The onset and progression of chronic heart failure （CHF） are closely associated with myocardial energy metabolism disorders， and this pathological process significantly affects patient prognosis. Traditional Chinese medicine （TCM）， grounded in time-based medical theories such as the correspondence between humans and nature and the theory of circadian flow of meridians （Ziwu Liuzhu）， exhibits intrinsic consistency with modern circadian rhythm theory， providing a unique theoretical framework for understanding and intervening in CHF from a temporal perspective. This article systematically explores the impact of circadian rhythms on energy metabolism and the potential mechanisms by which TCM active ingredients intervene in CHF through a review of relevant literature. It is found that various TCM active ingredients， including flavonoids （such as nobiletin）， alkaloids （such as berberine）， and polyphenols （such as resveratrol）， can improve mitochondrial function， promote fatty acid oxidation， enhance glucose uptake and utilization efficiency， maintain metabolic balance， and alleviate oxidative stress and inflammatory responses in myocardial cells by regulating the expression and rhythms of core circadian clock genes such as CLOCK， BMAL1， PER， and CRY. These actions thereby correct energy metabolism disorders and improve cardiac function. Further exploration of the interaction mechanisms between these components and the circadian rhythms holds promise for providing novel theoretical foundations and potential intervention strategies for the prevention and treatment of CHF.

Objective To investigate the diagnostic value of peripheral blood trimethylamine N-oxide(TMAO)combined with neutrophil-to-lymphocyte ratio(NLR)in patients with acute ische-mic stroke(AIS).Methods A total of 100 AIS patients were selected as study group,and 100 non-stroke study objects who underwent physical examinations during the same period were selected as con-trol group.Blood samples were collected from all participants,and plasma TMAO levels were meas-ured using high-performance liquid chromatography-tandem mass spectrometry.TMAO levels and NLR were compared between two groups,and Spearman correlation analysis,multivariate logistic regression analysis,and receiver operating characteristic(ROC)curve were applied to evaluate the diagnostic val-ue of TMAO and NLR in AIS.Results Compared with the control group,the AIS group had signifi-cantly higher TMAO levels and NLR(P＜0.05).Spearman correlation analysis indicated that TMAO and NLR were positively correlated with the occurrence of AIS(P＜0.05).Multivariate Logistic re-gression analysis revealed that age,TMAO,NLR,and hypertension were independent influencing fac-tors for the occurrence of AIS(P＜0.05).The ROC curve showed that the optimal cut-off values for TMAO and NLR in predicting AIS were 3.749 μmol/L and 2.210,respectively.The area under the curve for TMAO combined with NLR in predicting AIS was 0.902,which was higher than that of TMAO or NLR alone(0.808 and 0.801,respectively),and the Youden index for combined prediction was greater.Conclusion Peripheral blood TMAO and NLR are positively correlated with the occurrence of AIS,and the combination of TMAO and NLR can significantly improve the diagnostic efficacy of AIS,providing a basis for early clinical identification of AIS.

Cyperi Rhizoma is a common Chinese medicine in clinical practice， which has a long history of processing. In order to sort out the process of its processing， starting with the angle of processing excipients， the historical evolution and developmental venation of Cyperi Rhizoma processing were analyzed and summarized by consulting relevant literature of ancient medical records and modern codes. After combing the ancient and modern literature， it was found that there were many processing methods of Cyperi Rhizoma， the processing methods without auxiliary materials included frying， boiling， steaming and so on， and the adding auxiliary materials included vinegar， ginger， salt， multiple excipients， etc. However， with the evolution of history， some characteristic excipients have gradually disappeared， while vinegar-processed products are mainly used in modern times. Meanwhile， processing methods of Cyperi Rhizoma are well documented in various processing standards， the phenomenon of multiple methods adopted in one place and different methods in different places exists， which lacks unified quality standards and leads to uneven quality of Cyperi Rhizoma decoction pieces， which may even affect the safety and effectiveness of its clinical medication. Based on this， the problems existing in the processing research of Cyperi Rhizoma were analyzed in this paper， and made an outlook on the inheritance of the ancient processing methods and the quality standard improvement of the decoction pieces， in order to provide important literature evidence and theoretical support for the study of processing process and mechanism of Cyperi Rhizoma.

Objective:To explore the influencing factors of neutrophil to lymphocyte ratio (NLR) in patients with chronic heart failure (CHF) and the relationship between NLR and cardiac contractile function.Methods:From September 2016 to May 2018, 135 CHF patients were enrolled in the cardiovascular department of Fenyang hospital, Shanxi Province for prospective research.According to the level of NLR, the patients were divided into three groups: low NLR group (<2.3, 46 cases), middle NLR group (≥2.3~≤4.3, 45 cases), high NLR group (>4.3, 44 cases). The basic clinical data, laboratory examination data and noninvasive cardiac hemodynamic indexes of the three groups were compared.Results:(1) By comparing the data of different NLR groups, we found that there were significant differences in (N-terminal pro-brain natriuretic pepfide, NT-proBNP)( F=4.485, P=0.013), total bilirubin( F=6.085, P=0.003), albumin( F=3.695, P=0.027). (2)NLR was correlated with NT proBNP, total bilirubin, albumin( r=0.267, 0.256, -0.243, P=0.002, 0.003, 0.005, respectively). (3)Multiple linear regression analysis showed that NLR of CHF patients was correlated with left ventricular ejection fraction (LVEF), NT proBNP, total bilirubin and albumin (standard regression coefficients were -0.239, 0.223, 0.247 and -0.213, respectively, P<0.05). (4) Pearson correlation analysis showed that NLR and cardiac output ( r=-0.173, P=0.045), cardiac index ( r=-0.175, P=0.042), LVEF ( r=-0.278, P=0.001), maximum ejection velocity ( r=-0.207, P=0.016), systolic index ( r=-0.214, P=0.013), hearther index(HI) ( r=-0.179, P=0.038), cardiac work (CW) ( r=-0.235, P=0.006), cardiac workindex (CWI)=( r=-0.244, P=0.004) were negatively correlated. Conclusion:NT-proBNP, total bilirubin, albumin and LVEF are the factors that affect the NLR of patients with CHF.NLR has a certain value in the evaluation of CHF, therapeutic effect and prognosis prediction.

Objective To identify the threshold of percentage of body fat (BF％) associated with diabetes mellitus,hypertension and dyslipidemia in an elderly Chinese population.Methods An individual was considered as a subject if they exhibited any one of the three cardiovascular disease risk factors:diabetes mellitus,hypertension or dyslipidemia.A total of 1 140 subjects were recruited from the Physical Examination Center of Tianjin Hospital,China (male 511,female 629,aged ≥60 years).Questionnaire interview,physical examination,body composition measurement,blood biochemistry measurement,muscle strength measurement and other measurements were performed for each subject.Receiver operating curves (ROC) were created to determine the optimal percentage of body fat cutoff points,with the presence of diabetes mellitus,hypertension or dyslipidemia as outcome variable.Results The percentage of subjects with at least one of the following conditions (diabetes mellitus,hypertension or dyslipidemia) was 62.8％ for men and 73.9％ for women.Increased percentage of body fat was associated with an increased occurrence of diabetes mellitus,hypertension or dyslipidemia in the elderly,particularly among women.The ROC curve shows that the threshold of fat percentage in men and women was 28.2％ and 36.6％,respectively.Conclusion The risks of diabetes,hypertension and dyslipidemia is closely related to elevated body fat mass in the elderly.The percentage of body fat mass is an important indicator of obesity,threshold of BF ％ can provide reference for clinical obesity intervention in elderly patients.It also can provide reference for the treatment and prevention of cardiovascular disease.

Objective To compare theγpassing rate between measurements at actual degree gantry angle and zero degree gantry angle for dose verification of intensity?modulated radiotherapy ( IMRT) in the treatment of nasopharyngeal carcinoma ( NPC) and cervical carcinoma. Methods Thirty patients with NPC and thirty patients with cervical carcinoma were randomly chosen from 87 patients with NPC and 54 patients with cervical carcinoma, respectively. Using a gamma criterion of 3 mm/3%, the γ passing rates at actual gantry angle and zero degree gantry angle were measured using ArcCHECK and compared by paired t test. Results The γ passing rate was significantly lower at actual gantry angle than at zero degree gantry angle in patients with NPC or cervical carcinoma ((93.8±3. 6)% vs. (97.8±1. 1)%, P=0. 00;(96.3±2. 1)% vs. (98.2±1. 0)%, P=0. 00). Moreover, the variation range of the γ passing rate at actual gantry angle was larger than that at zero degree gantry angle. Bothγpassing rates at actual gantry angle and zero degree gantry angle were lower in the patients with NPC than in the patients with cervical carcinoma . Conclusions Compared with that at zero degree gantry angle, theγpassing rate at actual gantry angle is closer to reality. Therefore, the actual gantry angle is recommended for dose verification. In order to meet the clinical requirement, a higher standard of γ passing rate should be proposed when zero degree gantry angle is used for dose verification.

Objective To investigate the role of non-small cell lung cancer metastasis-related Trim72 gene in hepatocellular carcinoma (HCC) using clustered regularly interspaced short palindromic repeats (CRISPR) Cas9 system.Methods Hepa1-6 (Cas9) HCC cells were established with stable expression of Cas9 protein,and then specific gene knockout was performed using sgRNA targeting Trim72 gene.After obtaining the Hepa1-6 (Trim72-KO) cells,the metastasis and invasion abilities of the cells were evaluated by in vitro Transwell assay and in vivo subcutaneous lung metastasis examination.Results Hepa1-6 (Trim72-KO) cell line was successfully established by the CRISPR-Cas9 system.Transwell assay indicated that the mobility of Hepa1-6 (Trim72-KO) cells was increased compared to the control cells.Transwell assay indicated that the metastasis and invasion of Hepa1-6 (Cas9) HCC cells were enhanced after the knockout of Trim72 gene.The pathological examination of lung metastasis of subcutaneous tumor in vivo showed that the subcutaneously metastatic ability of Hepa1-6 (Trim72-KO) cells (the experimental group) was significantly stronger than Hepa1-6 (Cas9) cells (the control troup) that were not transferred to the corresponding sgRNA.Conclusions The trim72 gene knocked-out HCC cells were obtained by CRISPR-Cas9 system,which showed stronger metastasis and invasion abilities than the control cells.It is suggested that Trim72 gene may play an important role in the invasion and metastasis of HCC,and Trim 72 gene is expected to be a potential target for gene therapy of liver cancer.

Objective To investigate the effects and related mechanism of 5-aza-2'-deoxycytidine (Aza) on endothelial function in Hyperhomocysteinemia rats.Methods Adult male SD rats were divided into 3 groups (n =7 each):control group,hyperhomocysteinemia (HHcy) group and Aza group according to the random number table.Control group rats were fed with normal diet.HHcy group rats were fed with diet adding 3％ L-methionine.Aza group rats were fed with diet adding 3％ L-methionine and Aza (0.5 mg/kg) injection for consecutive three days per week for 8 weeks.After 8 weeks,content of rat plasma homocysteine (Hcy) was detected by enzyme linked immunosorbent assay (ELISA).The rat mesenteric artery endothelium-dependent diastolic function was detected.The nitric oxide synthase (eNOS) activity and asymmetric dimethyl fine ammonia acid (ADMA) content were detected by ELISA,and the content of nitric oxide was detected by nitrate reductase method in the mesenteric arteries.The mRNA expression of DNA methyl transferase 1 (DNMT1) and dimethyl arginine acid dimethylamine hydrolase 2 (DDAH2) in the mesenteric arteries were detected by real-time fluorescence quantitative PCR,and the protein expressions of DNMT1 and DDAH2 in the mesenteric arteries were detected by Western blot.The DDAH2 promoter methylation level in the mesenteric arteries was detected by nested methylation specific PCR.Results (1) The content of plasma Hcy was significantly higher in the HHcy group and Aza group compared to the control group ((29.00 ±0.94) μmol/L and (26.43 ±0.47) μmol/L vs.(10.34 ±0.63) μmol/L,both P ＜ 0.01),which was significantly reduced in the Aza group compared with the HHcy group (P ＜ 0.05).(2) Acetylcholine-mediated relaxation at various concentrations was significantly lower in the HHcy group and the Aza group compared with the control group (both P ＜ 0.05),which was significantly increased in Aza group compared with HHcy group (P ＜ 0.05).SNP-mediated relaxation at various concentrations was similar among the three groups(all P ＞0.05).(3) Compared with the control group,the content of nitric oxide in the HHcy group was significantly decreased ((0.52 ± 0.01) μmol/g vs.(0.42 ± 0.00) μmol/g,P ＜ 0.01),which could be increased by Aza((0.49 ± 0.01) μmol/g,P ＜ 0.05);the eNOS activity in the HHcy group was significantly decreased ((0.74 ± 0.01) U/mg vs.(0.57 ± 0.00) U/mg,P ＜ 0.01),which could be significantly increased by Aza ((0.65 ±0.01) U/mg,P ＜0.01);the content of ADMA in the HHcy group was significantly increased ((0.34 ± 0.01) μmol/g vs.(0.37 ± 0.00) μmol/g,P ＜ 0.05),which could be significantly decreased by Aza ((0.32 ± 0.01) μmo]/g,P ＜ 0.05).(4) Compared with the control group,the relative expression of DDHA2 mRNA in the HHcy group was significantly decreased (0.15 ±0.01 vs.0.12 s0.01,P ＜0.01),which could be significantly increased by Aza (0.13 ± 0.01,P＜ 0.05);the relative expression of DDHA2 protein in the HHcy group was significantly decreased (0.31 ± 0.02 vs.0.24 ± 0.01,P ＜ 0.01),which could be significantly increased by Aza (0.28 ± 0.01,P ＜ 0.01).Compared with the control group,the relative expression of DNMT1 mRNA in the HHcy group was significantly increased (0.23 ± 0.01 vs.0.43 ± 0.01,P ＜ 0.01),which could be significantly decreased by Aza (0.39 ±0.01,P ＜0.05);the relative expression of DNMT1 protein in the HHcy group was significantly increased (0.35 ±0.01 vs.0.50 ±0.01,P ＜0.01),which could be significantly decreased by Aza (0.47 ± 0.01,P ＜ 0.05).(5) Compared with the control group,the methylated/non methylated ratio of DDHA2 promoter in the HHcy group was significantly increased (1.04 ± 0.03 vs.1.26 ± 0.03,P ＜ 0.01),which could be significantly decreased by Aza (0.80 ± 0.03,P ＜ 0.01).Conclusion Aza can inhibit the activity of DNMT1,reduce DDAH2 promoter methylation level,increase the expression of DDAH2,decrease the content of ADMA,increase eNOS activity and content of nitric oxide,thus lead to the improvement of endothelial dysfunction in mesenteric artery of Hyperhomocysteinemia rats.

Objective To study the clinical significance of Raynaud phenomenon (RP) in systemic lupus erythematosus(SLE).Methods One hundred and twelve cases with SLE were divided into two groups according to the condition of RP and were analyzed retrospectively.The similarities and differences were investigated in system injury and laboratory examination in two groups.Results The occurrence rates of pulmonary arterial hypertension (PAH),interstitial lung disease (ILD),pericarditis,fatigue,pulmonary embolism (PE) and deep venous thrombosis (DVT) in patients with RP were higher than those in patients without RP [89.3％(25/28) vs.2.4％(2/84),57.1％(16/28) vs.16.7％(14/84),75.0％(21/28) vs.39.3％ (33/84),67.9％(19/28) vs.33.3％(28/84),21.4％(6/28) vs.4.8％(4/84),14.3％(14/28) vs.1.2％(1/84) ](P ＜ 0.05 ).The positive rates of anti-cardiolipin (ACL) antibody,anti-RNP antibody,anti-Sm antibody and LA in patients with RP were higher than those in patients without RP [46.4％(13/28) vs.9.5％(8/84),75.0％(21/28) vs.33.3％(28/84),57.1％(16/28) vs.23.8％(20/84),17.9％(5/28) vs.2.4％(2/84)] (P ＜0.05),while leucopenia in patients with RP was lower than that in patients without RP [7.1％(2/28) vs.45.2％ (38/84)] (P =0.001).Conclusion Heart,lung and vascular lesions such as PAH,ILD,pericarditis,PE and so on are easier to occur in SLE with RP,furthermore the positive rates of ACL,anti-RNP antibody,anti-Sm antibody,and LA are higher than those without RP.