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*

AIM:To investigate the effect of polycomb group ring finger 3(PCGF3)on the viability and apop-tosis of OSCC cells and its potential mechanism.METHODS:The data were downloaded from the online public database to predict the expression of PCGF3 in OSCC and its relationship with pathological stage survival rate.Fifty pairs of OSCC tissues and adjacent tissues were selected to analyze the relationship between the expression of PCGF3 and the survival rate of patients.The expression level of PCGF3 in the specimens was detected by IHC,and the extracted cancer and adja-cent tissues were homogenized to analyze its mRNA expression.The mRNA and protein expression levels of PCGF3 in the cells were analyzed by RT-qPCR and Western blot experiments,and the protein expressions of PCGF3,p-PI3K,p-AKT,cyclin D1 and cleaved caspase-3(cl-caspase-3)were further analyzed.In addition,the effects of PCGF3 on cell viability and apoptosis were also detected.Finally,subcutaneous tumor models in nude mice were constructed to verify the above experiments.RESULTS:PCGF3 was highly expressed in OSCC and was closely related to pathological stage,pathologi-cal grade,and survival rate of patients.PCGF3 was highly expressed in OSCC tissues and cell lines in the network online databases.Western blot results showed that the expressions of PCGF3,p-PI3K,p-AKT,cyclin D1 and cl-caspase-3 were decreased and increased respectively after knocking down or overexpressing PCGF3 in OSCC cells.And cell viability and apoptosis were affected.The volume and weight of tumors in sh-PCGF3 group were lower than those in sh-NC group,and HE results showed that the nuclear atypotype of tumor cells in sh-PCGF3 group was less than that in sh-NC group.CON-CLUSION:PCGF3 can significantly affect the viability and apoptosis of OSCC cells,and its potential mechanism is to ac-tivate the PI3K/AKT signaling pathway to participate in the proliferation and apoptosis of OSCC cells.

The mechanism of tinnitus remains undear.Currently,in addition to tinnitus induced by ear disea-ses,various systems of the body are also involved in the pathogenesis of tinnitus.Obstructive sleep apnea hypopnea syndrome(OSAHS)may be related to tinnitus,which has garnered increasing attention in recent years.This article reviews the latest research progress on the occurrence and possible mechanism of tinnitus in OSAHS,shedding new light on the treatment of tinnitus.

Fetal STR typing of aborted tissue has long been a major problem in forensic DNA.Especially for the first trimester abortion tissue,it is difficult to isolate the embryonic components by histomorphological means,resulting in the inability to accurately obtain the STR typing of the fetus.The mixed STR typing results of mother and fetus can provide a key basis for the identification of suspects in cases of rape-induced pregnancy.In this study,next generation sequencing was used to successfully detect mixed STR typing of mother and suspected fetus or single STR typing of suspected fetus in 4 rape-induced early pregnancy abortion tissues.Combined with Y-STR and flank sequence information,it provides a more comprehensive and reliable genetic basis for the identification of suspects.

Objective To compare the effects of the left and right stellate ganglion resection on myocardial injury in rats with acute myocardial infarction(AMI).Methods According to the random number table method,30 healthy male Sprague Dawley rats were divided into the AMI group,left stellate ganglionectomy group,and right stellate ganglionectomy group,with 10 rats in each group.AMI models were prepared by ligation of the left anterior descending branch of the coronary artery in all the three groups.In the AMI group,the stellate ganglion was isolated(randomly left or right)without excision.The rats in the left and right stellate ganglionectomy groups underwent the left and right stellate ganglionectomy,respectively.At 24 hours after modeling,2 mL of subclavian venous blood was extracted from the three groups of rats.The serum levels of cardiac troponin Ⅰ(cTnⅠ),noradrenaline(NE),interleukin(IL)-1β,IL-6,tumor necrosis factor-α(TNF-α),malondialdehyde(MDA),and superoxide dismutase(SOD)were detected by enzyme-linked immunosorbent assay.The left ventricular fractional shortening(LVFS),left ventricular ejection fraction(LVEF)and cardiac output(CO)of rats in the three groups were measured by echocardiography one week after modeling.Results The serum levels of NE,cTnⅠ and MDA in the left and right stellate ganglionectomy groups were significantly lower than those in the AMI group,and SOD level was significantly higher than that in the AMI group(P＜0.05);the serum levels of NE,cTnⅠ and MDA in the right stellate ganglionectomy group were significantly lower than those in the left stellate ganglionectomy group,and SOD level was significantly higher than that in the left stellate ganglionectomy group(P＜0.05).The levels of serum IL-1β,IL-6 and TNF-α in the left and right stellate ganglionectomy groups were significantly lower than those in the AMI group(P＜0.05);the levels of serum IL-1β,IL-6 and TNF-αin the right stellate ganglionectomy group were significantly lower than those in the left stellate ganglionectomy group(P＜0.05).LVEF,LVFS and CO in the left and right stellate ganglionectomy groups were significantly higher than those in the AMI group,and LVEF and LVFS in the right stellate ganglionectomy group were significantly higher than those in the left stellate ganglionectomy group(P＜0.05);there was no significant difference in CO between the left and right stellate ganglionectomy groups(P＞0.05).Conclusion Stellate ganglionectomy has a protective effect on AMI induced by ligation of the left anterior descending branch of the coronary artery,which may be related to reducing inflammatory reaction and oxidative stress damage.The right stellate ganglion resection has more protective effects on cardiac function than the left stellate ganglion resection.

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 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 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.