OBJECTIVES: Multimorbidity of non-communicable diseases (NCDs) has brought enormous challenges to public health, becoming a major medical burden. However, the patterns, temporal trends, and all-cause mortality associated with NCD multimorbidity over time have not been well described in the United States. METHODS: All adult participants were sourced from nationally representative data from the National Health and Nutrition Examination Survey. In total, 55,081 participants were included in trend analysis, and 38,977 participants were included in Cox regression. RESULTS: The 5 NCDs with the largest increases over the study period were diabetes, osteoporosis, obesity, liver conditions, and cancer. The estimated prevalence of multimorbidity increased with age, especially for middle-aged participants with 5 or more NCDs; in general, the prevalence of NCD multimorbidity was higher among females than males. Participants with 5 or more NCDs were at 4.49 times the risk of all-cause mortality of participants without any diseases. Significant interactions were found between multimorbidity and age group (p for interaction <0.001), race/ethnicity (p for interaction<0.001), and educational attainment (p for interaction=0.010). CONCLUSIONS The prevalence of multiple NCDs significantly increased from 1999 to 2018. Those with 5 or more NCDs had the highest risk of all-cause mortality, especially among the young population. The data reported by this study could serve as a reference for additional NCD research.

Objective: To compare the efficacy of unrelated cord blood transplantation (UCBT) and HLA-identical sibling peripheral blood stem cell transplantation (PBSCT) for the treatment of adult hematological malignancies. Methods: From April 2011 to December 2015, a total of 81 patients receiving single-unit UCBT and 57 patients receiving HLA-identical sibling PBSCT were enrolled in this study. All of the patients received myelablative conditioning. Cyclosporine combined with mycophenolate mofetil was adopted for GVHD prophylaxis. Results: The cumulative incidence of neutropil engraftment at day-42 was 95.0% and 100% in UCBT and sibling PBSCT groups, respectively (P=0.863) . Platelet engraftment at day 100 was 87.3% (95%CI 76.8%-93.1%) in UCBT group, which was significantly lower than that of sibling PBSCT group[98.2% (95%CI 87.3%-99.7%) ] (P=0.005) . There were no significant differences in terms of Ⅱ-Ⅳ acute GVHD or Ⅲ-Ⅳ acute GVHD in two groups (P=0.142, 0.521) . The 3-year chronic GVHD and extensive chronic GVHD were 14.9% (95%CI 5.2%-23.5%) and 11.2% (95%CI 2.9%-18.7%) , respectively in UCBT group, which was significantly lower than that of sibling PBSCT group[35.2% (95%CI 19.4%-47.8%) , 31.4% (95%CI 16.2%-43.9%) ] (P=0.008, 0.009) . The 3-year transplant-related mortality (TRM) was similar between two groups (30.1% vs 23.2%, P=0.464) . The relapse rate at 3-year in UCBT group[12.9% (95%CI 6.6%-21.5%) ]was significantly lower than that in sibling PBSCT group[24.3% (95%CI 13.5%-36.8%) ] (P=0.039) . There were no significant differences in terms of overall survival (OS) and disease-free survival (DFS) between two groups (58.6% vs 54.8%, P=0.634; 57.0% vs 52.4%, P=0.563) . But GVHD-free and relapse-free survival (GRFS) in UCBT group [55.7% (95%CI 44.1%-65.8%) ]was significantly higher than that of sibling PBSCT group[42.9% (95%CI 29.8%-55.3%) ] (P=0.047) . Conclusions For adult hematological malignancies, the incidences of acute GVHD and TRM were similar between UCBT and sibling PBSCT recipients, and the incidences of chronic GVHD and relapse were lower in UCBT recipients. UCBT recipients had higher GRFS rate although OS and DFS were similar between two groups, which may reflect the real recovery and better quality of life following UCBT.

Objective: To explore the clinical efficacy and safety of unrelated umbilical cord blood transplantation (UCBT) in the treatment of refractory and relapsed acute leukemia (AL) patients. Methods: The clinical data of 22 refractory and relapsed AL patients who were treated with UCBT as salvage therapy from November 2009 to May 2017 were retrospectively analyzed. All patients received a myeloablative conditioning regimen for prevention of graft-versus-host disease (GVHD) with cyclosporine A (CSA)/short course of mycophenolate mofetil (MMF). Results: ①Of 22 patients, 9 cases were male and 13 female. The median age was 23 (15-44) years and median weight of 52.5 (43-82) kg. All patients were transplanted with a median umbilical cord blood nucleated cells of 3.07 (1.71-5.30)×10⁷/kg (by weight), the median CD34⁺ cells was 1.60 (0.63-3.04)×10⁵/kg (by weight). ②The myeloid cumulative implantation rate was 95.5% (95%CI 45.2-99.7%) after transplantation of 42 d, with the median implantation time of 19 (13-27) d. The platelet cumulative implantation rate after transplantation of 120 d was 81.8% (95%CI 54.2-93.6%), the median implantation time of 42 (20-164) d. ③The incidence of Ⅱ-Ⅳ, Ⅲ-Ⅳ aGVHD and the 2 year cumulative incidence of cGVHD were 36.4%, 13.6% and 40.3% respectively. ④ The transplant related mortality (TRM) after transplantation of 180d was 22.7%, 2 year cumulative rate of relapse was 18.7% (95%CI 3.6-42.5%), 2 year disease-free survival rate (DFS) and overall survival rate (OS) were 53.7% and 58.1%, respectively. Conclusion The preliminary results show that the use of UCBT is safe and effective for refractory and relapsed AL patients who fail to respond to conventional chemotherapy.

Objective To study the curative efficacy and safety of single-unit umbilical cord blood transplantation (sUCBT) for malignant hematologic diseases,which is provided by China's public cord blood bank.Methods We retrospectively analyzed 409 cases of malignant hematologic diseases who accepted myeloablative single-unit unrelated donor UCBT without ATG at our center between May 2008 and December 2016.A comparative analysis was made on the total nuclear cells (TNC) of the umbilical cord blood before freezing and after thawing,the cells of CD34+,the recovery rate of cells and the clinical effect of UCBT.Result 409 units of umbilical cord blood used in UCBT respectively came from eight China's public cord blood banks.The average TNC of 409 units of umbilical cord blood before freezing and after the tubular recovery were respectively 18.5 × 108 and 16.34 × 108 (p =0.000).The average recovery rate of the tubular recovery was 88.5％,and there was significant difference among cord blood banks (P =0.000).The average TNC of umbilical cord blood before freezing and transfusion were respectively 18.5 × 108 and 15.86 × 108 (p =0.000).The average recovery rate of umbilical cord blood transfusion was 85.9％,with the difference being significant among cord blood banks (P =0.000).The average number of CD34+ cells before freezing and after the tubular recovery was 11.18 × 106and 8.68 × 106 (p =0.000).The average recovery rate of CD34+ cells after the tubular recovery was 80.75 ％,with the difference being significant among the cord blood banks (P =0.000).At 42nd day after UCBT,the cumulative incidence of neutrophil engraftment was 95.4％,and the median time of the engraftment was 17 days (11-38 days).The cumulative incidence of platelet engraftment at 120th day was 84.6％,and the median time of the engraftment was 36 days (14-93 days).The cumulative incidence of erythrocyte engraftment at 60th day was 92％,and the median time of engraftment was 22 days (9d-60 days).After the umbilical cord blood provided by each bank was used in UCBT,it got the difference in cumulative incidence of engraftment.The P values for cumulative incidence of neutrophil,platelet and erythrocyte engraftment were respectively 0.004,0.01 and 0.000 2,with the differences being statistically significant.At 100th day after UCBT,the cumulative incidence of Ⅱ-Ⅳ and Ⅲ-Ⅳ degrees of acute graft-versus-host disease (aGVHD) was respectively 28.63％ and 15.7％.After umbilical cord blood provided by each bank was used in UCBT,it got the difference in cumulative incidence of aGVHD.There was no significant difference between Ⅱ-Ⅳ and Ⅲ-Ⅳ degrees (P =0.809 and 0.68 respectively).At 3rd year after UCBT,the cumulative incidence of relapse was 15.89％.After umbilical cord blood provided by each bank was used in UCBT,there was no significant difference in the cumulative incidence of relapse (P =0.898).At 3rd year after UCBT,the overall survival (OS) rate and disease free survival (DFS) rate were respectively 66.7％ and 59％.After umbilical cord blood provided by each bank was used in UCBT,it got the difference in OS and DFS.There was no significant difference in OS and DFS (P =0.566 and 0.703 respectively).At 3rd year after sUCBT,the rate of graft-versus-host diseases/relapse-free survival (GRFS) was 54.3％.After umbilical cord blood provided by each bank was used in UCBT,there was no significant difference in the rate of GRFS (P =0.449).Conclusion The umbilical cord blood provided by China's public cord blood bank was used in UCBT.It has a high safety and good efficacy in treating malignant hematologic diseases.But it needs to set up the standardized and normalized quality-control system of umbilical cord blood for China's public cord blood bank.

Objective:To assess the association between diabetes mellitus and the risk of sudden cardiac death (SCD), and to identify potential contributing factors.Methods:This meta-analysis was an updated version of the original study Diabetes mellitus and the risk of sudden cardiac death： a systematic review and meta-analysis of prospective studies. The original review included all eligible case-control and cohort studies published in PubMed and Embase up to 2017 that investigated the association between diabetes and SCD risk. In this updated study, newly published studies were added, including those available in PubMed, Embase, China National Knowledge Infrastructure (CNKI), and WANFANG MED ONLINE up to December 3, 2023. Search terms included "diabetes""glucose""sudden cardiac death" "cardiac arrest" and their Chinese equivalent. The primary outcome was the risk of SCD, while factors such as country, ethnicity, skin color, follow-up duration, left ventricular ejection fraction (LVEF), baseline comorbidities, and other relevant variables were analyzed as potential influencing factors. Relative risk ( RR) was used as the summary measure. A random-effects model was used when significant heterogeneity was detected, otherwise a fixed-effects model was used. Cochran′s Q test was used for subgroup analysis to assess the influence of factors such as region, baseline diseases, LVEF, and ethnicity (based on skin color) on the outcomes. Results:A total of 32 cohort/case-control studies with a combined sample size of 3 252 954 individuals were included. The meta-analysis showed that the risk of SCD in patients with diabetes was double that of non-diabetics ( RR=2.00, 95% CI: 1.83-2.19, P<0.001). In Asian populations, the risk of SCD in diabetic patients was 1.78 times that of non-diabetic individuals ( RR=1.78, 95% CI: 1.51-2.10), 2.05 times that of in European populations ( RR=2.05, 95% CI: 1.79-2.34), and 2.12 times that of in American populations ( RR=2.12, 95% CI: 1.82-2.47), with no statistically significant heterogeneity between regions ( P=0.287). Among individuals without other baseline comorbidities, the risk of SCD was 2.12 times higher in diabetic patients than in those without diabetes ( RR=2.12, 95% CI: 1.89-2.38). In patients with baseline coronary heart disease, the risk was 1.75 times that of non-diabetics ( RR=1.75, 95% CI: 1.45-2.11). In those with baseline heart failure, the risk was 1.92 times that of non-diabetics ( RR=1.92, 95% CI: 1.51-2.43). In patients with baseline atrial fibrillation, the risk was 4.00 times that of non-diabetic individuals ( RR=4.00, 95% CI: 1.38-11.56). In patients undergoing hemodialysis due to renal failure, the risk was 1.76 times that of non-diabetic individuals ( RR=1.76, 95% CI: 1.25-2.48), with no statistically significant heterogeneity between groups ( P=0.262). In cardiac patients with LVEF>50%, the risk of SCD in diabetic patients was 2.08 times that of non-diabetic individuals ( RR=2.08, 95% CI: 1.57-2.75), and in those with LVEF<50%, the risk was 1.69 times that of non-diabetic individuals ( RR=1.69, 95% CI: 1.30-2.18), with no statistically significant heterogeneity between groups ( P=0.277). In yellow-skinned populations, the risk of SCD in diabetic patients was 1.80 times that of healthy individuals ( RR=1.80, 95% CI: 1.73-1.87), and in white-skinned populations, it was 2.18 times that of healthy individuals ( RR=2.18, 95% CI: 1.88-2.54), with statistically significant heterogeneity between groups ( P=0.014). Conclusions:Diabetes mellitus significantly increased the risk of SCD, and this effect may be more pronounced in white-skinned populations, while region, baseline comorbidities, and LVEF had no further effect.

Objective:To retrospectively analyze the clinical outcomes of single unrelated cord blood transplantation (UCBT) in children with high risk and refractory acute myeloid leukemia (AML) .Methods:Between June 2008 and December 2018, a total of 160 consecutive pediatric patients with AML received single UCBT (excluding acute promyelocytic leukemia) . Myeloablative conditioning (MAC) regimen were applied. All patients received a combination of cyclosporine A (CsA) and mycophenolate mofetil (MMF) for the prophylaxis of graft -versus- host disease (GVHD) .Results:The cumulative incidence of neutrophil cells engraftment at day +42 and platelet recovery at day +120 was 95.0% (95% CI 90.0%-97.5%) at a median of 16 days after transplantation (range, 11-38 days) and 85.5% (95% CI 83.3%-93.4%) with a median time to recovery of 35 days (range, 13-158) , respectively. Incidence of grades Ⅱ-Ⅳ and Ⅲ-Ⅳ acute GVHD and chronic GVHD were 37.3% (95%CI 29.3%-45.2%) , 27.3% (95% CI 20.0%-35.0%) and 22.4% (95% CI 15.5%-28.7%) , respectively. The transplant-related mortality (TRM) at 360 day was 13.1% (95% CI 8.4%-18.9%) . The 5-year cumulative incidence of relapse was 13.8% (95% CI 8.5%-20.3%) . The 5-year disease-free survival (DFS) and overall survival (OS) were 71.7% (95% CI 62.7%-77.8%) and 72.2% (95% CI 64.1%-78.7%) , respectively. The 5-year GVHD and relapse free survival (GRFS) was 56.1% (95% CI 46.1%-64.9%) . The 5-year cumulative recurrence rates of CR1, CR2, and NR groups were 5.3%, 19.9%, and 30.9% ( P=0.001) , and the 5-year OS rates were 79.9% (95% CI 70.3%-86.7%) , 71.1% (95% CI 50.4%-84.4%) and 52.9% (95% CI 33.0%-69.3%) ( χ2=7.552, P=0.020) , respectively. Conclusions:For pediatric patients with high risk and refractory AML, UCBT is a safe and effective treatment option, and it is favorable to improve the survival rate in CR1 stage.

OBJECTIVE: To identify pathogenic mutation in a Chinese family affected with hereditary spastic paraplegia (HSP) through genetic testing and a follow-up survey. METHODS: Whole exome sequencing was performed on DNA samples of two patients and one unaffected member to screen candidate mutations. Sanger sequencing was used to validate the suspected mutations in all ten family members. RESULTS: Four patients and three asymptomatic members (under 25 years old) carried a c.1771T>C mutation of the KIAA0196, while the other three asymptomatic members (over 40 years old) did not carry the mutation. The mutation was predicted to be "affect protein function", "probably damaging" and "disease causing" by SIFT, PolyPhen-2 and Mutation Taster, respectively. Three asymptomatic carriers were followed up and one of them developed HSP one year later, while the other two had no signs of the disease yet. CONCLUSION The clinical phenotype of the c.1771T>C mutation of KIAA0196 has a considerable heterogeneity and this mutation may be a common pathogenic site of KIAA0196 mutations among Chinese patients with hereditary spastic paraplegia.
Adult ; Asian Continental Ancestry Group ; Heterozygote ; Humans ; Mutation ; Pedigree ; Phenotype ; Proteins ; genetics ; Spastic Paraplegia, Hereditary ; genetics