AIM:To investigate the potential effect of Dabuyuan Jian(DBYJ)on peroxisome proliferator-acti-vated receptor γ(PPARγ)/nuclear factor-κB(NF-κB)signaling pathway and related inflammatory proteins in mice with mild cognitive impairment(MCI),and to explore the mechanism of DBYJ in improving the learning and memory ability of MCI mice.METHODS:Forty C57BL/6 male mice were randomly divided into 5 groups,including negative control(NC)group,D-galactose(D-Gal)group,D-Gal+DBYJ group,D-Gal+GW9662(PPARγ inhibitor)group and D-Gal+GW9662+DBYJ group,with 8 mice each.The mice in NC group were subcutaneously injected with 0.9%saline solution on the back of the neck for 8 weeks,while those in the remaining 4 groups were subcutaneously injected with D-Gal(100 mg·kg-1·d-1)on the back of the neck for 8 weeks to establish the MCI model.From week 5 to week 8,the mice in D-Gal+GW9662 and D-Gal+DBYJ+GW9662 groups were intraperitoneally injected with GW9662(1 mg·kg-1·d-1).From week 5,the mice in D-Gal+DBYJ and D-Gal+DBYJ+GW9662 groups were treated with DBYJ(13.2 g/kg)by gavage,while those in the re-maining 3 groups were administered an equal volume of purified water for 4 weeks.The Morris water maze(including posi-tioning navigation experiment and space exploration experiment)was used to assess the learning and memory ability of the mice.The structural integrity of the hippocampus of the mice was assessed by hematoxylin-eosin(HE)staining.Nissl staining was used to evaluate damage to hippocampal neurons in mice,and Western blot was applied to detect the protein levels of interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α),PPARγ,P65 and phosphorylated P65(p-P65)in the hippocampus of the mice.RESULTS:Compared with NC group,the escape latency of the mice in D-Gal+D-Gal and D-Gal+GW9662 groups significantly increased(P＜0.01),while the number of platform crossing and the duration of staying in the target quadrant within 60 s significantly decreased(P＜0.01).The number of neurons in the CA3 region remarkably decreased(P＜0.01),and pyramidal cell disarrangement and neuronal shrinkage were observed.The levels of TNF-α,IL-1β and p-P65 were up-regulated,while the expression of PPARγ was down-regulated(P＜0.05).Compared with D-Gal group,the escape latency of the mice in D-Gal+DBYJ group significantly decreased(P＜0.01),while the number of plat-form crossing and the duration of staying in the target quadrant within 60 s remarkably increased(P＜0.01).The number of neurons in the CA3 region increased(P＜0.01),the pyramidal cells were more neatly arranged,and the cytoarchitec-ture was intact.The levels of TNF-α,IL-1β and p-P65 were down-regulated,while the expression of PPARγ was up-regu-lated(P＜0.05).Compared with D-Gal+GW9662 group,significantly decreased escape latency was observed in D-Gal+DBYJ+GW9662 group(P＜0.01),and the number of platform crossing and the duration of staying in the target quadrant within 60 s remarkably increased(P＜0.05).The number of neurons in the CA3 region increased(P＜0.01),the pyrami-dal cells were arranged more neatly,and the cytoarchitecture was relatively intact.The levels of TNF-α,IL-1β and p-P65 were down-regulated,while the expression of PPARγ was up-regulated(P＜0.05).The effects shown in D-Gal+DBYJ+GW9662 group were inferior to those in D-Gal+DBYJ group,indicating that the therapeutic effect of DBYJ was inhibited after the addition of GW9662.CONCLUSION:Dabuyuan Jian improves the learning and memory ability of MCI mice,and the mechanism may be related to the expression of key proteins in the PPARγ/NF-κB signaling pathway.

Objective To explore the association between the ratio of red blood cell distribution width to albumin level(RAR)and the risk of non-valvular atrial fibrillation(NVAF)in patients with hyperuricemia.Methods A total of 8 277 patients with hyperuricemia who underwent physi-cal examinations at the Physical Examination Center of Northern Jiangsu People's Hospital from January 2021 to June 2024 were enrolled.From them,185 patients with AF were assigned into a case group,and 740 patients without AF were into a control group in a ratio of 1∶4 with propen-sity score matching(PSM).Logistic regression analysis,restricted cubic spline analysis,and sub-group analysis were employed to investigate the association between RAR and the risk of NVAF in hyperuricemic patients.Results The case group had significantly larger ratio of smoking,high-er levels of red blood cell distribution width,total bilirubin,hematocrit,and RAR index,but lower albumin,low-density lipoprotein cholesterol(LDL-C)and triglyceride(TG)levels,and smaller ra-tio of fatty liver than the control group(P＜0.01).Multivariate logistic regression analysis showed that the patients at Q2,Q3,and Q4 quartiles of RAR index have higher risk for AF than those at Q1 quartile(OR=2.843,OR=4.263,OR=7.801,P＜0.01).The effect of RAR index was significant when below the breakpoint of 2.85(OR=1.492,95％CI:1.151-1.993,P=0.004).Subgroup analysis indicated significant interactions between RAR index and age as well as smok-ing(P interaction＜0.05).The area under curve value of RAR index in predicting NVAF occurrence in male hyperuricemic patients was 0.679(95％CI:0.632-0.725).Conclusion In patients with hyperuricemia,a higher RAR index is associated with an increased risk of NVAF.RAR index has guiding significance for diagnosing male hyperuricemic patients complicated with AF.

Objective To explore the association between the ratio of red blood cell distribution width to albumin level(RAR)and the risk of non-valvular atrial fibrillation(NVAF)in patients with hyperuricemia.Methods A total of 8 277 patients with hyperuricemia who underwent physi-cal examinations at the Physical Examination Center of Northern Jiangsu People's Hospital from January 2021 to June 2024 were enrolled.From them,185 patients with AF were assigned into a case group,and 740 patients without AF were into a control group in a ratio of 1∶4 with propen-sity score matching(PSM).Logistic regression analysis,restricted cubic spline analysis,and sub-group analysis were employed to investigate the association between RAR and the risk of NVAF in hyperuricemic patients.Results The case group had significantly larger ratio of smoking,high-er levels of red blood cell distribution width,total bilirubin,hematocrit,and RAR index,but lower albumin,low-density lipoprotein cholesterol(LDL-C)and triglyceride(TG)levels,and smaller ra-tio of fatty liver than the control group(P＜0.01).Multivariate logistic regression analysis showed that the patients at Q2,Q3,and Q4 quartiles of RAR index have higher risk for AF than those at Q1 quartile(OR=2.843,OR=4.263,OR=7.801,P＜0.01).The effect of RAR index was significant when below the breakpoint of 2.85(OR=1.492,95％CI:1.151-1.993,P=0.004).Subgroup analysis indicated significant interactions between RAR index and age as well as smok-ing(P interaction＜0.05).The area under curve value of RAR index in predicting NVAF occurrence in male hyperuricemic patients was 0.679(95％CI:0.632-0.725).Conclusion In patients with hyperuricemia,a higher RAR index is associated with an increased risk of NVAF.RAR index has guiding significance for diagnosing male hyperuricemic patients complicated with AF.

AIM:To investigate the potential effect of Dabuyuan Jian(DBYJ)on peroxisome proliferator-acti-vated receptor γ(PPARγ)/nuclear factor-κB(NF-κB)signaling pathway and related inflammatory proteins in mice with mild cognitive impairment(MCI),and to explore the mechanism of DBYJ in improving the learning and memory ability of MCI mice.METHODS:Forty C57BL/6 male mice were randomly divided into 5 groups,including negative control(NC)group,D-galactose(D-Gal)group,D-Gal+DBYJ group,D-Gal+GW9662(PPARγ inhibitor)group and D-Gal+GW9662+DBYJ group,with 8 mice each.The mice in NC group were subcutaneously injected with 0.9%saline solution on the back of the neck for 8 weeks,while those in the remaining 4 groups were subcutaneously injected with D-Gal(100 mg·kg-1·d-1)on the back of the neck for 8 weeks to establish the MCI model.From week 5 to week 8,the mice in D-Gal+GW9662 and D-Gal+DBYJ+GW9662 groups were intraperitoneally injected with GW9662(1 mg·kg-1·d-1).From week 5,the mice in D-Gal+DBYJ and D-Gal+DBYJ+GW9662 groups were treated with DBYJ(13.2 g/kg)by gavage,while those in the re-maining 3 groups were administered an equal volume of purified water for 4 weeks.The Morris water maze(including posi-tioning navigation experiment and space exploration experiment)was used to assess the learning and memory ability of the mice.The structural integrity of the hippocampus of the mice was assessed by hematoxylin-eosin(HE)staining.Nissl staining was used to evaluate damage to hippocampal neurons in mice,and Western blot was applied to detect the protein levels of interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α),PPARγ,P65 and phosphorylated P65(p-P65)in the hippocampus of the mice.RESULTS:Compared with NC group,the escape latency of the mice in D-Gal+D-Gal and D-Gal+GW9662 groups significantly increased(P＜0.01),while the number of platform crossing and the duration of staying in the target quadrant within 60 s significantly decreased(P＜0.01).The number of neurons in the CA3 region remarkably decreased(P＜0.01),and pyramidal cell disarrangement and neuronal shrinkage were observed.The levels of TNF-α,IL-1β and p-P65 were up-regulated,while the expression of PPARγ was down-regulated(P＜0.05).Compared with D-Gal group,the escape latency of the mice in D-Gal+DBYJ group significantly decreased(P＜0.01),while the number of plat-form crossing and the duration of staying in the target quadrant within 60 s remarkably increased(P＜0.01).The number of neurons in the CA3 region increased(P＜0.01),the pyramidal cells were more neatly arranged,and the cytoarchitec-ture was intact.The levels of TNF-α,IL-1β and p-P65 were down-regulated,while the expression of PPARγ was up-regu-lated(P＜0.05).Compared with D-Gal+GW9662 group,significantly decreased escape latency was observed in D-Gal+DBYJ+GW9662 group(P＜0.01),and the number of platform crossing and the duration of staying in the target quadrant within 60 s remarkably increased(P＜0.05).The number of neurons in the CA3 region increased(P＜0.01),the pyrami-dal cells were arranged more neatly,and the cytoarchitecture was relatively intact.The levels of TNF-α,IL-1β and p-P65 were down-regulated,while the expression of PPARγ was up-regulated(P＜0.05).The effects shown in D-Gal+DBYJ+GW9662 group were inferior to those in D-Gal+DBYJ group,indicating that the therapeutic effect of DBYJ was inhibited after the addition of GW9662.CONCLUSION:Dabuyuan Jian improves the learning and memory ability of MCI mice,and the mechanism may be related to the expression of key proteins in the PPARγ/NF-κB signaling pathway.

Objective: To analysis the pathogenic mutation and the clinical characteristics of a three generation family with congenital pulverulent cataract. Methods: A congenital cataract family was chosen from the First Affiliated Hospital of AnHui Medical University, 5 ml peripheral blood was obtained from each family member to extract genomic DNA.Next generation sequencing was used to detect the mutation in proband (Ⅱ5), Ⅱ6 and Ⅲ8, and Sanger sequencing was applied to verify pathogenic mutation in the whole family members.The mutation site was compared with the gene sequence of 10 000 normal Chinese.PolyPhen-2 and SIFT were applied to analysis the alteration on the protein structure and function and its possible pathogenesis.This study followed the Declaration of Helsinki and was approved by the Ethics Committee of AnHui Medical University (NO.PJ2017-5-17). All patients signed informed consent. Results: The pedigree consisted of 19 members of three generations, including 10 patients and 9 normal family members.Heterozygous mutation of GJA3 gene c. 427G>A (p.G143R) was detected in all patients of the pedigree, but was not found in normal members of the pedigree and 10 000 normal Chinese.The score calculated from SIFT and PolyPhen-2 indicated that the mutation probably had malignant effect on normal protein structure, Swiss-model website analysis showed that the mutation likely altered the secondary structure of the protein CX 46 by reducing an α-helix between 107-115 amino acids.Meanwhile, c.1325-1G>T mutation of HSF4 gene were detected in Ⅱ5 and Ⅲ8, which was not found in other family members and 10 000 normal Chinese.HSF and MaxEntScan results showed that the mutation probably had serious effect on the splicing of mRNA.The cataract development rates of Ⅱ5 and Ⅲ8 were faster than that of the same age in the same generation of the pedigree, and the morphology of lens opacity was changed. Conclusions The heterozygous c. 427G>A mutation in GJA3 gene is responsible for pulverulent cataract in this family, meanwhile the c. 1325-1G>T mutation in HSF4 gene may change the type of phacoscotasmus and accelerate the progress of disease.

ObjectiveThe study is to investigate the predictive values of dosimetric parameters and patient related factors in severe acute radiation pneumonitis (SARP) after concurrent chemoradiotherapy in non-small cell lung cancer (NSCLC).Methods In all,147 NSCLC patients treated with concurrent chemotherapy and 3DCRT between 2006 and 2010 was collected.Independent sample t test was used to compare parameter values between patients with SARP and those without SARP.Logistic regression was used to identify significant determined factor.Predictive value of each parameter was tested by ROC analysis.Pearson correlation was used to analyze correlations between parameters.Represent factors were identified by factor analysis.ResultsThe incidence of SARP was 9.5％ ( 14/147 ).The means lung dose (MLD),V20,V30,V40,and V50 ( x2 =4.87 -6.84,P =0.009 -0.025,respectively ) were determining factors for SARP.Our datasets shows that for SARP ＜5％,MLD,V20,V30,V40 and V50 should be ≤16.77 Gy,V20≤34.15％,.V30 ≤23.62％,.V40 ≤ 18.57％,V50 ≤ 13.02％.ROC analysis show that areas under MLD,V20,V30,V40 and V50 curves was corresponding to 0.678,0.661,0.667,0.677,and 0.651,respectively.In addition,the sensitivity and specificity of each parameter at cutoff values are:78.0％ and 48.1％ for MLD;42.9％ and 82.0％ for V2o ;78.6％ and 52.9％ for V30 ;71.4％ and 61.7％ for V40,and 57.1％ and 67.7％ for V50.Factor analysis suggest that we can choose 1 or 2 parameters from MLD,V20,or V30,and another from V40 or V50 for predicting.The incidence of SARP was greater in patients with tumorsin right lower lung than other locations ( 22.2％ vs 6.7％,x2 =6.19,P =0.0 2 3 ).Conclusions The MLD,V20,V30,V40 and V50 are determining factors for SARP.As predictive value of each parameter alone is relatively week,using two or more parameters to predict SARP is recommended.