Objective:To explore the relevance of a new comprehensive respiratory mechanics parameter, elastic power, to the 28-day prognosis of ARDS patients.Methods:Patients with ARDS hospitalized for at least 48 h with invasive mechanical ventilation in five intensive care units in three local hospitals in Lianyungang City from June 2018 to June 2022 were included in the study. Their baseline data and respiratory mechanics parameters were collected. Elastic power, mechanical power, driving pressure and lung compliance are calculated according to the corresponding formulae. The prognostic risk factors of ARDS patients were analysed using COX multi-factor regression, and the predictive value of EP/Cst on the 28-day prognosis of ARDS patients was evaluated based on ROC curve analysis and Kaplan-Meier survival curve.Results:There was no significantly difference in tidal volume and PEEP settings between the patients in the ARDS survivor and death groups ( P> 0.05). However, the differences in respiratory rate, plateau pressure, driving pressure, lung compliance, mechanical work, elastic work, EP/cst and MP/cst between the two groups were significantly different (all P< 0.01). Multifactorial COX regression analysis showed that EP/cst ( HR=1.211, 95% CI:1.091-1.323) and RR ( HR=1.209, 95% CI:1.046-1.339) were strongly associated with a more severe degree of illness and a worse prognosis in ARDS. And the cumulative survival rate at 28 d was significantly lower in the high Cst-EP group than in the low Cst-EP group (50.00% vs. 82.40%, P < 0.01). Conclusions:The new respiratory mechanics parameters EP and EP/Cst can assess the severity of ARDS with a good predictive effect on patient prognosis at 28 days.

Objective:To investigate the clinical significances of CD4/CD8 ratio and neutrophil-to-lymphocyte ratio (NLR) in patients with multiple myeloma (MM).Methods:The clinical data of 124 MM patients in the Third Affiliated Hospital of Soochow University from December 2002 to April 2017 were retrospectively analyzed, and 31 healthy people were chosen as the controls. Peripheral blood T lymphocyte subsets were detected by using flow cytometry, and the correlations between CD4/CD8 ration and related clinical indicators were also investigated. All MM patients were divided into the high NLR group and the low NLR group according to the media of NLR, and the correlation of them with related clinical indicators, chromosome karyotype, overall survival (OS) and progression-free survival (PFS) was also compared.Results:Compared with the healthy control group, the proportion of CD4 + T cells [(35.28±6.58)% vs. (31.85±6.76)%, t = -2.067, P = 0.043], absolute value of NK cells [0.22×10 9/L (0.13×10 9/L-0.59×10 9/L) vs. 0.17×10 9/L (0.00×10 9/L-0.42×10 9/L), Z = -2.614, P = 0.009] and CD4/CD8 ratio [0.97 (0.50-2.69) vs. 0.81 (0.30-1.28), Z = -2.253, P = 0.024] was decreased, respectively. The proportion of CD8 + cells was increased [(36.93±7.38)% vs. (40.50±6.50)%, t = 2.074, P = 0.042] in MM group. The hemoglobin level of CD4/CD8 ratio ≥0.94 group was higher than that of CD4/CD8 ratio <0.94 [(98.89±21.35) g/L vs.(80.60±23.23) g/L, t = -2.066, P = 0.047]. Compared with the healthy control group, NLR was increased in MM group [1.54 (1.10-3.23) vs. 1.95 (0.29-12.70), Z = -2.384, P = 0.017]. Compared with the low NLR group (<1.95), serum β 2-microglobulin [4.56 mg/L (1.63-12.60 mg/L) vs. 6.17 mg/L (1.58-67.50 mg/L), Z = -2.586, P = 0.010] and serum creatinine [84.5 μmol/L (43.0-376.5 μmol/L) vs. 113.0 μmol/L (46.5-754.0 μmol/L), Z = -3.866, P < 0.001] was increased in the high NLR group for MM patients. The proportion of the male patients, β 2-microglobulin > 5.5 mg/L, serum creatinine > 177 μmol/L, stage Ⅲ of international staging system (ISS) in the high NLR group was higher than that in the low NLR group (all P < 0.05), and there was no statistically significant difference in the composition of chromosome karyotype (all P > 0.05). The median OS time in the low NLR group was longer than that in the high NLR group [30 months (20-40 months) vs. 17 months (7-27 months), χ 2 = 4.519, P = 0.034], and there was no statistically significant difference in the PFS of both groups ( P > 0.05). Multivariate Cox analysis demonstrated that the age, corrected serum calcium, serum creatinine, lactic dehydrogenase were the independent influencing factors of OS in MM (all P < 0.05), while NLR wasn′t an independent influencing factor of OS in MM ( P = 0.513). Conclusions:CD4/CD8 ratio is decreased and immune dysfunction occurs in MM patients. MM patients with high NLR have a shorter OS time.

One major strategy to generate genetically modified mouse models is gene targeting in mouse embryonic stem (ES) cells, which is used to produce gene-targeted mice for wide applications in biomedicine. However, a major bottleneck in this approach is that the robustness of germline transmission of gene-targeted ES cells can be significantly reduced by their genetic and epigenetic instability after long-term culturing, which impairs the efficiency and robustness of mouse model generation. Recently, we have established a new type of pluripotent cells termed extended pluripotent stem (EPS) cells, which have superior developmental potency and robust germline competence compared to conventional mouse ES cells. In this study, we demonstrate that mouse EPS cells well maintain developmental potency and genetic stability after long-term passage. Based on gene targeting in mouse EPS cells, we established a new approach to directly and rapidly generate gene-targeted mouse models through tetraploid complementation, which could be accomplished in approximately 2 months. Importantly, using this approach, we successfully constructed mouse models in which the human interleukin 3 (IL3) or interleukin 6 (IL6) gene was knocked into its corresponding locus in the mouse genome. Our study demonstrates the feasibility of using mouse EPS cells to rapidly generate mouse models by gene targeting, which have great application potential in biomedical research.

Objective: To evaluate the left ventricular systolic synchrony and investigate the early diagnostic value of left ventricular systolic dyssynchrony on cardiotoxicity caused by anthracyclines in patients with diffuse large B-cell lymphoma (DLBCL). Methods: Thirty-two patients (22 males, 10 females, age: 22-73(54.4±14.2) years) from June 2016 to January 2019 with confirmed DLBCL and normal gated myocardial perfusion imaging (GMPI) before anthracyclines chemotherapy were enrolled prospectively. GMPI was performed after 6 cycles or more of chemotherapy. Changes of myocardial markers, electrocardiogram (ECG) indicators, left ventricular function indicators including left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), peak filling rate (PFR), summed motion score (SMS) and summed thickening score (STS) as well as left ventricular systolic synchrony indicators including phase bandwidth (BW), phase standard deviation (SD) and entropy before and after anthracyclines chemotherapy were analyzed. Paired t test, Wilcoxon signed rank test and χ² test were used for data analysis. Results: Compared with pre-chemotherapy, the left ventricular systolic synchrony indicators were significantly higher than those before chemotherapy (BW: (42.81±11.37)° vs (29.28±8.68)°; SD: (11.65±4.64)° vs (8.79±3.14)°; entropy: (39.84±5.51)% vs (36.19±5.94)%; t values: -9.132 to -3.173, all P<0.05). There were no significant differences in other indicators (t values: -1.161 to 1.750, z values: -1.633 to -0.096, all P>0.05). Of 32 patients, 13 patients (40.62%) had left ventricular systolic dyssynchrony, and the rate of chemotherapy-induced left ventricular systolic dyssynchrony was significantly higher than that of left ventricular dysfunction (15.62%, 5/32; χ²=4.947, P=0.025). All 5 patients with left ventricular dysfunction caused by chemotherapy had left ventricular systolic dyssynchrony. The LVEF of the chemotherapy-induced left ventricular systolic dyssynchrony group was significantly lower than that of the left ventricular systolic synchronization group ((54.54±9.25)% vs (66.79±7.65)%; t=4.087, P<0.01). Conclusion Left ventricular systolic dyssynchrony can be appeared in DLBCL patients after chemotherapy and is significantly earlier than left ventricular dysfunction, which can be an early indicator of cardiotoxicity caused by anthracycline chemotherapy.

Objective To observe the alteration and clinical significances of blood coagulation indicators in patients with lymphoplasmacytic lymphoma (LPL). Methods Twenty patients who were newly diagnosed LPL in the First People's Hospital of Changzhou from January 2008 to October 2017 and twenty healthy controls were studied. The patients were treated by chemotherapy, plasma exchange, supplement of coagulation factor or other supportive therapy. The parameters of prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), thrombin time (TT), D-dimer (D-D), and platelet count (Plt) were detected in LPL group and healthy controls. Results The levels of PT and APTT in LPL group were dramatically higher than those in control group [(12.9±1.2) s vs. (11.6±0.9) s, (41.7±9.8) s vs. (24.7±2.9) s], and the level of Plt in LPL group was lower than that in control group [112×109/L (3×109/L - 379×109/L) vs. 210×109/L (170×109/L - 271×109/L)], and the differences were statistically significant (all P< 0.05). There were no significant differences in FIB, TT and D-D levels between LPL group and control group (all P ＞0.05). There were no statistical differences in PT, APTT, FIB, TT, D-D and Plt levels among LPL patients with different types of immunoglobins (all P ＞ 0.05). After treatment, all the coagulation abnormalities got relieved and no patient died of hemorrhage or thrombosis. Conclusions The LPL patients have coagulation disorders and hypercoagulability, and this is independent of the type of immunoglobulin. Clinical attention should be paid to monitoring coagulation indicators to prevent the occurrence of adverse reactions.

Objective To investigate the characteristics of activation-induced cytidine deaminase (AID) expression level in de novo acute leukemia (AL) patients, chronic myeloid leukemia chronic phase (CML-CP), chronic myeloid leukemia blastic crisis (CML-BC) patients and leukemia cell lines. Methods The expression level of AID mRNA was measured in 89 cases of newly-diagnosed acute lymphoblastic leukemia (ALL) patients, 79 cases of de novo acute myeloid leukemia (AML) patients, 5 cases of CML-BC patients, 5 cases of CML-CP patients and leukemia cell lines NB4, THP-1, KG-1, Raji, K562 by real-time quantitative reverse transcriptase polymerase chain reaction (RT-PCR), bone marrow mononuclear cells of 16 normal healthy donors were used as the control group. Results The expression levels of AID mRNA in 89 cases of ALL and 79 cases of AML were 0.006-7 463.175 and 0.005-69.107, the median expression levels were 3.785 and 1.812, the expression level of AID mRNA in the normal control group was 0.146-4.707, and the median expression level was 1.483, respectively. The AID expression levels of ALL, B-ALL, Burkitt leukemia, M4 patients and Raji cells were significantly higher than those of the normal control group (all P <0.05). Nevertheless, the AID mRNA expression levels of M3 patients and NB4, KG-1 cells were lower than those of the normal control group (all P <0.05). Furthermore, the AID mRNA expression levels of K562 cell were strikingly higher than that of the CML-CP patients (P<0.001), so were those of CML-BC, chronic myeloid leukemia myeloid blast crisis (CML-MBC), chronic myeloid leukemia lymphoblastic blast crisis (CML-LBC) patients. Conclusion AID gene shows high expression level in B-ALL, Burkitt leukemia and M4, low expression level in M3 and KG-1 cells, and obvious high expression level in CML-BC.

Objective To compare the efficacy and safety between flumatinib and imatinib in patients with newly diagnosed chronic myeloid leukemia (CML). Methods A multi-center, randomized and parallel comparison clinical trial was conducted in 24 newly diagnosed patients with Philadelphia chromosome-positive CML-chronic phase (Ph+ CML-CP) who were treated by flumatinib 400 mg/d, 600 mg/d or imatinib for 6 cycles (24 weeks). The hematology was evaluated at pre-medication and the 2nd, 4th, 6th, 8th, 10th, 12th, 16th, 20th, 24th week of post-medication. The morphology, cytogenetics and molecular biology were evaluated at pre-medication and 12th, 24th week of post-medication. Results In terms of efficacy, the main molecular remission (MMR) rate of flumatinib 600 mg/d group was higher than that of imatinib group after 24 weeks [44.44 % (4/9) vs. 14.29 % (1/7), P=0.017]. The rate of bcr-ablIS≤10 % in flumatinib 600 mg/d group was significantly higher than that in imatinib group (P=0.002). PK/PD analysis also hinted that patients treated by flumatinib 600 mg/d was more likely to get molecular reaction in the early stage compared with those treated by flumatinib 400 mg/d. In terms of safety, there was no significant difference in grade Ⅲ-Ⅳ of adverse events among flumatinib 400 mg/d group, flumatinib 600 mg/d group and imatinib group (P >0.05). The common adverse events in flumatinib group included skin toxicity, gastrointestinal reactions and diarrhea.There was no heart and cardiovascular toxicity in flumatinib group, and incidence of edema in flumatinib group was lower than that in imatinib group. Conclusions Flumatinib is a safe and effective drug for newly diagnosed patients with Ph+ CML-CP, and 600 mg/d is the appropriate clinical starting dose. Flumatinib and imatinib have similar safety in clinic.

Humans ; Kidney Transplantation ; Multiple Myeloma

Objective To investigate the immunophenotype characteristics,the clinical significance of CD28 and International staging system in multiple myeloma (MM).Methods BM aspirate samples from 49 newly diagnosed MM patients and 22 patients after treatment were assessed using 4 color flow cytometric analyses.These MM patients were classified according to International staging system and the consolidated risk staging system,and the survival rates and treatment efficiency of 2 staging system were compared.Results The higher stage,according to the international staging system,the lower treatment efficiency [the efficacy rates of Ⅰ,Ⅱ,Ⅲ stage were 83.3 ％ (4/6),38.5 ％ (5/13),38.5 ％ (5/13),36.5 ％ (19/52)](x2 =4.235,P =0.04),and the survival and progression-free survival time of high-risk group were significantly shortened (P ＜ 0.05).The rate of CD28 abnormal expression was no significant different between the initial and the treatment group [27 (55.1％),14 (63.4 ％)],also similar in the impact of survival and progression-free survival time (P ＞ 0.05).According to the consolidated risk staging system,the treatment efficiency,the survival and progression-free survival time of high-risk group were significantly shortened than the low ones (P =0.040).Conclusions The patients with higher ISS stage,abnormal expression of CD28,and high-risk group have poor prognosis.

Objective To investigate aberrations of bcl-6,p53,c-myc genes in diffuse large B-cell lymphoma (DLBCL) and its clinical significance.Methods Interphase fluorescence in situ hybridization (I-FISH) was detected in 59 DLBCL patients in vivo tissue bcl-6,p53 protein,c-myc gene status.The patients were treated with CHOP or R-CHOP chemotheralpy,and the survival rates and treatment efficiency were compared.Results The p53 deletion was detected in 18 of the 59 cases (30.5 ％),bcl-6 rearrangement in 11 cases (18.6 ％),5 cases with c-myc rearrangement (8.5 ％).In the aspects of remission rate,p53 deletion positive group contained less advantage than negative ones (33.3 ％ vs 75.6 ％,x2 =9.560,P =0.002).The prognosis of bcl-6 gene rearrangement positive group different from negative group,but the difference was not statistically significant (OS,P =0.107; PFS,P =0.094),p53 deletion positive patients was in significantly worse prognosis than the negative group (OS,P =0.031; PFS,P =0.028),c-myc rearrangement positive group difference in gene rearrangement negative group,but the difference was not statistically significant (OS,P =0.163; PFS,P =0.167).In the CHOP group,prognosis of p53 deletion,c-myc rearrangement positive group were significantly worse than the negative group,the difference was statistically significant (P ＜ 0.05).In R-CHOP group,the prognostic significance of bcl-6 gene rearrangement positive group were worse (OS,P =0.003; PFS,P =0.007).Conclusion DLBCL patients with bcl-6,p53,c-myc genes aberrations are related with poor prognosis,and they can be used as prognostic factors for predicting DLBCL and guiding therapy.