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 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 explore the correlation between the total imaging burden of cerebral small vessel disease(CSVD)and heart rate variability(HRV)in elderly patients with hypertension.Methods A total of 256 elderly patients with hypertension admitted to Department of Neurolo-gy,Changzhou Second People's Hospital form September 2021 to December 2022 were consecu-tively recruited in this study.According to the total brain MRI burden,they were divided into scored 0-2 group(180 cases)and 3-4 group(76 cases).Their general clinical data and HRV parameters were compared between the two groups.Multivariate logistic regression analysis was used to analyze the relationship between HRV and total CSVD burden in these patients,and Spearman correlation analysis was employed used to analyze the correlation between HRV and to-tal CSVD burden,and between blood pressure variability and HRV.Results Older age,longer course of hypertension,and higher homocysteine level were observed in the group of scored 3-4 than the group of 0-2(P＜0.01).The former group had significantly lower SDNN,SDANN,ASDNN,rMSSD,PNN50,LF and HF when compared with the latter group(all P＜0.01).But there was no statistical difference in LF/HF ratio between the two groups(P＞0.01).Multivariate logistic regression analysis indicated that SDNN(OR=0.989,95％CI:0.979-0.999,P=0.034),SDANN(OR=0.988,95％CI:0.977-0.999,P=0.039)and rMSSD(OR=0.965,95％CI:0.938-0.994,P=0.016)were independent risk factors for total burden of severe CSVD in elderly hypertensive patients.Spearman correlation analysis showed that SDNN,SDANN,ASDNN,rMSSD,PNN50,LF and HF were negatively correlated with the total CSVD burden(P＜0.01);the standard deviation of 24-h SBP was negatively correlated with SDNN,SDANN and rMSSD(P＜0.01);the coefficient of variation of 24-h SBP was negatively correlated with SDNN,SDANN and rMSSD(P＜0.01).Conclusion HRV is an independent risk factor for total burden of severe CSVD in elderly hypertensive patients,and HRV parameters are negatively correlated with the to-tal CSVD burden.

The adhesive protein secreted by marine sessile animals can resist the resistance of water and exert stickiness under the humid environment. It has become a candidate for the development of high-performance materials in the field of biomedicine and bionics. Barnacles are as one of the marine macrofoulers that can be firmly attached to the underwater substrate materials with different surface characteristics through its cement proteins. To date, the adhesion process of barnacle has been understood in-depth, but the specific underwater adhesion mechanism has not been elucidated and needs further exploration. This review first presented an overview of barnacle and its adhesion process, followed by summarizing the advances of barnacle adhesive protein, its production methods, and applications. Moreover, challenges and future perspectives were prospected.
Animals ; Thoracica/metabolism* ; Proteins/metabolism* ; Adhesives/metabolism*

Objective To explore the correlation between the pathogenesis of coronary heart disease and the polymorphism of methylenetetrahydrofolate reductase ( MTHFR ) .Methods 130 cases of coronary heart disease diagnosed and treated in Heze Municiple Hospital from July 2015 to July 2017 were selected as observation group .At the same time,130 healthy people were selected as control group .The serum folate and homocysteine ( HCY) levels were compared between the two groups .At the same time, polymerase chain reaction -restriction fragment length polymorphism was used to analyze the MTHFR gene polymorphisms .The distribution of MTHFR gene polymorphism was compared between the two groups .Results The level of serum folic acid in the observation group was (5.76 ± 2.14)g/L,which was significantly lower than (7.34 ±2.43)g/L in the control group (t=5.64,P<0.05).The level of serum HCY in the observation group was (15.46 ±5.74)μmol/L,which was significantly higher than (10.28 ± 4.38)μmol/L in the control group (t=6.43,P<0.05).The frequencies of TT type,TC type and CC type of MTHFR gene in the observation group were 36.92％,46.92％and 16.15％,respectively.The frequencies of TT type,TC type and CC type of MTHFR gene in the control group were 21.54％,55.38％ and 23.08％,respectively.The frequency of TT type in the observation group was significantly higher than that of the control group (χ2 =8.25,P<0.05). There were no statistically significant differences in folic acid levels among different gene types in the observationgroup(t=1.31,0.55,0.73,all P>0.05),but the serum HCY level of TT type was significantly higher than that of CT type and CC type in the observation group (t=5.33,4.62,all P<0.05).Conclusion Serum folic acid level, HCY level and homozygous mutations of MTHFR gene type have certain relationship with the occurrence of coronary heart disease ,the body serum folic acid level and the distribution of MTHFR genotypes can affect the concentration of HCY,thus affecting the occurrence of coronary heart disease .

Objective To study the risk factors of lymph node metastasis in the central neck compartment of thyroid carcinoma,and to explore the reasonable range of lymph node dissection in central neck dissection for clinically node-negative papillary thyroid microcarcinoma patients.Methods From Dec.2015 to Dec.2016,a total of 200 patients with CN0 papillary thyroid carcinoma were randomly divided into two groups according to the registration number:unilateral central neck dissection group and bilateral central neck dissection group in Department of Thyroid Surgery,Fujian Medical University Union Hospital.The risk factors of lymph node metastasis and value of bilateral central neck dissection were analyzed.Results The risk factors of lymph node metastasis in the central papillary thyroid carcinoma were ≥0.7 cm in diameter and older than 45 years in age and gender in male.Further analysis found that contralateral central lymph node metastasis occurred in patients with tumor diameter ≥0.5 cm.The positive rate was 22％.The number of lymph nodes detected in the unilateral and bilateral central areas was 9.53±6.04 and 12.19±7.18,P=0.035,respectively.The positive numbers of lymph nodes were 1.17±1.47 and 2.11±2.75,P=0,022 respectively.Conclusion In patients with tumor diameter ≥0.5 cm,bilateral central neck dissection is conducive to improving the thoroughness of tumor dissection and does not increase the risk of complications.