Objective To investigate the effect of the combination of Hyssop and White Peony on the nuclear factor E2-related factor-2(Nrf2)/heme oxygenase-1(HO-1)signaling pathway induced by the combination of NG-nitro-L-arginine methyl ester,hydrochloride(L-NAME)and Aconite in mice with hypertensive kidney injury and its therapeutic mechanism.Methods A total of 80 KM mice were randomly divided into blank group,model group and experimental A,B,C,D,E and F groups,with 10 mice per group.Except for the blank group,the remaining 7 groups were given aconite decoction+L-NAME by gavage to prepare a hypertensive kidney injury model.Experimental A,B,C,D,E,and F groups were given 6.83 g·kg-1·d-1 of different proportions of Hyssop-White Peony solution in different proportions with 5∶0,4∶1,3∶2,2∶3,1∶4,0∶5,respectively.Blank and model groups were given an equal volume of distilled water by gavage.All 8 groups of mice were intervened for 6 weeks.The blood pressure changes of mice in each group were compared;the levels of blood urea nitrogen(BUN)in serum and superoxide dismutase(SOD)in kidney tissue were detected by kit;and the expression of Nrf2 and HO-1 in kidney tissue was detected by immunohistochemistry.Results The systolic blood pressure levels of blank group,model group and experimental C,D groups were(99.56±4.13),(140.11±7.33),(106.23±8.41)and(105.97±6.43)mmHg;the blood urea nitrogen contents were(172.00±15.90),(352.64±17.23),(201.76±12.14)and(192.72±12.77)μg·mL-1;BUN contents were(232.14±8.58),(165.44±6.17),(205.06±5.34)and(182.94±9.91)μg·mL-1;the expression levels(optical density)of Nrf2 were 2.06±0.14,2.25±0.22,2.63±0.22 and 2.83±0.21;the expression levels(optical density)of HO-1 were 2.18±0.12,2.25±0.10,2.64±0.16 and 2.65±0.28,respectively.The above indexes in experimental C and D groups were statistically significant compared with those of the model group(all P＜0.01).Conclusion Hyssop and White Peony can enhance the ability of L-NAME and Aconite to resist oxidative stress in mice with hypertensive kidney injury induced by the combination of Nrf2/HO-1 pathway,and inhibit the process of apoptosis of kidney cells caused by kidney injury caused by hypertension,thereby exerting its protective effect on the kidney.

Objective To investigate the effect of the combination of Hyssop and White Peony on the nuclear factor E2-related factor-2(Nrf2)/heme oxygenase-1(HO-1)signaling pathway induced by the combination of NG-nitro-L-arginine methyl ester,hydrochloride(L-NAME)and Aconite in mice with hypertensive kidney injury and its therapeutic mechanism.Methods A total of 80 KM mice were randomly divided into blank group,model group and experimental A,B,C,D,E and F groups,with 10 mice per group.Except for the blank group,the remaining 7 groups were given aconite decoction+L-NAME by gavage to prepare a hypertensive kidney injury model.Experimental A,B,C,D,E,and F groups were given 6.83 g·kg-1·d-1 of different proportions of Hyssop-White Peony solution in different proportions with 5∶0,4∶1,3∶2,2∶3,1∶4,0∶5,respectively.Blank and model groups were given an equal volume of distilled water by gavage.All 8 groups of mice were intervened for 6 weeks.The blood pressure changes of mice in each group were compared;the levels of blood urea nitrogen(BUN)in serum and superoxide dismutase(SOD)in kidney tissue were detected by kit;and the expression of Nrf2 and HO-1 in kidney tissue was detected by immunohistochemistry.Results The systolic blood pressure levels of blank group,model group and experimental C,D groups were(99.56±4.13),(140.11±7.33),(106.23±8.41)and(105.97±6.43)mmHg;the blood urea nitrogen contents were(172.00±15.90),(352.64±17.23),(201.76±12.14)and(192.72±12.77)μg·mL-1;BUN contents were(232.14±8.58),(165.44±6.17),(205.06±5.34)and(182.94±9.91)μg·mL-1;the expression levels(optical density)of Nrf2 were 2.06±0.14,2.25±0.22,2.63±0.22 and 2.83±0.21;the expression levels(optical density)of HO-1 were 2.18±0.12,2.25±0.10,2.64±0.16 and 2.65±0.28,respectively.The above indexes in experimental C and D groups were statistically significant compared with those of the model group(all P＜0.01).Conclusion Hyssop and White Peony can enhance the ability of L-NAME and Aconite to resist oxidative stress in mice with hypertensive kidney injury induced by the combination of Nrf2/HO-1 pathway,and inhibit the process of apoptosis of kidney cells caused by kidney injury caused by hypertension,thereby exerting its protective effect on the kidney.

Humans ; Mycobacterium tuberculosis/genetics* ; Microspheres ; Antitubercular Agents/pharmacology* ; Mutation ; Microbial Sensitivity Tests ; Fluoroquinolones ; Drug Resistance, Bacterial/genetics* ; Tuberculosis, Multidrug-Resistant/microbiology*

Objective: Compare and analyze the results of the domestic Lanyi AH600 glycated hemoglobin analyzer and other different detection systems to understand the comparability of the detection results of different detectors, and establish the best cut point of Lanyi AH600 determination of haemoglobin A1c (HbA1c) in the diagnosis of diabetes. Methods: Multi center cohort study was adopted. The clinical laboratory departments of 18 medical institutions independently collected test samples from their respective hospitals from March to April 2022, and independently completed comparative analysis of the evaluated instrument (Lanyi AH600) and the reference instrument HbA1c. The reference instruments include four different brands of glycosylated hemoglobin meters, including Arkray, Bio-Rad, DOSOH, and Huizhong. Scatter plot was used to calculate the correlation between the results of different detection systems, and the regression equation was calculated. The consistency analysis between the results of different detection systems was evaluated by Bland Altman method. Consistency judgment principles: (1) When the 95% limits of agreement (95% LoA) of the measurement difference was within 0.4% HbA1c and the measurement score was≥80 points, the comparison consistency was good; (2) When the measurement difference of 95% LoA exceeded 0.4% HbA1c, and the measurement score was≥80 points, the comparison consistency was relatively good; (3) The measurement score was less than 80 points, the comparison consistency was poor. The difference between the results of different detection systems was tested by paired sample T test or Wilcoxon paired sign rank sum test; The best cut-off point of diabetes was analyzed by receiver operating characteristic curve (ROC). Results: The correlation coefficient R² of results between Lanyi AH600 and the reference instrument in 16 hospitals is≥0.99; The Bland Altman consistency analysis showed that the difference of 95% LoA in Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180) was -0.486%-0.325%, and the measurement score was 94.6 points (473/500); The difference of 95% LoA in the Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant II) was -0.727%-0.612%, and the measurement score was 89.8 points; The difference of 95% LoA in the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT) was -0.231%-0.461%, and the measurement score was 96.6 points; The difference of 95% LoA in the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT) was -0.469%-0.479%, and the measurement score was 91.9 points. The other 14 hospitals, Lanyi AH600, were compared with 4 reference instrument brands, the difference of 95% LoA was less than 0.4% HbA1c, and the scores were all greater than 95 points. The results of paired sample T test or Wilcoxon paired sign rank sum test showed that there was no statistically significant difference between Lanyi AH600 and the reference instrument Arkray HA8180 (Z=1.665,P=0.096), with no statistical difference. The mean difference between the measured values of the two instruments was 0.004%. The comparison data of Lanyi AH600 and the reference instrument of all other institutions had significant differences (all P<0.001), however, it was necessary to consider whether it was within the clinical acceptable range in combination with the results of the Bland-Altman consistency analysis. The ROC curve of HbA1c detected by Lanyi AH600 in 985 patients with diabetes and 3 423 patients with non-diabetes was analyzed, the area under curve (AUC) was 0.877, the standard error was 0.007, and the 95% confidence interval 95%CI was (0.864, 0.891), which was statistically significant (P<0.001). The maximum value of Youden index was 0.634, and the corresponding HbA1c cut point was 6.235%. The sensitivity and specificity of diabetes diagnosis were 76.2% and 87.2%, respectively. Conclusion: Among the hospitals and instruments currently included in this study, among these four hospitals included Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180), Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant Ⅱ), the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT), and the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT), the comparison between Lanyi AH600 and the reference instruments showed relatively good consistency, while the other 14 hospitals involved four different brands of reference instruments: Arkray, Bio-Rad, DOSOH, and Huizhong, Lanyi AH600 had good consistency with its comparison. The best cut point of the domestic Lanyi AH600 for detecting HbA1c in the diagnosis of diabetes is 6.235%.
Pregnancy ; Child ; Humans ; Female ; Glycated Hemoglobin ; Cohort Studies ; Diabetes Mellitus/diagnosis* ; Sensitivity and Specificity ; ROC Curve

Purpose: Capecitabine is an extensively used oral prodrug of 5-fluorouracil in treatment of colon cancer and is known to cause hand-foot syndrome (HFS). As the target enzyme for capecitabine, thymidylate synthase (TYMS) plays a key role for 5-fluorouracil metabolism and has been associated with some side effects caused by capecitabine. The aim of our study is to identify the possible genetic predictors of capecitabine-induced HFS (CAP-HFS) in Chinese colorectal cancer patients. Materials and Methods: Whole exons of TYMS were sequenced for 288 extreme phenotype HFS patients, including 144 severe or early-onset (first 2 cycles) moderate HFS extreme cases and 144 extreme controls with no reported HFS. The associations between polymorphisms and CAP-HFS were analyzed using logistic regression under an additive model. Results: We identified a novel risk mutation (c.1A>G, chr18:657743), was associated with severe HFS in an extreme case who was affected during the first cycle of treatment. Moreover, we identified three new variants, rs3786362, rs699517, rs2790, and two previously reported variants, 5’VNTR 2R/3R and 3′-untranslated region 6-bp ins-del, which were significantly associated with CAP-HFS (p < 0.05). In silico analysis revealed that the effect of these polymorphisms in the TYMS region on the development of HFS might not be restricted solely to the regulation of TYMS expression, but also the TYMS catalytic activity through the indirect effect on ENOSF1 expression. Conclusion This study identified new polymorphisms in TYMS gene significantly associated with CAP-HFS, which may serve as useful genetic predictors for CAP-HFS and help to elucidate the underlying mechanism of HFS.

Purpose: Capecitabine is an extensively used oral prodrug of 5-fluorouracil in treatment of colon cancer and is known to cause hand-foot syndrome (HFS). As the target enzyme for capecitabine, thymidylate synthase (TYMS) plays a key role for 5-fluorouracil metabolism and has been associated with some side effects caused by capecitabine. The aim of our study is to identify the possible genetic predictors of capecitabine-induced HFS (CAP-HFS) in Chinese colorectal cancer patients. Materials and Methods: Whole exons of TYMS were sequenced for 288 extreme phenotype HFS patients, including 144 severe or early-onset (first 2 cycles) moderate HFS extreme cases and 144 extreme controls with no reported HFS. The associations between polymorphisms and CAP-HFS were analyzed using logistic regression under an additive model. Results: We identified a novel risk mutation (c.1A>G, chr18:657743), was associated with severe HFS in an extreme case who was affected during the first cycle of treatment. Moreover, we identified three new variants, rs3786362, rs699517, rs2790, and two previously reported variants, 5’VNTR 2R/3R and 3′-untranslated region 6-bp ins-del, which were significantly associated with CAP-HFS (p < 0.05). In silico analysis revealed that the effect of these polymorphisms in the TYMS region on the development of HFS might not be restricted solely to the regulation of TYMS expression, but also the TYMS catalytic activity through the indirect effect on ENOSF1 expression. Conclusion This study identified new polymorphisms in TYMS gene significantly associated with CAP-HFS, which may serve as useful genetic predictors for CAP-HFS and help to elucidate the underlying mechanism of HFS.

Objective To study the effects of selecting different fixing segments on biomechanical characteristics of the spine during the treatment of early onset scoliosis（EOS） by growing rod technique. Methods By using finite element method, four spine models (C6-S1 segments) fixed by growing rod were established: preoperative model, T1-L4 fixed model, T2-L4 fixed model, T3-L4 fixed model. Then 7 N·m torque load and 1 rad angular displacement load were applied on superior surface of C6 segment to analyze biomechanical characteristics for adjacent structure of the fixed vertebral body. Results The whole spinal range of motion (ROM) decreased significantly after operation. When the T2-L4 segment was fixed, the spine activity was mostly restricted, the compensatory activity of adjacent vertebrae increased significantly, and the intervertebral disc stress increased significantly. Conclusions When T2 segment is selected as the upper instrumented segment, the risk of proximal junctional kyphosis and spinal degeneration is the highest, which should be avoided in clinical surgery.

Osteoarthritis(OA) is a common clinical disease. The incidence of OA increases significantly with age, and the quality of life of patients is seriously affected. In the pathogenesis of OA, cartilage degeneration is the main cause. There are many long non-coding RNA (lncRNA) specifically expressed in osteoarthritis, which is closely related to the occurrence and development of osteoarthritis. Based on the latest research from 2014 to 2019, this paper summarizes the differential expression of lncRNA in osteoarthritis, the mechanism of lncRNA regulating chondrocyte function, and the mechanism of lncRNA regulating cartilage matrix metabolism. The fact that the expression of lncRNA is altered at different stages of OA development indicates that lncRNA can be developed forlife. The biomarkers and therapeutic targets can provide reference for the prevention, treatment and research of osteoarthritis.
Chondrocytes ; Humans ; Osteoarthritis/genetics* ; Quality of Life ; RNA, Long Noncoding/genetics* ; Research

Objective To investigate whether elevated baseline levels of high sensitivity C-Reactive Protein (hsCRP) and neutrophil (NE) are associated with an increased risk of breast cancer in Kailuan female cohort. Methods Females from Kailuan cohort (2006-2007) were included in this study. Information on check-up, hsCRP and NE were collected at baseline for all subjects. Multivariable Cox proportional hazards regression models were used to calculate hazard ratios (HR) and 95% confidence intervals (95%CI) of association between baseline hsCRP and NE values and breast cancer risk. Results By December 31, 2015, a total of 18 866 participants were enrolled in this study. During the follow-up, 183 new cases of breast cancer were observed. All participants were divided into three groups according to the level of hsCRP (<1 mg/L, 1-3 mg/L and >3 mg/L). The cumulative incidence of breast cancer were 829/105, 1 211/105 and 1 495/105 in these 3 groups, respectively ( 2=12.08， P=0.002). Compared with participants with lower hsCRP levels (<1 mg/L), individuals with the highest hsCRP (>3 mg/L) levels had significantly increased risk of breast cancer (HR=1.71,95%CI: 1.18-2.47, P=0.005), howerver, we didn’t find the statistically significant association between NE level (<3.70×109/Lvs. ≥3.70×109/L) and the risk of brease cancer (P>0.05). Conclusions Elevated levels of hsCRP at baseline might increase the risk of breast cancer in females.

Background:Clinical outcomes of undifferentiated arthritis (UA) are diverse,and only 40 ％ of patients with UA develop rheumatoid arthritis (RA) after 3 years.Discovering predictive markers at disease onset for further intervention is critical.Therefore,our objective was to analyze the clinical outcomes of UA and ascertain the predictors for RA development.Methods:We performed a prospective,multi-center study from January 2013 to October 2016 among Chinese patients diagnosed with UA in 22 tertiary-care hospitals.Clinical and serological parameters were obtained at recruitment.Follow-up was undertaken in all patients every 12 weeks for 2 years.Predictive factors of disease progression were identified using multivariate Cox proportional hazards regression.Results:A total of 234 patients were recruited in this study,and 17 (7.3％) patients failed to follow up during the study.Among the 217 patients who completed the study,83 (38.2％) patients went into remission.UA patients who developed RA had a higher rheumatoid factor (RF)-positivity (42.9％ vs.16.8％,x2=8.228,P=0.008),anti-cyclic citrullinated peptide (CCP) antibodypositivity (66.7％ vs.10.7％,x2 =43.897,P ＜ 0.001),and double-positivity rate of RF and anti-CCP antibody (38.1％ vs.4.1％,x2 =32.131,P ＜ 0.001) than those who did not.Anti-CCP antibody but not RF was an independent predictor for RA development (hazard ratio 18.017,95％ confidence interval:5.803-55.938;P ＜ 0.001).Conclusion:As an independent predictor of RA,anti-CCP antibody should be tested at disease onset in all patients with UA.