BACKGROUND: Existing evidence suggests that fruit consumption is a significant influencing factor for chronic obstructive pulmonary disease (COPD), but this is unclear in the Chinese population. We examined the association of fresh fruit consumption with the risk of COPD-related hospitalization and death in a nationwide, population-based prospective cohort from China. METHODS: Between 2004 and 2008, the China Kadoorie Biobank recruited >0.5 million adults aged 30 to 79 years from ten diverse regions across China. After excluding individuals diagnosed with major chronic diseases and prevalent COPD, the prospective analysis included 421,428 participants. Cox regression was used to calculate the hazard ratios (HRs) for the association between fresh fruit consumption and risk of COPD-related hospitalization and death, with adjustment for established and potential confounders. RESULTS: During a mean follow-up of 10.9 years, 11,292 COPD hospitalization events and deaths were documented, with an overall incidence rate of 2.47/1000 person-years. Participants who consumed fresh fruit daily had a 22% lower risk of COPD-related hospitalization and death compared with non-consumers (HR = 0.78, 95% confidence interval [CI]: 0.71-0.87). The inverse association between fresh fruit consumption and COPD-related hospitalization and death was stronger among non-current smokers and participants with normal body mass index (BMI) (18.5 kg/m 2 ≤ BMI < 24.0 kg/m 2 ); the corresponding HRs for daily fresh fruit consumption were 0.78 (95% CI: 0.68-0.89) and 0.69 (95% CI: 0.59-0.79) compared with their counterparts, respectively. CONCLUSIONS High-frequency fruit consumption was associated with a lower risk of COPD in Chinese adults. Increasing fruit consumption, together with cigarette cessation and weight control, should be considered in the prevention and management of COPD.

Objective:To investigate the effect and prognostic factors of rituximab-containing chemotherapy regimen in treatment of patients with mantle cell lymphoma (MCL).Methods:The clinical data of 56 patients aged ≤65 years in the First Affiliated Hospital of Soochow University from June 2007 to November 2018 were retrospectively analyzed. Rituximab-containing chemotherapy regimen was used, and the effects of clinical features, treatment regimen and biological indexes on overall survival (OS) and progression-free survival (PFS) were observed.Results:The median age of 56 patients was 57 years old, including 43 males and 13 females. Among these cases, 24 patients received R-CHOP chemotherapy regimen; 29 patients received cytarabine-containing chemotherapy regimen, including R-hyper CVAD/R-MA regimen used in 15 patients and R-CHOP alternating with R-DAHP regimen used in 14 patients; and 3 patients received other treatment regimens. Among 56 patients, 19 patients received autologous hematopoietic stem cell transplantation (ASCT) consolidation therapy. The median OS time was 74 months, 2-year OS rate was 83.8%, 3-year OS rate was 70.9%, 2-year PFS rate was 72.0% and 3-year PFS rate was 49.7%. International prognostic index (IPI) high-risk and receiving ASCT or not during the treatment were independent influencing factors of OS and PFS in MCL patients. The overall response rate (ORR) in cytarabine-containing regimen group was higher compared with that in R-CHOP regimen group (93.1% vs. 83.3%), and there was no statistically significant difference ( χ2=0.465, P=0.495). In addition, there were no significant differences between two groups in both OS ( χ2=0.291, P=0.590) and PFS ( χ2=0.912, P=0.339). ASCT consolidation prolonged the median OS time (72 months vs.124 months, χ2=3.973, P=0.040) and the median PFS time (34 months vs. 90 months, χ2=3.984, P=0.046) in MCL patients achieving remission after induction therapy. Among patients in simplified MCL IPI (sMIPI) score middle-high risk group, compared with those not receiving ASCT, patients receiving ASCT therapy could obtain better OS and PFS (OS: χ2=5.037, P=0.025; PFS: χ2=6.787, P=0.009); among patients of sMIPI score low risk, there were no statistically significant differences in OS and PFS between the group receiving ASCT and not (all P > 0.05). Conclusions:Cytarabine-containing chemotherapy regimen has no predicatively satisfactory value in improving the prognosis and survival for MCL patients. For MCL patients who have achieved remission after reduction therapy and those in sMIPI score middle-high risk group, ASCT consolidation therapy can improve the prognosis and can be taken as the first-line consolidation treatment in young patients.

Objective:To examine the efficacy of haploidentical stem-cell transplantation (haplo-SCT) for patients with refractory relapsed (R/R) non-Hodgkin lymphoma (NHL) by comparing with those contemporaneously undergoing HLA-matched SCT in myeloablative conditioning settings.Methods:Between January 2006 and December 2018, a total of 151 patients undergoing haplo-SCT ( n=81) or HLA-matched SCT ( n=70, sibling or unrelated) were enrolled. Median age of alloSCT was 30(5-59) years. And 150 patients received myeloablative conditioning (MAC) consisting of total body irradiation (12 Gy) plus cyclophosphamide or busulfan plus cyclophosphamide. Only one case had reduced intensity conditioning (RIC) with R-FBA (fludarabine, busulfan & cytarabina). It was followed by an infusion of granulocyte-colony stimulating factor-primed bone marrow (G-BM) and/or peripheral blood stem cells without in vitro T cell depletion. In haplo-SCT and HLA-matched unrelated donor for SCT, GVHD prophylaxis consisted of antithymocyte globulin, cyclosporine A, mycophenolate mofetil and a short course of methotrexate. Clinical efficacy, hematopoietic reconstitution and transplant-related complications were retrospectively analyzed. Results:Among them, 146(96%) patients engrafted with a median time to neutrophil and platelet recovery of 12 and 15 days respectively. During a median follow-up period of 19 months, 66 of them survived (43.7%) and 67 (44.4%) died (39 disease recurrence, 27 transplantation-related mortality). Between haplo-SCT and HLA-matched SCT groups, progression-free survival (PFS) rate was 49.4% and 50.5% ( P=0.577); overall survival (OS) rate 56.7% and 57.4% respectively ( P=0.963). The cumulative incidences of relapse (CIR) were 36.6% and 37.7% ( P=0.836) and those of cumulative incidences of non-relapse mortality (NRM) 22.0% and 24.7% ( P=0.530). And the cumulative incidences of chronic GVHD were 42.3% and 39.6% ( P=0.46) respectively. Conclusions:No inter-group difference exists in each major HSCT endpoint. Multivariate analysis reveals that occurrence of grade Ⅲ-Ⅳ aGVHD has a significantly worse prognosis. And primary chemorefractoriness is a strongest relapsing factor.

Objective:To explore how to personalize lung cancer screening programs for prevention in Chinese populations based on individual genetic risk score.Methods:We constructed the lung cancer polygenic genetic risk score (PRS-19) based on the 19 previously published genetic variations, using 100 615 participants with genotyping data from the China Kadoorie Biobank (CKB). Using the 5-year absolute risk of lung cancer in a population (55 years old with at least 30-pack-year history of smoking) as reference, the trend of 5-year absolute risk in different genetic risk groups was calculated in smokers and non-smokers, respectively. Distribution curves of 5-year absolute risk were also described to determine the theoretical age or smoking dose when different genetic risk groups reached the reference values. Given the overall findings, the specific start age for lung cancer screening were suggested for different genetic risk groups.Results:The 5-year absolute risk of lung cancer was 0.67% in 55-year-old smokers with 30 packs per year in the CKB. Among smokers, 5-year absolute risk of participants increased as the genetic risk increased. Hence, it was recommended that people at high genetic risk should start screening earlier. For the highest genetic risk populations (the top 1% of PRS), the start age might be changed to 50 years old. If the start age remained at 55-year-old, the smoking dose should be set lowered in high genetic risk populations. For the highest genetic risk populations, they should be included in lung cancer screening regardless of the cumulative smoking exposure. Among nonsmokers, it was also valuable to screen people with high genetic risk, considering the start age of 62 for the highest genetic risk populations and 74 for the lowest genetic risk populations (the bottom 5% of PRS).Conclusions:PRS-19 can be effectively used in developing lung cancer screening program for individualized prevention in China. For smokers with high genetic risk, the recommended starting age and smoking dose could be lowered for lung cancer screening, and non-smokers with high genetic risk could also be included in the screening programs.

Objective:To describe the prevalence of heart failure in China and to explore the prospective association between smoking behavior and the risk of incident heart failure.Methods:The subjects were from the China Kadoorie Biobank (CKB) and the baseline survey was conducted from June 2004 to July 2008. A total of 487 197 subjects were included in this study, after excluding those with missing BMI information, lost follow-up immediately after baseline investigation, and self-reported coronary heart disease, stroke, or malignant tumor at baseline. This study included data from baseline and follow-up until December 31, 2016. Cox proportional hazards regression models were used to estimate the association between smoking behavior and the risk of heart failure.Results:The median follow-up time was 10.15 years, during which a total of 4 208 new cases of heart failure occurred, with a crude incidence rate of 0.87/1 000 person-years and a cumulative incidence rate of 0.86%. The higher the age at baseline, the higher the incidence of heart failure. The incidence of heart failure in high age group, rural area and male was higher than that in low age group, urban area and female population respectively. Compared with non-smokers, there was no significant difference in the risk of heart failure in occasional smokers ( HR=1.05; 95% CI: 0.91-1.22), while former smokers ( HR=1.48; 95% CI:1.31-1.67) and current smokers ( HR=1.34;95% CI:1.22-1.49) increased risk. Former smokers ( HR=1.33;95% CI:1.21-1.46) and current smokers ( HR=1.46; 95% CI:1.31-1.64) had higher risk of heart failure than non-smokers or occasional smokers. No dose-response relationship was observed between the number of cigarettes smoked per day and the risk of heart failure in current and former smokers (for trend P=0.347 and 0.066). Compared with non-smokers or occasional smokers, the hazard ratios of <5, 5-, 10- and ≥20 years since quit smoking were 1.61 (95% CI: 1.36-1.92), 1.55 (95% CI: 1.27-1.90), 1.24 (95% CI: 1.02-1.51) and 1.35 (95% CI: 1.08-1.68), respectively (for trend P=0.091). The hazard ratios of quitting smoking due to disease and other reasons were 1.62 (95% CI:1.41-1.86) and 1.23 (95% CI: 1.04-1.45). Healthy smoking behaviors had a significant protective effect on heart failure compared with non-healthy smoking behaviors ( HR=0.75, 95% CI:0.69-0.81). Area and family history of coronary heart disease, and the smoking behaviors interacted with the risk of heart failure (for all interactions were P<0.05). Conclusions:The incidence of heart failure in China is higher in males than females, higher in rural areas than in urban areas, and increases with age. Both former smokers and current smokers had a higher risk of heart failure than nonsmokers or occasional smokers, regardless of the frequency, amount, duration, and reason for quitting. Smoking is an important risk factor for heart failure and comprehensive anti-smoking measures should be maintained.

Objective: To study the value of unmethylated cytosine guanine dinucleotide oligodeoxynucleotide (DSP30) and IL-2 in the conventional cytogenetic (CA) detection of the chromosomal aberrations in chronic lymphocytic leukemia (CLL) . Methods: Bone marrow or peripheral blood cells of CLL patients were cultured with DSP30 plus IL-2 for 72 h, following which R-banding analysis was conducted. Fluorescence in situ hybridization (FISH) was performed in 85 patients. CA results were compared with data obtained by FISH. Results: Among 89 CLL patients, the success rate of chromosome analysis was 94.38% (84/89) . Clonal aberrations were detected in 51 patients (51/84, 60.71%) . Of them, 27 (27/51, 52.94%) were complex karyotype. Among 85 CLL patients tested by FISH, chromosomal abnormalities were detected in 74 (74/85, 87.06%) patients, of which 2 (2/74) patients were complex karyotypes, accounting for 2.70%. Of the 85 CLL patients examined by FISH, 50 had abnormal karyotype analysis, 30 had normal karyotype, 5 failed to have chromosome analysis. Among them, 25 cases showed clonal aberrations by FISH assay but normal by CA, and 4 cases were normal by FISH but displayed aberrations in chromosome analysis, and totally 78 (91.76%) cases with abnormality detected by the combination of the two methods. The frequency of 13q- abnormality detected by FISH was significantly higher than that by CA analysis (69.41%vs 16.67%, P<0.001) , while the frequency of 11q-,+12 and 17p- detected by two methods showed no significant difference (P>0.05) . The detection rate of complex abnormalities in conventional karyotype analysis was higher than that in FISH (50.98%vs 2.70%) . In addition, 11 low-risk and 9 intermediate-risk patients according to FISH results showed complex karyotype by cytogenetics, and were classified into high-risk cytogenetic subgroup. Conclusion DSP30 and IL-2 are effective in improving the detection rate of CA in CLL patients (60.71%) and CA is more effective to detect complex karyotype. However, FISH had a higher overall abnormality detection rate (87.06%) than CA, especially for 13q-. The combination of CA and FISH not only enhanced the detection rate of clonal aberrations to 91.76%, but also provided more precise prognosis stratification for CLL patients, thus to provide more information for clinical implication.

Objective: To assess the association of BMI and waist circumference (WC) with metabolic risk factors, and confirm the appropriate cut-off points of BMI and WC among Chinese adults. Methods: After excluding participants with missing or extreme measurement values, as well as individuals with self-reported histories of cancer, a total of 501 201 adults in baseline and 19 201 adults in the second re-survey from the China Kadoorie Biobank were included. The associations of BMI and WC with metabolic risk factors were estimated. Receiver operating characteristic (ROC) analyses were conducted to assess the appropriate cut-off values of BMI and WC to predict the risk of hypertension, diabetes, dyslipidemia and clustering of risk factors. Results: The prevalence of hypertension, diabetes, dyslipidemia and clustering of risk factors all presented ascending trends with the increasing levels of BMI or WC. Defined as the points on the ROC curve where Youden’s index reached the highest, the appropriate overweight cut-off points of BMI were around 24.0 kg/m² both in men and women, and the points of WC were around 85 cm in men and 80 to 85 cm in women. With specificity 90% for identification of risk factors, the appropriate obese cut-off points of BMI were around 28.0 kg/m² both in men and women, with the range of 27.0 to 28.9 kg/m². Conclusions The cut-off points for overweight and obesity recommended by Coorperative Meta-analysis Group of China Obesity Task Force was verified in the large sample survey conducted more recently. The cut-off points of BMI were 24.0 and 28.0 kg/m² for overweight and obesity, and the cut-off point of WC was 85 cm in men and 80 to 85 cm in women for central obesity.

Objective To compare the cognitive function of patients with carotid stenosis combined with white matter lesions (WML)after carotid artery stenting (CAS). Methods Total 166 patients with carotid artery stenosis were collected.According to MRI imaging,30 patients with no white matter lesions were included in the control group and 136 patients with white matter lesions were included in the white matter lesions group. They were treated with carotid artery stenting and underwent evaluation on the safety and efficacy of perioperative surgery. CAS failed in two patients because of the inability of guidewire crossing in WML group. Two patients died after CAS (one for cardiac death and one for traumatic accident) in WML group. 162 patients received 1 year follow-up. Cognitive function was assessed before and after CAS. Results Before CAS,WML group's MMSE, digit span forward/backward test, verbal fluency test and MoCA scores (21.8±3.3、6.3±2.1、4.1±1.0、15.1±3.6、20.6±3.1) were lower compared with control (24.3±3.9、7.3±2.6、4.7±1.8、17.7±5.2、22.7±4.2) and ADAS-Cog score was higher compared with control ((15.1±3.3) vs.(12.7±3.3)), P=0.000、0.026、0.039、0.012、0.000、0.011.Three months after CAS,the MMSE,digit span forward test and MoCA scores (23.7±3.6,7.5± 2.4, 23.1±6.9) was higher significantly than those before treatment (21.8±4.3, 6.3±2.09, 20.6±4.13), P<0.05.And the scores of ADAS-Cog was lower((13.2±4.)vs.(15.1±4.3),P<0.05).The scores of digit span backward test in 6 months after treatment was significant higher than those before treatment (4.9 ±2.8,4.1 ±2.2,P<0.05). After 1 year of CAS, the improvement in scores of MMSE, digit span forward test, ADAS-Cog and MoCA in patients with carotid stenosis complicated with WML(3.5±1.3,1.6±0.6,-2.6±0.8,3.6±1.1)was higher significant than control(2.7±1.8, 1.2±0.8, -2.0± 1.3, 2.7 ±1.5),P<0.05. Conclusion CAS can improve cognitive function in Patients with carotid artery stenosis complicated with WML than those who without WML.

Objective: To study the specific killing effect of CD4 membrane protein targeted chimeric antigen receptor modified T (CAR-T) cell. Methods: The second generation CD4 targeted chimeric antigen receptor containing 4-1BB costimulation domain was insert into lentiviral vector through recombinant DNA technology. Lentivirus was prepared and packaged by 293T cells with four plasmids. Beads activated T cells were transduced with lentivirus and the transduction efficiency was checked with Protein L and flow cytometry. T cell subsets and IFN-γ concentrations were detected with probe-tagged antibody and cytometric bead assay. Results: ①The transduction efficiency of activated T cells with prepared lentivirus were 50.0%-70.0%. A subset of CD8⁺ T cell acquired dim expression of CD4 membrane protein after activation. CD4⁺T cell and CD8⁺CD4^dim T cell were gradually killed by CD4 targeted CAR-T post lentivirus transduction. ②The kill efficacy of CD4 targeted CAR-T cell and control T cell toward KARPAS 299 T cell at an E∶T ratio of 8∶1 for 24 h was (96.9±2.1)% and (11.2±3.1)%, CAR-T cell has a higher killing efficacy than control T cell (t=7.137, P=0.028). The IFN-γ concentrations in culture supernatant of CAR-T cell with K562-CD4 cell, CAR-T cell with K562 cell and CAR-T cell alone were (15 648±2 168), (1 978±354) and (1 785±268) pg/ml, CAR-T cell cocultured with K562-CD4 cell produced more IFN-γ than the other two controls (P<0.01). Conclusions CD4 targeted CAR-T has an immunophenotype of CD8⁺CD4^-T cell. CD4 targeted CAR-T cell has killing efficacy toward normal CD4⁺T cell and CD4⁺T lymphoma cell. CD4 targeted CAR-T cell also has a killing efficacy toward CD4^dim target cell.

Objective To analyze the factors that influence joint function after plate fixation of unstable pelvic fractures.Methods A retrospective study was conducted to analyze the 109 patients with unstable pelvic fracture who had been treated with plate fixation from January 2007 to September 2014.They were 69 men and 40 women,23 to 72 years of age (average,46.3 years).By the Tile classification,15 cases were type B1,37 type B2,14 type B3,19 type C1,16 type C2,and 8 type C3.Their postoperative joint function was evaluated according to the Majeed criteria for functional evaluation.There were 86 cases in the good-to-excellent group (78.9％) and 23 in the fair-to-poor group (21.1％).Their data were analyzed in terms of gender,age,preoperative injury severity scale (ISS),body mass index (BMI),operation time,fracture type,reduction quality,postoperative complications,bone density,and postoperative weight bearing time.The influential factors were determined using Logistic regression analysis.Results All the 109 patients obtained a mean follow-up of 18.7 months (from 12 to 53 months).Preoperative ISS (P =0.000),fracture type (P =0.008),reduction quality (P =0.009) and postoperative complications (P =0.000) were identified as the factors influencing joint function after plate fixation of unstable pelvic fractures.Conclusion Preoperative assessment by ISS,a clear understanding of the pelvic fracture type,anatomical reduction of the fracture and efforts to reduce postoperative complications can effectively improve functional recovery of the joint after plate fixation of unstable pelvic fractures.