Disease burden based on gender and age and risk factors for stroke in China, 2019 / 中南大学学报(医学版)

OBJECTIVES@#Stroke has become the leading cause of death and disability among adults in China. This study aims to analyze the disease burden based on gender and age and the risk factors for stroke subtypes in China 2019, and to provide reference for targeted stroke prevention and control.@*METHODS@#Based on 2019 data of the Global Burden of Disease (GBD), the gender and age in patients with different stroke subtypes (ischemic stroke, intracranial hemorrhage, subarachnoid hemorrhage) in China 2019 was described by using disability-adjusted life years (DALY), and attributable burden of related risk factors was analyzed.@*RESULTS@#In 2019, the burden of intracranial hemorrhage was the heaviest one in China, resulting in 22.210 6 million person years of DALY, following by ischemic stroke and subarachnoid hemorrhage, resulting in 21.393 9 and 2.344 7 million person years of DALY, respectively. Among them, except the 0-14 age group, the disease burden of different subtypes of stroke in men was higher than that in women. The disease burden of ischemic stroke was increased with age in both men and women, with the heaviest disease burden in ≥70 years group. The disease burden of intracranial hemorrhage and subarachnoid hemorrhage was the heaviest in males aged 50-69 years old, and in females aged ≥70 years and 50-69 years, respectively. Metabolic factors were the main risk factors in all ages of different stroke subtypes, and the most important risk factor was high systolic blood pressure. Other risk factors were different between men and women. Smoking, high body mass index, high low-density lipoprotein, and outdoor particulate matter pollution were the main risk factors for stroke in men, while high body mass index, outdoor particulate matter pollution, and high fasting blood glucose were the main risk factors of stroke in women. The main risk were different among different age groups.@*CONCLUSIONS@#The burden and attributable risk factors for different stroke subtypes are discrepancy in different gender and age groups. Targeted interventions should be conducted in the future to reduce the burden of stroke.

Clinical observation of acupuncture with host-guest combination using Yuan-Primordial and Luo-Connecting points plus Tuina for the third lumbar transverse process syndrome / 针灸推拿医学（英文版）

Objective: To observe the effects of acupuncture at Yuan-Primordial and Luo-Connecting points by host-guest combination plus Tuina (Chinese therapeutic massage) on the third lumbar transverse process syndrome. Methods: A total of 88 patients with the third lumbar transverse process syndrome were selected and divided into an observation group and a control group according to the random number table method, with 44 cases in each group. The control group was treated with Tuina, and the observation group was treated with additional acupuncture at Yuan-Primordial and Luo-Connecting points by host-guest combination. The clinical efficacy of the two groups was compared after treatment. The changes in the scores of physical signs, Roland-Morris disability questionnaire (RMDQ), Oswestry disability index (ODI), Quebec back pain disability scale (QBPDS), and pain factors [including serum prostaglandin (PG) E2, neuropeptide Y (NPY), and matrix metalloproteinase-3 (MMP-3)] were observed. Results: After treatment, the total effective rate in the observation group was 93.2％, higher than 75.0％ in the control group; the difference between the two groups was statistically significant (P<0.05). Compared with those before treatment, the scores of physical signs and each low back pain scale, and the levels of serum pain factors in the two groups were decreased (P<0.05), and those in the observation group were lower than those in the control group (P<0.05). Conclusion: Acupuncture at Yuan-Primordial and Luo-Connecting points by host-guest combination plus Tuina is effective in the treatment of the third lumbar transverse process syndrome; it can improve the patient's physical signs, relieve low back pain, and reduce the levels of serum pain factors.

Effects of Notch1 signaling on regulatory T cells and coronary artery lesions in childhood Kawasaki disease / 中华风湿病学杂志

Objective:To explore the effect of Notch1 signaling on regulatory T cells and its roles in vascular damage in patients with Kawasaki disease (KD).Methods:A total of 42 children with KD were enrolled in the present study from March 2019 to June 2020, as 32 age-matched healthy children were recruited as control. The proportions of CD4 +CD25 hiFoxp 3+ regulatory T cells (Treg) and expressions of transcription factor forkhead box protein 3 (Foxp3), cytotoxic T lymphocyte associated antigen-4 (CTLA4), glucocorticoid-induced tumor necrosis factor receptor (GITR), and Notch1 protein were evaluated by flow cytometry. Chromatin immunoprecipitation was conducted to detect acetylation level of histone H4 (H4Ac) associated with the promoter of Foxp3 gene and its binding abilities of Notch1 intracellular domain 1 (NICD1), recombination signal binding protein for immunoglobulin kappa J region (RBP-J) and p300 in CD4 + T cells. Transcription levels of Foxp3, presenilin 1 (PSEN1), mastermind like transcriptional coactivator 1 (MAML1), and RBP-J in CD4 + T cells were determined by real-time polymerase chain reaction (PCR). Concentrations of interleukin (IL)-10 and transforming growth factor-β (TGF-β) in plasma and culture supernatant stimulated with Jagged1 were measured by enzyme linked immunosorbent assay. Independent-sample t-test, Pearson correlation analysis was used as the statistical method in this study. Results:① The frequencies of Treg in acute KD patients decreased significantly [(4.3±1.5)% vs (7.9±2.9)%; t=6.41, P<0.001], as protein levels of Foxp3, CTLA4 and GITR and concentrations of IL-10 and TGF-β in plasma reduced remarkably in acute KD patients ( t=6.87, P<0.001; t=4.26, P<0.001; t=7.88, P<0.001; t=8.42, P<0.001; t=13.01, P<0.001). All parameters afore-mentioned in patients combined with coronary artery lesions (CAL) were lower than those of patients without coronary artery lesions (NCAL) ( t=5.83, P<0.001; t=3.83, P<0.001; t=3.28, P=0.002; t=5.05, P<0.001; t=5.96, P<0.001; t=5.17, P<0.001), and increased after therapy ( t=7.13, P<0.001; t=6.10, P<0.001; t=4.31, P<0.001; t=6.55, P<0.001; t=7.40, P<0.001; t=7.84, P<0.001). ② H4Ac associated with promoter of Foxp3 gene and the binding abilities of NICD1 and p300 in acute KD patients were lower than those of the controls ( t=10.25, P<0.001; t=6.93, P<0.001; t=6.75, P<0.001), and increased remarkably after therapy ( t=7.72, P<0.001; t=4.16, P<0.001; t=5.76, P<0.001). Meanwhile, the three items in CAL group were found to be less than those of NCAL group ( t=6.08, P<0.001; t=2.66, P=0.011; t=6.02, P<0.001). Pearson correlation analysis showed a positive correlation between H4Ac associated with Foxp3 promoter and its mRNA level in acute KD patients ( r=0.47, P<0.001). No statistical significant difference about the binding ability of RBP-J with Foxp3 promoter were found among the groups ( t=0.57, P>0.05; t=0.61, P>0.05; t=1.20, P>0.05). ③ Protein level of Notch1 and the expressions of PSEN1, MAML1 and RBP-J mRNA in CD4 + T cells from acute KD patients were down-regulated remarkably ( t=5.28, P<0.001; t=6.31, P<0.001; t=11.78, P<0.001; t=8.06, P<0.001), and restored after therapy ( t=4.77, P<0.001; t=6.43, P<0.001; t=11.95, P<0.001; t=7.79, P<0.001). In parallel, the four indexes aforementioned of CAL group were lower than those of NCAL group ( t=3.16, P=0.003; t=4.13, P<0.001; t=5.42, P<0.001; t=4.05, P<0.001). Upon rhJagged1 stimulation for 48 hours, H4Ac level of Foxp3 promoter and its binding abilities with NICD1 and p300 in CD4 + T cells in KD patients and control group was significantly higher than those of untreated group [(KD: t=15.36, P<0.001; t=7.25, P<0.001; t=14.29, P<0.001), (Ctrl: t=7.87, P<0.001; t=5.71, P<0.001; t=8.74, P<0.001)], as the binding ability of RBP-J with Foxp3 promoter increased slightly without statistically significant difference (KD: t=1.11, P>0.05; Ctrl: t=1.37, P>0.05). Simultaneously, H4Ac level of Foxp3 promoter and its binding abilities with NICD1 and p300 in KD group were still lower than those of the control group after stimulation ( t=3.86, P<0.001; t=3.42, P=0.001; t=2.85, P=0.006). ④ After incubation of PBMC from heathy children with KD serum, the proportion of Treg cells, protein level of Foxp3 and expressions of Notch1 and RBP-J in CD4 + T cells in the group treated with IVIG increased significantly compared with the untreated group ( t=7.10, P<0.001; t=10.16, P<0.001; t=8.06, P<0.001; t=9.77, P<0.001), as well as H4Ac level of Foxp3 promoter and its binding abilities with NICD1 in the group treat with IVIG were also higher than the latter ( t=7.24, P<0.001; t=8.24, P<0.001). Conclusion:Insufficiency and impaired function of Treg caused by aberrant Notch1 signaling may be the important factor contributing to immune dysfunction and vascular damage in KD.

Changes and significance of CD8 + CD28 - regulatory T cells in acute phase of Kawasaki disease / 中华微生物学和免疫学杂志

Objective:To investigate the changes of CD8 + CD28 - regulatory T cells (Treg) and its role in the pathogenesis of Kawasaki disease (KD). Methods:A total of 48 children with KD were enrolled in the present study from June 2019 to December 2021. Blood samples were collected from them during acute phage of KD and after intravenous immunoglobulin (IVIG) treatment. Another 32 age-matched healthy children were recruited as control group. The proportions of CD8 + CD28 -Treg cells and the expression of programmed cell death protein 1 (PD-1), factor associated suicide ligand (FasL), inducible T-cell co-stimulator ligand (ICOSL), CD80 and CD86 protein were evaluated by flow cytometry. The expression of Helios, perforin, granzyme B, immunoglobulin-like transcript 3 (ILT3) and ILT4 at the transcription level was measured by real-time PCR. Concentrations of IL-10 and TGF-β in the culture supernatants of CD8 + CD28 -Treg cells stimulated with activated CD4 + T cells were measured by ELISA. Results:⑴ The proportions of CD8 + CD28 -Treg cells and the expression of Helios in patients with acute KD were higher than those in the control group ( P<0.05), and reduced remarkably after IVIG therapy ( P<0.05). The two afore-mentioned indexes were lower in patients combined with coronary artery lesion (CAL) than in those without coronary artery lesion (NCAL) ( P<0.05). ⑵ Compared with the control group, the patients with acute KD showed increased expression of FasL, PD-1, ICOSL and perforin in CD8 + CD28 -Treg cells ( P<0.05). The concentrations of IL-10 and TGF-β1 in the culture supernatants of CD8 + CD28 -Treg cells from patients with acute KD were lower than those in the control group after stimulation with activated CD4 + T cells ( P<0.05), which restored to some extent after IVIG treatment ( P<0.05). All of the six above-mentioned indexes in the CAL group were found to be lower than those in the NCAL group ( P<0.05). There were slight differences in granzyme B expression between different groups ( P>0.05). (3) In comparison with the healthy controls, the patients with acute KD showed overexpressed co-stimulatory molecules such as CD80 and CD86 on CD14 + cells ( P<0.05) and up-regulated expression of inhibitory molecules ILT3 and ILT4 ( P<0.05), which were restored remarkably after IVIG treatment ( P<0.05). Furthermore, the expression of CD80 and CD86 at protein level increased in the CAL group than in the NCAL group ( P<0.05), while the expression of ILT3 and ILT4 at transcriptional level decreased in the CAL group ( P<0.05). Conclusions:Relative insufficiency and impaired function of CD8 + CD28 -Treg cells might be one of the important factors resulting in immune dysfunction and vascular damage in KD patients.

DSA study of the effect of vasopressin on the small bowel circulation before and after embolization / 介入放射学杂志

Objective To study the effect of vasopressin (VS) on the small bowel circulation and the safety of emboliotherapy for the small intestinal hemorrhage by DSA. Methods Ten dogs were divided into three groups. Vasa recta were ligated 30min after VS infusion ended in group A( n =4), and 2h after VS infusion ended in group B( n =4), they were ligated without VS infusion in control group ( n =2). DSA were performed before and after VS infusion, before and after the ligation. The tested parts of intestine were resected to make the pathologic examination a week late. Results All branches of mesenteric arteries contracted and the contrast developed light in the intestinal wall after VS infusion. Branches contraction recovered but the contrast developed still slight in the intestinal wall about 30min after infusion ended. All manifestation of DSA recovered to normal 2h after infusion ended. In all groups, the blood vessel net can be seen but is fewer and scattered in the area of ligation. The collorate presented soon after the ligation. The pathologic examination proved that there was only mind mucosal ischemia in all groups. Conclusion The repressive effect of VS to the circulation of intestine weakened and then disappeared rapidly after the infusion ended. VS infusion had no significant effect on the safety of emboliotherapy for small intestinal bleeding when the infusion has been finished for more than 2hr. DSA can demonstrated the circulation state of the intestine before and after embolization.