Objective The aim of this study was to investigate the effect of p38 on stem cell maintenance of pancreatic cancer. Methods Human pancreatic cancer cells PANC-1 were treated with different concentrations of 5-fluorouracil(5-FU)(0.5×IC₅₀, IC₅₀, and 2×IC₅₀) for 24 hours, and VX-702 (p38 phosphorylation inhibitor) was added, and the cells were inoculated in 6-well culture dishes with ultra-low adhesion to observe the changes of sphere tumors. The expression levels of cyclin-dependent kinase 2(CDK2), cyclin B1 and D1, Octamer-binding transcription factor 4(OCT4), SRY-box transcription factor 2(SOX2), Nanog and p38 were measured by Western blot. The mRNA expression levels of p38, OCT4, Nanog and SOX2 were tested by RT-PCR. Cell cycle, apoptosis, and the proportion of CD44⁺CD133⁺PANC-1 cells were evaluated by flow cytometry. Results The results showed that 5-FU inhibited the formation of tumor spheres in PANC-1 cells, increased CD44⁺CD133⁺cell fragments, down-regulated the expression of OCT4, Nanog and SOX2, and inhibited the stemness maintenance of PANC-1 tumor stem cells. Phosphorylation of PANC-1 cells was inhibited by a highly selective p38 MAPK inhibitor, VX-702(p38 mitogen-activated protein kinase inhibitor), which had the same effect as 5-FU treatment. When VX-702 combined with 5-FU was used to treat PANC-1 cells, the therapeutic effect was enhanced. Conclusion p38 inhibitors decreased PANC-1 cell activity and increased cell apoptosis. p38 inhibitors inhibit the stemness maintenance of pancreatic cancer stem cells.
Humans ; Phosphorylation/drug effects* ; Cell Line, Tumor ; p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors* ; Neoplastic Stem Cells/metabolism* ; Drug Resistance, Neoplasm/drug effects* ; Fluorouracil/pharmacology* ; Pancreatic Neoplasms/pathology* ; Apoptosis/drug effects* ; SOXB1 Transcription Factors/genetics* ; Octamer Transcription Factor-3/genetics*

Objective This study aimed to explore the relationships between residential greenness and cardiometabolic risk factors among rural adults in Xinjiang Uygur Autonomous Region(Xinjiang)and thus provide a theoretical basis and data support for improving the health of residents in this region. Methods We recruited 9,723 adult rural residents from the 51st Regiment of the Third Division of the Xinjiang Production and Construction Corps in September 2016.The normalized difference vegetation index(NDVI)was used to estimate residential greenness.The generalized linear mixed model(GLMM)was used to examine the association between residential greenness and cardiometabolic risk factors. Results Higher residential greenness was associated with lower cardiometabolic risk factor prevalence.After adjustments were made for age,sex,education,and marital status,for each interquartile range(IQR)increase of NDVI500-m,the risk of hypertension was reduced by 10.3%(OR=0.897,95%CI=0.836-0.962),the risk of obesity by 20.5%(OR=0.795,95%CI=0.695-0.910),the risk of type 2 diabetes by 15.1%(OR=0.849,95%CI=0.740-0.974),and the risk of dyslipidemia by 10.5%(OR=0.895,95%CI=0.825-0.971).Risk factor aggregation was reduced by 20.4%(OR=0.796,95%CI=0.716-0.885)for the same.Stratified analysis showed that NDVI500-m was associated more strongly with hypertension,dyslipidemia,and risk factor aggregation among male participants.The association of NDVI500-m with type 2 diabetes was stronger among participants with a higher education level.PM10 and physical activity mediated 1.9%-9.2%of the associations between NDVI500-m and obesity,dyslipidemia,and risk factor aggregation. Conclusion Higher residential greenness has a protective effect against cardiometabolic risk factors among rural residents in Xinjiang.Increasing the area of green space around residences is an effective measure to reduce the burden of cardiometabolic-related diseases among rural residents in Xinjiang.

Objective:To analyze the changes of fasting plasma glucose(FPG)level before and after menopause.Methods:Kailuan health checkup cohort was used to extract data of women aged≥18 years who participated in the first physical examination of Kailuan physical examination cohort and had menopausal age at the end of the seventh physical examination. A total of 3 749 women with 22 057 physical examination records were included in the analysis. Natural logarithmic transformation was applied to FPG, and a segmented linear mixed-effects model was used to analyze the changes in ln-transformed FPG before and after menopause. Additionally, an interaction analysis was performed to assess the multiplicative effect of baseline age and baseline body mass index(BMI)on ln-transformed FPG concerning pre- and post-menopausal periods.Results:The average age of the first physical examination for women in this study was (45.63±4.52)years, the median menopausal age was 51(50~53)years, and the median number of physical examinations was 6(5~7)times. The results of the piecewise linear mixed effect model showed that lnFPG increased from 1 year before menopause, with an average annual increase of 0.021 mmol/L, and continued to increase from menopause to 5 years after menopause, with an average annual increase of 0.007 mmol/L. LnFPG tended to be stable after 5 years of menopause. Baseline age could affect the changes of lnFPG before and after menopause, and there was a negative multiplicative interaction between baseline age ≥45 years and the time period from 6 years to 1 year before menopause( P=0.032). Women with baseline age ≥45 years had a higher average annual increase in lnFPG from 1 year before menopause to 5 years after menopause than women with baseline age <45 years( P<0.05). On lnFPG, there was a positive multiplicative interaction between baseline BMI and time segments around menopause. Compared to women with BMI <24.0 kg/m 2, obese women displayed more annual increase in lnFPG from 6 years to 1 year before menopause as well as from menopause to 5 years after menopause( P<0.05). Conclusions:Menopause has an adverse impact on FPG, with the most significant changes occurring within the period of one year before menopause and up to five years after menopause. Age and BMI significantly influence the changes in FPG before and after menopause.

BACKGROUND:Previous brain studies have mostly focused on adults and fetuses,and the developmental characteristics of young children's brainstems have rarely been studied. OBJECTIVE:To observe the brainstem development characteristics of healthy young children and to explore the age-related differences and their correlation with sex. METHODS:From January 2019 to April 2022,a retrospective study of 3.0T MRI images of 174 children aged 2 to 6 years in the Affiliated Hospital of Inner Mongolia Medical University was conducted,and the median sagittal diameter,area and angle of the brainstem(including midbrain,pons and medulla oblongata)were measured. RESULTS AND CONCLUSION:There is an age-related increase in the anterior and posterior diameters of the midbrain,pons and medulla oblongata in the 2-5 years old group as well as in the longitudinal diameter and area of the midbrain,pons and medulla oblongata in the 2-6 years old group.Except for the longitudinal diameter of the medulla oblongata,all others show a positive correlation with age(r>0,P<0.05).In the 2-3 years old group and 4-5 years old group,the children are in the rapid growth and development stage,and these two age groups can be used as the key observation indicators for the development of young children.The anterior-posterior diameter,longitudinal diameter,area of the pons and total brainstem area are strongly correlated with age,which can be used as the key observation indicators for the brainstem development in young children.

BACKGROUND:Inhibitory control and drug craving are the core elements of evaluating drug withdrawal in methamphetamine addicts,which has attracted much attention in academic circles.As we all know,in order to achieve complete abstinence from drug addiction,the key is to restore the damaged inhibition and control function of drug addicts and effectively reduce the craving for drugs. OBJECTIVE:To systematically analyze the relationship between exercise and methamphetamine abstinence inhibitory control and drug craving,to find out an effective exercise intervention scheme that can promote methamphetamine abstinence,and to further explore the internal mechanism of exercise,in order to provide theoretical support and applied reference for the future use of exercise in drug withdrawal. METHODS:CNKI,WanFang,VIP,Web of Science,and PubMed databases were searched for relevant literature using the keywords of"exercise,physical activity,methamphetamine,inhibitory function,craving,addiction"in Chinese and"sport*,exercise,methamphetamine,drug craving,executive function,addiction"in English.According to the inclusion and exclusion criteria,86 documents were finally included for review. RESULTS AND CONCLUSION:In terms of inhibitory control in methamphetamine abstinent individuals,either acute and long-term moderate-intensity aerobic exercise or acute high-intensity interval training can significantly improve the inhibitory control capacity of methamphetamine abstinent individuals.For long-term aerobic exercise,aerobic group exercise or full-body comprehensive exercise is more effective.If the exercise format is power cycling,it is recommended to increase the frequency of exercise intervention.In terms of the drug craving intensity in methamphetamine abstinent individuals,acute moderate-intensity aerobic exercise and resistance training,as well as long-term moderate-intensity,high-intensity,or progressive load aerobic and resistance training,can effectively reduce the drug craving in methamphetamine abstinent individuals.Exercise exerts intrinsic regulatory effects on methamphetamine-mediated addiction.Exercise can influence the expression of tyrosine hydroxylase in the brain's ventral tegmental area,thereby stimulating the expression of dopamine receptor coupling proteins and promoting dopamine synthesis in the brain's reward regions,thereby compensating for dopamine depletion caused by methamphetamine addiction.Furthermore,exercise can also regulate protein kinase A inhibitors,affecting the protein kinase A signaling pathway mediated by dopamine D1 receptors,by inhibiting protein kinase A,thus affecting cAMP response element-binding protein and regulating methamphetamine addiction.Additionally,exercise can also,at the genetic level,affect the expression of the c-fos gene in the brain's nucleus accumbens region,activate a subset of glutamatergic neurons in this area,generate a rewarding effect,and thus improve methamphetamine addiction.Although current research has confirmed the relationship between exercise and methamphetamine addiction and has clarified the brain mechanisms underlying the effects of exercise,whether there are other brain regulatory pathways for the effects of exercise remains to be explored through more scientifically rigorous animal or human experiments,starting from the cellular or molecular level.

OBJECTIVE To provide reference for improving the construction of China's emergency drugs supply guarantee mechanism. METHODS Based on the 4R model, the literature research method was used to carry out a systematic analysis of the management measures and operation of emergency drugs in China and the United States in four stages: reduction, readiness, response and recovery, and to make a side-by-side comparison. RESULTS The flexibility of the United States in its legal system had contributed to the maturity of strategic national stockpile, with a dedicated Administration for Strategic Preparedness and Response responsible for the implementation and management of the entire supply process, focusing on the development of information systems and the maintenance of physical stockpiles. In contrast, China's national pharmaceutical reserve emphasized its respective roles and responsibilities, with joint management of institutions, and the reserve tasks and transportation and distribution were mainly undertaken by enterprises, which provided more room for operation in the overall supply process, but the regulatory rules for enterprises had yet to be further improved. CONCLUSION It is recommended that China, on the basis of its own national conditions, draw on the characteristics and experience of the United States strategic national stockpile, improve and perfect the relevant laws and regulations as soon as possible, build a management system with an efficient management organization at its core, supplemented by an information management system, and at the same time, assist in promoting the virtuous cycle of rotational stockpiling by enterprises, and actively carry out summary and assessment work, in order to promote the optimization and development of the mechanism of guaranteeing the supply of emergency drugs in the long term.

Objective To identify factors associated with gastrointestinal heat retention in preschool children,and to provide a foundational understanding for future clinical investigations. Methods A case-control study was performed,which involved children from kindergartens in the Longgang District of Shenzhen City,Guangdong Province,from May to July 2021. Using the Children's Gastrointestinal Heat Retention Diagnostic Self-assessment Scale,subjects were allocated into a case group (children diagnosed with gastrointestinal heat retention) and a control group (children without this condition). An online survey was used to collect data on dietary behaviors,caregivers' feeding behaviors,early antibiotic use,daily routines,and birth conditions. SPSS 27.0 software was used to facilitate precise sociodemographic matching and paired logistic regression analysis to explore the association between gastrointestinal heat retention and the above factors. Results From the analysis of 51,252 matched cases,the study found that several factors contributed to an increased risk of gastrointestinal heat retention. These factors included reduced food intake compared to peers,reports of picky eating by caregivers,distractions during meals,pronounced dietary preferences,disinterest in food,meal durations ≥ 25 min,reluctance to sample new foods,consistent refusal of specific food types for over one month,irregular meal locations,coercive feeding practices,use of micronutrient supplements,allowing children too much freedom in food choice,persuading children to eat,infrequent encouragement to experiment with new foods,early antibiotic introduction,inadequate sleep,and premature birth (P<0.05). In contrast,exclusive breastfeeding in the first six months,engagement in moderate to massive physical activity,and regular napping patterns were associated with a reduced risk of gastrointestinal heat retention (P<0.05). Conclusion The suboptimal dietary habits,improper feeding practices,insufficient physical activity,inadequate sleep,and premature antibiotic exposure may be significant risk factors for gastrointestinal heat retention. Future research dedicated to unraveling the cause of gastrointestinal heat retention should prioritize these elements.

Herb-induced liver injury(HILI)tends to have complex toxic material basis and toxic mechanism,which greatly affects the safety of traditional Chinese medicine.This article summarizes the main toxic components of Chinese herbal medicine causing liver injury and their mechanism of action.The toxic components of Chinese herbal medicine causing liver injury can be classified into two categories of drug-derived and non-drug-derived toxic components.Drug-derived toxic components mainly include alkaloids,terpenoids,anthraquinones,and phenylpropanoids,and their mechanism of action involves oxidative stress,apoptosis and necrosis,CYP450 enzymes,and genotoxicity.Non-drug-derived toxic components mainly include pesticide residues,sulfur dioxide residues,heavy metals,fungi,and plant growth regulators,and their mechanisms involve oxidative stress,apoptosis,metabolic disorders,and CYP450 enzymes.On this basis,this article further proposes the unsolved problems and research difficulties,in order to promote the basic research on the hepatotoxicity of traditional Chinese medicine.

Background Schizophrenic patients have metabolic disorders,impaired language and information processing function.Inflammatory factors may play an important role in the occurrence and development of schizophrenia.Objective To explore the relationship of the inflammatory factor levels with metabolic levels,language fluency and information processing function in patients with schizophrenia,so as to provide references for clinical understanding of the neuropathological mechanisms of schizophrenia.Methods A total of 96 patients with schizophrenia were included in the study group,who were hospitalized in the Fourth People's Hospital of Hefei from January 2021 to December 2022 as well as met the diagnostic criteria of Diagnostic and Statistical Manual of Mental Disorders,fifth edition(DSM-5)and Mini-International Neuropsychiatric Interview(MINI)6.0.Meanwhile,population who underwent physical examination at the same hospital were included in the control group(n=42).A high-sensitivity multi factor electrochemiluminescence analyzer was used to detect the levels of inflammatory factors IL-4,IL-5,IL-7,IL-8,IL-10 and IL-13.A fully automated biochemical analyzer was used to detect the levels of metabolic indicators such as fasting blood glucose,triglycerides,high-density lipoprotein,apolipoprotein A,creatinine and urea nitrogen.Verbal fluency and information processing function of all participants were assessed by using Verbal Fluency Test(VFT)and Stroop Color Word Test(SCWT).Results There were statistically significant differences in the levels of IL-4,IL-5,IL-7,IL-8,IL-10,IL-13 and IL-15 between the study group and the control group(P<0.05).There were statistically significant differences in BMI,waist circumference,fasting blood glucose,triglycerides,high-density lipoprotein,urea nitrogen,apolipoprotein A and creatinine levels between the two groups(P<0.05).The differences in the correct number of household appliances,animals,fruits,vegetables,names starting with"water"and"self"in VFT between the two groups were statistically significant(P<0.05).The differences in point reaction time,character reaction time and character color reaction time in SCWT between the two groups were statistically significant(P<0.05).Correlation analysis showed that except for creatinine levels,the levels of IL-4 and IL-5 in patients with schizophrenia were correlated with other indicators(P<0.05).IL-7 levels were correlated with creatinine levels,household appliances,animals,fruits,correct number of names starting with"water"in VFT,point reaction time and word reaction time in SCWT(P<0.05).IL-8 levels were correlated with triglyceride levels,household appliances,animals,fruits,vegetables,correct number of names starting with"water"and"self"in VFT and word reaction time in SCWT(P<0.05).Except for creatinine levels and the correct number of names starting with"self",IL-10 levels were correlated with all other indicators(P<0.05).Except for creatinine and urea nitrogen levels,IL-13 levels were correlated with other indicators(P<0.05).Conclusion The levels of inflammatory factors in patients with schizophrenia may be related to their metabolic levels,language fluency and information processing function.