To investigate the association between neutrophil to lymphocyte ratio (NLR) andestimated glomerular filtration rate (eGFR) in patients with diabetes using large-scale data.

AIM:To investigate the mechanism of Piezo1 channel activation promoting the increase in intra-cellular Ca2+ concentration([Ca2+]i)of rat coronary artery smooth muscle cells(CASMCs).METHODS:The primary CASMCs of SD rats were cultured,and the expression and subcellular localization of Piezo1 in the cells were observed by immunofluorescence staining.The Piezo1 and stromal interaction molecule 1(STIM1)in CASMCs were knocked down by siRNA transfection,and the expression levels of the proteins were detected by Western blot.Utilizing laser confocal mi-croscopy,the change of[Ca2+]i in CASMCs was detected by Fluo-4 AM fluorescent probes.RESULTS:It was confirmed by immunofluorescence staining that the expression of Piezo1 existed in primary rat CASMCs.Immunofluorescence staining also showed that Piezo1 was co-located with sarco-/endoplasmic reticulum Ca2+-ATPase 2(SERCA2),mitochondrial outer membrane protein TOM20 and nuclear membrane protein lamin B1.Western blot results showed that the protein expres-sion levels of STIM1 and Piezo1 were significantly down-regulated by siRNA transfection(P<0.05).Compared with con-trol group,Yoda1,the agonist of Piezo1,could increase the extracellular Ca2+ influx of CASMCs(P<0.01).However,the Ca2+ influx mediated by Yoda1 was not affected by the inhibition of L-type calcium channels.Treatment with Yoda1 in-creased the intracellular Ca2+ release of CASMCs(P<0.01).However,inhibition of calcium channels on endoplasmic re-ticulum,ryanodine receptor and inositol 1,4,5-triphosphate receptor,did not affect intracellular Ca2+ release mediated by Yoda1.After the Ca2+ in endoplasmic reticulum was emptied using thapsigargin(TG),Yoda1 also mediated the Ca2+ re-lease of other organelles in CASMCs(P<0.01).After inhibition of L-type calcium channels,treatment with store-operated calcium channel(SOCC)inhibitor BTP2 or knockdown of STIM1 led to the decrease in extracellular Ca2+ influx of CASMCs mediated by Yoda1(P<0.01).Treatment with TG increased the release of Ca2+ from the endoplasmic reticulum of CASMCs after knockdown of Piezo1(P<0.05),but the extracellular Ca2+ influx mediated by TG was not affected.After inhibition of L-type calcium channels and SOCC,knockdown of Piezo1 led to the decreases in intracellular Ca2+ release and extracellular Ca2+ influx induced by Yoda1(P<0.01).CONCLUSION:The Piezo1 agonist orchestrates the influx of extracellular Ca2+ by activating Piezo1 channels on the cell membrane and inducing the indirect activation of SOCC.More-over,it facilitates the release of Ca2+ from organelles.Consequently,these pathways synergistically elevate the[Ca2+]i of rat CASMCs.

AIM:To investigate the influence of fat mass and obesity-associated(Fto)gene on the aberrant contraction of aortic smooth muscle in diabetes mellitus(DM)mice,and to explore the mechanism of Fto gene underlying the calcium regulation.METHODS:Smooth muscle-specific Fto gene knockout(FtoSMKO)mice were generated using Cre-loxP technology.The experiment involved 3 groups of mice:wild-type(WT)group,DM model group and FtoSMKO-DM group,with 15 mice in each group.In DM group and FtoSMKO-DM group,type 1 DM was induced by intraperitoneal injec-tion of streptozotocin.The mice in WT group were injected with equal volume of citric acid-sodium citrate buffer solution.The influences of different drugs on the contraction responses of aortic smooth muscle in mice were analyzed using a multi-myograph system.The expression level of FTO protein in the aortic tissues was detected by Western blot.RESULTS:(1)Compared with WT mice,the expression levels of FTO protein in the aortic tissues of DM mice were significantly in-creased(P＜0.01).(2)The expression level of FTO protein in smooth muscle was significantly decreased after knockout of Fto gene(P＜0.01).Compared with WT group,the mice in DM group exhibited a significant decrease in body weight and a marked increase in fasting blood glucose level(P＜0.05).There were no noticeable differences in body weight or fasting blood glucose level between FtoSMKO-DM group and DM group(P＞0.05).(3)The contraction responses of aortic smooth muscle in DM group were substantially increased by phenylephrine compared with WT group.Specifically,vaso-constriction responses mediated by non-L-type calcium channels and store-operated calcium channels(SOCC)were signifi-cantly enhanced in DM group.In addition,the responses mediated by inositol 1,4,5-trisphosphate receptors(IP3R),which facilitate calcium release from the sarcoplasmic reticulum,were significantly enhanced.However,the responses mediated by caffeine-activated ryanodine receptors(RyR),which also facilitate calcium release from the sarcoplasmic re-ticulum,were significantly inhibited(P＜0.05).(4)Compared with DM group,the phenylephrine-induced contraction re-sponses of aortic smooth muscle in FtoSMKO-DM group were greatly weakened(P＜0.05).In particular,the vasoconstriction responses mediated by non-L-type calcium channels and SOCC in FtoSMKO-DM group were greatly suppressed(P＜0.05),while those mediated by caffeine-activated RyR were dramatically boosted(P＜0.05).However,IP3R-mediated responses were not affected(P＞0.05).CONCLUSION:Smooth muscle-specific Fto gene knockout suppresses contractile hyperre-sponsiveness in the aortic smooth muscle of DM mice,which may be attributed to involvement of FTO protein in calcium regulation in the vascular smooth muscle.

AIM:The objective of this study is to examine the expression of profilin 1(PFN1)in mice with di-abetic nephropathy and determine its association with immune cell infiltration.METHODS:This study presents an analy-sis of PFN1 expression and immune cell infiltration in patients with diabetic nephropathy,utilizing transcriptome expres-sion data from kidney tissue microarray.Additionally,the findings were validated in a diabetic nephropathy mouse model.Sixteen C57BL/6 mice were randomly assigned into two groups,namely the normal group and the model group,in an equal manner.The model group underwent the establishment of the diabetic nephropathy model through intraperitoneal injection of streptozotocin.Subsequently,the expression levels of CD11b,F4/80,CC chemokine receptor 4(CCR4),interleukin-1 receptor type I(IL-1R1),B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax)and caspase-3 in kidney tissue were assessed upon successful establishment of the diabetic nephropathy model.Furthermore,the overexpression of PFN1 was observed in a cellular model of diabetic nephropathy,and the protein expression levels of monocyte chemotactic pro-tein-1(MCP-1)and caspase-3 were assessed.RESULTS:The expression of PFN1 was found to be significantly in-creased in the GSE30122 dataset of transcriptome expression in kidney tissues affected by diabetic nephropathy(P＜0.01).This increase in PFN1 expression was found to be correlated with the presence of macrophages and T cells.Fur-thermore,the renal tissue of the diabetic nephropathy model group exhibited significant pathological changes.In this mod-el group,the expression levels of PFN1,CD11b,F4/80,CCR4,IL-1R1,Bax,Bcl-2,and caspase-3 were all significant-ly increased(P＜0.01).Overexpression of PFN1 could enhance the expression of MCP-1 and caspase-3 proteins.CON-CLUSION:Macrophages and Th17 cells were identified within the renal tissue of mice with diabetic nephropathy,con-comitant with an up-regulation in the expression of PFN1.This up-regulation was observed to facilitate the induction of apoptosis in the context of diabetic nephropathy.

Objective To explore the mediating role of eating disorders in the relationship between body image satisfaction and anxiety symptoms among college students,and further examine the moderating effect of mindfulness on this mediating pathway.Methods By using convenience sampling,we conducted baseline and follow-up surveys among freshmen and sophomores at two universities in Xizang Autonomous Region from September to December 2021.Measurements included the Generalized Anxiety Disorder Scale,the body image satisfaction subscale of the Multidimensional Body-Self Relations Questionnaire,the Eating Attitudes Test,and the Mindful Attention Awareness Scale.Data analyses performed using SPSS 23.0 included Pearson correlation analysis,mediation(model 4),and moderation(model 58)effect analysis.Results A total of 2 993 students participated in both the baseline and follow-up surveys,including 1 007 males(34.3％)and 1,666 Tibetan and other ethnic minorities(56.8％),with an average age of 19.8(SD=1.3)years.Body image satisfaction significantly predicted anxiety symptoms,and this relationship was partially mediated by disordered eating.The presence of mindfulness moderated the impact of body image satisfaction on disordered eating and the influence of disordered eating on anxiety symptoms,indicating varying strengths of these relationships at different levels of mindfulness.Conclusion This study demonstrates that body image satisfaction can significantly predict anxiety symptoms,with disordered eating playing a mediating role in this relationship.The moderating effect of mindfulness further reveals that students with high levels of mindfulness are less likely to experience eating disorders influenced by body image dissatisfaction.Interventions for college students'mental health should consider including management of body image and eating behaviors,as well as mindfulness training.

Objective:To investigate clinical features, imaging characteristics, etiology, and potential mechanisms of medullary "comma-shaped" infarctions.Methods:Patients with common-shaped infarction treated at Weihai Central Hospital Affiliated to Qingdao University from January 2020 to September 2023 were retrospectively collected, and their clinical manifestations, imaging findings, treatment, and outcome were analyzed and summarized.Results:A total of 9 patients with medullary common-shaped infarction were enrolled, including 3 males, aged 67.22±14.66 years (ranging from 39 to 83 years). Main clinical symptoms and signs included the decreased pain and temperature sensation on the contralateral limb (66.67%, 6/9), coughing or choking while drinking liquids/dysphagia (66.67%, 6/9), ipsilateral pharyngopalatine muscle paralysis (66.67%, 6/9), and dizziness (66.67%, 6/9). Seven patients (77.78%, 7/9) had severe stenosis or occlusion at the ipsilateral vertebral artery, one (11.11%, 1/9) had occlusion at the left middle cerebral artery, and one (11.11%, 1/9) did not have large vessel stenosis. At 90 days after onset, the follow-up showed that the modified Rankin Scale scores were all <2.Conclusions:Medullary comma-shaped infarctions are rare in clinical practice, its main manifestations include the decreased pain and temperature sensation on the contralateral limb, coughing or choking while drinking liquids/dysphagia, ipsilateral pharyngopalatine muscle paralysis, dizziness, etc. The pathogenesis is mainly hypoperfusion caused by vertebral artery stenosis.

Background::Breast cancer (BC) risk-stratification tools for Asian women that are highly accurate and can provide improved interpretation ability are lacking. We aimed to develop risk-stratification models to predict long- and short-term BC risk among Chinese women and to simultaneously rank potential non-experimental risk factors.Methods::The Breast Cancer Cohort Study in Chinese Women, a large ongoing prospective dynamic cohort study, includes 122,058 women aged 25-70 years old from the eastern part of China. We developed multiple machine-learning risk prediction models using parametric models (penalized logistic regression, bootstrap, and ensemble learning), which were the short-term ensemble penalized logistic regression (EPLR) risk prediction model and the ensemble penalized long-term (EPLT) risk prediction model to estimate BC risk. The models were assessed based on calibration and discrimination, and following this assessment, they were externally validated in new study participants from 2017 to 2020.Results::The AUC values of the short-term EPLR risk prediction model were 0.800 for the internal validation and 0.751 for the external validation set. For the long-term EPLT risk prediction model, the area under the receiver operating characteristic curve was 0.692 and 0.760 in internal and external validations, respectively. The net reclassification improvement index of the EPLT relative to the Gail and the Han Chinese Breast Cancer Prediction Model (HCBCP) models for external validation was 0.193 and 0.233, respectively, indicating that the EPLT model has higher classification accuracy.Conclusions::We developed the EPLR and EPLT models to screen populations with a high risk of developing BC. These can serve as useful tools to aid in risk-stratified screening and BC prevention.

Membranous nephropathy(MN)is the predominant cause of primary nephrotic syn-drome(NS)among adults.The identification of PLA2R as target antigen has brought about a pro-found transformation in the management of MN,offering a basis for the utilization of B-cell deplet-ing agents such as rituximab(RTX).The question of whether early intervention targeting antibodies can effectively impede the progression of MN,contrib-uting to enhanced disease control and long-term renal outcomes for patients,remains further explo-ration.We analyzed demographic data,laboratory parameters,and renal involvement in 13 patients with PLA2R antibody-related MN who received at least one RTX treatment at our center from Octo-ber 2019 to March 2023.Early-stage medium-to-high-risk MN was defined as baseline or admission anti-PLA2R antibody levels exceeding 50 RU/mL,ex-cluding patients who already presented with ne-phrotic syndrome at baseline.The median duration of MN at the initiation of the first RTX treatment was 4.1 months(IQR 1-7.7),and the median follow-up time after RTX therapy was 27 months(IQR 23-45).All patients had commenced renin-angiotensin system inhibitors before receiving RTX.Following RTX therapy,none of the 13 patients progressed to NS during the follow-up period,and 12 patients achieved complete or partial remission at the 2-year follow-up or the last visit.No deaths,severe infections,or other serious adverse reactions oc-curred during the follow-up period.In conclusion,RTX demonstrates favorable efficacy and safety in early-stage,medium-to-high-risk MN patients.Initi-ating antibody clearance therapy in these patients may be beneficial for long-term disease control and distant renal outcomes.

Objective:To analyze the correlation between related indexes of serum lipid and insulin resistance and cognitive impairment in middle-aged and elderly people with mild cognitive impairment (MCI).Methods:In this cross-sectional study, 262 middle-aged and elderly patients with a Montreal Cognitive Function Scale (MoCA) cognitive score greater than or equal to 18 points who underwent physical examination in the Health Management Center of Beijing Tiantan Hospital Affiliated to Capital Medical University from January 1 to July 31, 2021 were selected as subjects. According to the cognitive function and MoCA score, the patients were divided into MCI group (143 cases) and normal cognition group (119 cases). Basic data, fasting blood glucose, triglyceride (TG), total cholesterol, apolipoprotein E(ApoE) genotype and other clinical indicators were collected. Hypothesis test was used to compare the differences in basic data, related indicators of blood lipid and insulin resistance between the two groups. Spearman correlation analysis was used to analyze the correlation between related indicators of blood lipid and insulin resistance and MoCA score in the two groups.Results:The age and the proportion of patients with hypertension, coronary heart disease and diabetes in the MCI group were all significantly higher than those in normal cognition group [(54.83±8.29) vs (50.76±6.34) years, 37.76% vs 31.93%, 4.20% vs 0.84%, 16.08% vs 8.40%] (all P<0.05). The elevation of serum TG ( r=-0.50, 95% CI:-0.88--0.12), TG glucose product index (TyG) ( r=-0.75, 95% CI:-1.29--0.20) and TG to high-density lipoprotein cholesterol ratio (TG/HDL-C) ( r=-0.52, 95% CI:-0.91--0.13) were all negatively correlated with MoCA score (all P<0.05). After adjusting for age and gender, the elevation of TG ( r=-0.39, 95% CI:-0.75--0.31) and TG/HDL-C ( r=-0.43, 95% CI:-0.80--0.05) were both still negatively correlated with MoCA score (both P<0.05). There was no significant correlation between all indexes and MoCA scores in the normal cognition group (all P>0.05). The elevated TG was negatively correlated with MoCA score in the MCI group ( r=-0.70, 95% CI:-1.23-0.16, P=0.017). There was no significant correlation between elevated TG and MoCA score in patients carrying ApoE ε2 and ApoE ε3 genotypes in MCI group (all P>0.05). Conclusion:Elevated related indexes of blood lipids and insulin resistance are negatively correlated with cognitive scores in middle-aged and elderly people with MCI, and it′s more obvious in patients with ApoE ε4 genotype.

In order to build a unified teaching pattern integrating knowledge delivery, skill cultivation and value guidance, this article, based on the targets of cultivating medical talents in the new era, aims to explore the pathway of curriculum ideological and political education in Medical Parasitology teaching based on the situation of Yunnan Province. By analyzing the epidemiology of parasitic diseases in Yunnan Province, the remarkable achievements of parasitic diseases control in China and Yunnan Province, cases with parasitic disease misdiagnosis, parasitologists ’ selfless contributions, the contributions of traditional Chinese medicines to parasitic diseases control and the contributions of traditional Chinese medicines in Yunnan Province, the ideological and political education is naturally integrated into Medical Parasitology teaching, to create an educational model combining professional course teaching with ideological and political education curriculum.