BACKGROUND:Long non-coding RNA(LncRNA)plays an important role in nervous system development and neurological diseases.Previous studies by the research team have demonstrated that human umbilical cord mesenchymal stem cells overexpressing erythropoietin(EPO-MSCs)under ischemic and hypoxic conditions have better neuroprotective functions and significantly activate the expression of LncRNA XIST.Research suggests that XIST is related to the pathogenesis of hypoxic-ischemic encephalopathy,but the role and mechanism of its regulation by EPO-MSCs in protecting ischemic-hypoxic neurons remain unclear.OBJECTIVE:To explore the new mechanism by which LncRNA XIST,in response to EPO-MSC signaling,affects the apoptosis of ischemic-hypoxic SH-SY5Y cells.METHODS:(1)SH-SY5Y cell lines with knockdown of LncRNA XIST(sh-XIST)and negative control(NC-XIST)were constructed through lentiviral transfection.Oxygen-glucose deprivation was used to induce ischemic-hypoxic injury in the cells.Transwell chambers were used to create a non-contact co-culture system with EPO-MSCs,sh-XIST,and NC-XIST ischemic-hypoxic SH-SY5Y cells.Cell proliferation ability was detected using the CCK-8 assay.Cell migration ability was assessed using the scratch assay,and cell apoptosis was measured by flow cytometry.(2)RNA-seq bioinformatics analysis was performed to screen for differentially expressed genes and pathways between sh-XIST and NC-XIST cell lines.Dual-luciferase experiments were used to verify the relationship between miR-124-3p and the target genes XIST and GRIN1.qRT-PCR was conducted to validate the expression levels of downstream miR-124-3p and GRIN1 genes.(3)miR-124-3p inhibitors and mimics were added to verify phenotypic changes in SH-SY5Y cells after ischemic-hypoxic injury and co-culture with EPO-MSCs.RESULTS AND CONCLUSION:(1)Compared with the NC-XIST group,SH-SY5Y cells in the sh-XIST group showed reduced proliferation and migration abilities and increased apoptosis after ischemic-hypoxic injury and co-culture with EPO-MSCs.(2)Dual-luciferase experiments showed that miR-124-3p interacted with the target gene XIST.SH-SY5Y cells transfected with miR-124-3p mimics and co-cultured with EPO-MSCs showed decreased apoptosis after ischemic-hypoxic injury,while SH-SY5Y cells transfected with miR-124-3p inhibitors showed increased apoptosis after co-culture with EPO-MSCs.(3)Transcriptomic sequencing and bioinformatics analysis of sh-XIST revealed significant downregulation of the neuroactive ligand-receptor pathway and the key receptor gene GRIN1 for central nervous system development.(4)Dual-luciferase experiments showed that miR-124-3p interacted with GRIN1.GRIN1 expression was significantly downregulated in the sh-XIST group after ischemic-hypoxic injury compared with the NC-XIST group.These findings indicate that LncRNA XIST promotes GRIN1 expression by upregulating miR-124-3p,thereby reducing cell apoptosis after ischemic-hypoxic injury and co-culture with EPO-MSCs and enhancing proliferation and migration.sh-XIST can block this protective function.

Objective:To explore the spatial clustering of the mortality rate of cervical cancer in different counties (cities, districts) in Shandong Province from 1970 to 2021 and its 50-year changing trend, so as to provide basis for the implementation and evaluation of prevention and control strategies and programs such as cervical cancer screening, early diagnosis and treatment, human papilloma virus (HPV) vaccination, etc.Methods:The mortality data of cervical cancer were obtained from the death registration system of Shandong Province and the data of three retrospective surveys of death causes. The mortality rate and age-standardized mortality rate (using the population composition of China in 1964) are used to describe the changing trend of cervical cancer in different years. The contribution values of population factors and non-population factors in cervical cancer mortality change are calculated by mortality differential decomposition method. ArcGIS 10.8 software is used for spatial distribution and spatial autocorrelation analysis.Results:From 1970 to 2021, the crude mortality rate and age standardized mortality rate of cervical cancer in Shandong Province showed a trend of first rapid decline and then slow increase. The crude mortality rate and standardized mortality rate of female cervical cancer in Shandong Province in 1970-1974 were the highest, reaching 17.22/10 5 and 13.17/10 5, respectively. In 2004-2005, it dropped to the lowest levels of 1.50/10 5 and 0.83/10 5. Subsequently, it slowly rose to 4.12/10 5 and 1.56/10 5 in 2020-2021. The differential analysis of cervical cancer mortality in different years found that the change of cervical cancer mortality was caused by the combined action of population factors and non-population factors. Among them, demographic factors (aging population) led to the increase of cervical cancer mortality, but non-demographic factors (early diagnosis and treatment, HPV infection level, medical technology level, etc) lead to the decrease of cervical cancer mortality. Compared with 1970-1974, with the passage of time, the absolute values of the contribution values of population factors and non-population factors showed an increasing trend, while the contribution of non-population factors was greater than that of population factors, which led to the decline of cervical cancer mortality. From the perspective of spatial distribution, there were great regional differences in the mortality rate of cervical cancer in different counties of Shandong Province. In 2020-2021, the mortality rate of cervical cancer in all counties decreased to a great extent compared with that in 1970-1974, and the high-high and low-low concentration areas of cervical cancer mortality in different years changed obviously. The high-aggregation areas of the cervical cancer mortality rate in Shandong Province from 2020 to 2021 were mainly distributed in some counties and districts of Linyi City, Zaozhuang City, and Heze City in the southwest. Conclusions:There are significant temporal and spatial changes in the mortality rate of cervical cancer in Shandong Province from 1970 to 2021. According to these trends and their geographical and spatial clustering, prevention and control strategies of cervical cancer in different regions should be further formulated and evaluated.

Objective:To understand spatial aggregation of lung cancer mortality and its changing trends over the past fifty years in different counties and districts of Shandong Province from 1970 to 2021.Methods:The mortality data of lung cancer were obtained from the death registration system of Shandong province and three retrospective surveys of death cause. The mortality rate and age-standardized mortality rate were used to describe the changing trend of lung cancer in different years, and the contribution value of population factors and non-population factors in lung cancer mortality change was calculated by the mortality differential decomposition method. GeoDa 1.20 and ArcGIS 10.8 software were used for spatial autocorrelation analysis and visualization map display.Results:The crude mortality rate of lung cancer in Shandong Province showed a significant upward trend from 1970 to 2021, rising from 7.22 per 100 000 in 1970-1974 to 62.73 per 100 000 in 2020-2021, with an increase of 7.69 times. Meanwhile, the standardized mortality rate of lung cancer exhibited a trend of increasing first and then decreasing. The differential analysis of lung cancer mortality in different years revealed that changes in crude mortality rates were the result of the combined effects of demographic and non-demographic factors. The proportion of population factors (aging population) leading to an increase in lung cancer mortality rate rose from 2.12% in 1990-1992 to 40.20% in 2020-2021. From a spatial distribution perspective, there were significant regional differences in lung cancer mortality rates among counties (cities, districts) in Shandong Province across different eras. Compared to the period of 1970-1974, the lung cancer mortality rates in all counties and districts in 2020-2021 showed a considerable increase, and there were noticeable changes in the areas of high-high and low-low clustering of lung cancer mortality rates across different eras.Conclusion:There have been significant temporal and spatial changes in the mortality rate of lung cancer in Shandong Province from 1970 to 2021. The crude mortality rate has shown an upward trend, while the standardized mortality rate increases first and then decreases. The concentration of lung cancer mortality rates in counties and districts has also undergone significant changes.

Objective To evaluate the added value of ciprofol and to provide the reference for clinical selection of ciprofol and propofol in patient individualized anesthesia and sedation program.Methods The relative safety,relative effectiveness,innovation/suitability,and economy of propofol and ciprofol were compared and scored according to the Guidelines for Drug Added Value Evaluation based on Health Technology Evaluation.Results Compared with the value of propofol,the total value of ciprofol was 57 points,which was reflected as a small increase.The sedation effect of the two drugs was similar,but propofol had more economic cost advantages,and ciprofol was better than propofol in injection pain,hypotension,and other adverse reactions.Conclusion Propofol and ciprofol should be used reasonably in anesthesia and sedation,considering the health status and economic condition of patients.

Objective: To analyze the effects of health literacy on overweight and obesity among primary school students and their parents in terms of salt, oil and sugar reduction (referred to as the "three reductions"), so as to provide a theoretical basis for the development of obesity control measures. Methods: From March to April 2024, a total of 1 022 fourthgrade primary school students and 913 parents were surveyed in 24 classes in six counties in Shandong Province using multistage cluster random sampling, and physical measurements of primary school students were conducted. Pearsons correlation analysis and ordered multivariate Logistic regression were used to investigate the associations between health literacy of primary school students and their parents with overweight and obesity among children. Results: The detection rates of overweight and obesity primary school students in Shandong Province were 14.87% and 24.66%, respectively, with significant sex difference in obesity rate (29.46% for boys and 19.76% for girls) (χ2=12.93, P<0.01). In addition to students reducing oil scores, parental reducing salt,reducing oil,reducing sugar, comprehensive health literacy scores and students reducing salt,reducing sugar and comprehensive health literacy scores showed a negative relationship with students overweight and obesity (r=-0.10, -0.08, -0.07, -0.10, -0.04, -0.07, -0.03, P<0.05). The overweight and obesity rates among primary school students with high parental reducing salt,reducing oil,reducing sugar and composite health literacy scores were lower (OR=0.69, 0.69, 0.71, 0.63, P<0.05); and the overweight and obesity rate among students with high parental and low parental and high and low parental health literacy scores were lower (OR=0.68, 0.57, P<0.05). Conclusion Improving health literacy regarding "three reductions" for parents and children, especially parents, can effectively reduce the risk of childhood overweight and obesity.

Objective:To understand spatial aggregation of lung cancer mortality and its changing trends over the past fifty years in different counties and districts of Shandong Province from 1970 to 2021.Methods:The mortality data of lung cancer were obtained from the death registration system of Shandong province and three retrospective surveys of death cause. The mortality rate and age-standardized mortality rate were used to describe the changing trend of lung cancer in different years, and the contribution value of population factors and non-population factors in lung cancer mortality change was calculated by the mortality differential decomposition method. GeoDa 1.20 and ArcGIS 10.8 software were used for spatial autocorrelation analysis and visualization map display.Results:The crude mortality rate of lung cancer in Shandong Province showed a significant upward trend from 1970 to 2021, rising from 7.22 per 100 000 in 1970-1974 to 62.73 per 100 000 in 2020-2021, with an increase of 7.69 times. Meanwhile, the standardized mortality rate of lung cancer exhibited a trend of increasing first and then decreasing. The differential analysis of lung cancer mortality in different years revealed that changes in crude mortality rates were the result of the combined effects of demographic and non-demographic factors. The proportion of population factors (aging population) leading to an increase in lung cancer mortality rate rose from 2.12% in 1990-1992 to 40.20% in 2020-2021. From a spatial distribution perspective, there were significant regional differences in lung cancer mortality rates among counties (cities, districts) in Shandong Province across different eras. Compared to the period of 1970-1974, the lung cancer mortality rates in all counties and districts in 2020-2021 showed a considerable increase, and there were noticeable changes in the areas of high-high and low-low clustering of lung cancer mortality rates across different eras.Conclusion:There have been significant temporal and spatial changes in the mortality rate of lung cancer in Shandong Province from 1970 to 2021. The crude mortality rate has shown an upward trend, while the standardized mortality rate increases first and then decreases. The concentration of lung cancer mortality rates in counties and districts has also undergone significant changes.

BACKGROUND:Long non-coding RNA(LncRNA)plays an important role in nervous system development and neurological diseases.Previous studies by the research team have demonstrated that human umbilical cord mesenchymal stem cells overexpressing erythropoietin(EPO-MSCs)under ischemic and hypoxic conditions have better neuroprotective functions and significantly activate the expression of LncRNA XIST.Research suggests that XIST is related to the pathogenesis of hypoxic-ischemic encephalopathy,but the role and mechanism of its regulation by EPO-MSCs in protecting ischemic-hypoxic neurons remain unclear.OBJECTIVE:To explore the new mechanism by which LncRNA XIST,in response to EPO-MSC signaling,affects the apoptosis of ischemic-hypoxic SH-SY5Y cells.METHODS:(1)SH-SY5Y cell lines with knockdown of LncRNA XIST(sh-XIST)and negative control(NC-XIST)were constructed through lentiviral transfection.Oxygen-glucose deprivation was used to induce ischemic-hypoxic injury in the cells.Transwell chambers were used to create a non-contact co-culture system with EPO-MSCs,sh-XIST,and NC-XIST ischemic-hypoxic SH-SY5Y cells.Cell proliferation ability was detected using the CCK-8 assay.Cell migration ability was assessed using the scratch assay,and cell apoptosis was measured by flow cytometry.(2)RNA-seq bioinformatics analysis was performed to screen for differentially expressed genes and pathways between sh-XIST and NC-XIST cell lines.Dual-luciferase experiments were used to verify the relationship between miR-124-3p and the target genes XIST and GRIN1.qRT-PCR was conducted to validate the expression levels of downstream miR-124-3p and GRIN1 genes.(3)miR-124-3p inhibitors and mimics were added to verify phenotypic changes in SH-SY5Y cells after ischemic-hypoxic injury and co-culture with EPO-MSCs.RESULTS AND CONCLUSION:(1)Compared with the NC-XIST group,SH-SY5Y cells in the sh-XIST group showed reduced proliferation and migration abilities and increased apoptosis after ischemic-hypoxic injury and co-culture with EPO-MSCs.(2)Dual-luciferase experiments showed that miR-124-3p interacted with the target gene XIST.SH-SY5Y cells transfected with miR-124-3p mimics and co-cultured with EPO-MSCs showed decreased apoptosis after ischemic-hypoxic injury,while SH-SY5Y cells transfected with miR-124-3p inhibitors showed increased apoptosis after co-culture with EPO-MSCs.(3)Transcriptomic sequencing and bioinformatics analysis of sh-XIST revealed significant downregulation of the neuroactive ligand-receptor pathway and the key receptor gene GRIN1 for central nervous system development.(4)Dual-luciferase experiments showed that miR-124-3p interacted with GRIN1.GRIN1 expression was significantly downregulated in the sh-XIST group after ischemic-hypoxic injury compared with the NC-XIST group.These findings indicate that LncRNA XIST promotes GRIN1 expression by upregulating miR-124-3p,thereby reducing cell apoptosis after ischemic-hypoxic injury and co-culture with EPO-MSCs and enhancing proliferation and migration.sh-XIST can block this protective function.

Objective To evaluate the added value of ciprofol and to provide the reference for clinical selection of ciprofol and propofol in patient individualized anesthesia and sedation program.Methods The relative safety,relative effectiveness,innovation/suitability,and economy of propofol and ciprofol were compared and scored according to the Guidelines for Drug Added Value Evaluation based on Health Technology Evaluation.Results Compared with the value of propofol,the total value of ciprofol was 57 points,which was reflected as a small increase.The sedation effect of the two drugs was similar,but propofol had more economic cost advantages,and ciprofol was better than propofol in injection pain,hypotension,and other adverse reactions.Conclusion Propofol and ciprofol should be used reasonably in anesthesia and sedation,considering the health status and economic condition of patients.

Objective:To explore the spatial clustering of the mortality rate of cervical cancer in different counties (cities, districts) in Shandong Province from 1970 to 2021 and its 50-year changing trend, so as to provide basis for the implementation and evaluation of prevention and control strategies and programs such as cervical cancer screening, early diagnosis and treatment, human papilloma virus (HPV) vaccination, etc.Methods:The mortality data of cervical cancer were obtained from the death registration system of Shandong Province and the data of three retrospective surveys of death causes. The mortality rate and age-standardized mortality rate (using the population composition of China in 1964) are used to describe the changing trend of cervical cancer in different years. The contribution values of population factors and non-population factors in cervical cancer mortality change are calculated by mortality differential decomposition method. ArcGIS 10.8 software is used for spatial distribution and spatial autocorrelation analysis.Results:From 1970 to 2021, the crude mortality rate and age standardized mortality rate of cervical cancer in Shandong Province showed a trend of first rapid decline and then slow increase. The crude mortality rate and standardized mortality rate of female cervical cancer in Shandong Province in 1970-1974 were the highest, reaching 17.22/10 5 and 13.17/10 5, respectively. In 2004-2005, it dropped to the lowest levels of 1.50/10 5 and 0.83/10 5. Subsequently, it slowly rose to 4.12/10 5 and 1.56/10 5 in 2020-2021. The differential analysis of cervical cancer mortality in different years found that the change of cervical cancer mortality was caused by the combined action of population factors and non-population factors. Among them, demographic factors (aging population) led to the increase of cervical cancer mortality, but non-demographic factors (early diagnosis and treatment, HPV infection level, medical technology level, etc) lead to the decrease of cervical cancer mortality. Compared with 1970-1974, with the passage of time, the absolute values of the contribution values of population factors and non-population factors showed an increasing trend, while the contribution of non-population factors was greater than that of population factors, which led to the decline of cervical cancer mortality. From the perspective of spatial distribution, there were great regional differences in the mortality rate of cervical cancer in different counties of Shandong Province. In 2020-2021, the mortality rate of cervical cancer in all counties decreased to a great extent compared with that in 1970-1974, and the high-high and low-low concentration areas of cervical cancer mortality in different years changed obviously. The high-aggregation areas of the cervical cancer mortality rate in Shandong Province from 2020 to 2021 were mainly distributed in some counties and districts of Linyi City, Zaozhuang City, and Heze City in the southwest. Conclusions:There are significant temporal and spatial changes in the mortality rate of cervical cancer in Shandong Province from 1970 to 2021. According to these trends and their geographical and spatial clustering, prevention and control strategies of cervical cancer in different regions should be further formulated and evaluated.

Objective:To analyze the trend of incidence and mortality of thyroid cancer and estimate its age-period-cohort effect in Shandong Province from 2012 to 2022.Methods:The Joinpoint regression was used to analyze the trend of incidence and mortality of thyroid cancer and calculate the average annual percentage change (AAPC) based on the data on thyroid cancer from 2012 to 2022. The age-period-cohort model was used to analyze the age-effect, time-effect and cohort-effect of thyroid cancer risk in the population aged over 20 years.Results:From 2012 to 2022, the incidence of thyroid cancer in Shandong province showed a significant upward trend, with an AAPC of 21.68% (95% CI: 19.14%-24.27%, P<0.001). The incidence of females was higher than that of males, and the incidence of urban areas was higher than that of rural areas. The trend of thyroid cancer mortality was relatively stable with an AAPC of -3.04% (95% CI:-8.81%-3.09%, P=0.323). The age effect of incidence increased with age before 60 years old and decreased with age after 60 years old. The incidence peaked in the age group of 55-59. The period effect increased with time. The cohort effect showed that the cohort born before 1957 had a downward trend over time, while the cohort born after 1957 had an upward trend. Conclusion:The incidence of thyroid cancer in Shandong shows a rising trend from 2012 to 2022. Age is an important factor affecting the risk of thyroid cancer. The mortality of thyroid cancer remains stable.