Objective:To investigate the effects of Leflunomide and Azathioprine on serum chemokine cx3cl1(fractalkine), cathepsin S and vascular cell adhesion molecule-1(VCAM-1)in elderly patients with lupus nephritis.Methods:Sixty elderly patients with lupus nephritis admitted to our hospital from January 2017 to July 2019 were selected as the research objects.Patients were divided into two groups by using a random number table method: the Leflunomide group(treated with Leflunomide plus conventional treatment)and the Azathioprine group(treated with azathioprine plus conventional treatment)(n=30, each group). Serum levels of fractalkine and cathepsin S and urine VCAM-1 level before and 6, 9 and 12 months after treatment were measured in the two groups and statistically analyzed.Results:In both groups, serum fractalkine levels were decreased after versus before treatment( F=123.029 and 99.041 respectively, P=0.000). At 6 months after treatment, serum fractalkine level was lower in the leflunomide group(2.34±0.95)μg/L than in the Azathioprine group(2.97±1.01)μg/L( t=2.489, P=0.016). Serum cathepsin S levels were decreased in both groups after treatment( F=106.733 and 64.928, P=0.000). Serum cathepsin S levels were lower in the Leflunomide group that in the azathioprine group at 6 and 9 months after treatment[(24.31±3.15)μg/L vs.(26.92±4.02)μg/L, (21.72±2.67)μg/L vs.(23.89±2.75)μg/L, t=2.799 and 3.101, P=0.007 and 0.003]. After treatment, urinary VCAM-1 levels were decreased in both two treatment groups( F=907.450 and 858.114, P=0.000). At 6 months after treatment, urine VCAM-1 level was lower in the Leflunomide group than in the Azathioprine group[(74.36±9.17)μg/L Cr vs.(86.91±9.22)μg/L Cr, t=5.286, P=0.000)]. The incidences of adverse reactions were low in the two groups, and the difference was not statistically significant. Conclusions:Leflunomide and Azathioprine can effectively reduce serum levels of fractalkine and cathepsin S and urinary VCAM-1 in elderly patients with lupus nephritis, which suggests that Leflunomide and Azathioprine have similar effects in inhibiting inflammatory reaction, cell matrix degradation and remodeling and vascular cell adhesion.But at early stage of therapy, the effect of Leflunomide was better than that of Azathioprine.And two drugs can be selected according to the specific clinical situation.

Objective:To investigate a classification on age of diagnosis and its clinical characteristics in hospitalized elderly patients with first diagnosed Crohn's disease.Methods:This was retrospective case-control study.A total of 181 newly diagnosed CD patients were admitted to Huadong Hospital from January 2005 to December 2019.According to Montreal CD classification criteria based on the age at the time of diagnosis(sub-grouping A3 into A3 and A4 in this paper), 181 CD patients were classified into four groups: the A1 group(≤16 years, n=4), A2 group(17-40 years, n=60)and A3 group(41-59 years, n=63)(above three as control groups), and the A4 group[≥60 years, with elder-onset Crhon's disease(EOCD), n=54]as a study group.Results:A total of 181 first diagnosed CD patients who met the diagnostic criteria were included in this study.During the investigation period, the total incidence rate of CD was 37.90/100, 000, and the total prevalence rate of CD was 142.79/100, 000.Among the 181 first diagnosed CD patients, there were 4 patients(2.2%)with age of diagnosis of ≤16 years(group A1), 60 patients(33.2%)with age of diagnosis of 16-40 years(A2), 63 patients(34.8%)with age of diagnosis of 41-59 years(A3)and 54 patients(29.8%)with age of diagnosis of ≥=60 years(A4). Of these first diagnosed CD patients, male were dominant in A2 group(51 males / 9 females), while the ratio of males and females tended to be the same(32 males /31 females)in A3 group, and the proportion of female patients was greater than that of male patients in A4 group(25 males /29 females)( P<0.0001). The main CD lesion was ileocolic type in the EOCD group, accounting for 57.4%( P=0.0077). The incidence rate of ileus type CD was 42.6%( P=0.1942). Among the 163 CD patients who underwent colonoscopy, under Simple Endoscopic Score for CD(SES-CD)evaluation, the proportion of SES-CD severity type in EOCD group was as high as 82.2%, which was higher than that in the A3 group(51.7%, P=0.0187). All CD patients underwent pathological examination.There were 173 cases(95.6%)with focal lymphocytic infiltration, 120 cases(66.3%)with inflammatory infiltration on the crypt epithelial and 82 cases(45.3%)with non-caseous granuloma tissue.In the EOCD group, non-caseous granuloma accounted for 61.1%, which was higher than that in the A3 and A2 groups( P=0.0318). In the EOCD group, the non-complication rate was 1.89%, and the incidence rates of 3, 4 and ≥5 complications were 14.8%, 22.2% and 24.1%, respectively( P<0.0001, P=0.0280, 0.0141 and 0.0013). The sulphasalazine(SASP)alone was the main treatment method, accounting for 42.6%( P=0.0038), and the surgery accounted for 24.1%( P=0.9598). Conclusions:The incidence and trend of EOCD are basically consistent with those of adult-onset CD and showed an rising volatility.Incidence rate of EOCD is higher in females than in males.EOCD lesions of visual observation under endoscope are serious.The detection rate of non-caseous granulomas and related scars is high under microscope.EOCD patients have many complications, and SASP alone is the main treatment method.

Objective To investigate the role of TLR4/NF-kB signaling pathway in inhibited invasion ability of pancreatic cancer cells caused by triptolide (TP).Methods PANC1 cells were divided into parental cells group,TP group,lipopolysaccharide (LPS) group and TP + LPS group.50 ng/ml of TP was added in culture medium in TP group,and 1 μg/ml of LPS was added in culture medium in LPS group,while 50 ng/ml of TP was pretreated for 2 h and 1 μg/ml of LPS was added in culture medium in TP + LPS group.All the ceils were cultured for 24 h.The TLR4 and matrix metalloproteinase-9 (MMP-9) mRNA and protein expression were evaluated by real-time PCR and Western blot.The NF-kB activity was determined by dual-luciferase reporter assay system.The invasion ability of pancreatic cancer cells was evaluated by transwell invasion chamberassay.Results The TLR4 mRNA expressions in parental cells group,TP group,LPS group and TP + LPS group were 0.41 ± 0.06,0.46 ± 0.10,0.20 ± 0.04,0.25 ± 0.06 ; the TLR4 protein expressions were 0.55 ±0.06,0.55 ±0.06,0.18 ±0.04,0.13 ±0.00; the activities of NF-kB were 13.0 ±3.0,31.6 ±4.3,7.3 ±1.5 and 10.8 ± 2.1,and the numbers of invasion cell were (56.8 ± 8.6),(104.5 ± 12.8),(32.0 ± 5.7) and (46.8 ± 7.0) ; the MMP-9 mRNA expressions were 0.36 ± 0.05,0.58 ± 0.07,0.18 ± 0.03,0.30 ± 0.004 ;the MMP-9 protein expressions were 0.31 ± 0.04,0.53 ± 0.08,0.11 ± 0.02,0.15 ± 0.00.In LPS group,TLR4 mRNA and protein expressions were not statistic significant when compared with those in parental cells group,but the activities of NF-kB,the numbers of invasion cell,MMP 9 mRNA and protein expressions were statistically increased when compared with those in parental cells group (t =8.654,7.593,6.655,4.982,P ＜0.01).TLR4 mRNA and protein expressions,activities of NF-kB,the numbers of invasion cell,MMP 9 mRNA and protein expressions in TP group were significantly lower than those in parental cells group (t =-7.609,-9.948,-4.176,-5.915,-8.179,-9.948,P＜ 0.01).TLR4 mRNA and protein expressions,activities of NF-kB,the numbers of invasion cell,MMP 9 mRNA and protein expressions in TP +LPS group were significantly lower than those in LPS group (t =-4.437,-14.805,-10.506,-9.700,-9.055,-8.932,P＜ 0.01).Conclusions TP can inhibit pancreatic cancer cell invasion,and the mechanism is related to the inhibition of TLR4/NF-kB signaling pathway and down-regulation of MMP-9 expression.

Objective To develop a stroke knowledge instrument for middle-aged and aged people in community general outpatient clinics.Methods A stroke knowledge measurement tool was developed and the reliability and validity of the tool were evaluated.The developed measurement tool was applied for patients aged 45 to 75 years old from 10 community health service centers of three Shanghai districts,and the knowledge scores of the target population were analyzed.Results A total of three dimensions and 14 items were made up of the stroke knowledge instrument.A total of 1 750 subjects,including 709 males and 1 041 females with an average age of (65.93±3.67) years,were included in the survey.The standardized Cronbach's coefficient was 0.742,and split-half correlation coefficient was 0.686 (P＜0.01) for instrument test performance.There was a positive correlation between the sub-instrument and the overall-instrument,and the correlation coefficient was 0.448-0.728 (P＜0.01) for content validity.The full score rate of overall stroke knowledge instrument was 8.46％(148/1 750),the full score rate for disease early symptomswas 46.00％(805/1 750),that for drug-related knowledge was 54.40％(95/1 750) and that for high risk factors was 17.94％(314/1 750).Logistic regression analysis showed that females,subjects with higher education level and married/cohabitation state had higher knowledge scores (P＜0.01).Conclusions The developed stroke knowledge instrument has good reliability and validity for the middle-aged and aged population of community general outpatient clinic.The stroke knowledge levels are less satisfactory for this study population.

Objective:To analyze the associations between sleep status and the risk for kidney stone in Chinese adults.Methods:This study used baseline and long-term follow-up data of China Kadoorie Biobank. After excluding those with self-reporting of diagnosed chronic kidney disease and cancer and those with extreme values of sleep duration at baseline survey, 501 701 participants were included in this study. The information about their sleep status were collected, including insomnia symptoms, daytime sleepiness, nap habit, snoring and sleep duration. The sleep score was constructed based on insomnia symptoms, daytime sleepiness, and sleep duration, ranging from 0 to 3. Cox proportional hazards regression models were used to evaluate the association of sleep status with the risk for kidney stone, including individual sleep factors and combined sleep score.Results:During the follow-up for average (10.7±2.2) years, 12 381 cases of kidney stone were recorded for the first time. Compared with participants without insomnia symptoms, the multivariable-adjusted HR of kidney stone in those with difficulty falling asleep and waking up early were 1.12 (95% CI: 1.06-1.18) and 1.06 (95% CI: 1.00-1.12), respectively. There was no statistically significant association of kidney stone risk with sleeping pill use, daytime sleepiness, nap habit, or snoring. Compared with participants with sleep duration ≥7 hours per day, the HR of kidney stone in those with sleep duration <7 hours per day was 1.13 (95% CI: 1.08-1.18). Compared with participants with sleep score of 3 (highest sleep quality), the HR of kidney stone in those with sleep score of 2, 1, and 0 were 1.08 (95% CI: 1.03-1.13), 1.16 (95% CI: 1.10-1.23), and 1.19 (95% CI: 1.03-1.37), respectively. Conclusion:In China, adults with insomnia symptoms or short sleep duration have increased risk for kidney stone.

Objective:To evaluate the associations of sociodemographic characteristics and lifestyle factors with longevity status in older adults in China.Methods:After excluding those born after 31 st December 1938, a total of 51 870 older adults from the China Kadoorie Biobank (CKB) were included. The attained age was defined according to the survival age or age on 31 st December 2018. According to the attained age, the old persons were categorized into non-longevity (died before age 80 years) and longevity (attained age ≥80 years). The longevity group was further divided into two groups: longevity with death occurring before 2019, and longevity and survival to 2019. The information about socio-demographic characteristics and lifestyles was collected at the 2004-2008 baseline survey. Multinomial logistic regression models were used to analyze the associations between exposure factors and outcomes by taking the non-longevity group as the reference group. Results:A total of 51 870 older adults aged 65-79 years in the baseline survey were included for analysis. During a follow-up for (10.2±3.5) years, 38 841 participants were longevity, and 30 354 participants still survived at the end of 2018. Compared to men, rural populations, non-married individuals, those with an annual household income of less than 10 000 yuan, and those with education levels of primary school or below, the adjusted ORs(95% CI) for longevity and survival to 2019 in women, urban residents, married individuals, those with annual household incomes ≥20 000 yuan, and those with education levels of college or university were 1.68 (1.58-1.78), 1.69 (1.61-1.78), 1.15 (1.10-1.21), 1.44 (1.36-1.53), and 1.32 (1.19-1.48), respectively. The OR (95% CI) for longevity and survival to 2019 was 1.09 (1.08-1.10) for those with an increase of 4 MET-hour/day in total physical activity level. With those who never or almost never smoked, had no alcohol drinking every week, had normal weight (BMI: 18.5-23.9 kg/m 2), and WC <85 cm (man)/<80 cm (woman) as the reference groups, the ORs(95% CI) of longevity and survival to 2019 were 0.64 (0.60-0.69) for those smoking ≥20 cigarettes per day, 1.29 (1.14-1.46) for those with alcohol drinking every week, 1.13 (1.01-1.26) for those with pure alcohol drinking <30 g per day, 0.56 (0.52-0.61) for those being underweight, 1.27 (1.19-1.36) for those being overweight, 1.23 (1.11-1.36) for those with obesity, and 0.86 (0.79-0.93) for those with central obesity. Further stratified analysis by WC was performed. In the older adults with WC <85 cm (man)/<80 cm (woman), the ORs (95% CI) of longevity and survival was 1.80 (1.69-1.92) for those with each 5 kg/m 2 increase in BMI and 1.02 (0.96-1.08) for those with WC ≥85 cm (man)/≥80 cm (woman). There was a statistically significant difference in the association between BMI and longevity between the two WC groups (interaction test P<0.001). Conclusion:This study showed that women, the married, those with higher socioeconomic status and education level, and those with healthy lifestyles were more likely to achieve longevity.

Objective To explore the mechanism of Yangxue Qingnao Granules(Siwu Decoction modified)in the treatment of hypertension based on network pharmacology and molecular docking.Methods The chemical composition analysis results of Yangxue Qingnao Granules in the early stage of the research group were used as the basis for the screening of active compounds.The oral bioavailability≥30%and drug-likeness≥0.18 were used as the screening conditions,and the blood components were supplemented in combination with the literature.TCMSP,chemical professional database and SWISS database were used to predict the targets of potential active compounds of Yangxue Qingnao Granules.Hypertension-related targets were obtained through GeneCards and DiGSeE databases.The intersection of the targets related to hypertension disease and the targets of the potential active compounds of Yangxue Qingnao Granules(common targets)is the potential target of Yangxue Qingnao Granules for the treatment of hypertension.The potential targets were matched with the potential active compounds of Yangxue Qingnao Granules to obtain the antihypertensive active compounds of Yangxue Qingnao Granules.PPI analysis was performed on the potential targets of serum brain granules in the treatment of hypertension through the STRING database,and the core targets were screened according to the degree value.The David database was used to analyze the GO function and KEGG pathway enrichment of the core targets.The core targets with the top six degrees were selected as the docking target proteins,and molecular docking verification was performed with the antihypertensive active compounds.Results A total of 32 potential active compounds,161 active compound targets and 1 539 hypertension-related targets were obtained.After intersection,88 potential targets(common targets)of Yangxue Qingnao Granules in the treatment of hypertension were obtained,involving 29 antihypertensive active compounds.PPI analysis screened 14 core targets:PPARG,ACHE,IL4,CCL2,JUN,NOS3,APP,IL1B,CAT,PTGS2,CASP3,TP53,TNF,IL6,involving 158 GO entries and 13 signaling pathways.Five key active ingredients,chlorogenic acid,rosmarinic acid,paeoniflorin catechinic acid and aloe emodin,were obtained by molecular docking,which were combined with PTGS2,CASP3,TNF,CAT,TP53 and IL6,respectively.Conclusion Yangxue Qingnao Granules may act on core targets such as PTGS2 and CASP3 through key active components such as chlorogenic acid and rosmarinic acid,regulate key pathways such as TNF signaling pathway,MAPK signaling pathway and Toll-like receptor signaling pathway,and play a role in the treatment of hypertension through anti-inflammatory effects.

ObjectiveTo investigate the role of silent information regulatory protein （SIRT6）/hypoxia-inducible factor-1α （HIF-1α） pathway in regulating the reprogramming of glucose metabolism in ulcerative colitis （UC） and the mechanism of intervention of Shaoyaotang. MethodsForty-eight c57bL/6 mice were randomly divided into a blank group， a model group， a Mesalazine group （0.42 g·kg^-1）， a Shaoyaotang group （31.08 g·kg^-1）， an inhibitor group （OSS-128167， 50 mg·kg^-1）， and an inhibitor + Shaoyaotang group （50 mg·kg^-1 OSS-128167 + 31.08 g·kg^-1 Shaoyaotang）. A UC model was established by the administration of 2.5% dextran sulfate sodium （DSS） solution for mice in other groups for 7 d， except for the blank group. The mice in each group were treated with saline， Mesalazine， Shaoyaotang， inhibitor， and inhibitor + Shaoyaotang， respectively， for 7 d. The mice were necropsied 24 h after the last administration of the drug. The blood was collected from the orbital region， and colon tissue was taken. Hematoxylin-eosin （HE） staining was used to observe the pathological changes in colon tissue. Enzyme-linked immunosorbent assay （ELISA） was employed to detect serum interleukin （IL）-10， IL-17， and IL-6 levels. A biochemical method was used to detect glucose and lactate dehydrogenase A （LDHA） levels. Immunohistochemistry （IHC） was employed to detect IL-22 and transforming growth factor-β₁ （TGF-β₁） levels in colon tissue， and Western blot and real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） were used to detect relative protein and mRNA expressions of SIRT6， HIF-1α， and LDHA. ResultsCompared with those of the blank group， disease activity index （DAI） scores of mice in the model group and inhibitor group were significantly increased （P<0.01）. The length of colon tissue was significantly shortened， and colon tissue was congested and eroded. The pathohistological scores were significantly increased （P<0.01）. The levels of serum inflammatory factors IL-17 and IL-6 were significantly elevated， and the levels of IL-10 were significantly decreased （P<0.01）. The protein expressions of IL-22 and TGF-β₁ were significantly reduced in colon tissue （P<0.01）. The relative protein and mRNA expressions of SIRT6 were significantly decreased （P<0.01）， and the relative protein and mRNA expressions of HIF-1α and LDHA and the contents of glucose and lactate were significantly elevated （P<0.01）. The level of inflammation in the colon of the mice in the inhibitor group was more severe than that in the model group （P<0.01）. Compared with the model group， the Mesalazine group， the Shaoyaotang group， and the inhibitor + Shaoyaotang group showed reduced colonic injury， significant decrease in serum IL-17 and IL-6， significant increase in IL-10 （P<0.01）， significant increase in the protein expressions of IL-22 and TGF-β₁ in colon tissue （P<0.01）， significant increase in the protein expressions of SIRT6 and the relative mRNA expressions （P<0.01）， and significant reduction in the protein expressions of HIF-1α and LDHA， the relative mRNA expressions， and the contents of glucose and lactate （P<0.01）. Compared with those in the Shaoyaotang group， the serum IL-17 and IL-6 were significantly increased， and IL-10 was significantly decreased in the inhibitor + Shaoyaotang group （P<0.01）. The protein expressions of IL-22 and TGF-β₁ in colon tissue were significantly decreased （P<0.01）. The expressions of SIRT6 protein and the relative mRNA expressions were significantly decreased （P<0.01）. The protein expressions of HIF-1α and LDHA， the relative mRNA expressions， and the contents of glucose and lactate were significantly elevated （P<0.01）. However， the difference between the Shaoyaotang group and the Mesalazine group was not significant. ConclusionShaoyaotang can effectively treat DSS-induced mice with UC through the SIRT6/HIF-1α pathway， and its mechanism of action may be related to the regulation of the SIRT6/HIF-1α pathway and glucose metabolism reprogramming and the inhibition of glycolysis.

ObjectiveTo investigate the role of silent information regulatory protein （SIRT6）/hypoxia-inducible factor-1α （HIF-1α） pathway in regulating the reprogramming of glucose metabolism in ulcerative colitis （UC） and the mechanism of intervention of Shaoyaotang. MethodsForty-eight c57bL/6 mice were randomly divided into a blank group， a model group， a Mesalazine group （0.42 g·kg^-1）， a Shaoyaotang group （31.08 g·kg^-1）， an inhibitor group （OSS-128167， 50 mg·kg^-1）， and an inhibitor + Shaoyaotang group （50 mg·kg^-1 OSS-128167 + 31.08 g·kg^-1 Shaoyaotang）. A UC model was established by the administration of 2.5% dextran sulfate sodium （DSS） solution for mice in other groups for 7 d， except for the blank group. The mice in each group were treated with saline， Mesalazine， Shaoyaotang， inhibitor， and inhibitor + Shaoyaotang， respectively， for 7 d. The mice were necropsied 24 h after the last administration of the drug. The blood was collected from the orbital region， and colon tissue was taken. Hematoxylin-eosin （HE） staining was used to observe the pathological changes in colon tissue. Enzyme-linked immunosorbent assay （ELISA） was employed to detect serum interleukin （IL）-10， IL-17， and IL-6 levels. A biochemical method was used to detect glucose and lactate dehydrogenase A （LDHA） levels. Immunohistochemistry （IHC） was employed to detect IL-22 and transforming growth factor-β₁ （TGF-β₁） levels in colon tissue， and Western blot and real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） were used to detect relative protein and mRNA expressions of SIRT6， HIF-1α， and LDHA. ResultsCompared with those of the blank group， disease activity index （DAI） scores of mice in the model group and inhibitor group were significantly increased （P<0.01）. The length of colon tissue was significantly shortened， and colon tissue was congested and eroded. The pathohistological scores were significantly increased （P<0.01）. The levels of serum inflammatory factors IL-17 and IL-6 were significantly elevated， and the levels of IL-10 were significantly decreased （P<0.01）. The protein expressions of IL-22 and TGF-β₁ were significantly reduced in colon tissue （P<0.01）. The relative protein and mRNA expressions of SIRT6 were significantly decreased （P<0.01）， and the relative protein and mRNA expressions of HIF-1α and LDHA and the contents of glucose and lactate were significantly elevated （P<0.01）. The level of inflammation in the colon of the mice in the inhibitor group was more severe than that in the model group （P<0.01）. Compared with the model group， the Mesalazine group， the Shaoyaotang group， and the inhibitor + Shaoyaotang group showed reduced colonic injury， significant decrease in serum IL-17 and IL-6， significant increase in IL-10 （P<0.01）， significant increase in the protein expressions of IL-22 and TGF-β₁ in colon tissue （P<0.01）， significant increase in the protein expressions of SIRT6 and the relative mRNA expressions （P<0.01）， and significant reduction in the protein expressions of HIF-1α and LDHA， the relative mRNA expressions， and the contents of glucose and lactate （P<0.01）. Compared with those in the Shaoyaotang group， the serum IL-17 and IL-6 were significantly increased， and IL-10 was significantly decreased in the inhibitor + Shaoyaotang group （P<0.01）. The protein expressions of IL-22 and TGF-β₁ in colon tissue were significantly decreased （P<0.01）. The expressions of SIRT6 protein and the relative mRNA expressions were significantly decreased （P<0.01）. The protein expressions of HIF-1α and LDHA， the relative mRNA expressions， and the contents of glucose and lactate were significantly elevated （P<0.01）. However， the difference between the Shaoyaotang group and the Mesalazine group was not significant. ConclusionShaoyaotang can effectively treat DSS-induced mice with UC through the SIRT6/HIF-1α pathway， and its mechanism of action may be related to the regulation of the SIRT6/HIF-1α pathway and glucose metabolism reprogramming and the inhibition of glycolysis.