Objective : To investigate the effect and mechanism of silencing circFADS2 on ferroptosis in colorectal cancer (CRC) cells . Methods: The human colon adenocarcinoma cell line SW480 was used as the research ob- ject. circFADS2 siRNA interference plasmid (si-circFADS2) and its negative control si-NC , miR-152-3p inhibitor and its negative control inhibitor-NC , miR-152-3p mimics and its negative control mimics NC , SLC7A11 overex- pression plasmid (oe-SLC7A11) and its negative control vector were transfected into SW480 cells . Methylthiazolyl- diphenyl-tetrazolium bromide (MTT) method was used to detect cell proliferation activity; The contents of ferrous ion (Fe2 + ) , malondialdehyde (MDA) and the activities of superoxide dismutase (SOD) and glutathione (GSH) in cells were detected by chemical method . Dichlorodihydrofluorescein diacetate ( DCFH-DA) probe was used to detect the level of reactive oxygen species ( ROS) in cells . Quantitative Real-time polymerase chain reaction (qPCR) was used to detect the expression levels of miR-152-3p and SLC7A11 mRNA in cells . Western blot was used to detect the expression levels of ferroptosis-related proteins such as SLC7A11 and GPX4 in cells . Dual lucif- erase reporter gene experiment was used to verify the sponge adsorption relationship between miR-152-3p and circFADS2 , and the targeted regulation relationship between miR-152-3p and SLC7A11 . Results : Compared with blank group , the proliferation activity of si-circFADS2 group decreased , the levels of Fe2 + , MDA and ROS in- creased , and the levels of SOD and GSH decreased; At the same time , the expression level of miR-152-3p in- creased , and the protein expression levels of SLC7A11 and GPX4 decreased in cells ( all P < 0. 05) . Compared with si-circFADS2 group , the proliferation activity of si-circFADS2 + inhibitor group increased , the levels of Fe2 + , MDA and ROS in cells decreased , and the levels of SOD and GSH increased; At the same time , the expression level of miR-152-3p decreased , and the protein expression levels of SLC7A11 and GPX4 increased (all P < 0. 05) . The results of dual luciferase reporter gene experiment showed that SLC7A11 was a downstream target gene of miR- 152-3p . Conclusion Silencing circFADS2 can induce ferroptosis in CRC cells possibly by targeting the miR-152 - 3p/SLC7A11 signaling axis .

Objective:To compare the efficacy of body posture combined with pharmacotherapy and pharmacotherapy alone in the treatment of chronic subdural hematoma(CSDH).Methods:Firstly, retrospective case series study was conducted. Thirty cases of CSDH that had received body posture combined with pharmacotherapy at Department of Neurosurgery, Huashan Hospital Affiliated to Fudan University from December 2016 to October 2020 were studied retrospectively. Twenty-seven patients were male, and 3 patients were female. The age of patients ( M(IQR)) was 66(16) years (range:28 to 84). Nineteen patients had unilateral hematoma, and 11 patients had bilateral hematoma. All patients received pharmacotherapy and body posture therapy that was to raise their lower limbs 20 to 30 cm with leg lift pad and get abdominal compressed with customized abdominal belt in supine position. Patients were required to maintain the body posture as much as possible, with the maximum to 16 to 18 hours per day. Patients with unilateral hematoma should tilt the head to the affected side and avoid tilting it to the opposite side. For patients with bilateral hematoma, there was no need for head lateralization. Patient were treated with oral dexamethasone and atorvastatin simultaneously. The preliminary efficacy of body posture combined with pharmacotherapy was determined by hematoma improvement rate which was analyzed by Clopper-Pearson method. Then, the multi-center, prospective, randomized controlled trial had carried out in 9 medical centers from August 2020 to November 2021. The stratified block randomization method was adopted. Patients were randomized in a ratio of 1∶1 to either receive pharmacotherapy alone(the control group) or body posture combined with pharmacotherapy(the experiment group) for 3 months and followed up for 6 months. Effective treatment was defined as complete absorption of hematoma, or the hematoma volume decreased by more than 10 ml and Markwalder grading scale score had improved by more than 1 point compared to the baseline. The efficacy rate and surgery conversion rate at 3 months and recurrence at 6 months were observed. Comparison between groups was performed with paired sample t test, Mann-Whitney U test, χ2 test, corrected χ2 test, or Fisher exact probability method. Logistic regression was used to compare the effective rate and operation rate between the two groups. Results:In the respective study, 30 patients completed follow-up 13 to 353 days after treatment. At the last follow-up, the incidence of almost complete absorption or significantly absorption of hematoma (hematoma volume was significantly reduced accompanied by symptom improvement) was 93.3%. The 95% CI for the incidence that analyzed by the Clopper-Pearson method was 77.9% to 99.2%. One hundred and six patients were enrolled in the multicenter study. Fifty-five patients underwent body posture combined with pharmacotherapy. The age was 74(17) years (range:26 to 92). Thirty-nine patients were males and 16 were females. Fifty-one patients underwent pharmacotherapy alone. The age was 69(12) years (range:48 to 84). Thirty-seven patients were males and 14 were females. The length of body posture recorded in diary card was (15.7±2.3) hours(range:7.6 to 19.3 hours). The efficacy rate in the body posture combined with pharmacotherapy group and pharmacotherapy alone group were 83.6% (46/55) and 56.9% (29/51), respectively at 3 months. The result of the logistic regression analysis showed that the efficacy of body posture combined with pharmacotherapy group was better than that of pharmacotherapy alone group ( OR=3.88,95% CI:1.57 to 9.58, P=0.003). Surgery rate in the body posture combined with pharmacotherapy group and pharmacotherapy alone group were 5.5% (3/55) and 21.6% (11/51) respectively. The result of Logistic regression showed that the pharmacotherapy alone group was more likely to be converted to surgery ( OR=0.21,95% CI:0.05 to 0.80, P=0.023). At the 6 months, no recurrence of cases was found in the body posture combined with pharmacotherapy group. However, the recurrence rate of pharmacotherapy alone group was 6.3% (3/48), there was no significant difference between the two groups ( P>0.05). Conclusion:The effect of body posture combined with pharmacotherapy for chronic subdural hematoma is better than that of pharmacotherapy alone.

Objective To investigate the relationship between plasma homocysteine(Hcy)levels and cognitive impairment(CI).Methods From November 2018 to January 2019,baseline data and cognitive function were collected from the participants aged≥40 years who lived in two villages in Huyi District,Xi'an,China.Their global cognitive function was assessed by Mini-Mental State Examination(MMSE)and the diagnosis of cognitive impairment was based on international guidelines.Fasting blood was collected in the morning,and plasma Hcy level was measured by the chemiluminometric assay.Multivariate Logistic regression analysis,subgroup analysis,and interaction analysis were performed to investigate the relationship between plasma Hcy and CI.Results A total of 1 805 subjects were included in the analysis.There were 1 056 females(58.5％),age ranged from 40 to 88 years[mean(58.99±9.52)years],and 145 participants(8.0％)were diagnosed as CI.The median plasma Hcy level in the overall population was 14.1(11.6,17.8)μmol/L.There were 729(40.4％)subjects in the HHcy group(＞15.0 μmol/L)and 1 076(59.6％)in the normal group(≤15.0 μmol/L).Univariate analysis showed that the prevalence of CI was higher in the HHcy group than in the normal Hcy group(11.4％vs.5.8％,P＜0.001).In multivariable Logistic regression fully adjusted for potential confounders,each 1 μmol/L increase in plasma Hcy level was associated with a 3.0％increased risk of CI(OR=1.030,95％CI:1.012-1.048,P=0.001).Interaction analysis indicated that sex,age,BMI,systolic blood pressure,history of stroke,and diabetes did not significantly modify this association.Conclusion Elevated plasma Hcy levels are associated with an increased risk of CI in people aged≥40 years.This indicates that HHcy may be a risk factor for CI.

Objective To explore the relationship between carotid atherosclerosis(CAS)and cognitive impairment in the stroke high-risk population aged 40 years and above in the rural area of Xi'an City and determine whether CAS is a risk factor for cognitive impairment.Methods In this study,stroke high-risk population found in the Community and Rural Population Stroke High-risk Group Screening and Intervention Project carried out in Huyi District,Xi'an City,from October 2014 to March 2015 were selected as the research subjects.Color Doppler ultrasound was used to evaluate CAS,and CAS was defined as:carotid intima-media thickness(CIMT)≥1.0 mm,or carotid arteries(including common carotid artery,carotid sinus,internal carotid artery,and external carotid artery)have atherosclerotic plaques,or carotid stenosis.Mini-Mental State Examination(MMSE)was used to assess cognitive function.The MMSE score lower than the cut-off value(illiteracy ≤17,primary school ≤ 20 points,and junior high school and above education level ≤24 points)is defined as cognitive impairment.The study population was grouped according to the presence of CAS or cognitive impairment;univariate difference test and bivariate logistic regression were used to analyze the relationship between CAS and cognitive impairment.Results A total of 451 subjects were included in the analysis.The average age of the subjects was(58.7±9.83)years old,and 44.3％were female.Among them,329 cases(72.9％)had CAS and 57 cases(12.6％)met the diagnostic criteria for cognitive impairment.The prevalence of cognitive impairment in CAS group was significantly higher than that in non-CAS group(14.6％vs.7.4％,P=0.041).Multivariate logistic regression analysis showed that cognitive impairment was significantly correlated with age(OR=1.121,95％CI:1.056-1.189,P＜0.001),but not with CAS(OR=1.008,95％CI:0.202-5.170,P=0.992).Conclusion No significant association between CAS and cognitive impairment was found in high stroke risk group aged 40 and above in rural areas of Xi'an.

BACKGROUND: Temozolomide (TMZ) resistance is a significant challenge in treating glioblastoma (GBM). Collagen remodeling has been shown to be a critical factor for therapy resistance in other cancers. This study aimed to investigate the mechanism of TMZ chemoresistance by GBM cells reprogramming collagens. METHODS: Key extracellular matrix components, including collagens, were examined in paired primary and recurrent GBM samples as well as in TMZ-treated spontaneous and grafted GBM murine models. Human GBM cell lines (U251, TS667) and mouse primary GBM cells were used for in vitro studies. RNA-sequencing analysis, chromatin immunoprecipitation, immunoprecipitation-mass spectrometry, and co-immunoprecipitation assays were conducted to explore the mechanisms involved in collagen accumulation. A series of in vitro and in vivo experiments were designed to assess the role of the collagen regulators prolyl 4-hydroxylase subunit alpha 1 (P4HA1) and yes-associated protein (YAP) in sensitizing GBM cells to TMZ. RESULTS: This study revealed that TMZ exposure significantly elevated collagen type I (COL I) expression in both GBM patients and murine models. Collagen accumulation sustained GBM cell survival under TMZ-induced stress, contributing to enhanced TMZ resistance. Mechanistically, P4HA1 directly binded to and hydroxylated YAP, preventing ubiquitination-mediated YAP degradation. Stabilized YAP robustly drove collagen type I alpha 1 ( COL1A1) transcription, leading to increased collagen deposition. Disruption of the P4HA1-YAP axis effectively reduced COL I deposition, sensitized GBM cells to TMZ, and significantly improved mouse survival. CONCLUSION P4HA1 maintained YAP-mediated COL1A1 transcription, leading to collagen accumulation and promoting chemoresistance in GBM.
Temozolomide ; Humans ; Glioblastoma/drug therapy* ; Animals ; Mice ; Cell Line, Tumor ; Drug Resistance, Neoplasm/genetics* ; YAP-Signaling Proteins ; Hydroxylation ; Dacarbazine/pharmacology* ; Adaptor Proteins, Signal Transducing/metabolism* ; Transcription Factors/metabolism* ; Collagen/biosynthesis* ; Collagen Type I/metabolism* ; Prolyl Hydroxylases/metabolism* ; Antineoplastic Agents, Alkylating/therapeutic use*

Objective To investigate the relationship between plasma homocysteine(Hcy)levels and cognitive impairment(CI).Methods From November 2018 to January 2019,baseline data and cognitive function were collected from the participants aged≥40 years who lived in two villages in Huyi District,Xi'an,China.Their global cognitive function was assessed by Mini-Mental State Examination(MMSE)and the diagnosis of cognitive impairment was based on international guidelines.Fasting blood was collected in the morning,and plasma Hcy level was measured by the chemiluminometric assay.Multivariate Logistic regression analysis,subgroup analysis,and interaction analysis were performed to investigate the relationship between plasma Hcy and CI.Results A total of 1 805 subjects were included in the analysis.There were 1 056 females(58.5％),age ranged from 40 to 88 years[mean(58.99±9.52)years],and 145 participants(8.0％)were diagnosed as CI.The median plasma Hcy level in the overall population was 14.1(11.6,17.8)μmol/L.There were 729(40.4％)subjects in the HHcy group(＞15.0 μmol/L)and 1 076(59.6％)in the normal group(≤15.0 μmol/L).Univariate analysis showed that the prevalence of CI was higher in the HHcy group than in the normal Hcy group(11.4％vs.5.8％,P＜0.001).In multivariable Logistic regression fully adjusted for potential confounders,each 1 μmol/L increase in plasma Hcy level was associated with a 3.0％increased risk of CI(OR=1.030,95％CI:1.012-1.048,P=0.001).Interaction analysis indicated that sex,age,BMI,systolic blood pressure,history of stroke,and diabetes did not significantly modify this association.Conclusion Elevated plasma Hcy levels are associated with an increased risk of CI in people aged≥40 years.This indicates that HHcy may be a risk factor for CI.

Objective To explore the relationship between carotid atherosclerosis(CAS)and cognitive impairment in the stroke high-risk population aged 40 years and above in the rural area of Xi'an City and determine whether CAS is a risk factor for cognitive impairment.Methods In this study,stroke high-risk population found in the Community and Rural Population Stroke High-risk Group Screening and Intervention Project carried out in Huyi District,Xi'an City,from October 2014 to March 2015 were selected as the research subjects.Color Doppler ultrasound was used to evaluate CAS,and CAS was defined as:carotid intima-media thickness(CIMT)≥1.0 mm,or carotid arteries(including common carotid artery,carotid sinus,internal carotid artery,and external carotid artery)have atherosclerotic plaques,or carotid stenosis.Mini-Mental State Examination(MMSE)was used to assess cognitive function.The MMSE score lower than the cut-off value(illiteracy ≤17,primary school ≤ 20 points,and junior high school and above education level ≤24 points)is defined as cognitive impairment.The study population was grouped according to the presence of CAS or cognitive impairment;univariate difference test and bivariate logistic regression were used to analyze the relationship between CAS and cognitive impairment.Results A total of 451 subjects were included in the analysis.The average age of the subjects was(58.7±9.83)years old,and 44.3％were female.Among them,329 cases(72.9％)had CAS and 57 cases(12.6％)met the diagnostic criteria for cognitive impairment.The prevalence of cognitive impairment in CAS group was significantly higher than that in non-CAS group(14.6％vs.7.4％,P=0.041).Multivariate logistic regression analysis showed that cognitive impairment was significantly correlated with age(OR=1.121,95％CI:1.056-1.189,P＜0.001),but not with CAS(OR=1.008,95％CI:0.202-5.170,P=0.992).Conclusion No significant association between CAS and cognitive impairment was found in high stroke risk group aged 40 and above in rural areas of Xi'an.

Objective:To compare the efficacy of body posture combined with pharmacotherapy and pharmacotherapy alone in the treatment of chronic subdural hematoma(CSDH).Methods:Firstly, retrospective case series study was conducted. Thirty cases of CSDH that had received body posture combined with pharmacotherapy at Department of Neurosurgery, Huashan Hospital Affiliated to Fudan University from December 2016 to October 2020 were studied retrospectively. Twenty-seven patients were male, and 3 patients were female. The age of patients ( M(IQR)) was 66(16) years (range:28 to 84). Nineteen patients had unilateral hematoma, and 11 patients had bilateral hematoma. All patients received pharmacotherapy and body posture therapy that was to raise their lower limbs 20 to 30 cm with leg lift pad and get abdominal compressed with customized abdominal belt in supine position. Patients were required to maintain the body posture as much as possible, with the maximum to 16 to 18 hours per day. Patients with unilateral hematoma should tilt the head to the affected side and avoid tilting it to the opposite side. For patients with bilateral hematoma, there was no need for head lateralization. Patient were treated with oral dexamethasone and atorvastatin simultaneously. The preliminary efficacy of body posture combined with pharmacotherapy was determined by hematoma improvement rate which was analyzed by Clopper-Pearson method. Then, the multi-center, prospective, randomized controlled trial had carried out in 9 medical centers from August 2020 to November 2021. The stratified block randomization method was adopted. Patients were randomized in a ratio of 1∶1 to either receive pharmacotherapy alone(the control group) or body posture combined with pharmacotherapy(the experiment group) for 3 months and followed up for 6 months. Effective treatment was defined as complete absorption of hematoma, or the hematoma volume decreased by more than 10 ml and Markwalder grading scale score had improved by more than 1 point compared to the baseline. The efficacy rate and surgery conversion rate at 3 months and recurrence at 6 months were observed. Comparison between groups was performed with paired sample t test, Mann-Whitney U test, χ2 test, corrected χ2 test, or Fisher exact probability method. Logistic regression was used to compare the effective rate and operation rate between the two groups. Results:In the respective study, 30 patients completed follow-up 13 to 353 days after treatment. At the last follow-up, the incidence of almost complete absorption or significantly absorption of hematoma (hematoma volume was significantly reduced accompanied by symptom improvement) was 93.3%. The 95% CI for the incidence that analyzed by the Clopper-Pearson method was 77.9% to 99.2%. One hundred and six patients were enrolled in the multicenter study. Fifty-five patients underwent body posture combined with pharmacotherapy. The age was 74(17) years (range:26 to 92). Thirty-nine patients were males and 16 were females. Fifty-one patients underwent pharmacotherapy alone. The age was 69(12) years (range:48 to 84). Thirty-seven patients were males and 14 were females. The length of body posture recorded in diary card was (15.7±2.3) hours(range:7.6 to 19.3 hours). The efficacy rate in the body posture combined with pharmacotherapy group and pharmacotherapy alone group were 83.6% (46/55) and 56.9% (29/51), respectively at 3 months. The result of the logistic regression analysis showed that the efficacy of body posture combined with pharmacotherapy group was better than that of pharmacotherapy alone group ( OR=3.88,95% CI:1.57 to 9.58, P=0.003). Surgery rate in the body posture combined with pharmacotherapy group and pharmacotherapy alone group were 5.5% (3/55) and 21.6% (11/51) respectively. The result of Logistic regression showed that the pharmacotherapy alone group was more likely to be converted to surgery ( OR=0.21,95% CI:0.05 to 0.80, P=0.023). At the 6 months, no recurrence of cases was found in the body posture combined with pharmacotherapy group. However, the recurrence rate of pharmacotherapy alone group was 6.3% (3/48), there was no significant difference between the two groups ( P>0.05). Conclusion:The effect of body posture combined with pharmacotherapy for chronic subdural hematoma is better than that of pharmacotherapy alone.

Objective: To understand the prevalence of Lying Flat behaviors and its association with depressive symptoms among Chinese college students, so as to provide a scientific basis for promoting the physical and mental health development of adolescents. Methods: From July to October 2023, three universities were selected through convenient sampling from Jiangxi Province, Liaoning Province and Beijing City, respectively. Selfdesigned questionnaire links were distributed on campus to collect basic information and Lying Flat behaviors among college students, and the Patient Health Questionnaire-9 (PHQ-9) was utilized to screen for students with depressive symptoms. Finally, a total of 4 225 valid questionnaires were obtained. Chisquare was used to compare of report rates of Lying Flat behaviors across different demographic characteristics. Ordered Logistic regression analysis was used to explore the association between Lying Flat behaviors and depressive symptoms, with Z test used to assess variations in the strength of associations. Results: The reporting rates of academic, life, and social Lying Flat were 32.7%, 17.8% and 17.5%, respectively. And 6.7% of the participants were found of all three Lying Flat behaviors simultaneously.Among college students with three Lying Flat behaviors, the constituent ratios of no, mild, moderate and above depressive symptoms were 9.9%, 30.5% and 59.6%, respectively. Additionally, college students who had three Lying Flat behaviors were more likely to show mild, moderate and above depressive symptoms [OR(95%CI)=2.49(1.60-3.87), 7.69(5.01-11.79), P<0.01]. Conclusions Academic Lying Flat behavior is most prevalent among college students. Academic, life and social Lying Flat behaviors are all significantly positively correlated with depressive symptoms. Attention should be paid to the Lying Flat behaviors and college students psychological health conditions to promote their physical and mental health development.

Objective To explore the regulatory effect of miR-6838-5p on DDR1 gene expression and proliferation of breast cancer cells.Methods The expression levels of miR-6838-5p in normal breast epithelial cells and breast cancer cells were detected using qRT-PCR,and the potential target genes of miR-6838-5p was predicted using TargetscanV 8.0.Double luciferase reporter gene experiment was performed to verify the binding between miR-6838-5p and DDR1.Breast cancer MCF-7 cells were transfected via liposome,miR-6838-5p mimic,miR-6838-5p inhibitor,DDR1 siRNA,DDR1-overexpresisng vector,or both miR-6838-5p mimic and DDR1-overexpressing vector,and the changes in cell proliferation were examined with CCK-8 and EdU assays;Western blotting was used to detect the expression of DDR1.The mediating role of DDR1 in miR-6838-5p overexpression-induced inhibition of MCF-7 cell proliferation was verified in a nude mouse model bearing MCF-7 cell xenografts.Results The expression of miR-6838-5p was significantly lower in breast cancer cells than in normal breast epithelial cells.In MCF-7 cells,miR-6838-5p overexpression induced significant inhibition of cell proliferation.Dual luciferase reporter gene experiment demonstrated a binding relationship between miR-6838-5p and DDR1(P<0.01).Western blotting showed that miR-6838-5p overexpression significantly lowered DDR1 expression in MCF-7 cells,and DDR1 overexpression promoted proliferation of the cells;co-transfection of the cells with DDR1-overexpressing vector significantly attenuated the inhibitory effect of miR-6838-5p mimic on cell proliferation.In the tumor-bearing nude mice,the xenografts overexpressing miR-6838-5p showed a significantly smaller volum with obviously the expression of DDR1.Conclusion Overexpression of miR-6838-5p inhibits breast cancer cell proliferation by regulating DDR1 expression.