BACKGROUND: The American Heart Association (AHA) introduced the concept of cardiovascular-kidney-metabolic (CKM) health and stage, reflecting the interaction among metabolism, chronic kidney disease (CKD), and the cardiovascular system. However, the association between CKM stage and the long-term risk of cardiovascular disease (CVD) has not been validated. This study aimed to evaluate the long-term CVD risk associated with CKM health metrics and CKM stage using data from a population-based cohort study. METHODS: In total, 5293 CVD-free participants were followed up to around 13 years in the Chinese Multi-provincial Cohort Study (CMCS). Considering the pathophysiologic progression of CKM health metrics abnormalities (comprising obesity, central adiposity, prediabetes, diabetes, hypertriglyceridemia, CKD, and metabolic syndrome), participants were divided into CKM stages 0, 1, and 2. The time-dependent Cox regression models were used to estimate the cardiovascular risk associated with CKM health metrics and stage. Additionally, broader CVD outcomes were examined, with a specific assessment of the impact of stage 3 in 2581 participants from the CMCS-Beijing subcohort. RESULTS: Among participants, 91.2% (4825/5293) had at least one abnormal CKM health metric, 8.8% (468/5293), 13.3% (704/5293), and 77.9% (4121/5293) were in CKM stages 0, 1, and 2, respectively; and 710 incident CVD cases occurred during a median follow-up time of 13.3 years (interquartile range: 12.1 to 13.6 years). Participants with each poor CKM health metric exhibited significantly higher CVD risk. Compared with stage 0, the hazard ratio (HR) (95% confidence interval [CI]) for CVD incidence was 1.31 (0.84-2.04) in stage 1 and 2.27 (1.57-3.28) in stage 2. Significant interactive impacts existed between CKM stage and age or sex, with higher CVD risk related to increased CKM stages in participants aged <60 years or females. CONCLUSION These findings highlight the contribution of CKM health metrics and CKM stage to the long-term risk of CVD, suggesting the importance of multi-component recognition and management of poor CKM health in CVD prevention.
Humans ; Female ; Male ; Cardiovascular Diseases/etiology* ; Middle Aged ; Adult ; Cohort Studies ; Renal Insufficiency, Chronic/metabolism* ; Aged ; Risk Factors ; Metabolic Syndrome/metabolism* ; China ; East Asian People

The zebrafish model has attracted much attention due to its strong reproductive ability, short research cycle, and ease of maintenance. It has always been an important vertebrate model system, often used to carry out human disease research. Its motor behavior features have the advantages of being simpler, more intuitive, and quantifiable. In recent years, it has received widespread attention in the study of traditional Chinese medicine(TCM)for the treatment of sleep disorders, neurodegenerative diseases, fatigue, epilepsy, and other diseases. This paper reviews the characteristics of zebrafish motor behavior and its applications in the pharmacodynamic verification and mechanism research of TCM extracts, active ingredients, and TCM compounds, as well as in active ingredient screening and safety evaluation. The paper also analyzes its advantages and disadvantages, with the aim of improving the breadth and depth of zebrafish and its motor behavior applications in the field of TCM research.
Zebrafish/physiology* ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/therapeutic use* ; Disease Models, Animal ; Drug Evaluation, Preclinical/methods* ; Animals ; Sleep Wake Disorders/physiopathology* ; Epilepsy/physiopathology* ; Neurodegenerative Diseases/physiopathology* ; Fatigue/physiopathology* ; Behavior, Animal/physiology* ; Motor Activity/physiology*

OBJECTIVE: To explore the role of the natural compound hesperidin in glycolysis, the key ratelimiting enzyme, in colorectal cancer (CRC) cell lines. METHODS: In vitro, HCT116 and SW620 were treated with different doses of hesperidin (0-500 µmol/L), cell counting kit-8 and colone formation assays were utilized to detected inhibition effect of hesperidin on CRC cell lines. Transwell and wound healing assays were performed to detect the ability of hesperidin (0, 25, 50 and 75 µmol/L) to migrate CRC cells. To confirm the apoptotic-inducing effect of hesperidin, apoptosis and cycle assays were employed. Western blot, glucose uptake, and lactate production determination measurements were applied to determine inhibitory effects of hesperidin (0, 25 and 50 µmol/L) on glycolysis. In vivo, according to the random number table method, nude mice with successful tumor loading were randomly divided into vehicle, low-dose hesperidin (20 mg/kg) and high-dose hesperidin (60 mg/kg) groups, with 6 mice in each group. The body weights and tumor volumes of mice were recorded during 4-week treatment. The expression of key glycolysis rate-limiting enzymes was determined using Western blot, and glucose uptake and lactate production were assessed. Finally, protein interactions were probed with DirectDIA Quantitative Proteomics, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. RESULTS: Hesperidin could inhibit CRC cell line growth (P<0.05 or P<0.01). Moreover, hesperidin presented an inhibitory effect on the migrating abilities of CRC cells. Hesperidin also promoted apoptosis and cell cycle alterations (P<0.05). The immunoblotting results manifested that hesperidin decreased the levels of hexokinase 2, glucose transporter protein 1 (GLUT1), GLUT3, L-lactate dehydrogenase A, 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2 (PFKFB2), PFKFB3, and pyruvate kinase isozymes M2 (P<0.01). It remarkably suppressed tumor xenograft growth in nude mice. GO and KEGG analyses showed that hesperidin treatment altered metabolic function. CONCLUSION Hesperidin inhibits glycolysis and is a potential therapeutic choice for CRC treatment.
Hesperidin/therapeutic use* ; Colorectal Neoplasms/metabolism* ; Glycolysis/drug effects* ; Animals ; Humans ; Apoptosis/drug effects* ; Mice, Nude ; Cell Movement/drug effects* ; Cell Line, Tumor ; Cell Proliferation/drug effects* ; Glucose/metabolism* ; Cell Cycle/drug effects* ; Mice, Inbred BALB C ; Mice ; HCT116 Cells ; Lactic Acid

177Lu-prostate specific membrane antigen(PSMA)radio-ligand therapy has been approved abroad for advanced prostate cancer and has been in several clinical trials in China.Based on domestic clinical practice and experimental data and referred to international experience and viewpoints,the expert group forms a consensus on the clinical application of 177Lu-PSMA radio-ligand therapy in prostate cancer to guide clinical practice.

Objective To observe the value of dual-source CT(DECT)virtual monoenergetic imaging(VMI)for differentiating prostate cancer(PC)and benign prostatic hyperplasia(BPH).Methods Thirty-three patients with PC(PC group)and 44 patients with BPH(BPH group)were retrospectively enrolled,and 40-100 keV(with 10 keV interval)VMI were reconstructed based on arterial phase DECT images,respectively.Clinical data,focal CT value and contrast-to-noise ratio(CNR)of VMI with different energy levels and conventional linear fusion images of arterial phase were compared between groups.Binary logistic regression models were constructed based on clinical data being significantly different between groups,focal CT value of VMI with energy level with the highest CNR,also focal CT value of conventional linear fusion images of arterial phase,respectively.The area under the receiver operating characteristic curve(AUC)was calculated to evaluate the efficacy of each model for differentiating PC and BPH.Results Free prostate-specific antigen(f-PSA),total prostate-specific antigen(t-PSA),focal CT value of 40-100 keV VMI and conventional linear fusion images of arterial phase in PC group were all higher,while short diameter in PC group was smaller than those in BPH group(all P＜0.05).Logistic regression models were constructed based on f-PSA,t-PSA,short diameter,CT value at 40 keV VMI and CT value at conventional linear fusion images of arterial phase,respectively,with AUC for differentiating PC and BPH of 0.879,0.902,0.701,0.911 and 0.857,respectively.Conclusion DECT VMI could be used as a supplementary examination for prostate diseases,and 40 keV VMI had the best efficacy for differentiating PC and BPH.

Herpes simplex virus encephalitis is the most common type of infectious encephalitis with a poor progno-sis,and some patients may develop recurrent or secondary autoimmune encephalitis.This article reports a case of anti-Ri antibody encephalitis secondary to herpes simplex virus encephalitis,in order to improve the understanding of this disease among clinicians and avoid misdiagnosis and missed diagnosis.Antibodies associated with paraneoplastic syndrome should be screened for patients with a previous history of tumor,and early diagnosis and immunotherapy play an important role in improving the prognosis of patients.

Objective The oxidative damage of DNA can be caused by excessive levels of Reactive oxygen species(ROS).Monitoring of DNA oxidative damage enables effective evaluation of ROS damage effects.Although the detection of DNA damage effects based on microbial sensor allows quantitative analysis of oxidative damage,the ROS clearance mechanism existed in bacterial will affect the sensitive of detection.The work of this article is to knockout the key genes of ROS clearance mechanism and construct an antioxidant gene-knock-out microbial sensor.The microbial sensor can realize sensitive monitoring of DNA damage effects and then evaluates the damage effects of cells by ROS.Methods The antioxidant damage genes of bacterial ahpCF,katE and katG were knocked out by λ-Red homologous recombination and antioxidant gene-knockout microbial sensor was constructed.The nalidixic acid sodium salt and UV irradiation were used to characterize the performance for monitoring of DNA damage effects.Results The antioxidant gene-knockout microbial sensors ΔahpC,ΔahpCF/ΔkatEG and ΔahpCF/ΔkatE/ΔkatG were constructed successfully.The results showed that the microbial sensor ΔahpCF/ΔkatE/ΔkatGl had the highest sensitive of damage effects and the limit of detection for nalidixic acid sodium salt was 0.40 μmol/L.In addition,1.80 min of UV irradiation(254 nm)was sufficient to induce a significant fluorescent expression effect in the engineered bacteria.Conclusion In this article,antioxidant gene-knockout microbial sensors had been constructed to realize active and sensitive monitoring of DNA damage effects such as DNA damage reagents and UV irradiation.The sensors could provide an active,effective,and sensitive potential monitoring method for future evaluation of radiation effects in space.

OBJECTIVE: To investigate the imaging effect of a near-infrared fluorescent targeted probe ICG-NP41 on the neurovascular bundles (NVB) around the prostate in rats. METHODS: A near-infrared fluorescent targeted probe ICG-NP41 was synthesized. An animal model for NVB imaging was established using Sprague-Dawley rats (250-400 g). Experiments were conducted using a custom-built near-infrared windowⅡ(NIR-Ⅱ) small animal in vivo imaging system, and images collected were processed using ImageJ and Origin. The fluorescence signal data were statistically analyzed using GraphPad Prism. The signal-to-background ratio (SBR) for NVB was quantitatively calculated to explore the effective dosage and imaging time points. Finally, paraffin pathology sections and HE staining were performed on the imaging structures. RESULTS: Except for rats in the control group (n=2), right-sided NVB of the rats injected with ICG-NP41 (n=2 per group) were all observed in NIR-Ⅱ fluorescence mode 2 h and 4 h after administration. At 2 h and 4 h, average SBR of cavernous nerve in 2 mg/kg group in fluorescence mode was 1.651±0.142 and 1.619±0.110, respectively, both higher than that in white light mode (1.111±0.036), with no significant difference (P>0.05); average SBR of 4 mg/kg group in fluorescence mode were 1.168±0.066 and 1.219±0.118, respectively, both higher than that in white light mode (1.081±0.040), with no significant difference (P>0.05). At 2 h and 4 h, the average SBR of 2 mg/kg and 4 mg/kg groups in fluorescence mode were higher than that of the control group (SBR=1), the average SBR of the 2 mg/kg group was higher than that of the 4 mg/kg group, and all the above with no significant difference (P>0.05). The average diameter of the nerve measured by full width at half maxima method was about (178±15) μm. HE staining of paraffin sections showed the right major pelvic ganglion. CONCLUSION The near-infrared fluorescent targeted probe ICG-NP41 can be used for real-time imaging of the NVB around the prostate in rats, providing a potential feasible solution for localizing NVB in real time during nerve-sparing radical prostatectomy.
Male ; Rats ; Animals ; Prostate/diagnostic imaging* ; Paraffin ; Indocyanine Green ; Rats, Sprague-Dawley ; Fluorescent Dyes

Objective:To assess the predictive performance of the risk of cardiovascular diseases (CVD) derived from the China Kadoorie Biobank (CKB-CVD) model, prediction for atherosclerotic cardiovascular disease (ASCVD) risk in China (China-PAR) model, and the risk of fatal and nonfatal ischemic cardiovascular diseases derived from the USA-People′s Republic of China Collaborative Study (USA-PRC) model in Chinese Multi-provincial Cohort Study (CMCS).Methods:In this prospective cohort study, a total of 21 948 individuals aged ≥35 years without CVD were selected from 8 provinces and cities in China during the CMCS survey from 1992 to 2005 for 10-year follow-up. The occurrence of CVD or ASCVD events during the follow-up period was used as the gold standard. The CKB-CVD and China-PAR models were used to calculate the predicted risk of CVD events, while the USA-PRC model was used to calculate the predicted risk of ASCVD events. The discrimination of the models was evaluated using the C-statistic, and the calibration was assessed using the Hosmer-Lemeshow χ2 test and decile plot. Results:During the 10-year follow-up, a total of 955 (4.4%) CVD events, including 791 (3.6%) ASCVD events, were recorded among the study participants. The C-index for the CKB-CVD, China-PAR, and USA-PRC models were 0.775 (95% CI: 0.757-0.793), 0.781 (95% CI: 0.763-0.798), and 0.769 (95% CI: 0.750-0.789) for men, and 0.762 (95% CI: 0.737-0.788), 0.769 (95% CI: 0.745-0.794), and 0.767 (95% CI: 0.741-0.794) for women, respectively. China-PAR model showed good calibration for men ( χ2=2.20), however, both CKB-CVD and USA-PRC models demonstrated poor calibration in both men and women ( χ2>20). The results indicated that the CKB-CVD model overestimated the risk of CVD events in both males and females, while the China-PAR model underestimated the risk in females. Furthermore, the USA-PRC model underestimated the risk of ASCVD in both males and females in most decile groups, but overestimated the risk in the highest decile group. Conclusion:The CKB-CVD, China-PAR, and USA-PRC risk assessment models show some degree of deviation from the actual risk of events in the CMCS cohort, but all exhibit good discrimination.