Objective:To establish a prognostic model based on endoplasmic reticulum stress-related genes for evaluating the prognosis of patients with renal cell carcinoma.Methods:This study utilized Non-negative Matrix Factorization to identify molecular subgroups based on endoplasmic reticulum stress-related genes and employed Weighted Correlation Network Analysis to determine co-expressed genes associ-ated with these subgroups.A risk prognostic model was constructed using univariate Cox regression analysis and Lasso regression analysis.Preliminary experimental validations were conducted to elucidate the biological functions of model genes in renal cell carcinoma.Results:Two molecular subgroups with distinct survival prognoses were identified,and an intersection of related genes was used to construct a nov-el endoplasmic reticulum stress-related prognostic model.Patients in the high-risk group exhibited significantly poorer overall survival in both the training and validation cohorts.In vivo experiments demonstrated that PCK1,a model gene,could inhibit the proliferation,migra-tion,and invasion of renal cell carcinoma cells.Conclusions:The risk scoring model developed in this study effectively predicts the survival probability of renal cell carcinoma patients and can serve as an independent prognostic indicator.This model offers a new direction for per-sonalized treatment strategies in renal cell carcinoma patients.

Objective:To establish a prognostic model based on endoplasmic reticulum stress-related genes for evaluating the prognosis of patients with renal cell carcinoma.Methods:This study utilized Non-negative Matrix Factorization to identify molecular subgroups based on endoplasmic reticulum stress-related genes and employed Weighted Correlation Network Analysis to determine co-expressed genes associ-ated with these subgroups.A risk prognostic model was constructed using univariate Cox regression analysis and Lasso regression analysis.Preliminary experimental validations were conducted to elucidate the biological functions of model genes in renal cell carcinoma.Results:Two molecular subgroups with distinct survival prognoses were identified,and an intersection of related genes was used to construct a nov-el endoplasmic reticulum stress-related prognostic model.Patients in the high-risk group exhibited significantly poorer overall survival in both the training and validation cohorts.In vivo experiments demonstrated that PCK1,a model gene,could inhibit the proliferation,migra-tion,and invasion of renal cell carcinoma cells.Conclusions:The risk scoring model developed in this study effectively predicts the survival probability of renal cell carcinoma patients and can serve as an independent prognostic indicator.This model offers a new direction for per-sonalized treatment strategies in renal cell carcinoma patients.

Objective:To explore the relationship between marital status and mild cognitive impairment in older adults.Methods:This study is a cluster random sampling.From January to December 2020, a questionnaire survey was conducted among older adults aged 60 years and over in four cities of Hebei Province.Finally, 2690 older adults with mild cognitive impairment and normal cognitive function were enrolled.The older adults were divided into 2 groups according to their marital status: married and living with their spouses(group E1), divorced or living alone(group E2). The mini-mental state examination(MMSE)scores of older adults in the two groups were compared.Moreover, the cognitive differences of older adults between the two groups and the interaction of marital status, social activities and life events on cognitive outcomes were analyzed.Results:The married older adults with partners had better cognitive preservation( P<0.01). The more life events were more likely to cause cognitive impairment( P<0.01), and the interaction of marital status, social activities and life events had a significant impact on cognition( P<0.01). Older men who were married and lived with spouse had better cognition than older women who were married and lived with spouse( P<0.05 in Model 3). The cognition of widowed elderly women was better than those of widowed elderly men( P<0.1 in Model 1; P<0.1 in Model 2). Among elderly men, the cognition of those married and living with spouse was better than that those of widowed( P<0.01 in models 1 and 2, P<0.1 in model 3). Among elderly women, those married and living with spouse had better cognitive outcomes than those widowed( P<0.01 in Model 1, P<0.01 in Model 2). Conclusions:Marital companionship is a protective factor for the cognition of older adults, and there are gender differences in the impact of marital status on cognition in late life.

Objective:To investigate the effect of salvianolic acid on depressive behavior in depression model rats induced by chronic mild stress (CMS) and its mechanism.Methods:Fifty healthy male clean grade Sprague-Dawley(SD) rats were divided into five groups according to a random number table with 10 in each group: control group (nCMS+ Nal group), CMS+ normal saline group (CMS+ Nal group), CMS+ fluoxetine group (CMS+ Flu group), CMS+ salvia acid group (CMS+ Sal group), CMS+ fluoxetine+ Salvia acid group (CMS+ Flu+ Sal group). Except the control group, the rats in the other four groups were all received CMS modeling for 21 days. Twenty-one days after CMS modeling, rats were intraperitoneally injected with 0.9% normal saline (10 mg·kg -1·d -1), fluoxetine (20 mg·kg -1·d -1), salvia acid(40 mg·kg -1·d -1), fluoxetine(20 mg·kg -1·d -1)+ salvia acid(40 mg·kg -1·d -1)for 21 days. During the administration period, rats in the other four groups continued to receive CMS intervention for 21 days. Forced swimming test and sucrose preference test were conducted at baseline (day 0), after modeling (day 21) and after intervention (day 42) so as to evaluate depression like behavior. Then the rats were sacrificed and the hippocampus and prefrontal cortex were taken. The mRNA levels of Toll like receptor 4 (TLR4) and myeloid differentiation primary response 88 (MyD88) were detected by RT-qPCR. The cytokines including interleukin-1β(IL-1β), interleukin-2(IL-2), interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) were detected by Luminex technique.SPSS 21.0 was used for statistical analysis.Repeated measurement ANOVA was used for behavioral data analysis, one-way ANOVA was used for molecular index data analysis, and Spearman was used for correlation analysis. Results:The results of repeated measurement ANOVA showed that the interaction effects between group and time of body mass, sucrose preference, forced swimming immobility time were significant at baseline, after modeling and after intervention ( F=18.238, 6.921, 7.591, all P<0.05). After modeling, compared with nCMS+ Nal group, the rats in CMS+ Flu group, CMS+ Sal group, CMS+ Flu+ Sal group and CMS+ Nal group had lower body weight, lower sucrose preference rate and longer forced swimming immobility time (all P<0.05). After intervention, compared with CMS+ Nal group(body weight (350.15±41.65)g, sucrose preference(52.95±11.13)%, static time(91.40±15.22)s), the body weight((378.21±30.78)g, (385.12±43.19)g, (391.41±31.21)g, (402.33±18.67)g, all P<0.05) and sucrose preference((69.30±15.56)%, (68.12±10.99)%, (71.18±9.51)%, (75.47±11.55)%, all P<0.05) of CMS+ Flu group, CMS+ Sal group, CMS+ Flu+ Sal group and nCMS+ Nal group were all increased, while the forced swimming immobility time ((68.81±21.74)s, (66.10±25.51)s, (63.53±22.32)s, (71.21±21.41)s, all P<0.05) were shorter (all P<0.05). After intervention, among the body weight, sucrose preference and the immobility time of CMS+ Flu group、CMS+ Sal group and CMS+ Flu+ Sal group, there were no differences between each two groups(all P>0.05). After intervention, the levels of TLR4 mRNA and MyD88 mRNA in prefrontal cortex and hippocampus of CMS+ Flu group, CMS+ Sal group, CMS+ Flu+ Sal group and nCMS+ Nal group were all lower than those in CMS+ Nal group (all P<0.05). In prefrontal cortex, the levels of TLR4 mRNA (0.715±0.358) and MyD88 mRNA (0.739±0.233) in CMS+ Flu+ Sal group were lower than those in CMS+ Sal group (1.943±0.606, 1.815±0.897) (both P<0.05). The level of TLR4 mRNA in prefrontal cortex and hippocampus of rats were positively correlated with the level of MyD88 mRNA and TNF-α level and forced swimming immobility time and negatively correlated with sucrose preference rate (prefrontal cortex r=0.915, 0.041, 0.027, -0.178, all P<0.05; hippocampus r=0.810, 0.070, 0.011, -0.153, all P<0.05). Conclusion:The antidepressant effect of salvianolic acid is presumedly achieved by inhibiting the immunoinflammatory response mediated by the TLR4/Myd88 signaling pathway in CMS rats.

Objective:This study aims to explore the change of blood and brain telomere length and the effect of salvianolic acid B on it in a rat chronic mild stress (CMS) model of depression.Methods:A total of 45 Sprague-Dawley (SD) male rats were randomly divided into 5 groups using a random number table, which were the control group, CMS group, fluoxetine group, salvianolic acid B group, and combined medication group, with nine rats in each group. All rats received CMS for 6 weeks. After successfully establishing the depression model (day 22 to day 42 after enrollment), each rat was intraperitoneally injected with 0.9% normal saline, salvianolic acid B (40 mg·kg -1·d -1), and/or fluoxetine (20 mg·kg -1·d -1) respectively according to its belonging group. The body mass of each group was tested before admission and every weekend after admission. The depressant-like behaviors were evaluated using sucrose preference test (SPT) and forced swimming test (FST) before (day-1 and-2) and after the depression model established (day 21 and 22) and after treatment (day 42 and 43) respectively. The relative telomere length in the blood, hippocampus, cortex, and cerebellum were analyzed using RT-PCR, respectively. Two-factor repeated analysis of variance was used to analyze the differences in body mass, sucrose preference, and immobility time among the five groups. The Kruskal-Wallis H test was used to compare the relative telomere length among the five groups. The Spearman's rank correlation test was used to analyze the correlation between the telomere length and body mass, sucrose preference, and immobility time at different body parts. Results:After 3 weeks of intervention, compared with those in the CMS group, rats in the salvianolic acid B group, fluoxetine group, and combination medication group showed increased body mass ( P=0.049, P=0.008, P=0.036), raised sucrose preference value ( P=0.089, P=0.094, P=0.041), and shortened forced swimming immobility time (all P<0.01). Compared with the control group, the CMS group presented statistically significantly shortened blood relative telomere length (8.53 (3.95) vs. 0.12 (0.23), P<0.01, Bonferroni adjusted P=0.002). The relative telomere length of the bilateral hippocampus, cortex, and cerebellum did not significantly differ between the control group and the CMS group. Compared with the CMS group, the relative telomere length in the salvianolic acid B group ( P=0.005, Bonferroni adjusted P=0.051), fluoxetine group ( P<0.01, Bonferroni adjusted P=0.005), and combined medication group ( P=0.001, Bonferroni adjusted P=0.007) increased significantly in the blood sample but not in different brain regions. Spearman correlation analysis showed that there was no correlation between the telomere length of different body parts and the body weight, sucrose preference value, and forced swimming immobility time that assessed after the intervention. Conclusion:The shortened telomeres length in the peripheral blood in depression model rats cannot indicate the change of telomere length in the brain. Salvianolic acid B can block the shortening of blood telomere length in depression model rats, with comparable efficacy of fluoxetine.

Objective:This study aims to explore the change of blood and brain telomere length and the effect of salvianolic acid B on it in a rat chronic mild stress (CMS) model of depression.Methods:A total of 45 Sprague-Dawley (SD) male rats were randomly divided into 5 groups using a random number table, which were the control group, CMS group, fluoxetine group, salvianolic acid B group, and combined medication group, with nine rats in each group. All rats received CMS for 6 weeks. After successfully establishing the depression model (day 22 to day 42 after enrollment), each rat was intraperitoneally injected with 0.9% normal saline, salvianolic acid B (40 mg·kg -1·d -1), and/or fluoxetine (20 mg·kg -1·d -1) respectively according to its belonging group. The body mass of each group was tested before admission and every weekend after admission. The depressant-like behaviors were evaluated using sucrose preference test (SPT) and forced swimming test (FST) before (day-1 and-2) and after the depression model established (day 21 and 22) and after treatment (day 42 and 43) respectively. The relative telomere length in the blood, hippocampus, cortex, and cerebellum were analyzed using RT-PCR, respectively. Two-factor repeated analysis of variance was used to analyze the differences in body mass, sucrose preference, and immobility time among the five groups. The Kruskal-Wallis H test was used to compare the relative telomere length among the five groups. The Spearman's rank correlation test was used to analyze the correlation between the telomere length and body mass, sucrose preference, and immobility time at different body parts. Results:After 3 weeks of intervention, compared with those in the CMS group, rats in the salvianolic acid B group, fluoxetine group, and combination medication group showed increased body mass ( P=0.049, P=0.008, P=0.036), raised sucrose preference value ( P=0.089, P=0.094, P=0.041), and shortened forced swimming immobility time (all P<0.01). Compared with the control group, the CMS group presented statistically significantly shortened blood relative telomere length (8.53 (3.95) vs. 0.12 (0.23), P<0.01, Bonferroni adjusted P=0.002). The relative telomere length of the bilateral hippocampus, cortex, and cerebellum did not significantly differ between the control group and the CMS group. Compared with the CMS group, the relative telomere length in the salvianolic acid B group ( P=0.005, Bonferroni adjusted P=0.051), fluoxetine group ( P<0.01, Bonferroni adjusted P=0.005), and combined medication group ( P=0.001, Bonferroni adjusted P=0.007) increased significantly in the blood sample but not in different brain regions. Spearman correlation analysis showed that there was no correlation between the telomere length of different body parts and the body weight, sucrose preference value, and forced swimming immobility time that assessed after the intervention. Conclusion:The shortened telomeres length in the peripheral blood in depression model rats cannot indicate the change of telomere length in the brain. Salvianolic acid B can block the shortening of blood telomere length in depression model rats, with comparable efficacy of fluoxetine.

Objective To investigate the effect of prenatal stress (PS) at different pregnant time on emotion and cognition of adult offspring rats.Methods Twelve healthy female Sprague Dawley (SD) rats were randomly divided into control group(CON,n=4),the early pregnancy group(PS1,the 1～ 7 days of pregnancy,n=4) and the late pregnancy group(PS3,the 15 ～ 21 days of pregnancy,n=4).The pregnant rats were exposed to single-prolonged stress(SPS) on gestational day 7 or 15 respectively,except control group.The offspring were measured every weekend from 1-7 week after birth.At the eighth weekend,the sucrose intake (anhedonia) and Morris water maze (MWM) were performed to assess depression-like behavior and spatial learning and memory.Results The body weight of the first to seventh weeks after birth showed that there was a statistically significant difference among the three groups (F=28.207,P＜0.01),and there was a significant difference in time effect (F=1 041.546,P＜0.01).The body weight of two PS groups was significantly lower than those of control group(P＜0.05).The body weight of PS3 was lower than that of PS1 significantly(P＜0.05).Sucrose preference:PS3((27.70± 19.31) ％) were reductive on sucrose consumption than CON significantly((66.93±19.67) ％)(P＜0.05)while PS1 ((89.80±6.79) ％) increased in sucrose consumption compared with the CON significantly(P＜0.05).MWM:in training stage the difference of average avoid latency was existed in the three groups of the first 5 days(F=11.121,P＜0.01).Similarly,there was a significant difference in measure time(F=91.327,P＜0.01),the escape latency of the PS3 was decreased,while PS1 was significantly increased compared with CON;in testing stage,PS3 ((54.50±4.64) s,(53.21±4.45)) showed a significant increase in the duration in target site and numbers of times across the target site compared with CON((32.24±.4.17) s,(31.68±4.00)) (P＜0.05).Conclusion The acceptance of stress in the late pregnancy may lead to depression like behavior in the adult offspring and also enhance the learning and memory ability.And acceptance of stress in early pregnancy can cause impairment of learning and memory ability in adult offspring rats.

OBJECTIVE: To optimize the extraction technology of ardicrenin from Ardisia crenata.METHODS: The content of ardicrenin was determined by RP-HPLC. The extraction technology was optimized by orthogonal experiment with the extraction rate of ardicrenin as evaluation index and with the volume fraction of ethanol,the extraction temperature,extraction time and extraction times as factors.RESULTS: The optimum extraction technology was determined as follows: 80%ethanol was used as solvent;the extraction temperature was 80 ℃;the extraction time was 20 min and the extraction was conducted for 3 times.The extraction rate of ardicrenin was 6.04%.CONCLUSION: The optimized extraction technology is feasible and reproducible,and it provides theoretical basis for mass extraction of the ardicrenin from A.crenata.

Objective To evaluate the production and regulation of platelet derived growth factor (PDGF) in the skin. Methods Normal human keratinocytes (NHKs) and human dermal fibroblasts (HDFs) were cultured, PDGF peptides were measured by ELISA and PDGF B chain mRNA was detected by Northern hybridization. Results The results showed that NHKs constitutively produced PDGF molecules, phorbol 12 myristate 13 acetate (PMA) inhibited PDGF production, while 1, 25 dihydroxyvitamin D 3 enhanced its production. TNF alpha, interferon ? and interleukin 1 alpha all failed to affect PDGF production. On the other hand, HDFs produced no PDGF molecule in spite of a low level of PDGF B chain mRNA expression in Northern hybridization, suggestting a post transcriptional blocking of PDGF production in HDFs. Conclusion The results obtained above indicate that epidermal keratinocytes may be the major PDGF generating cells, whereas dermal fibroblasts the PDGF responsive cells in the skin.