL-21/4-1BB to induce NK cell expansion. Changes in the NK cell phenotype, cytokine secretion, and cytotoxicity before and after expansion were detected. We also evaluated the safety and clinical efficacy of two different expansion strategies for patients received NK infusion. Results: Compared with the CD3/CD52 monoclonal antibody amplification system, the feeder cell expansion group had a higher purity of NK cells and higher expression ratios of NK cell surface activation receptors such as DNAM-1 and NKp30, while inhibitory receptor CTLA-4 expression was low and NKG2D/CD25/CD69/ Trail/PD-1/TIM-3/TIGIT had no statistically significant differences between the groups. Further functional results showed that the expression level of KI67 in NK cells after expansion in the two groups increased significantly, especially in the feeder cell expansion group. Simultaneously, the perforin and granzyme B levels of NK cells in the feeder cell expansion group were significantly higher than in the CD3/CD52 expansion group. A retrospective analysis of eight patients who received monoclonal antibody-expanded NK cell reinfusion and nine patients with trophoblast cell-expanded NK cell reinfusion was done. The disease characteristics of the two groups were comparable, NK cell reinfusion was safe, and there were no obvious adverse reactions. Clinical prognostic results showed that in the CD3/CD52 monoclonal antibody amplification group, the MRD conversion rate was 50% (2/4) , and the feeder cell expansion group was 50% (3/6) . After 5 years of follow-up from allo-HSCT, three patients in the monoclonal antibody expansion group had long-term survival without leukemia, and the remaining five patients had died; two patients died in the feeder cell expansion group, and the other six patients had long-term survival. Six cases had GVHD before NK cell reinfusion, and GVHD did not aggravate or even relieved after NK cell reinfusion. Conclusions: Preliminary results show that the biological characteristics of NK cells with diverse expansion strategies are significantly different, which may affect the clinical prognosis of patients with recurrence or persistent minimal residual disease after HSCT. The two groups of patients treated with NK cells from different expansion strategies had no obvious adverse reactions after NK cell infusion, but efficacy still needs to be further confirmed.

PMID:35680598 | DOI:10.3760/cma.j.issn.0253-2727.2022.05.009

Zhonghua Xue Ye Xue Za Zhi. 2022 May 14;43(5):388-392. doi: 10.3760/cma.j.issn.0253-2727.2022.05.007.

ABSTRACT

Objective: To improve the positivity rate and accuracy of MYD88 mutation detection in patients with Waldenström macroglobulinemia (WM) . Methods: MYD88 mutation status was retrospectively evaluated in 66 patients diagnosed with WM in Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from June 2017 to June 2021. The positivity rate and accuracy of the different methods and specimens for MYD88 mutation detection were analyzed. Results: MYD88 mutations were detected in 51 of 66 patients with WM, with an overall positivity rate of 77%. The positivity rate of the next-generation sequencing (NGS) or allele-specific polymerase chain reaction (AS-PCR) was significantly higher than that of the first-generation Sanger sequencing (84% vs 71% vs 46%, P<0.05) . For the different specimens, the positivity rate for the lymph nodes or bone marrow was significantly higher than that of peripheral blood (79% vs 84% vs 52%, P<0.05) . The positivity rate of the MYD88 mutation in the lymph nodes, bone marrow, and peripheral blood determined by NGS was 86%, 90%, and 67%, respectively. The positivity rate in the lymph nodes, bone marrow, and peripheral blood detected by AS-PCR was 78%, 81%, and 53%, respectively. Thirty-nine patients with WM underwent ≥ 2 MYD88 mutation detections. The final MYD88 mutational status for each patient was used as the standard to determine the accuracy of the different methods and in different specimens. The accuracy of MYD88 mutation detection in the lymph nodes (n=18) and bone marrow (n=13) by NGS was significantly higher than that in the peripheral blood (n=4) (100% vs 100% vs 75%, P<0.05) . There was no statistically significant difference in the accuracy of MYD88 mutation detection by AS-PCR in the lymph nodes (n=15) , bone marrow (n=11) , or peripheral blood (n=16) (93% vs 91% vs 88%, P>0.05) . Conclusions: In the detection of the MYD88 mutation in patients diagnosed with WM, NGS or AS-PCR is more sensitive than Sanger sequencing. Lymph nodes and bone marrow specimens are better than peripheral blood specimens.

PMID:35680596 | DOI:10.3760/cma.j.issn.0253-2727.2022.05.007

Zhonghua Xue Ye Xue Za Zhi. 2022 May 14;43(5):383-387. doi: 10.3760/cma.j.issn.0253-2727.2022.05.006.

ABSTRACT

Objective: To compare the efficacy of two induction regimens, namely, idarubicin combined with cytarabine (IA) versus the combination of homoharringtonine, daunorubicin, and cytarabine (HAD) , in adult patients with newly diagnosed de novo acute myeloid leukemia (AML) . Methods: From May 2014 to November 2019, 199 patients diagnosed with AML receiving either the IA or HAD regimens were assessed for overall survival (OS) , relapse-free survival (RFS) , as well as the CR rate and the MRD negative rate after induction therapy. The differences in prognosis between the two induction therapy groups was assessed according to factors, including age, white blood cell (WBC) count, NPM1 mutation, FLT3-ITD mutation, 2017 ELN risk stratification, CR(1) transplantation, and the use of high-dose cytarabine during consolidation therapy, etc. Results: Among the 199 patients, there were 104 males and 95 females, with a median age of 37 (15-61) years. Ninety patients received the IA regimen, and 109 received the HAD regimen. Comparing the efficacy of the IA and HAD regimens, the CR rates after the first induction therapy were 71.1% and 63.3%, respectively (P=0.245) , and the MRD negative rates after the first induction therapy were 53.3% and 48.6%, respectively (P=0.509) . One patient in the IA group and two in the HAD group died within 60 days after induction. The two-year OS was 61.5% and 70.6%, respectively (P=0.835) , and the two-year RFS was 51.6% and 57.8%, respectively (P=0.291) . There were no statistically significant differences between the two groups. Multivariate analysis showed that the ELN risk stratification was an independent risk factor in both induction groups; CR(1) HSCT was an independent prognostic factor for OS and RFS in the IA patients and for RFS in the HAD patients but not for OS in the HAD patients. Age, WBC level, NPM1 mutation, and FLT3-ITD mutation had no independent prognostic significance. Conclusion: The IA and HAD regimens were both effective induction regimens for AML patients.

PMID:35680595 | DOI:10.3760/cma.j.issn.0253-2727.2022.05.006

Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi. 2022 May 20;40(5):358-361. doi: 10.3760/cma.j.cn121094-20210316-00146.

ABSTRACT

Objective: To understand the incidence of pneumoconiosis in the non-coal mining industry in Jiangsu Province, and provide reference for the prevention and control of pneumoconiosis in the non-coal mining industry. Methods: The data of 7019 newly diagnosed pneumoconiosis patients in non-coal mining industry in Jiangsu Province from January 1956 to December 2019 were collected through the Jiangsu Province Pneumoconiosis Follow-up Network Report System, including the gender of the pneumoconiosis patients, the name of the employer and the location, the industry classification of the employer, the duration of dust exposure in dust exposure, the name of occupational pneumoconiosis disease, the date of diagnosis of pneumoconiosis, etc. The collected case data of patients with pneumoconiosis were entered into the statistical software, and the characteristics of the patients’ diagnosis time, region and industry were analyzed. Results: The number of confirmed pneumoconiosis patients in the non-coal mining industry in Jiangsu Province was mostly in 2007 (395 cases) , concentrated in Wuxi City (40.96%, 2875/7019) and Suzhou City (27.72%, 1946/7019) . The industries to which the patients belonged were mainly non-metallic mining and dressing (60.95%, 4278/7019) , and the most common type of pneumoconiosis was silicosis (96.40%, 6766/7019) . The patients were mainly stageⅠpneumoconiosis (61.33%, 4305/7019) . There were statistically significant differences in the mean age of diagnosis and the average duration of dust exposure among patients with different pneumoconiosis stages (P<0.01) . The differences in the average diagnosis age and the average duration of dust exposure of patients with different types of pneumoconiosis were statistically significant (P<0.05) , the mean age of diagnosis and the average duration of dust exposure of electric welders were the smallest, which were (44.92±7.74) years old and (17.38±10.15) years, respectively. Conclusion: The regional and industry distribution characteristics of new pneumoconiosis patients in the non-coal mining industry in Jiangsu Province are obvious, and attention should be paid to the treatment of pneumoconiosis patients with young diagnosed age and short duration of dust exposure, as well as the personal protection and health protection of front-line workers such as electric welders who are exposed to productive dust in a short period of time.

PMID:35680579 | DOI:10.3760/cma.j.cn121094-20210316-00146

Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi. 2022 May 20;40(5):347-353. doi: 10.3760/cma.j.cn121094-20210207-00085.

ABSTRACT

Objective: To quantitatively evaluate the content differences of trace elements in workers with occupational exposure to lead. Methods: In January 2021, relevant literatures on the contents of trace elements in workers with occupational exposure to lead published from 1990 to 2020 were searched through CNKI, Wanfang, VIP, PubMed, web of science and Embase. Screened and extracted the literatures, and evaluated the quality of the included literatures with Newcastle Ottawa Scale. Meta analysis was performed with Review Manager 5.3 software, and standardized mean difference (SMD) and its 95% confidence interval were used as effect indicators. Results: A total of 20 literatures were included, and the quality scores were 5-7. The results of Meta-analysis showed that compared with the control group, the contents of blood zinc (SMD=-1.01, 95%CI: -1.53, -0.49) , hair zinc (SMD=-0.17, 95%CI: -0.33, -0.01) , hair copper (SMD=-0.50, 95%CI: -1.01, 0) , hair iron (SMD=-3.91, 95%CI: -5.80, -2.03) and hair manganese (SMD=-1.09, 95%CI: -2.02, -0.15) in occupational lead exposure group were significantly lower (P<0.05) . Compared with the control group, the content of cobalt in hair of occupational lead exposure group (SMD=1.41, 95%CI: 0.72, 2.10) was higher, and the difference was statistically significant (P<0.05) . There was no significant difference in the contents of blood chromium, blood copper, blood iron, blood manganese, blood selenium and hair nickel between the two groups (P>0.05) . Conclusion: Workers with occupational exposure to lead have abnormal trace elements.

PMID:35680577 | DOI:10.3760/cma.j.cn121094-20210207-00085

Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi. 2022 May 20;40(5):328-332. doi: 10.3760/cma.j.cn121094-20210302-00119.

ABSTRACT

Objective: To construct a recombinant lentiviral vector for mouse miR-204 overexpression, and to verify the targeted regulation of miR-204 and DVL3 in silica (SiO(2)) -induced mouse lung epithelial cells (MLE-12 cells) . Methods: In October 2019, the pre-miR-204 gene was amplified from the mouse genome by the polymerase chain reaction (PCR) method. After sequencing, the amplified product was cloned into the pLenti-CMV-EGFP lentiviral vector. The positive clones were identified by PCR screening and sequencing. The miR-204 overexpressed lentiviral vector was transfected into 293T cells, and lentiviral packaging and titer determination were performed. The experiment was divided into SiO(2) control group, virus control group, and miR-204 virus group, and the expressions of miR-204 and DVL3 gene were detected by real-time PCR. Results: The miR-204 lentiviral expression vector Lv-miR-204-5p was constructed and identified correctly by PCR and sequencing, and a virus dilution with a titer of 9.57×10(8) IU/ml was obtained. The results of real-time PCR showed that the expression of miR-204 in MLE-12 cells of the miR-204 virus group was higher than that of SiO(2) control group and virus control group, and the expression of DVL3 gene was lower than that of SiO(2) control group and virus control group, the differences were statistically significant (P<0.05) . Conclusion: Overexpression of miR-204 by lentiviral vector may inhibit the expression of DVL3 gene in silica-induced mouse lung epithelial cells.

PMID:35680573 | DOI:10.3760/cma.j.cn121094-20210302-00119

Clin Pharmacol Ther. 2022 Jun 9. doi: 10.1002/cpt.2684. Online ahead of print.

ABSTRACT

This study aims to compare the risks of major adverse cardiac events (MACEs), including cardiovascular death, myocardial infarction, ischemic stroke and transient ischemic attack, and major bleeding across different antithrombotic regimens in Asian atrial fibrillation (AF) patients with stent insertions. We conducted a retrospective cohort study using Taiwan’s National Health Insurance Research Database and National Mortality Registry. A total of 10,208 nonvalvular AF patients who had undergone percutaneous coronary intervention (PCI) with stents for the first time in 2007-2017 were identified. Most patients (68.4%) were prescribed dual antiplatelet therapy (DAPT) at discharge. During follow-up, the use of anticoagulants increased, and double therapy (an antiplatelet plus an anticoagulant) was the most frequently prescribed therapy. The risks of MACEs were comparable in double therapy and had a similar risk of MACEs compared to DAPT (aHR 0.86; 95% CI 0.67-1.11). Triple therapy (DAPT plus an anticoagulant) also had similar effectiveness to double therapy (1.23; 0.84-1.80) or DAPT (1.06; 0.77-1.45). However, triple therapy was associated with a nearly twofold higher major bleeding risk than DAPT and double therapy (1.97; 1.31-2.94 and 1.80; 1.10-2.95, respectively). DAPT was the most frequently prescribed antithrombotic regimen at discharge for Asian AF patients who had undergone stent insertions. DAPT and double and triple therapy had comparable effectiveness, but triple therapy had a significantly higher major bleeding risk than either DAPT or double therapy.

PMID:35680555 | DOI:10.1002/cpt.2684

Am J Geriatr Psychiatry. 2022 May 18:S1064-7481(22)00416-X. doi: 10.1016/j.jagp.2022.05.009. Online ahead of print.

ABSTRACT

OBJECTIVES: To determine if behavioral activation (BA) delivered by trained staff decreases prevalence of clinically significant symptoms of depression among older adults living in residential aged care facilities (RACFs).

METHODS: Clustered, randomized, single-blinded, controlled trial of BA for adults aged over 60 years living permanently in a RACF with symptoms of depression (Patient Health Questionnaire, PHQ-9 ≥ 5). BA was delivered over 8-12 weeks using a structured workbook. The proportion of residents with PHQ-9 ≥ 10 at weeks 12, 26, and 52, as well as anxiety symptoms (GAD-7), physical (PCS), and mental (MCS) quality of life, loneliness, and loss to follow-up were main outcomes of interest RESULTS: We recruited 54 RACFs (26 intervention) and 188 of their residents (89 intervention). Participants were aged 61-100 years and 132 (70.2%) were women. PHQ-9 ≥ 10 interacted with BA at week 12 (OR = 0.34, 95%CI = 0.11-1.07), but differences between the groups were not statistically significant at any time-point. GAD-7 ≥ 10 interacted with BA at week 26 (OR = 0.12, 95%CI = 0.02-0.58), but not at any other time-point. Overall, the intervention had no effect on the scores of the PHQ-9, GAD-7, PCS, MCS, and loneliness scale. Loss to follow-up was similar between groups. Adherence to all stages of the intervention was poor (36.2%).

CONCLUSIONS: Disruption by the COVID-19 pandemic and staffing issues in RACFs undermined recruitment and adherence. In such a context, a BA program delivered by RACF staff was not associated with better mental health outcomes for residents over 52 weeks.

PMID:35680539 | DOI:10.1016/j.jagp.2022.05.009

Semin Cell Dev Biol. 2022 Jun 6:S1084-9521(22)00173-2. doi: 10.1016/j.semcdb.2022.05.016. Online ahead of print.

ABSTRACT

The purpose of this review is to explore and discuss the impacts of augmented training volume, intensity, and duration on the phosphorylation/activation of key signaling protein – AMPK, CaMKII and PGC-1α – involved in the initiation of mitochondrial biogenesis. Specifically, we explore the impacts of augmented exercise protocols on AMP/ADP and Ca²⁺ signaling and changes in post exercise PGC – 1α gene expression. Although AMP/ADP concentrations appear to increase with increasing intensity and during extended durations of higher intensity exercise AMPK activation results are varied with some results supporting and intensity/duration effect and others not. Similarly, CaMKII activation and signaling results following exercise of different intensities and durations are inconsistent. The PGC-1α literature is equally inconsistent with only some studies demonstrating an effect of intensity on post exercise mRNA expression. We present a novel meta-analysis that suggests that the inconsistency in the PGC-1α literature may be due to sample size and statistical power limitations owing to the effect of intensity on PGC-1α expression being small. There is little data available regarding the impact of exercise duration on PGC-1α expression. We highlight the need for future well designed, adequately statistically powered, studies to clarify our understanding of the effects of volume, intensity, and duration on the induction of mitochondrial biogenesis by exercise.

PMID:35680515 | DOI:10.1016/j.semcdb.2022.05.016

J Formos Med Assoc. 2022 Jun 6:S0929-6646(22)00216-9. doi: 10.1016/j.jfma.2022.05.011. Online ahead of print.

ABSTRACT

BACKGROUND: The primary aim of this essay was to explore the best fitting model in remifentanil-propofol combined administrations during esophageal instrumentation (EI) from five distinct response surface models. The secondary aim was to combine the models to give appropriate effect-site drug concentrations (Ces) range with maximal comfort and safety.

METHODS: The Greco, reduced Greco, Minto, Scaled C50 Hierarchy and Fixed C50 Hierarchy models were constructed to fit four drug effects: loss of response to esophageal instrumentation (LREI), loss of response to esophageal instrumentation revised (LREIR), intolerable ventilatory depression (IVD) and respiratory compromise (RC). Models were tested by chi-square statistical test and evaluated with Akaike Information Criterion (AIC). Model prediction performance were measured by successful prediction rate (SPR) and three prediction errors.

RESULTS: The reduced Greco model was the best fitting model for LREI and RC, and the Minto model was the best fitting model for LREIR and IVD. The SPRs of reduced Greco model for LREI and RC were 81.76% and 79.81%. The SPRs of Minto model for LREIR and IVD were 80.32% and 80.12%. Overlay of the reduced Greco model for LREI and Minto model for IVD offered visual aid for guidance in drug administration.

CONCLUSIONS: Using proper response surface model to fit different drug effects will describe the interactions between anesthetic drugs better. Combining response surface models to select the more reliable effect-site drug concentrations range can be used to guide clinical drug administration with greater safety and provide an improvement of anesthesia precision.

PMID:35680472 | DOI:10.1016/j.jfma.2022.05.011