The relationship between exercise and cardiac health has always been a hotspot in the fields of medicine and exercise science. Recently, with the in-depth study of the biological clock, people have gradually realized the close relationship between cardiac metabolic activity and circadian rhythms. The mammalian circadian system includes the central circadian clock and peripheral circadian clocks, the central circadian clock is the main clock system responsible for regulating the circadian rhythms in organisms, located in the suprachiasmatic nucleus (SCN) of the hypothalamus in mammals, which receives light signals from the retina and translates them into neural signals to regulate peripheral circadian clocks distributed throughout the body. Peripheral circadian clocks exist in various tissues and organs of organisms, coordinating with the central circadian clock to maintain the circadian rhythms of the organism. A series of clock genes regulate downstream clock-controlled genes through the transcriptional-translational feedback loop (TTFL), profoundly affecting the physiological activities of the heart, including cardiac contraction, relaxation, and metabolic processes. Factors such as sleep disorders, shift work, light pollution, and excessive use of electronic devices in modern lifestyles have led to widespread disruption of circadian rhythms, which are significantly correlated with increased cardiovascular disease incidence and mortality. Studies have found that dysregulation of the cardiac circadian clock can not only lead to myocardial lipid degeneration and weakened metabolic rhythms but also decrease myocardial glucose utilization, thereby increasing the risk of adverse cardiac events. Exercise, as a key zeitgeber, has been widely demonstrated to regulate the circadian clocks of peripheral organs such as skeletal muscle, kidneys, and liver. Additionally, exercise, as an important means to improve cardiovascular function, can effectively enhance cardiac metabolic function and resistance to stress stimuli, playing a significant role in promoting heart health. However, the specific mechanisms by which exercise affects the cardiac circadian clock and its related genes are currently unclear. Therefore, this review will focus on the relationship between the cardiac circadian clock and cardiac metabolic activity, summarize previous research to review the possible mechanisms of exercise-mediated regulation of cardiac metabolic activity on the cardiac circadian clock. The cardiac circadian clock plays an important role in maintaining cardiac metabolic activity and physiological functions. The loss of cardiac circadian clock genes Bmal1 and Clock can significantly reduce cardiac fatty acid and glucose utilization rates, increase myocardial lipotoxicity, weaken the circadian rhythm of myocardial triglyceride metabolism, and lead to abnormalities in the circadian clocks of other peripheral organs. Exercise, as a zeitgeber, can independently regulate the cardiac circadian clock apart from the central circadian clock. Additionally, exercise, as an important means to improve cardiovascular function, may regulate cardiac metabolic activity and the transcription of clock genes by activating the hypothalamic-pituitary-adrenal axis (HPA) and sympathetic-adrenal-medullary axis (SAM) and regulating energy metabolism, thereby maintaining the stability of the cardiac circadian clock and promoting heart health. Future research on the molecular mechanisms of exercise regulation of the cardiac circadian clock will help clarify the role and impact of clock genes in cardiac metabolism and physiological activities, providing new preventive and treatment strategies for shift workers, night owls, and patients with cardiovascular diseases. Therefore, future research should focus on (1) the mechanisms by which exercise regulates cardiac metabolic activity and the circadian clock, (2) the effects and mechanisms of exercise on the disruption of cardiac circadian clock induced by light-dark cycle disturbances, and (3) the effects of exercise on the metabolic activity and circadian rhythms of other peripheral organs regulated by the cardiac circadian clock.

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

Objective: Systematically summarize the research progress of clinical trials of gastric cancer oncology drugs and the overview of marketed drugs in China from 2012 to 2021, providing data and decision-making evidence for relevant departments. Methods: Based on the registration database of the drug clinical trial registration and information disclosure platform of Food and Drug Administration of China and the data query system of domestic and imported drugs, the information on gastric cancer drug clinical trials, investigational drugs and marketed drugs from January 1, 2012 to December 31, 2021 was analyzed, and the differences between Chinese and foreign enterprises in terms of trial scope, trial phase, treatment lines and drug type, effect and mechanism studies were compared. Results: A total of 114 drug clinical trials related to gastric tumor were registered in China from 2012 to 2021, accounting for 3.7% (114/3 041) of all anticancer drug clinical trials in the same period, the registration number showed a significant growth rate after 2016 and reached its peak with 32 trials in 2020. Among them, 85 (74.6%, 85/114) trials were initiated by Chinese pharmaceutical enterprise. Compared with foreign pharmaceutical enterprise, Chinese pharmaceutical enterprise had higher rates of phase I trials (35.3% vs 6.9%, P=0.001), but the rate of international multicenter trials (11.9% vs 67.9%, P<0.001) was relatively low. There were 76 different drugs involved in relevant clinical trials, of which 65 (85.5%) were targeted drugs. For targeted drugs, HER2 is the most common one (14 types), followed by PD-1 and multi-target VEGER. In the past ten years, 3 of 4 marketed drugs for gastric cancer treatment were domestic and included in the national medical insurance directory. Conclusions: From 2012 to 2021, China has made some progress in drug research and development for gastric carcinoma. However, compared with the serious disease burden, it is still insufficient. Targeted strengthening of research and development of investment in many aspects of gastric cancer drugs, such as new target discovery, matured target excavating, combination drug development and early line therapy promotion, is the key work in the future, especially for domestic companies.
China ; Gastrointestinal Agents/therapeutic use* ; Gastrointestinal Neoplasms ; Humans ; Pharmaceutical Preparations ; United States ; United States Food and Drug Administration

In this study, we investigated the pharmacological effect and possible molecular mechanism of higenamine (HG) in isoproterenol (ISO)-induced myocardial infarction (MI). All procedures were approved by the Institutional Animal Care and Use Committee of the Guangzhou University of Chinese Medicine. ISO was used to induce MI model in rats and H9c2 cells. The effects of HG on biomarkers and cardiac function in MI rats were evaluated by enzyme linked immunosorbent assay (ELISA), echocardiography and hematoxylin-eosin staining (HE). The expression of apoptosis and autophagy related proteins were detected by Western blot in myocardial tissue and H9c2 cells, as well as methyltransferase-like 3 (METTL3) and transcription factor EB (TFEB) protein expression. Molecular docking was used to evaluate the interaction between HG and METTL3. The results showed that HG significantly improved cardiac function and pathologic changes in ISO-induced MI, and inhibited the levels of MI-related biomarkers such as creatine kinase Mb (CK-MB), creatine kinase (CK) and lactate dehydrogenase (LDH). Mechanism studies showed that HG inhibited the expression of apoptosis-related proteins (Bax/Bcl2, caspase3, cleaved-caspase3). Interestingly, HG up-regulated the expression of autophagy related protein Beclin1, promoted autophagy flux, and decreased the ratio of light chain 3B-I/light chain 3B-II (LC-3B-I/LC-3B-II). Further studies found that HG increased the autophagy regulator TFEB and inhibited METTL3 expression. Molecular docking results showed that HG had a good interaction with METTL3. Taken together, HG has a potential anti-MI effect via regulating METTL3/TFEB signaling pathway-mediated autophagy.

Traditional Chinese medicine （TCM） and western medicine have their respective advantages and limitations in the diagnosis and treatment of common otorhinolaryngology head and neck diseases. Although the integrated TCM and western medicine exhibits definite curative effects， there is no consensus on the otorhinolaryngology head and neck diseases responding specifically to TCM or integrated TCM and western medicine， as well as the diagnosis and treatment schemes. The China Association of Chinese Medicine （CACM） thus organized the otorhinolaryngology head and neck specialists of both TCM and western medicine to discuss the etiology， pathogenesis， and clinical diagnosis and treatment methods of common otorhinolaryngology head and neck diseases with the results of multiple clinical trials taken into account. The acute pharyngitis， chronic pharyngolaryngitis， paraesthesia pharyngis， hysterical aphasia， allergic rhinitis， subjective tinnitus， and otogenic vertigo were confirmed to respond specifically to TCM or integrated TCM and western medicine. Then a mutually agreed diagnosis and treatment scheme and recommendation with integrated TCM and western medicine was formulated as a reference for clinical practice， thus benefiting more patients.

Objective The aim of this study was to investigate associations of overall obesity (OO) and abdominal obesity (AO) with brachial-ankle pulse wave velocity (baPWV) among type 2 diabetes(T2DM) patients. Methods A community-based study for T2DM patients was conducted in rural communities in Beijing．Every patient completed a questionnaire to collect demography, lifestyle and diseases history, and underwent physical examinations, baPWV assessments and blood biochemical tests. Multivariate linear regression was used to assess the relationship between obesity index and baPWV. Abnormal baPWV was defined as patients with baPWV≥1,700 cm/s. Logistic regression model was performed to explore the risk of abnormal baPWV after adjusting for poetential confounders step by step. Results A total of 2 048 T2DM patients were recruited. The average age was (59.2±8.3) years and total prevalence of abnormal baPWV was 49.7%. After multivariable adjustment, linear regression showed that there was a negative correlation between body mass index(BMI) and baPWV and a positive correlation between waist-to-hip ratio (WHR) and baPWV. Compared to normal weight group, those with BMI≥28 kg/m2 had lower risk of abnormal baPWV (OR=0.59, 95% CI: 0.44-0.78，P<0.001), but there was an increased risk of 46% among patients with obesity in WHR (OR=1.46, 95% CI:1.07-2.00，P=0.018). Compared to those without OO and AO, patients without OO but with AO had a 1.67-fold increasesd risk of abnormal baPWV (OR=1.67, 95% CI: 1.19-2.35，P=0.003). Conclusions Abdominal obesity is related with arterial stiffnening among T2DM patients, and it is critical to evaluate arterial stiffness of T2DM patients with abdmonal obesity and normal BMI in order to reduce future risk of cardiovascular diseases.

Objective To study the effects of Twist gene silencing on migration and invasion of human triple-nega-tive breast cancer cell Hs578T and its potential mechanisms. Methods The lentiviral vectors with Twist gene-targe-ted specific shRNA and the negative control were constructed,then transfected into the human triple-negative breast cancer cell line Hs578T to establish the stable cell lines of Twist gene silencing. The blank group(blank),negative control group(shNC) and Twist gene silencing group(shTwist) were set up.After screening by puromycin,the fluo-rescence expression and the infection efficiency of each group cells were observed by inverted fluorescence micro-scope. The expression of Twist mRNA and protein level was detected by quantitative real-time PCR and Western blot.Transwell migration and invasion experiments were performed to measure cell migration and invasion abilities, re-spectively. Western blot was used to detect the levels of p-AKT, AKT, p-ERK1/2 and ERK1/2 proteins. Results Twist gene was successfully knockdown in human triple-negative breast cancer cell line Hs578T. Compared with the blank group and shNC group cells,the cell migration and invasion ability of the shTwist group cells were decreased significantly(P<0.05,P<0.05),and the expression of Twist downstream p-AKT and p-ERK1/2 proteins were al-so reduced notably in the shTwist group cells(P<0.05,P<0.05). Conclusions Twist promotes cell migration and invasion via AKT/ERK signaling axis in human triple-negative breast cancer cell line Hs578T.

We explore the association of the mycoplasma infection with genital system tumor.Some index word including prostate cancer,cervical cancer,ovarian cancer and mycoplasma were used in some electronic databases (including PubMed,Web of Science,Chinese biomedical database,wanfang database,CNKI) to search literatures.The R software was used for the meta-analysis.The Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of the literature.Publication bias was evaluated by funnel figure,and the fail-safe number (Nfs) was calculated to estimate the reliability of the meta-analysis.Result showed that 20 articles were included,the numbers of cases and controls were 2 345 and 2 728 respectively.The pooled OR of Ureaplasma urealyticum(Uu),Mycoplasma hominis(Mh),other mycoplasma,mixture of mycoplasma and the whole mycoplasma was 2.19(95％CI:1.27-3.79),1.74(95％CI:1.28-2.35),1.97(95％CI:1.03-3.77),3.54 (95％CI:1.33-9.41),1.29(95％CI:1.53-2.60),respectively.The fail-safe number of Uu,Mh,other mycoplasma and mixture of mycoplasma was 254,42,31,157 respectively.There are some possibility about the association between the mycoplasma infection and the genital system cancer;maybe the infection would increase the tumorigenesis risk.It is necessary to research further about these associations in different mycoplasmas respectively.

AIM: To investigate the efficiency of intravitreal ranibizumab therapy ( IVR ) for polypoidal choroidal vasculopathy ( PCV) in single or multiple polyps.
METHODS: A total 63 patients diagnosed with PCV in Shaoxing City People's Hospital from May 2013 to May 2015 were enrolled and divided into single polyp group and multiple polyps group. All patients received intravitreal ranibizumab 3 monthly and were followed up for 12mo. Observe the changes of best corrected visual acuity ( BCVA ) and central retinal thickness ( CRT ) at different time points.
RESULTS: The single polyps group exhibited a better BCVA, shorter greatest linear dimension, and lower prevalence of fibro - vascular pigment epithelial detachment compared with the multiple polyp group before treatment (P<0. 05). Significant difference of BCVA were observed at 3, 6 and 12mo between the two groups (P<0. 05). BCVA at 3, 6, 12mo was significantly better than that at baseline in single polyps group. The single polyp group exhibited a significantly thinner CRT at 6 and 12mo compared with multiple polyps group (P<0. 05). The single polyp group showed improvement in CRT over the followed up period(P<0. 05). The CRT in multiple polyps group at 3 and 6mo significantly decreased compared with preoperative (P<0. 05).
CONCLUSION: IVR meet better result in PCV patients with multiple polyp and polyp numbers may be valuable to prognosis.

AlM:To compare the efficacy and safety of latanoprost and brimonidine in the treatment of open angle glaucoma, and provide reference for rational drug use.METHODS:A total of 121 cases ( 136 eyes ) who were diagnosed as primary open angle glaucoma were selected in this study, and they were randomly divided into experimental group (62 cases, 70 eyes) and control group ( 59 cases, 66 eyes) according to different drug treatment. Patients in the control group received brimonidine eye drops twice a day, while patients in the experimental group received latanoprost eye drops once a day. The intraocular pressure, visual acuity and adverse reactions were checked of the two groups in the following 3mo.RESULTS:The intraocular pressure of patients in the control group was 18. 1 ± 1. 3mmHg, while the experimental group was 17. 0 ± 0. 9mmHg after 12wk of treatment, which were both lower than before (P<0. 05). The fluctuation of intraocular pressure in the experimental group was significantly lower than that of the control group. There was no significant difference in the LogMAR visual acuity between before and after treatment in the control group, while the LogMAR visual acuity of the experimental group was significantly improved. The control group had hyperemia, burning sensation, tearing, eyelid edema and other adverse side effects, and the experimental group had little adverse reactions. CONCLUSlON: Latanoprost can significantly reduce intraocular pressure in glaucoma patients with in the follow- up time, and reduce the impact of elevated intraocular pressure in the vision of glaucoma patients, with little adverse reaction, worthy of clinical application.