Objective: To understand the current status of diagnosis and treatment of chronic lymphocytic leukemia (CLL) /small lymphocytic lymphoma (SLL) among hematologists, oncologists, and lymphoma physicians from hospitals of different levels in China. Methods: This multicenter questionnaire survey was conducted from March 2021 to July 2021 and included 1,000 eligible physicians. A combination of face-to-face interviews and online questionnaire surveys was used. A standardized questionnaire regarding the composition of patients treated for CLL/SLL, disease diagnosis and prognosis evaluation, concomitant diseases, organ function evaluation, treatment selection, and Bruton tyrosine kinase (BTK) inhibitor was used. Results: ①The interviewed physicians stated that the proportion of male patients treated for CLL/SLL is higher than that of females, and the age is mainly concentrated in 61-70 years old. ②Most of the interviewed physicians conducted tests, such as bone marrow biopsies and immunohistochemistry, for patient diagnosis, in addition to the blood test. ③Only 13.7% of the interviewed physicians fully grasped the initial treatment indications recommended by the existing guidelines. ④In terms of cognition of high-risk prognostic factors, physicians' knowledge of unmutated immunoglobulin heavy-chain variable and 11q- is far inferior to that of TP53 mutation and complex karyotype, which are two high-risk prognostic factors, and only 17.1% of the interviewed physicians fully mastered CLL International Prognostic Index scoring system. ⑤Among the first-line treatment strategy, BTK inhibitors are used for different types of patients, and physicians have formed a certain understanding that BTK inhibitors should be preferentially used in patients with high-risk factors and elderly patients, but the actual use of BTK inhibitors in different types of patients is not high (31.6%-46.0%). ⑥BTK inhibitors at a reduced dose in actual clinical treatment were used by 69.0% of the physicians, and 66.8% of the physicians had interrupted the BTK inhibitor for >12 days in actual clinical treatment. The use of BTK inhibitors is reduced or interrupted mainly because of adverse reactions, such as atrial fibrillation, severe bone marrow suppression, hemorrhage, and pulmonary infection, as well as patients' payment capacity and effective disease progression control. ⑦Some differences were found in the perceptions and behaviors of hematologists and oncologists regarding the prognostic assessment of CLL/SLL, the choice of treatment options, the clinical use of BTK inhibitors, etc. Conclusion: At present, a gap remains between the diagnosis and treatment of CLL/SLL among Chinese physicians compared with the recommendations in the guidelines regarding the diagnostic criteria, treatment indications, prognosis assessment, accompanying disease assessment, treatment strategy selection, and rational BTK inhibitor use, especially the proportion of dose reduction or BTK inhibitor discontinuation due to high adverse events.
Female ; Humans ; Male ; Aged ; Middle Aged ; Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy* ; Prognosis ; Lymphoma, B-Cell ; Immunohistochemistry ; Immunoglobulin Heavy Chains/therapeutic use*

OBJECTIVE: To evaluate the efficacy of sepsis risk calculator (SRC) in guiding antibiotic use in neonates with suspected early-onset sepsis (EOS). METHODS: A total of 284 neonates with a gestational age of ≥ 35 weeks were enrolled as the control group, who were hospitalized in the Children's Hospital of Chongqing Medical University from March to July, 2019 and were suspected of EOS. Their clinical data were retrospectively collected and the use of antibiotics was analyzed based on SRC. A total of 170 neonates with a gestational age of ≥ 35 weeks were enrolled as the study group, who were admitted to the hospital from July to November, 2020 and were suspected of EOS. SRC was used prospectively for risk scoring to assist the decision making of clinical antibiotic management. The two groups were compared in terms of the rate of use of antibiotics, blood culture test rate, clinical outcome, and adherence to the use of SRC. RESULTS: Compared with the control group, the study group had a significantly higher SRC score at birth and on admission ( CONCLUSIONS The use of SRC reduces the rate of empirical use of antibiotics in neonates with suspected EOS and does not increase the risk of adverse outcomes, and therefore, it holds promise for clinical application.
Anti-Bacterial Agents/therapeutic use* ; Child ; Humans ; Infant ; Infant, Newborn ; Neonatal Sepsis/drug therapy* ; Retrospective Studies ; Risk Assessment ; Sepsis/drug therapy*

OBJECTIVE: Obesity is recognized as a significant risk factor for diabetes and hypertension. The present study aimed to examine the associations between adults'obesity risk and childhood and parental obesity. METHODS: A total of 204 children aged 6-17 years were recruited in 2002 with an average follow-up period of 13.2 years. Height and body weight were measured by trained staffs. Overweight and obesity were defined based on the Chinese standard for children and adults. T-test, analysis of variance, and Chi-square analysis were used for single factor analysis. Multiple linear and logistic regression analyses were used to perform multifactor analysis. RESULTS: The percentage of non-obese children who grew up to be non-obese adults was 62.6%, and that of obese children who grew up to be obese adults was 80.0%. There was a significant association between childhood body mass index (BMI) and adulthood BMI with a β regression coefficient of 3.76 [95% confidence interval (CI): 1.36-6.16], and between childhood obesity and adulthood obesity with an odds ratio of 5.76 (95% CI: 1.37-24.34). There was no statistical difference between parental obesity at baseline and children's adulthood obesity, after adjustment of confounders. Male participants and those aged 10.0-13.0 years had a higher risk of adulthood obesity with odds ratios of 2.50 (95% CI: 1.12-5.26) and 3.62 (95% CI: 1.17-11.24), respectively. CONCLUSION Childhood obesity is an important predictor of adulthood obesity.
Adolescent ; Adult ; Body Mass Index ; Child ; China ; epidemiology ; Female ; Follow-Up Studies ; Humans ; Male ; Obesity ; epidemiology ; etiology ; Odds Ratio ; Parents ; Pediatric Obesity ; epidemiology ; etiology ; Prevalence ; Prospective Studies ; Young Adult

Objective: To analyze the clinical and laboratory characteristics, and prognosis of adult acute myeloid leukemia (AML) patients with MLL gene rearrangements. Methods: The medical records of 92 adult AML patients with MLL gene rearrangements from January 2010 to December 2016 were retrospectively analyzed. Results: 92 cases (6.5%) with MLL gene rearrangements were identified in 1 417 adult AML (Non-M(3)) patients, the median age of the patients was 35.5 years (15 to 64 years old) with an equal sex ratio, the median WBC were 21.00(0.42-404.76)×10(9)/L, and 78 patients (84.8%) were acute monoblastic leukemia according to FAB classification. Eleven common partner genes were detected in 32 patients, 9 cases (28.1%) were MLL/AF9(+), 5 cases (15.6%) were MLL/AF6(+), 5 cases (15.6%) were MLL/ELL(+), 2 cases (6.3%) were MLL/AF10(+), 1 case (3.1%) was MLL/SETP6(+), and the remaining 10 patients' partner genes weren't identified. Of 92 patients, 83 cases with a median follow-up of 10.3 (0.3-74.0) months were included for the prognosis analysis, the complete remission (CR) rate was 85.5% (71/83), the median overall survival (OS) and relapse free survival (RFS) were 15.4 and 13.1 months, respectively. Two-year OS and RFS were 36.6% and 29.5%, respectively. Of 31 patients underwent allogeneic hematopoietic stem-cell transplantation (allo-HSCT), two-year OS and RFS for patients received and non-received allo-HSCT were 57.9% and 21.4%, 52.7% and 14.9%, respectively (P<0.001). Among patients with partner genes tested, 9 of 32 cases (28.1%) were MLL/AF9(+), the median follow-up was 6.0(4.1-20.7) months. 3 patients with MLL/AF9 underwent allo-HSCT. 23 cases (71.9%) were non- MLL/AF9(+), the median follow-up was 7.8 (0.3-26.6) months. 14 patients (60.1%) with non-MLL/AF9 underwent allo-HSCT. One-year OS for patients with MLL/AF9 and non-MLL/AF9 were 38.1% and 55.5%, respectively (P=0.688). Multivariate analysis revealed that high WBC (RR=1.825, 95% CI 1.022-3.259, P=0.042), one cycle to achieve CR (RR=0.130, 95% CI 0.063-0.267, P<0.001), post-remission treatment with allo-HSCT (RR=0.169, 95% CI 0.079-0.362, P<0.001) were independent prognostic factors affecting OS. Conclusions: AML with MLL gene rearrangements was closely associated with monocytic differentiation, and MLL/AF9 was the most frequent partner gene. Conventional chemotherapy produced a high response rate, but likely to relapse, allo-HSCT may have the potential to further improve the prognosis of this group of patients.
Adolescent ; Adult ; Aged ; Gene Rearrangement ; Hematopoietic Stem Cell Transplantation ; Histone-Lysine N-Methyltransferase ; Humans ; Leukemia, Myeloid, Acute ; Middle Aged ; Myeloid-Lymphoid Leukemia Protein ; Prognosis ; Retrospective Studies ; Young Adult

BACKGROUNDThere remains significant debate as to the relationship between fragmented QRS (fQRS) complexes on electrocardiogram (ECG) and acute myocardial infarction (AMI). Few studies have reported on this relationship in non-ST elevated AMI (NSTEMI), and thus, we attempt to assess this relationship and its potential short-term prognostic value.

METHODSThis was a single-center, observational, retrospective cohort study. A total of 513 consecutive patients (399 men, 114 women) with NSTEMI within 24 h who underwent coronary angiography at our department, between January 1, 2014, and December 31, 2014. Patients were divided into 2 groups according to the presence or absence of fQRS complex on the admission ECG. fQRS complexes were defined as the existence of an additional R' or crochetage wave, notching in the nadir of the S wave, RS fragmentation, or QS complexes on 2 contiguous leads. All patients were followed up for 6 months, and all major adverse cardiac events (MACE) were recorded.

RESULTSIn this study, there were 285 patients with fQRS ECG in the 513 patients with NSTEMI. The number of patients with 0-2 coronary arteries narrowed by ≥50% in fQRS group were less while patients with 3 narrowed arteries were more than in the non-fQRS group (P = 0.042). There were fewer Killip Class I patients in the fQRS group (P = 0.019), while Killip Class II, III, and IV patients were more in the fQRS group than in the non-fQRS group (P = 0.019). Left ventricular ejection fraction levels were significantly lower in the fQRS group (P = 0.021). Baseline total cholesterol, low-density lipoprotein, creatinine, creatine kinase, homocysteine, high-sensitivity C-reactive protein (CRP), and red blood cells distribution width levels were significantly higher in the fQRS group. Total MACE (MACE, P = 0.028), revascularization (P = 0.005), and recurrent angina (P = 0.005) were also significantly greater in the fQRS group. On final logistic regression analysis, after adjusting for baseline variables, the following variables were independent predictors of fQRS: Coronary artery narrowing (P = 0.035), Killip classification (P = 0.026), and total cholesterol (P = 0.002). The following variables were found to be independent predictors of preoperative MACE: Hemoglobin (P = 0.000), gender (P = 0.026), fQRS (P = 0.016), and time from myocardial infarction to balloon or coronary artery bypasses grafting (P = 0.013).

CONCLUSIONSThe fQRS complexes are commonly present in NSTEMI and the fQRS complexes are an independent predictor of MACE in NSTEMI patients. The number of narrowed coronary arteries, Killip classification, and total cholesterol are all independent predictors of the fQRS complexes.

Aged ; C-Reactive Protein ; analysis ; Electrocardiography ; Female ; Humans ; Logistic Models ; Male ; Middle Aged ; Myocardial Infarction ; blood ; physiopathology ; Prognosis ; Retrospective Studies

OBJECTIVETo investigate the correlation between the polymorphism of the tumor necrosis factor-related apoptosis inducing ligand (TRAIL) and the genetic susceptibility to prostate cancer (PCa) in the Chinese Han population in Nanjing.

METHODSWe performed a case control study on 187 cases of PCa and 237 cancer-free healthy controls. Peripheral blood genome DNA was extracted from the subjects for analysis of the polymorphism of the TRAIL-716 locus by polymerase chain reaction-ligase detection reaction (PCR-LDR). The correlations between the susceptibility to PCa and different genotypes were compared.

RESULTSAn SNP (-716A/G) was found in the promoter of the TRAIL gene. AA, AG and GG genotypes were identified. Logistic regression analysis suggested that AG, GG and AG + GG genotypes had no significant correlation with the risk of PCa (OR = 0.89, 95% CI = 0.54 -1.47; OR = 0.94, 95% CI = 0.69 -1.27; OR = 0.87, 95% CI = 0.54 - 1.41).

CONCLUSIONThe TRAIL-716 polymorphism is not directly related with the genetic susceptibility to PCa in the Chinese Han population of Nanjing.

Aged ; Aged, 80 and over ; Asian Continental Ancestry Group ; genetics ; Case-Control Studies ; China ; Genetic Predisposition to Disease ; Genotype ; Humans ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Prostatic Neoplasms ; genetics ; TNF-Related Apoptosis-Inducing Ligand ; genetics

BACKGROUNDTissue-engineered bioartificial muscle-based gene therapy represents a promising approach for the treatment of heart diseases. Experimental and clinical studies suggest that systemic administration of insulin-like growth factor-1 (IGF-1) protein or overexpression of IGF-1 in the heart exerts a favorable effect on cardiovascular function. This study aimed to investigate a chronic stage after myocardial infarction (MI) and the potential therapeutic effects of delivering a human IGF-1 gene by tissue-engineered bioartificial muscles (BAMs) following coronary artery ligation in Sprague-Dawley rats.

METHODSLigation of the left coronary artery or sham operation was performed. Primary skeletal myoblasts were retrovirally transduced to synthesize and secrete recombinant human insulin-like growth factor-1 (rhIGF-1), and green fluorescent protein (GFP), and tissue-engineered into implantable BAMs. The rats that underwent ligation were randomly assigned to 2 groups: MI-IGF group (n = 6) and MI-GFP group (n = 6). The MI-IGF group received rhIGF-secreting BAM (IGF-BAMs) transplantation, and the MI-GFP group received GFP-secreting BAM (GFP-BAMs) transplantation. Another group of rats served as the sham operation group, which was also randomly assigned to 2 subgroups: S-IGF group (n = 6) and S-GFP group (n = 6). The S-IGF group underwent IGF-1-BAM transplantation, and S-GFP group underwent GFP-BAM transplantation. IGF-1-BAMs and GFP-BAMs were implanted subcutaneously into syngeneic rats after two weeks of operation was performed. Four weeks after the treatment, hemodynamics was performed. IGF-1 was measured by radioimmunoassay, and then the rats were sacrificed and ventricular samples were subjected to immunohistochemistry. Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to examine the mRNA expression of bax and Bcl-2. TNF-α and caspase 3 expression in myocardium was examined by Western blotting.

RESULTSPrimary rat myoblasts were retrovirally transduced to secrete rhIGF-1 and tissue-engineered into implantable BAMs containing parallel arrays of postmitotic myofibers. In vitro, they secreted consistent levels of hIGF (0.4 - 1.2 µg×BAM(-1)×d(-1)). When implanted into syngeneic rat, IGF-BAMs secreted and delivered rhIGF. Four weeks after therapy, the hemodynamics was improved significantly in MI rats treated with IGF-BAMs compared with those treated with GFP-BAMs. The levels of serum IGF-1 were increased significantly in both MI and sham rats treated with IGF-BAM. The mRNA expression of bax was lower and Bcl-2 expression was higher in MI-IGF group than MI-GFP group (P < 0.05). Western blotting assay showed TNF-α and caspase 3 expression was lower in MI-IGF group than MI-GFP group after therapy.

CONCLUSIONSrhIGF-1 significantly improves left ventricular function and suppresses cardiomyocyte apoptosis in rats with chronic heart failure. Genetically modified tissue-engineered BAMs provide a method delivering recombinant protein for the treatment of heart failure.

Animals ; Apoptosis ; Caspase 3 ; analysis ; Desmin ; analysis ; Genetic Therapy ; Heart Failure ; pathology ; physiopathology ; therapy ; Insulin-Like Growth Factor I ; genetics ; secretion ; Myoblasts, Skeletal ; metabolism ; Myocytes, Cardiac ; pathology ; Rats ; Rats, Sprague-Dawley ; Recombinant Proteins ; secretion ; Retroviridae ; genetics ; Tissue Engineering ; Tumor Necrosis Factor-alpha ; analysis ; Ventricular Function, Left

BACKGROUNDExperimental studies and preliminary clinical studies have suggested that growth hormone (GH) treatment may improve cardiovascular parameters in chronic heart failure (CHF). Recombinant human GH (rhGH) has been delivered by a recombinant protein, by plasmid DNA, and by genetically engineered cells with different pharmacokinetic and physiological properties. The present study aimed to examine a new method for delivery of rhGH using genetically modified bioartificial muscles (BAMs), and investigate whether the rhGH delivered by this technique improves left ventricular (LV) function in rats with CHF.

METHODSPrimary skeletal myoblasts were isolated from several Sprague-Dawley (SD) rats, cultured, purified, and retrovirally transduced to synthesize and secrete human rhGH, and tissue-engineered into implantable BAMs. Ligation of the left coronary artery or sham operation was performed. The rats that underwent ligation were randomly assigned to 2 groups: CHF control group (n = 6) and CHF treatment group (n = 6). The CHF control group received non-rhGH-secreting BAM (GFP-BAMs) transplantation, and the CHF treatment group received rhGH-secreting BAM (GH-BAMs) transplantation. Another group of rats served as the sham operation group, which was also randomly assigned to 2 subgroups: sham control group (n = 6) and sham treatment group (n = 6). The sham control group underwent GFP-BAM transplantation, and the sham treatment group underwent GH-BAM transplantation. GH-BAMs and GFP-BAMs were implanted subcutaneously into syngeneic rats with ligation of the left coronary artery or sham operation was performed. Eight weeks after the treatment, echocardiography was performed. hGH, insulin-like growth factor-1 (IGF-1) and TNF-alpha levels in rat serum were measured by radioimmunoassay and ELISA, and then the rats were killed and ventricular samples were subjected to immunohistochemistry.

RESULTSPrimary rat myoblasts were retrovirally transduced to secrete rhGH and tissue-engineered into implantable BAMs containing parallel arrays of postmitotic myofibers. In vitro, they secreted 1 to 2 microg of bioactive rhGH per day. When implanted into syngeneic rat, GH-BAMs secreted and delivered rhGH. Eight weeks after therapy, LV ejection fraction (EF) and fractional shortening (FS) were significantly higher in CHF rats treated with GH-BAMs than in those treated with GFP-BAMs ((65.0 +/- 6.5)% vs (48.1 +/- 6.8)%, P < 0.05), ((41.3 +/- 7.4)% vs (26.5 +/- 7.1)%, P < 0.05). LV end-diastolic dimension (LVEDD) was significantly lower in CHF rats treated with GH-BAM than in CHF rats treated with GFP-BAM (P < 0.05). The levels of serum GH and IGF-1 were increased significantly in both CHF and sham rats treated with GH-BAM. The level of serum TNF-alpha decreased more significantly in the CHF treatment group than in the CHF control group.

CONCLUSIONSrhGH significantly improves LV function and prevents cardiac remodeling in rats with CHF. Genetically modified tissue-engineered bioartificial muscle provides a method delivering recombinant protein for the treatment of heart failure.

Animals ; Bioartificial Organs ; Echocardiography ; Heart Failure ; therapy ; Human Growth Hormone ; administration & dosage ; Myoblasts, Skeletal ; metabolism ; Myocardial Infarction ; pathology ; physiopathology ; therapy ; Rats ; Rats, Sprague-Dawley ; Recombinant Proteins ; administration & dosage ; Tissue Engineering ; Tumor Necrosis Factor-alpha ; blood ; Ventricular Function, Left

BACKGROUNDCell transplantation for myocardial repair is limited by early cell death. Gene therapy with human growth hormone (hGH) has been shown to promote angiogenesis and attenuate apoptosis in the experimental animal. This study was conducted to explore the effects of myoblast-based hGH gene therapy on heart function restoration and angiogenesis after myocardial infarction, and to compare the differences between myoblast-based hGH gene therapy and myoblast therapy.

METHODSMyoblasts were isolated from several SD rats, cultured, purified, and transfected with plasmid pLghGHSN and pLgGFPSN. Radioimmunoassay (RIA) was used to detect the expression of hGH in these myoblasts. SD rats underwent the ligation of the left anterior descending coronary artery so as to establish a heart ischemia model. Thirty surviving rats that underwent ligation were randomly divided into 3 equal groups 2 weeks after left coronary artery occlusion: pLghGHSN group received myoblast infected with hGH gene transplantation; pLgGFPSN group received myoblast infected with GFP gene transplantation; control group: received cultured medium only. Four weeks after the injection the surviving rat underwent evaluation of cardiac function by echocardiography. The rats were killed and ventricular samples were undergone immunohistochemistry with hematoxylin-eosin and factor VIII. Cryosection was analyzed by fluorescence microscopy to examine the expression of green fluorescent protein. Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to examine the mRNA expression of vascular endothelial growth factor (VEGF), bax and Bcl-2. hGH expression in myocardium was examined by Western blot.

RESULTSMyoblast can be successfully isolated, cultured and transfected. The expression of hGH in transfected myoblast was demonstrated with RIA. Four weeks after therapy, the cardiac function was improved significantly in pLghGHSN group and pLgGFPSN group. Fractional shortening (FS) and ejection fraction (EF) in pLghGHSN group were elevated significantly compared with pLgGFPSN group and control group after therapy (FS: 36.9+/-5.3 vs 29.5+/-3.5, 21.8+/-2.9; EF: 56.9+/-4.3 vs 47.1+/-3.6, 38.4+/-4.8, P<0.05). Left ventricular end-diastolic dimension (LVEDD) and heart infracted size in pLghGHSN group were decreased significantly compared with pLgGFPSN group and control group after therapy (LVEDD: 5.9+/-0.3 vs 6.8+/-0.2, 8.6+/-0.3; heart infracted size: (34.5+/-4.2)% vs (40.0+/-3.9)%, (46.1+/-3.8)%, P<0.05); Green fluorescence was detected in cryosection of pLgGFPSN group. The capillary density of the pLgGFPSN group was significantly greater than those of the pLghGHSN group and control group (P<0.05). The mRNA expression of VEGF and Bcl-2/bax in pLghGHSN group was higher than in pLgGFPSN group or control group (P<0.05). The expression of hGH gene in myocardium tissue can be detected by Western blot assay in pLghGHSN group.

CONCLUSIONSTransplantation of heart cells transfected with hGH induced greater angiogenesis and effect of antiapoptosis than transplantation of cells transfected with GFP. Combined GH gene transfer and cell transplantation provided an effective strategy for improving postinfarction ventricular function.

Animals ; Blotting, Western ; Cells, Cultured ; Echocardiography ; Genetic Therapy ; Human Growth Hormone ; blood ; genetics ; Immunohistochemistry ; Myoblasts, Skeletal ; transplantation ; Myocardial Infarction ; physiopathology ; therapy ; RNA, Messenger ; analysis ; Rats ; Rats, Sprague-Dawley ; Transfection ; Ventricular Function