The circadian clock is a highly conserved timekeeping system in organisms, which maintains physiological homeostasis by precisely regulating periodic fluctuations in gene expression. Substantial clinical and experimental evidence has established a close association between circadian rhythm disruption and the development of various malignancies. Research has revealed characteristic alterations in the circadian gene expression profiles in tumor tissues, primarily manifested as a dysfunction of core clock components (particularly circadian locomotor output cycles kaput (CLOCK) and brain and muscle ARNT-like 1 (BMAL1)) and the widespread dysregulation of their downstream target genes. Notably, CLOCK demonstrates non-canonical oncogenic functions, including epigenetic regulation via histone acetyltransferase activity and the circadian-independent modulation of cancer pathways. This review systematically elaborates on the oncogenic mechanisms mediated by CLOCK/BMAL1, encompassing multidimensional effects such as cell cycle control, DNA damage response, metabolic reprogramming, and tumor microenvironment (TME) remodeling. Regarding the therapeutic strategies, we focus on cutting-edge approaches such as chrononutritional interventions, chronopharmacological modulation, and treatment regimen optimization, along with a discussion of future perspectives. The research breakthroughs highlighted in this work not only deepen our understanding of the crucial role of circadian regulation in cancer biology but also provide novel insights for the development of chronotherapeutic oncology, particularly through targeting the non-canonical functions of circadian proteins to develop innovative anti-cancer strategies.
Humans ; ARNTL Transcription Factors/physiology* ; Neoplasms/therapy* ; CLOCK Proteins/physiology* ; Circadian Clocks/genetics* ; Animals ; Circadian Rhythm/genetics* ; Tumor Microenvironment ; Epigenesis, Genetic ; Gene Expression Regulation, Neoplastic

Objective:To clarify the changes of intrahepatic ultrasound hemodynamics before and after hepatic artery thrombosis (HAT) after liver transplantation (LT), providing early warning and anticoagulation guidance to clinicians.Methods:The clinical data of patients who underwent liver transplantation at Zhongshan Hospital of Fudan University between June 2006 and October 2022 were retrospectively analyzed, 47 patients with a diagnosis of HAT confirmed by DSA (digital subtraction angiography) were included in the HAT group, and 71 patients without vascular complications were included in the non-HAT group. Differences in peak flow velocity (PSV), resistance index (RI), and portal vein velocity (PVV) were compared between the two groups. Logistic regression analysis was used to determine the relationship between postoperative PSV decline and HAT occurrence, while ROC curve were used to determine the critical value and evaluate the diagnostic efficacy. Patients with HAT were divided into well-treatment group and poor-treatment group according to whether the blood flow was restored after multiple surgeries or thrombolytic treatments. The changes of early intrahepatic hemodynamics after surgical or thrombolytic therapy were compared between the two groups.Results:①A decrease in PSV of the transplanted hepatic artery was measured 1 d before HAT, and PSV<0.39 m/s predicted thrombus formation with a sensitivity of 0.70, specificity of 0.86, and the AUC was 0.83. ②After treatment, PSV in the HAT group increased immediately, approaching the normal level on the 2nd day. In the well-treatment group, PSV and PVV reached normal levels on the first day after treatment, which were significantly higher than the corresponding values in the poor-treatment group ( P=0.030, 0.021). Conclusions:In the early stage after liver transplantation, a PSV<0.39 m/s is related to the occurrence of HAT thrombosis 1 d later. A significant increase in PSV on the first day after treatment indicates a good treatment response, and there is no need for further DSA re-examination or increasing the number of thrombolysis.

Objective:To evaluate the feasibility of using two-dimensional shear wave elastography (2D-SWE) based liver and spleen elastic hardness (L/S-SWE) in patients with liver cirrhosis, and to determine the exclusion and diagnostic thresholds for early identification of liver cirrhosis.Methods:A total of 574 patients with chronic hepatitis B (hepatitis B for short) were included in this study. The clinical characteristics, L-SWE and S-SWE of the patients were collected, and the differences between cirrhosis group ( n=311) and non cirrhosis group ( n=263) were analyzed. The success rate and stability of liver and spleen elastic surgery were evaluated in two groups. The receiver operating characteristic (ROC) curve was used to analyze the efficacy of L-SWE, S-SWE, aspartate aminotransferase to platelet ratio index (APRI) alone and in combination in diagnosing liver cirrhosis. By analyzing the ROC curve, the double threshold for excluding and diagnosing liver cirrhosis was determined. Results:There was a statistically significant difference in platelet count and APRI between the cirrhosis group and the non cirrhosis group (all P<0.05). In the feasibility assessment of 2D-SWE technology, the success rate and stability of liver and spleen elastic operation were relatively high (success rate: 97.2% vs 81.3%; stability: 0.92 vs 0.84), and the success rate and stability of L-SWE operation were slightly better than S-SWE. The success rate of S-SWE operation in the cirrhosis group was higher than that in the non cirrhosis group ( P<0.05). The correlation analysis results showed that L-SWE, S-SWE, APRI were positively correlated with liver tissue pathological grading ( r=0.677, 0.528, 0.149, all P<0.05). The areas under the ROC curve for identifying liver cirrhosis using L-SWE, S-SWE, and APRI were 0.959, 0.896, and 0.706, respectively. When L-SWE and S-SWE were combined, the area under the ROC curve was 0.987, the sensitivity was 92.6%, and the specificity was 96.0%. The Delong test showed that the combined diagnosis of L-SWE and S-SWE had the same diagnostic efficacy as using L-SWE alone for liver cirrhosis ( P>0.05). Further analysis of the ROC curve showed that the likelihood of liver cirrhosis was low when L-SWE was less than 9.4 kPa, and high when L-SWE was greater than 12.0 kPa. Patients between 9.4 and 12.0 kPa can undergo further S-SWE testing; If the S-SWE was between 17.5 and 29.3 kPa, it was classified as 2D-SWE, which was difficult to determine whether there was liver cirrhosis, and further liver puncture and other examinations were needed. Conclusions:2D-SWE technology has high operational feasibility in the diagnosis of liver cirrhosis, and combined with S-SWE, it helps to improve the diagnostic efficiency of early non-invasive identification of liver cirrhosis, enabling more patients to avoid unnecessary liver puncture examinations.

Objective:To investigate the regulation and possible mechanism of hyperthermia (HT) on the ferroptosis of squamous cell carcinoma of the tongue cell line CAL-27.Methods:Half maximal inhibitory concentration (IC 50) of Fer-1, an inhibitor of ferroptosis, was detected by CCK-8 assay and used for subsequent experiments. CAL-27 cells were divided into the HT, control, Fer-1 and HT+ Fer-1 groups according to experimental design. Reactive oxygen species (ROS) levels and iron ion concentration were determined by corresponding detection kits. The p53 and TfR1 mRNA levels were detected by real-time reverse transcription PCR. Cell migration was detected by cell scratch test and cell apoptosis was detected by flow cytometry. Results:HT significantly up-regulated the ROS levels ( P<0.01) and iron ion concentration ( P<0.001), and significantly increased the expression levels of p53 and TfR1 mRNA (both P<0.01). The cell migration ability was decreased ( P<0.001), whereas cell apoptosis rate was increased by HT ( P<0.01). In the HT+Fer-1 group, the ROS levels ( P<0.001), iron ion concentration ( P<0.001), expression levels of p53 and TfR1 mRNA (both P<0.01) were significantly down-regulated, the cell migration ability was recovered ( P<0.01), and cell apoptosis rate was decreased ( P<0.01) compared with those in the HT group, respectively. Conclusions:HT may induce the ferroptosis of CAL-27 cell line, inhibit cell migration ability and promote cell apoptosis by activating the p53/TfR1 pathway.

Tumor microenvironment possesses immunosuppression characteristics via the mechanism of inducing tumor cell immune escape. The interaction between tumor cells and tumor microenvironment is an important factor affecting tumor genesis and development. As an important part of tumor microenvironment, cancer-associated fibroblasts interact directly or indirectly with tumor cells and produce various cytokines to regulate tumor immune microenvironment. In recent years, hyperthermia has become an auxiliary means of anti-tumor therapy. With the development of research on tumor hyperthermia and tumor microenvironment, a large number of studies have found that hyperthermia can regulate cancer-associated fibroblasts in tumor microenvironment. In this article, recent research progresses of the effects of hyperthermia on cancer-associated fibroblasts and related cells and cytokines in tumor microenvironment were reviewed, providing a new way for clinical application of hyperthermia combined with immune or targeted therapy.

Objective:To analyze the viscosity characteristics of liver tumors and investigate the clinical value of shear wave dispersion (SWD) in the differentiation of benign and malignant liver tumors.Methods:A total of 103 patients with focal liver lesions were prospectively collected in Zhongshan Hospital Affiliated to Fudan University from October 2020 to July 2021, including 80 cases with single lesion and 23 cases with multiple lesions, and only the largest lesion was observed in patients with multiple lesions. SWD values were measured within the tumor and in the liver parenchyma 2 cm away from the tumor, and were compared between benign tumor group and maligant tumor group. The ROC curves of SWD value, SWD ratio and their combination in differentiating benign and malignant liver tumors were plotted respectively, and the optimal diagnostic threshold, the sensitivity, specificity and accuracy of different diagnostic methods were analyzed.Results:Among the 103 patients, 35 were benign and 68 were malignant. The SWD value of liver benign tumor group was lower than that of liver malignant tumor group [(16.38±3.58)m·s -1·kHz -1 vs (18.59±3.12)m·s -1·kHz -1], the SWD value of liver parenchyma background in liver benign tumor group was lower than that in liver malignant tumor group [(10.88±3.37)m·s -1·kHz -1 vs (14.31±3.34)m·s -1·kHz -1], and the differences were statistically significant (all P<0.05). The SWD ratio of benign tumor to surrounding liver parenchyma was higher than that of malignant tumor group [1.57(1.25, 2.00) vs 1.27(1.06, 1.57)], and the difference was statistically significant ( P<0.05). When the SWD value >15.60 m·s -1·kHz -1 was used as the cut-off value, the area under ROC curve (AUC) was 0.72, the sensitivity was 88.2%, the specificity was 51.4%, and the accuracy was 75.7%. The sensitivity, specificity, accuracy and AUC were 58.8%, 74.2%, 63.1%, and 0.68, respectively, when the ratio of SWD value<1.32 was used as the cut-off value. SWD value combined with SWD ratio for the diagnosis of liver malignant tumor, the AUC was 0.88, the sensitivity was 82.3%, the specificity was 83.0%, and accuracy was 81.6%. The diagnostic efficacy of the two in combination for liver malignant tumor was superior to SWD value ( Z=2.678, P=0.007 4) and SWD value ratio ( Z=3.822, P=0.000 1). Conclusions:SWD imaging can reflect the viscosity information of liver tumors and surrounding liver parenchyma, and has potential clinical application value in the differentiation of benign and malignant tumors.

Background and objective Our previous study found that nicotine could induce lung cancer cell epithelial-mesenchymal transition (EMT). The aim of this study is to explore the relationship between nicotine-induced EMT and lung cancer invasion and metastasis. Methods Real-time PCR and Western blot were used to detect the expression changes of EMT-related markers, E-cadherin and Vimentin, in A549 lung cancer cells treated with nicotine;hTe transposition ofβ-catenin protein expression was determined by immunolfuorescence;Scratch test and Transwell invasion assay were used to detect the effects of nicotine on lung cancer cell migration and invasion. Results Nicotine can signiifcantly down-regulate the expressional level of E-cadherin mRNA and protein of A549 cells in a manner of dose and time-dependent (P<0.01, P<0.01);Nicotine can signiifcantly up-regulate the expressional level of Vimentin mRNA and protein of A549 cells in a manner of dose and time-dependent (P<0.01, P<0.01);Immunolfuorescence results showed thatβ-catenin protein was signiifcantly transfered to nucleus;Scratch test and Transwell assay showed that Nicotine could remarkably increase the migration and invasion poten-tial of lung cancer cells (P<0.01, P<0.01). Conclusion Nicotine can induce cancer cells EMT, and promote the invasion and metastasis ability of lung cancer cells.

PurposeTo assess the level of agreement and interchangeability among Excel and CMRtools (2012) for calculation of T2* values in iron overload.Materials and Methods T2* images in 27 cases withβ-thalassemia major were imported into CMRtools (2012). The regions of interest (ROI) were drawn and interference signal removed to obtain T2* values. The T2* images were also measured using default MR software and manually entered into Excel to obtain T2* values after removal of the interference signal. The agreement between the two methods in calculating T2* values was compared.Results For 27 patients withβ-thalassemia major, 10 cases showed myocardial iron overload. 25 cases had liver iron overload. The T2* values from two methods were not statistically significant (t=-0.152 and-0.691,P>0.05) for the liver.Conclusion There is good agreement and interchangeability between Excel and CMRtools (2012) in calculating T2* values. Excel can be used clinically to evaluate iron overload.

Background and objective Cisplatin is the ifrst-line drug for the chemotherapy of non-small cell lung cancer (NSCLC), but the acquired chemoresistance restricted the effect of its treatment. hTe aim of this study is to validate the miRNAs related to the Cisplatin resistance in lung cancer and elucidate the molecular mechanisms. Methods We performed miRNA microarray and RT-PCR to obtain the aberrant differential expressed miRNAs between A549 and its paired Cisplatin-resistant cell line A549/DDP cells, and then we investigated the biological functions of miR-192, which is the aberrant differen-tial expressed miRNA. Atfer transfection of the miR-192 into A549 cells, we measured the half inhibition concentration (IC50), cell apoptosis of the trasfectant cells, and then we used biological sotfwares and dual-luciferase report assay to explore the target gene of the miR-192, which was further validated by RT-PCR and Western blot. Result MiR-192 was highly over-expressed in A549/DDP cells , whose quantity was 37.59±0.35 fold higher than that in A549 cells. Overexpression of miR-192 in A549 cells signiifcantly conferred resistance to Cisplatin and inhibited apoptosis. By contrast, down-expression of miR-192 in A549/DDP cells remarkably restrained the Cisplatin resistance and induced apoptosis. MiR-192 binded to Bim 3’-UTR and negatively regulated Bim expression at the post-transcriptional level in lung adenocarcinoma cells. Conclusion Our data suggested that miR-192 induced Cisplatin-resistance and inhibited cell apoptosis in lung cancer via negative targeting Bim expression.

A remote interactive consultation system based on wireless sensor networks is proposed for family health care works and non-hospital special case patient monitoring. The sensor nodes are integrated into a local area network to collect a variety of human physiological information, which is uploaded to Internet through the Code-Division Multiple Access (CDMA) wireless network technology and sent to the database based on GIS spatial location query technology for achieving electronic diagnosis. Users or administrators can visit remote monitor region through Internet. The results show that the system, using a star passive topology of static gateway and mobile detection node, combines intelligent-distributed wireless sensing, computing and wireless communication technologies. Hence the proposed system has a great practical value.
Biosensing Techniques ; methods ; Computer Communication Networks ; Diagnosis, Computer-Assisted ; instrumentation ; Equipment Design ; Humans ; Monitoring, Ambulatory ; instrumentation ; methods ; Monitoring, Physiologic ; methods ; Signal Processing, Computer-Assisted ; instrumentation ; Telemedicine