Recent studies have shown that the physiological homeostasis of oral mucosal cells is regulated by the circadian clock.Dis-ruption or dysfunction of the circadian clock is closely associated with the development of oral squamous cell carcinoma(OSCC).Research based on the circadian clock offers a novel perspective on the pathogenesis and therapeutic strategies for OSCC.However,there is current-ly limited research on this topic,and people generally have insufficient understanding and recognition of the circadian clock.Given the complexity and challenges of circadian clock which is the fourth dimension of medical research,we organize relevant experts based on summarizing the current research results of circadian clock in the pathogenesis and precision diagnosis and treatment of OSCC,combining the scientific principles of the circadian clock's role and their long-term research experience,then summarizes and recommends the con-sensus opinions for the research of circadian clock in the pathogenesis mechanism and precision diagnosis and treatment of human OSCC,with the hope of providing guidance for the basic research and clinical application of circadian clock or circadian rhythm in the pathogene-sis mechanism and precision diagnosis and treatment of oral and maxillofacial squamous cell carcinoma.

Recent studies have shown that the physiological homeostasis of oral mucosal cells is regulated by the circadian clock.Dis-ruption or dysfunction of the circadian clock is closely associated with the development of oral squamous cell carcinoma(OSCC).Research based on the circadian clock offers a novel perspective on the pathogenesis and therapeutic strategies for OSCC.However,there is current-ly limited research on this topic,and people generally have insufficient understanding and recognition of the circadian clock.Given the complexity and challenges of circadian clock which is the fourth dimension of medical research,we organize relevant experts based on summarizing the current research results of circadian clock in the pathogenesis and precision diagnosis and treatment of OSCC,combining the scientific principles of the circadian clock's role and their long-term research experience,then summarizes and recommends the con-sensus opinions for the research of circadian clock in the pathogenesis mechanism and precision diagnosis and treatment of human OSCC,with the hope of providing guidance for the basic research and clinical application of circadian clock or circadian rhythm in the pathogene-sis mechanism and precision diagnosis and treatment of oral and maxillofacial squamous cell carcinoma.

Objective:To explore the feasibility of automatic assessment of abdominal and pelvic CT radiation dose index (CTDI vol) based on deep learning models. Methods:A retrospective analysis was conducted on clinical abdominal and pelvic CT data collected continuously from February 2021 to February 2022. A total of 1 084 sets of patient images were obtained using equipment of Siemens SOMATOM Definition Flash CT, Philips iCT, and GE lightspeed VCT. The volume CT dose index (CTDI vol) prediction model consisted of two functional modules: organ segmentation and dose prediction. Based on the result of actual scanning area segmentation in the abdominal and pelvic area, CTDI vol was evaluated automatically by dose regression prediction module. The images of 1 084 patients included in the study were randomly divided into a training set of 784, a validation set of 196 and a test set of 104. Dice coefficient was used to evaluate the abdominal and pelvic segmentation performance of the hybrid model, and accurate number proportion and root-mean-square logarithm error (RMSLE) were used as the evaluation index of the CTDI vol estimation model performance. Results:In the test set, the Dice coefficient of the deep learning model in the task of CT abdominal image segmentation was as high as 0.998, and the RMSLE of the CTDI vol regression model in estimation of radiation dose was 9.41%, with an accuracy rate of 92%. Scatter plot analysis showed that some CTDI vol estimates had significant errors, indicating that the model might need to be further optimized in these situations. Conclusions:The deep learning models can accurately and automatically segment CT abdominal images and estimate radiation dose, which can be used for clinical radiation dose monitoring and management.

Objective:To explore the impacts of thermotherapy combined with gemcitabine on the biological behavior of tongue squamous cell carcinoma cells.Methods:Human tongue squamous cell carcinoma Tca8113 cells were divided into the control group (blank control), gemcitabine group, thermotherapy group (heated in an incubator at 43℃ for 1 h and then incubated at 37℃ for 24 h) and thermotherapy + gemcitabine group. The proliferation ability of Tca8113 cells was assessed by EdU staining and CCK-8 assay. Cell apoptosis and cell cycle of Tca8113 cells were detected by flow cytometry. The invasion of Tca8113 cells was determined by Transwell chamber assay. The expression levels of cyclin D1 (CyclinD1), Bcl-2-associated X protein (Bax), matrix metalloproteinase (MMP)-9, phosphorylated histone H2AX (γH2AX) and Nijmegen breakage syndrome 1 (NBS1) proteins in Tca8113 cells were measured by Western blot. The changes of tumor mass and volume were detected by xenograft tumor in vivo test in nude mice. Multi-group comparison was performed by one-way ANOVA. Two group comparison was conducted by SNK- q test. Results:Compared with the control group, EdU positive cell percentage, OD 450 value, invasive cell number, CyclinD1, MMP-9 and NBS1 protein expression of Tca8113 cells were decreased, whereas the apoptosis rate, the expression of Bax and γH2AX proteins were increased in the gemcitabine, thermotherapy and thermotherapy + gemcitabine groups ( q=4.45-72.06, all P<0.001). Compared with the control group, the proportion of G 0/G 1 phase cells was decreased, whereas the proportion of S and G 2/M phase cells was increased in the gemcitabine and thermotherapy + gemcitabine groups, the proportion of G 0/G 1 phase cells was decreased and the proportion of G 2/M phase cells was increased in the hyperthermia group ( q=10.36-61.09, all P<0.001). Compared with the gemcitabine and thermotherapy groups, EdU positive cell percentage, OD 450 value, G 0/G 1 phase cell proportion, invasive cell number, CyclinD1, MMP-9 and NBS1 protein expression of Tca8113 cells were decreased, whereas apoptosis rate, S, G 2/M phase cell proportion, Bax and γH2AX protein expression were increased in the thermotherapy + gemcitabine group ( q=4.45-28.73, all P<0.001). Xenograft tumor in vivo test in nude mice showed that the tumor volume and mass of nude mice in the gemcitabine, thermotherapy, and thermotherapy + gemcitabine groups were decreased compared with those in the control group ( q=5.58-73.02, all P<0.001). Compared with the gemcitabine and thermotherapy groups, the tumor volume and mass in the thermotherapy + gemcitabine group were decreased ( q=5.58-21.45, all P<0.001). Conclusion:The combination of thermotherapy and gemcitabine can inhibit the proliferation and invasion, block the cell cycle, and induce cell apoptosis of Tca8113 cells.

Objective To investigate the clinical value of intracoronary injection of recombinant human prourokinase for injection in patients with acute ST-segment elevation myocardial infarction(STEMI)undergoing emergency percutaneous coronary intervention(PCI).Methods Retrospective analysis was used to collect STEMI patients who underwent emergency PCI in department of cardiology from January to December 2019.According to the targeted injection of drugs through a guided catheter by intraoperative patients before stent implantation,the patients were divided into a tirofiban group(70 cases)and a recombinant human urokinase group(70 cases).TIMI blood flow grade,ST segment fall value(STR)of infarct-related artery,plasma D-dimer,left ventricular ejection fraction(LVEF)and coronary microcirculation dysfunction were compared between the two groups.At the same time,the general information of the patients,major adverse cardiovascular events(MACE)and bleeding were recorded.Results Compared with the tirofiban group,the TIMI blood flow level,LVEF,plasma D-dimer,and the proportion of the patients with STR＞70％in the recombinant human prourokinase group were significantly increased,while the incidence of slow flow/no reflow and MACE were significantly reduced,and the differences between the two groups were statistically significant(P＜0.05).The incidence of bleeding events in the recombinant human prourokinase group showed a downward trend,but there was no significant difference between the two groups(P＞0.05).Conclusion Intracoronary injection of recombinant human prourokinase through the guiding catheter can significantly improve myocardial perfusion and prognosis in patients with STEMI.It also reduces adverse cardiovascular events and has a high safety margin,which is worth promoting in the clinic.

Objective:To investigate mechanisms whereby phospholipase D1(PLD1)promotes pancreatic ductal adenocarcinoma(PDAC)progression.Methods:Targets were identified by screening the Genomic Spatial Event(GSE)database for genes differentially expressed in metastatic and primary tumors.Xenograft models were constructed by orthotopic injection of KPC cells into the mouse pancreas.Differential PLD1 expression in paired primary tumors and liver metastases derived from C57 mice and PDAC patients was confirmed using immunohistochemical staining.The effect of PLD1 expression on PDAC prognosis was assessed using a PDAC tissue microarray and clinical data.The effect of PLD1 expression on PDAC metastasis was assessed using transwell migration and scratch assays of cell lines ectopically expressing/silencing PLD1.The role of PLD1 in tumor metastasis was investigated using xenograft models constructed by orthotopic injection of PLD1-overexpression cell lines or vector control into the pancreas of C57 mice.Growth of primary tumors and liver metastases was monitored using bioluminescent imaging.The role of PLD1 in tumor progression was assessed using western blotting,transwell migration and scratch assays,and PLD1 enzyme-mutation cell lines.Downstream PLD1 target genes were identified using quantitative real-time PCR(qPCR),transcriptome sequencing,and response blocking.The effect of downstream target FSTL1 on liver metastasis in mice was assessed using bioluminescent imaging.Results:PLD1 expression was significantly higher in metastases than in primary tumors in KPC mice and patients.In the tissue microarray analysis,PLD1 expression was associated with diminished survival in PDAC patients;PLD1 overexpression in MIA PaCa-2 cells or knockdown in SW1990 cells could significantly affect the ability of invasion and migration.Xenograft models were established via orthotopic injections of the KPC cell line into the pancreas.Bioluminescent imaging demonstrated that PLD1 overexpression significantly increased signal intensity in the mouse liver(P<0.01);Treating the SW1990 cell line with PA and choline(PLD1 pathway products)did not restore loss of PDAC cell migration and invasion ability.Transwell and scratch assays in KRM,a PLD1 catalytic-mutation cell line,suggested that PLD1 activity is not required for PDAC metastasis;Transcriptome sequencing identified FSTL1 as a downstream molecule of PLD1.qPCR confirmed the consistency of mRNA levels between PLD1 and FSTL1.A blocking-rescue experiment suggested that FSTL1 is a downstream target of PLD1.A splenectomy metastasis model was constructed by injecting nude mice with tumor cells overexpressing FSTL1 and the results confirmed that overexpression of FSTL1 could induce liver metastases in PDAC cell due to tumor progression.Conclusion:PLD1 upregulates FSTL1 expression,promotes epithelial-mesenchymal transition of tumor cells,and enhances PDAC metastasis.Thus,PLD1 blockade could inhibit PDAC progression.

Objective:To investigate mechanisms whereby phospholipase D1(PLD1)promotes pancreatic ductal adenocarcinoma(PDAC)progression.Methods:Targets were identified by screening the Genomic Spatial Event(GSE)database for genes differentially expressed in metastatic and primary tumors.Xenograft models were constructed by orthotopic injection of KPC cells into the mouse pancreas.Differential PLD1 expression in paired primary tumors and liver metastases derived from C57 mice and PDAC patients was confirmed using immunohistochemical staining.The effect of PLD1 expression on PDAC prognosis was assessed using a PDAC tissue microarray and clinical data.The effect of PLD1 expression on PDAC metastasis was assessed using transwell migration and scratch assays of cell lines ectopically expressing/silencing PLD1.The role of PLD1 in tumor metastasis was investigated using xenograft models constructed by orthotopic injection of PLD1-overexpression cell lines or vector control into the pancreas of C57 mice.Growth of primary tumors and liver metastases was monitored using bioluminescent imaging.The role of PLD1 in tumor progression was assessed using western blotting,transwell migration and scratch assays,and PLD1 enzyme-mutation cell lines.Downstream PLD1 target genes were identified using quantitative real-time PCR(qPCR),transcriptome sequencing,and response blocking.The effect of downstream target FSTL1 on liver metastasis in mice was assessed using bioluminescent imaging.Results:PLD1 expression was significantly higher in metastases than in primary tumors in KPC mice and patients.In the tissue microarray analysis,PLD1 expression was associated with diminished survival in PDAC patients;PLD1 overexpression in MIA PaCa-2 cells or knockdown in SW1990 cells could significantly affect the ability of invasion and migration.Xenograft models were established via orthotopic injections of the KPC cell line into the pancreas.Bioluminescent imaging demonstrated that PLD1 overexpression significantly increased signal intensity in the mouse liver(P<0.01);Treating the SW1990 cell line with PA and choline(PLD1 pathway products)did not restore loss of PDAC cell migration and invasion ability.Transwell and scratch assays in KRM,a PLD1 catalytic-mutation cell line,suggested that PLD1 activity is not required for PDAC metastasis;Transcriptome sequencing identified FSTL1 as a downstream molecule of PLD1.qPCR confirmed the consistency of mRNA levels between PLD1 and FSTL1.A blocking-rescue experiment suggested that FSTL1 is a downstream target of PLD1.A splenectomy metastasis model was constructed by injecting nude mice with tumor cells overexpressing FSTL1 and the results confirmed that overexpression of FSTL1 could induce liver metastases in PDAC cell due to tumor progression.Conclusion:PLD1 upregulates FSTL1 expression,promotes epithelial-mesenchymal transition of tumor cells,and enhances PDAC metastasis.Thus,PLD1 blockade could inhibit PDAC progression.

[摘 要] 目的：探讨中药地黄提取物梓醇（Cat）对乳腺癌MCF-7细胞增殖与凋亡，以及裸鼠移植瘤生长的影响及其机制。方法：以不同质量浓度（0、5、25、50、100、200 μg/mL）Cat处理人乳腺癌MCF-7细胞，用MTT法筛选Cat给药浓度。将MCF-7细胞分为空白对照组、Cat低剂量组、Cat中剂量组、Cat高剂量组、Cat+sh-NC组和Cat+sh-FOXO3组，采用Edu细胞增殖实验、平板克隆实验、流式细胞术分别检测各组细胞的增殖与克隆形成能力、凋亡率和细胞周期，WB法检测各组细胞中FOXO3、FOXM1、caspase-3和caspase-8蛋白表达。构建乳腺癌MCF-7细胞裸鼠移植瘤模型，观察Cat对移植瘤生长的影响，WB法检测移植瘤组织中FOXO3和FOXM1蛋白表达。结果：Cat低（50 μg/mL）、中（100 μg/mL）、高（200 μg/mL）剂量处理的MCF-7细胞的增殖能力均显著下降（均P<0.05）。与空白对照组比较，Cat低、中、高剂量组Edu阳性细胞率、克隆形成数、S期与G2/M期细胞比例及FOXO3蛋白表达均显著降低（均P<0.05），细胞凋亡率、G0/G1期细胞比例及FOXM1、caspase-3、caspase-8蛋白表达均显著升高（均P<0.05）；与Cat+sh-NC组比较，Cat+sh-FOXO3组Edu阳性细胞率、克隆形成数、S期与G2/M期细胞比例及FOXO3蛋白表达均显著升高（均P<0.05），细胞凋亡率、G0/G1期细胞比例及FOXM1、caspase-3和caspase-8蛋白表达均显著下降（均P<0.05）。Cat组MCF-7细胞裸鼠移植瘤体积、质量和FOXO3蛋白表达均显著降低（均P<0.05），FOXM1的蛋白表达显著升高（P<0.05）。结论：Cat抑制乳腺癌MCF-7细胞增殖并促进凋亡，在体内抑制裸鼠移植瘤的生长，其机制可能与上调FOXO3、下调FOXM1的表达有关。

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.

Currently, the total ureteral avulsion are mainly secondary to ureteroscopy, and it is rarely caused by uterine evacuation clinically. This paper reported a case of total ureter avulsion after uterine evacuation, treating by ileal replacement for ureter under general anesthesia, and the surgical outcome was good. Uterine evacuation is a routine, less risky procedure, but it also can lead to serious complications such as total ureteral avulsion or bladder rupture. For potential high-risk patients with uterine evacuation, preventive measures such as accurate localization under B-ultrasound guidance or pre-operative ureteral stents indwelling are useful to avoid the occurrence of such serious complications. If total ureteral avulsion occurs, ileal replacement for ureter is a viable and effective treatment.