BACKGROUND:Psoralen has a strong anti-osteoporotic activity and may have a restorative effect on chemotherapy-induced osteoporosis. OBJECTIVE:To explore the restorative effect of psoralen on the osteogenic differentiation of bone marrow mesenchymal stem cells in mice inhibited by cyclophosphamide and its mechanism. METHODS:C57BL/6 mouse bone marrow mesenchymal stem cells were isolated and cultured.Effect of psoralen on viability of bone marrow mesenchymal stem cells was detected by MTT assay.Osteogenic induction combined with alkaline phosphatase staining was used to determine the optimal dose of psoralen to restore the osteogenic differentiation of bone marrow mesenchymal stem cells inhibited by cyclophosphamide.The mRNA expression levels of Runx2,alkaline phosphatase,Osteocalcin,osteoprotegerin,and Wnt/β-catenin signaling pathway-related genes Wnt1,Wnt4,Wnt10b,β-catenin,and c-MYC were measured by RT-qPCR at different time points under the intervention with psoralen.The protein expression of osteogenic specific transcription factor Runx2 and Wnt/β-catenin signaling pathway related genes Active β-catenin,DKK1,c-MYC,and Cyclin D1 was determined by western blot assay at different time points under the intervention with psoralen. RESULTS AND CONCLUSION:(1)There was no significant effect of different concentrations of psoralen on the viability of bone marrow mesenchymal stem cells.The best recovery of the inhibition of osteogenic differentiation of bone marrow mesenchymal stem cells caused by cyclophosphamide was under the intervention of psoralen at a concentration of 200 μmol/L.(2)Psoralen reversed the reduction in osteogenic differentiation marker genes Runx2,alkaline phosphatase,Osteocalcin and osteoprotegerin mRNA expression and Runx2 protein expression in bone marrow mesenchymal stem cells caused by cyclophosphamide conditioned medium.(3)Psoralen reversed the decrease in Wnt/β-catenin pathway-related genes Wnt4,β-catenin,c-MYC mRNA and Active β-catenin,c-MYC,and Cyclin D1 protein expression and the increase in DKK1 protein expression in bone marrow mesenchymal stem cells caused by cyclophosphamide conditioned medium.(4)The results showed that cyclophosphamide inhibited osteogenic differentiation of bone marrow mesenchymal stem cells in mice,and psoralen had a restorative effect on it.The best intervention effect was achieved at a concentration of 200 μmol/L psoralen,and this protective effect might be related to the activation of Wnt4/β-catenin signaling pathway by psoralen.

Objective:To understand the characteristics and trends of acute myocardial infarction (AMI) in Shandong Province and to provide evidence for formulating prevention and control strategies.Methods:Data were derived from the AMI incidence reports of Shandong Province's Chronic Disease Surveillance Information Management System in 2012-2021. The crude and standardized incidence rates were used as indicators to describe the incidence level of AMI. Joinpoint regression analysis was used to analyze the trends in the incidence and age of onset over the years. The contribution of population aging to the increase in AMI incidence was assessed using the rate difference decomposition method. The incidence of AMI in each district (county) in Shandong Province was visualized using ArcGIS 10.8 software, and global and local spatial autocorrelation analysis was performed using DeoDa 1.12 software.Results:From 2012 to 2021, 198 233 cases of AMI were reported from 19 provincial monitoring sites in Shandong Province, of which 53.13% were males and 97.12% were ≥45 years old. The reported crude incidence increased from 90.12 per 100 000 in 2012 to 176.54 per 100 000 in 2021, with an average annual increase of 7.01% ( Z=7.35 , P<0.001). There was no significant upward trend in standardized incidence ( Z=1.64 , P=0.140), but the standardized incidence of male residents showed an increasing trend ( Z=2.76 , P=0.028). Before 2014, the reported crude incidence of males was similar to that of females, but after 2014, the reported crude incidence of males was continuously higher than that of females. However, males' standardized incidence was higher than females in all years. Both crude and standardized incidence rates were higher in rural residents than in urban areas. The median onset of AMI increased from 71.6 years old in 2012 to 73.5 years old in 2021. The median age of onset in males was lower than that in females in all years, and in most years, the median age of onset in urban residents was lower than that in rural residents. The incidence of AMI in males showed a trend in younger age groups. According to the seasonal decomposition, the incidence peak of AMI was in January, and the trough was in September. The contribution of aging population to the increase in crude incidence of AMI increased from 8.63% in 2013 to 52.58% in 2021. The global spatial autocorrelation analysis showed that the incidence of AMI presented an obvious spatial clustering distribution. Local spatial autocorrelation analysis found that the high-incidence areas (counties) were mainly concentrated in Liaocheng City and Dezhou City in the northwest region of Shandong Province and Heze City in the southwest. Conclusions:The incidence of AMI among residents in Shandong Province was rising, with spatial clustering and seasonal clustering characteristics. People aged 45 years and older, male residents, and rural residents were at high risk of developing AMI. There was a certain trend of younger age at onset among men. Targeted prevention and control measures should be taken for high-incidence seasons, high-risk groups, and high-incidence clustering areas in northwestern Shandong Province.

Objective To investigate the predictive value of vitamin D,sex hormones and their receptors in the development and regression of male patients with clinical isolated syndrome(CIS).Methods A total of 40 male CIS patients were included in the CIS group and 30 healthy subjects matched in age and long-term res-idence were included in the control group.The levels of vitamin D[1,25(OH)2D2 and 1,25(OH)2D3]inpe-ripheral blood of the included individuals and the first relapsed multiple sclerosis patients(MS group)were detected by ultra-high-performance liquid chromatography-tandem mass spectrometry.The levels of testoster-one(T),progesterone(P),and estradiol(E2)in peripheral blood were detected by electrochemiluminescence.Estrogen receptor(ERα,ERβ),androgen receptor(AR)and vitamin D receptor(VDR)levels in lymphocyte supernatant were detected by enzyme-linked immunosorbent assay(ELISA).Results After a median follow-up of 31.5 months,29 patients(72.5％)with CIS were converted to multiple sclerosis.Compared with pa-tients with non-recurrent CIS patients,patients with multiple sclerosis had a younger age of onset and were prone to positive oligoclonal bands.Compared with HC group,vitamin D levels were reduced in CIS patients,and the difference was statistically significant(P＜0.05).When CIS patients reverted to multiple sclerosis,se-rum levels of E2,ERα,and ERβ were elevated compared with those before relapse,and the levels of testosteroneand AR were decreased,and the difference was statistically significant(P＜0.05).Correlation analysis showed no correlation between peripheral blood levels of vitamin D,sex hormones and their receptors and EDSS in CIS patients.Conclusion Male CIS patients with younger onset age and positive oligoclonal bands are prone to transition to multiple sclerosis.The decrease of vitamin D level may be associated with the onset of male CIS.Vitamin D,sex hormones,and their receptors have no predictive value in the conversion of CIS to multiple sclerosis.

Objective:To estimate the deaths and life expectancy losses attributed to diet with high salt in Shandong province.Methods:Based on 24 h urinary sodium and blood pressure levels from the final evaluation survey of Shandong-Ministry of Health Action on Salt and Hypertension Project (SMASH) in 2016 and death cause data from Shandong Mortality Surveillance System, the population attributable fractions (PAF) and the deaths due to high-salt diet were calculated based on the framework of comparative risk assessment and the life expectancy loss was calculated by life table method.Results:A total of 32 987 deaths caused by high-salt diets were reported in 2016, accounting for 11.74% of related disease deaths and 4.95% of all deaths. The proportion of deaths due to high-salt diet in men (13.51%) was higher than that in women (9.17%). Cardiovascular diseases were the major causes of deaths due to high salt diet, accounting for 90.82% of all disease deaths caused by high-salt diets. The other causes were gastric cancer (8.10%) and chronic kidney disease (1.08%). The PAF in urban residents (13.87%) was higher than that in rural residents (10.87%). A loss of 0.58 years of the life expectancy were attributed to the high-salt diet. The different diseases caused by high-salt diet had different effects on life expectancy loss, ischemic heart disease ranked first, followed by cerebral hemorrhage and cerebral infarction.Conclusions:The proportion of deaths attributed to high-salt diets was high in Shandong. Cardiovascular diseases were the most important causes of deaths caused by high-salt diets. High-salt diet is still seriously affecting the health of residents in Shandong, indicating that salt reduction interventions need to be strengthened.

Objective:To investigate the distribution characteristics and trends of mortality and spatial aggregation of gastric cancer in Shandong Province from 1970 to 2013.Methods:The mortality data of gastric cancer from 1970 to 1974, 1990 to 1992 and 2004 to 2005 were collected from the first, second and third retrospective sampling survey of causes of death in Shandong Province, respectively. The mortality data of gastric cancer from 2011 to 2013 were collected from the all-cause surveillance data of Shandong Province. The crude mortality rate and age-standardized mortality rate were used to describe the death level of gastric cancer. The age-standardized mortality rate of Shandong Province was calculated based on Segi′s world standard population, and the age-standardized mortality rate of counties (cities and districts) was calculated based on the Chinese population in 1964.The factors influencing the difference of gastric cancer mortality in different periods were decomposed by using the method of differential decomposition of mortality, and the contributions of population and non-population factors in different periods were estimated.Using ArcGIS 10.2 software, the death level of gastric cancer in different counties (cities and districts) in Shandong province from 1970 to 1974 and 2011 to 2013 were visualized. DeoDa 1.12 software was used for global and local spatial autocorrelation analysis.Results:The crude death rate and age-standardized death rate of gastric cancer in Shandong province increased firstly and then decreased during 1970-2013, and the crude death rate of gastric cancer increased from 18.33/100 000 in 1970-1974 to 28.51/100 000 in 2011-2013. Segi′s age-standardized mortality rate for gastric cancer decreased from 20.94 per 100 000 in 1970-1974 to 18.17 per 100 000 in 2011-2013.From 1990 to 1992, from 2004 to 2005 and from 2011 to 2013, the contribution value of non-population factors to the increase of crude gc mortality was 95.59%, 48.45% and -20.57%, respectively, showing a continuous downward trend. The Moran′s I index of crude mortality of gastric cancer in Shandong province from 1970 to 1974 and from 2011 to 2013 were 0.77 and 0.57, respectively, and the Moran′s I index of age-normalized mortality was 0.75 and 0.44, respectively. Local autocorrelation analysis showed that there were 31 and 19 high aged-mortality areas of gastric cancer in 1970-1974 and 2011-2013 respectively, and 7 overlapping counties (cities and districts), 6 of which were located in Jiaodong area. Conclusion:The crude mortality and age-standardized mortality of gastric cancer in Shandong province increased first and then decreased from 1970 to 2013, and the distribution of gastric cancer mortality had obvious spatial aggregation and changed with time.

Objective:To investigate the distribution characteristics and trends of mortality and spatial aggregation of gastric cancer in Shandong Province from 1970 to 2013.Methods:The mortality data of gastric cancer from 1970 to 1974, 1990 to 1992 and 2004 to 2005 were collected from the first, second and third retrospective sampling survey of causes of death in Shandong Province, respectively. The mortality data of gastric cancer from 2011 to 2013 were collected from the all-cause surveillance data of Shandong Province. The crude mortality rate and age-standardized mortality rate were used to describe the death level of gastric cancer. The age-standardized mortality rate of Shandong Province was calculated based on Segi′s world standard population, and the age-standardized mortality rate of counties (cities and districts) was calculated based on the Chinese population in 1964.The factors influencing the difference of gastric cancer mortality in different periods were decomposed by using the method of differential decomposition of mortality, and the contributions of population and non-population factors in different periods were estimated.Using ArcGIS 10.2 software, the death level of gastric cancer in different counties (cities and districts) in Shandong province from 1970 to 1974 and 2011 to 2013 were visualized. DeoDa 1.12 software was used for global and local spatial autocorrelation analysis.Results:The crude death rate and age-standardized death rate of gastric cancer in Shandong province increased firstly and then decreased during 1970-2013, and the crude death rate of gastric cancer increased from 18.33/100 000 in 1970-1974 to 28.51/100 000 in 2011-2013. Segi′s age-standardized mortality rate for gastric cancer decreased from 20.94 per 100 000 in 1970-1974 to 18.17 per 100 000 in 2011-2013.From 1990 to 1992, from 2004 to 2005 and from 2011 to 2013, the contribution value of non-population factors to the increase of crude gc mortality was 95.59%, 48.45% and -20.57%, respectively, showing a continuous downward trend. The Moran′s I index of crude mortality of gastric cancer in Shandong province from 1970 to 1974 and from 2011 to 2013 were 0.77 and 0.57, respectively, and the Moran′s I index of age-normalized mortality was 0.75 and 0.44, respectively. Local autocorrelation analysis showed that there were 31 and 19 high aged-mortality areas of gastric cancer in 1970-1974 and 2011-2013 respectively, and 7 overlapping counties (cities and districts), 6 of which were located in Jiaodong area. Conclusion:The crude mortality and age-standardized mortality of gastric cancer in Shandong province increased first and then decreased from 1970 to 2013, and the distribution of gastric cancer mortality had obvious spatial aggregation and changed with time.

HDA9, a member of the deacetylase family, plays a vital role in regulating plant flowering time through flowering integrator SOC1 and AGL24. However, it remains elusive how HDA9 interacts with SOC1 and AGL24 in flowering time control. Here, HDA9 was cloned in Brassica juncea and then its three active sites were separately replaced with Ala via overlap extension PCR. Thus, mutants of HDA9(D172A), HDA9(H174A) and HDA9(D261A) were constructed and fused into the pGADT7 vector. The yeast one-hybrid assays indicated that HDA9 mutants remained the interactions with the promoters of SOC1 and AGL24. Furthermore, the aforementioned results were confirmed in the dual luciferase assays. Interestingly, the DNA-protein interactions were weakened significantly due to the mutation in the three active sites of HDA9. It suggested that flowering signal integrator SOC1 and AGL24 were regulated by the key amino acid residues of 172th, 174th and 261th in HDA9. Our results provide valuable information for the in-depth study of the biological function and molecular regulation of HDA9 in Brassica juncea flowering time control.
Flowers ; genetics ; Gene Expression Regulation, Plant ; genetics ; Mustard Plant ; enzymology ; genetics ; Mutation ; Plant Proteins ; genetics ; metabolism ; Promoter Regions, Genetic ; genetics

Objective:Breast cancer has been the first cancer among women with the incidence increasing gradually. In September 2016, the Breast Cancer Cohort Study in Chinese Women (BCCS-CW) was initiated, aiming to establish a standardized and sharable breast cancer-specific cohort by integrating the existing cohort resource and improving the quality of follow-up. The BCCS-CW may provide a research basis and platform for the precision prevention and treatment of breast cancer in etiology identification, prevention, early diagnosis, treatment, and prognosis prediction.Methods:We conducted a population-based perspective cohort by questionnaire interview, anthropometry, biological specimens, breast ultrasound and mammography. The cohort was followed by using regional health surveillance and ad hoc survey.Results:Finally, BCCS-CW included 112 118 women, in which 55 419 women completed the standardized investigation and blood specimens were collected from 54 304 women. The mean age of participants was 51.7 years old, 62.7% were overweight or obese, and 48.9% were menopausal.Conclusion:The BCCS-CW will provide population-based cohort resource and research platform for the precise prevention and treatment of breast cancer in Chinese women.

Early hemoperfusion in poisoned patients can remove poisons rapidly and effectively, which plays an important role in improving the prognosis of patients. The key of hemoperfusion therapy is the safe and effective anticoagulation. The local citrate anticoagulation effect acid is good, it also has little effect on the systemic coagulation mechanism and internal environment of patients, so it is worthy of promotion. We retrospectively analyzed the clinical data and treatment of 273 patients who were poisoned by citrate anticoagulant in the emergency intensive care unit of the Second Affiliated Hospital of Shandong First Medical University, aiming at perfusion of citrate anticoagulant in patients with poisoning. Provide a certain clinical reference.

In order to evaluate the intervention effect of the school-based salt reduction model, 28 primary schools were selected in Shandong Province in September 2014 and randomly divided into intervention group (1 361 students, 1 306 parents) and control group (1 364 students,1 340 parents). A series of "small hands and big hands" salt reduction intervention activities were conducted in intervention group for 8 months. After the intervention, the total awareness rate of salt reduction knowledge, the total holding rate of related beliefs and the total reporting rate of related behaviors were 70.65%, 80.30% and 67.03% among students, and 85.66%, 93.77% and 87.93% among parents, in the intervention group, which were higher than those in the control group (37.12%, 66.52% and 50.07% among students; 55.11%, 87.52% and 57.96% among parents) (all P values <0.05). The school-based salt reduction model is effective and feasible.