1.Effect of Oral Sodium Butyrate on Skeletal Muscle Atrophy via The Gut-muscle Axis in Antibiotic-pretreated CT26 Tumor-bearing Mice and Its Mechanism
Shu-Ling ZHANG ; Jun-Wei WANG ; Shi-Liang HU ; Tu-Tu WANG ; Shun-Chang LI ; Jia FAN ; Jun-Zhi SUN
Progress in Biochemistry and Biophysics 2026;53(3):724-739
ObjectiveTo explore the effect of oral sodium butyrate on skeletal muscle atrophy in CT26 tumor mice through the gut microbiota-skeletal muscle axis and its potential mechanism. MethodsSixty SPF BALB/c male mice aged 8 weeks were randomly divided into a normal control group (NC, n=18) and a ABX-depleted group (ABX, n=42). The ABX mice were pretreated with a quadruple antibiotic cocktail via oral gavage (0.2 ml per administration, once daily, 6 d per week, for 2 weeks), whereas NC received an equal volume of sterile water. The quadruple antibiotic cocktail consisted of metronidazole (1 g/L), vancomycin (0.5 g/L), ampicillin (1 g/L), and gentamicin (1 g/L). Following successful pretreatment, six mice from each group were randomly selected for gut microbiota sequencing analysis and designated as the Abx group and the NC0 group, respectively. Theremaining mice in ABX were subcutaneously inoculated in the dorsum with 0.2 ml of CT26 cell suspension (at a cell density of 1×107/ml). Then these mice were randomly allocated into three subgroups: a control tumor bearing model group (0_NaB, n=12), a tumor-bearing model group receiving low-dose oral sodium butyrate (L_NaB, n=12), a tumor-bearing model group receiving high-dose oral sodium butyrate (H_NaB, n=12). And mice in NC were inoculated at the same site with 0.2 ml of normal saline. The administration dose for L_NaB was 0.3 g/(kg·d), that for H_NaB was 0.5 g/(kg·d), while NC and 0_NaB were given the same volume of normal saline (0.2ml per time, once daily, 6 d per week, for 4 weeks). The general condition of mice was monitored, and forelimb grip strength gastrocnemius muscle mass and its muscle fiber cross-sectional area were measured for each group. The structural changes in gut microbiota were assessed by 16S rRNA sequencing of cecal contents. Pathological alterations in the intestinal wall were examined via HE staining. Serum and gastrocnemius muscle levels of TNF‑α, IL-6, IL-1β, and LPS were quantified using ELISA. The protein expression of ZO-1 and occludin in the small intestine, as well as proteins associated with the TLR4/MyD88/NF-κB signaling pathway in the gastrocnemius muscle, were detected by Western blot analysis. Results(1) The alpha-diversity in Abx was significantly lower than that in NC0 (P<0.01), a significant decrease of the mass and muscle fiber cross-sectional area of the gastrocnemius (P<0.01), with the majority of gut microbiota being effectively depleted. (2) Compared with NC, the subcutaneous tumors of mice in 0_NaB were prominent, a significant increase of the mass and muscle fiber cross-sectional area of the gastrocnemius, accompanied by a significant decrease in body weight at the end of the 3th and 4th week (P<0.05), and a significant weakening of the forelimb grasping strength at the 5th and 6th week (P<0.01). Compared with 0_NaB, the tumor mass of mice in L_NaB and H_NaB showed a significant decreasing trend, and the grip strength of the forelimbs significantly increased at the 5th and 6th week (P<0.05, P<0.01). (3) Compared with 0_NaB, the Shannon and Observed species indices in α diversity of L_NaB and H_NaB were significantly increased (P<0.05). At the genus level, compared with 0_NaB, L_NaB exhibited a significant decrease in the relative abundance of Parasutterella (P< 0.01), while H_NaB showed significant reductions in the relative abundances of both Escherichia-Shigella and Parasutterella (P < 0.01). (4) Compared with 0_NaB, the small intestinal tissue structure in L_NaB and H_NaB was more intact, the infiltration of inflammatory cells was significantly reduced, and the capillaries were slightly dilated. The expression levels of ZO-1 and occludin proteins in L_NaB were significantly increased (P<0.01). (5) The LPS concentration in the gastrocnemius muscle and the protein expression levels of TLR4, MyD88, p-IκBα, and p-NF‑κB p65 in L_NaB and H_NaB were significantly lower than those in 0_NaB (P<0.05). The serum TNF‑α concentration in H_NaB and TNF-α concentration in the gastrocnemius muscle of the L_NaB and H_NaB were significantly lower than those in 0_NaB (P<0.05, P<0.01, P<0.01). ConclusionOral administration of NaB can improve gut microbiota α diversity, adjusting its composition, improving intestinal mucosal barrier function, reducing the LPS-induced pro-inflammatory response, and delaying skeletal muscle atrophy. The underlying mechanism may involve down regulation of TLR4/MyD88/NF-κB signaling in skeletal muscle.
2.Impact of Intrapartum Ultrasound as a Replacement for Vaginal Examination in Labor Assessment on Vaginal Delivery Complications
Jinhui CUI ; Xinjuan CHEN ; Liping OUYANG ; Ling LI ; Jianhui FAN ; Zeping HUANG ; Ping LI
Journal of Sun Yat-sen University(Medical Sciences) 2026;47(2):360-367
ObjectiveTo evaluate whether the use of intrapartum ultrasound (IPUS) to monitor the labor process, as alternative method of traditional vaginal examination (VE), could reduce the incidence of postpartum complications associated with vaginal delivery. MethodsA total of 360 primiparas who underwent cervical dilation balloon induction of labor (IOL) and achieved successful vaginal delivery after childbirth at the Third Affiliated Hospital of Sun Yat-sen University between January 2022 and December 2023, were included in the retrospective study with half assessed for labor progress using IPUS (n=180) and the other half using VE (n=180). The differences in the relevant indicators of the labor process and the complications of vaginal delivery were compared between the two groups of pregnant women. ResultsThere was no significant difference in the duration of membrane rupture, the first stage of labor and the second stage of labor between the two groups. However, the number of VE in the IPUS group was significantly lower [nulliparous: 4 (3-4) vs. 6 (5-8), P<0.001; multiparous: 2 (2-3) vs. 4 (3-5), P<0.001]. The IPUS group experienced a lower incidence of postpartum fever compared to the VE group [1.67%(3/180) vs. 7.22%(13/180), P=0.006], while other complications of vaginal delivery, such as fever during labor, postpartum hemorrhage (PPH), laceration, poor wound healing and uroschesis, were not significantly different (all P > 0.05). The logistic regression analysis confirmed that the use of IPUS served as a protective factor for postpartum fever with an OR of 0.06 [95% CI (0.01, 0.36); P=0.002], while the duration of membrane rupture was a risk factor [OR: 1.12; 95% CI (1.03, 1.22); P = 0.011]. ConclusionsIPUS, as an alternative to traditional VE, does not affect the progress of labor. However, it can significantly reduce the frequency of VE and the incidence of postpartum fever, thereby facilitating the rapid recovery of postpartum women, which makes it clinically valuable for application.
3.Mechanism of SOS1-IT1 promoting EZH2 expression in human endometrial cancer cells by regulating acetylation modification
Hong-Yang LIU ; Xue-Ling LOU ; Rong-Jing ZHANG ; Quan-Ling FENG ; Kai-Ge GUO ; Hao-Fan WANG ; Ying-Ying LI ; Jun-Hu WAN ; Lin-Dong ZHANG
Acta Anatomica Sinica 2025;56(4):444-451
Objective To explore the molecular mechanism by which SOS Ras/Rac guanine nucleotide exchange factor 1-intronic transcript 1(SOS1-IT1)affects enhancer of zeste homolog 2(EZH2)protein expression in endometrial cancer cells Ishikawa and RL95-2.Methods Lentiviral transfection of short hairpin RNA(shRNA)and overexpression plasmid were used in Ishikawa and RL95-2 cell lines to knock down and overexpress SOS1-IT1.The mechanism of EZH2 expression regulation was studied using Real-time PCR,Western blotting,and chromatin immunoprecipitation.Results The expression of SOS1-IT1 and EZH2 genes was positively correlated in endometrial cancer tissues.Knocking down SOS1-IT1 significantly reduces the expression of EZH2,inhibited the proliferation and migration of Ishikawa and RL95-2 cells,and could reduced the acetylation of histone H3 at position 27(H3K27)and the enrichment of CREB binding protein(CBP)in the EZH2 gene promoter region.Overexpression of SOS1-IT1 could increased the expression of EZH2 and enhance the acetylation of H3K27 and the enrichment of CBP.CBP could bind to SOS1-IT1 RNA,and this binding ability was weakened when CBP was knocked down.Conclusion SOS1-IT1 can promote the expression level of EZH2 in endometrial cancer cells Ishikawa and RL95-2 by regulating the acetylation modification level of the EZH2 gene promoter region,thereby affecting the proliferation and migration ability of endometrial cancer cells.
4.A Survey on the Perceived Experience and Acceptance of Intrapartum Ultrasound as a Novel Method for Labor Progress Assessment
Xinjuan CHEN ; Jinhui CUI ; Liping OUYANG ; Ling LI ; Jianhui FAN ; Ping LI
Journal of Sun Yat-sen University(Medical Sciences) 2025;46(3):535-540
ObjectiveTo investigate the perceived experience and acceptance of intrapartum ultrasound (IPUS) as a novel method for labor progress assessment among pregnant women. MethodsFrom February 2023 to December 2024, a total of 180 pregnant women admitted to the Labor Ward of Lingnan Hospital, the Third Affiliated Hospital of Sun Yat-sen University, who were planned for vaginal trial of labor , were accessed for labor progress using IPUS and vaginal examination (VE) after the onset of labor and prior to the initiation n of labor analgesia. A self-designed questionnaire was used to investigate the women's perceived experiences with both examination methods and their acceptance of IPUS. The pain intensity associated with the examinations was evaluated using the visual analogue pain scale (VAS). Differences in the women's experiences and pain intensity between the two labor progress assessment methods were compared. ResultsThe acceptance rate of IPUS was 96.67% (174/180), with the remaining 6 cases undecided. Over 60% of the pregnant women reported IPUS assessment as comfortable and none of them felt discomfort, whereas 32.8% felt uncomfortable with VE (χ2=196.02, P<0.001). Nearly two-thirds of the pregnant women believed that VE would cause psychological distress, while none reported such effect with IPUS (χ2=261.52, P<0.001). Approximately 77.78% (140/180) of the pregnant women believed that IPUS could reduce their fear of vaginal delivery and enhance their confidence if it replaced VE. The VAS score for IPUS [0 (0, 2)] was significantly lower than that for VE [4 (4, 6)] (Z=-14.62, P<0.001). Further stratified analysis showed that over 90% (164/180) of the pregnant women found IPUS painless, with no moderate or severe pain reported, compared to 43.33% (78/180) experienced moderate or severe pain with VE (P<0.001). ConclusionAs a novel approach for labor progress assessment, IPUS not only alleviates the pain and discomfort associated with traditional VE and reduces the fear of childbirth but also enhances women's confidence in delivery, thereby achieving a high level of acceptance among parturient women in China.
5.Study on the chemical constituents of the active parts of Piper wallichii
Ling ZENG ; Yujie HU ; Ling LI ; Xiaojian GONG ; Chanyuan ZHOU ; Dongsheng FAN
China Pharmacy 2025;36(21):2632-2637
OBJECTIVE To analyze the chemical constituents of the active parts of Piper wallichii. METHODS The petroleum ether-extract fraction was prepared from the methanol extract of P. wallichii. Separation and purification were performed using semi-preparative high-performance liquid chromatography. The structures of the compounds were identified by nuclear magnetic resonance spectroscopy. RESULTS Nineteen compounds were isolated from the petroleum ether-extract fraction from the methanol extract of P. wallichii, identified as 3-acetoxybenzyl benzoate (1), 2-acetoxybenzyl benzoate (2), 2-methoxybenzyl benzoate (3), 3-methoxybenzyl benzoate (4), 4-hydroxy-3-methoxybenzyl benzoate (5), 3-hydroxybenzyl benzoate(6), benzyl benzoate (7), ganschisandrine (8), lancifolin A (9), (7R,8R,3′R)-7-acetoxy-3′,4′-dimethoxy-3,4-methylenedioxy-6′-oxo- Δ1′,4′,8′-8.3′-lignan (10), (7S,8R,3′S)-Δ8′-3′,6′-dihydro-3′-methoxy-3,4-methylenedioxy-6′-oxo-8.3′,7.O.4′-lignan (11), (7R, 8R,3′S)-Δ8′-3′,6′-dihydro-3′-methoxy-3,4-methylenedioxy-6′-oxo-8.3′,7.O.4′-lignan (12), isodihydrofutoquinol A (13), licarin A (14), licarin B (15), 2-(2′,5′-dimethoxyphenyl)-3,4- dimethyl-5-(3″,4″-dimethoxyphenyl)- tetrahydrofuran (16), galgravin (17), velutin (18), and piyunin A (19). CONCLUSIONS Compound 1 is a new benzyl benzoate compound. Compounds 3-5, 8 and 9 are isolated from the Piper genus for the first time, while compounds 2, 6, 10-13 and 15-19 are isolated from P. wallichii for the first time.
6.Specific effect of inserted sham acupuncture and its impact on the estimation of acupuncture treatment effect in randomized controlled trials: A systematic survey.
Xiao-Chao LUO ; Jia-Li LIU ; Ming-Hong YAO ; Ye-Meng CHEN ; Arthur Yin FAN ; Fan-Rong LIANG ; Ji-Ping ZHAO ; Ling ZHAO ; Xu ZHOU ; Xiao-Ying ZHONG ; Jia-Hui YANG ; Bo LI ; Ying ZHANG ; Xin SUN ; Ling LI
Journal of Integrative Medicine 2025;23(6):630-640
BACKGROUND:
The use of inserted sham acupuncture as a placebo in randomized controlled trials (RCTs) is controversial, because it may produce specific effects that cause an underestimation of the effect of acupuncture treatment.
OBJECTIVE:
This systematic survey investigates the magnitude of insert-specific effects of sham acupuncture and whether they affect the estimation of acupuncture treatment effects.
SEARCH STRATEGY:
PubMed, Embase and Cochrane Central Register of Controlled Trials were searched to identify acupuncture RCTs from their inception until December 2022.
INCLUSION CRITERIA:
RCTs that evaluated the effects of acupuncture compared to sham acupuncture and no treatment.
DATA EXTRACTION AND ANALYSIS:
The total effect measured for an acupuncture treatment group in RCTs were divided into three components, including the natural history and/or regression to the mean effect (controlled for no-treatment group), the placebo effect, and the specific effect of acupuncture. The first two constituted the contextual effect of acupuncture, which is mimicked by a sham acupuncture treatment group. The proportion of acupuncture total effect size was considered to be 1. The proportion of natural history and/or regression to the mean effect (PNE) and proportional contextual effect (PCE) of included RCTs were pooled using meta-analyses with a random-effect model. The proportion of acupuncture placebo effect was the difference between PCE and PNE in RCTs with non-inserted sham acupuncture. The proportion of insert-specific effect of sham acupuncture (PIES) was obtained by subtracting the proportion of acupuncture placebo effect and PNE from PCE in RCTs with inserted sham acupuncture. The impact of PIES on the estimation of acupuncture's treatment effect was evaluated by quantifying the percentage of RCTs that the effect of outcome changed from no statistical difference to statistical difference after removing PIES in the included studies, and the impact of PIES was externally validated in other acupuncture RCTs with an inserted sham acupuncture group that were not used to calculate PIES.
RESULTS:
This analysis included 32 studies with 5492 patients. The overall PNE was 0.335 (95% confidence interval [CI], 0.255-0.415) and the PCE of acupuncture was 0.639 (95% CI, 0.567-0.710) of acupuncture's total effect. The proportional contribution of the placebo effect to acupuncture's total effect was 0.191, and the PIES was 0.189. When we modeled the exclusion of the insert-specific effect of sham acupuncture, the acupuncture treatment effect changed from no difference to a significant difference in 45.45% of the included RCTs, and in 40.91% of the external validated RCTs.
CONCLUSION
The insert-specific effect of sham acupuncture in RCTs represents 18.90% of acupuncture's total effect and significantly affects the evaluation of the acupuncture treatment effect. More than 40% of RCTs that used inserted sham acupuncture would draw different conclusions if the PIES had been controlled for. Considering the impact of the insert-specific effect of sham acupuncture, caution should be taken when using inserted sham acupuncture placebos in RCTs. Please cite this article as: Luo XC, Liu JL, Yao MH, Chen YM, Fan AY, Liang FR, Zhao JP, Zhao L, Zhou X, Zhong XY, Yang JH, Li B, Zhang Y, Sun X, Li L. Specific effect of inserted sham acupuncture and its impact on the estimation of acupuncture treatment effect in randomized controlled trials: A systematic survey. J Integr Med. 2025; 23(6):630-640.
Acupuncture Therapy/methods*
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Humans
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Randomized Controlled Trials as Topic
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Placebo Effect
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Placebos
;
Treatment Outcome
7.Synaptic Vesicle Glycoprotein 2A Slows down Amyloidogenic Processing of Amyloid Precursor Protein via Regulating Its Intracellular Trafficking.
Qian ZHANG ; Xiao Ling WANG ; Yu Li HOU ; Jing Jing ZHANG ; Cong Cong LIU ; Xiao Min ZHANG ; Ya Qi WANG ; Yu Jian FAN ; Jun Ting LIU ; Jing LIU ; Qiao SONG ; Pei Chang WANG
Biomedical and Environmental Sciences 2025;38(5):607-624
OBJECTIVE:
To reveal the effects and potential mechanisms by which synaptic vesicle glycoprotein 2A (SV2A) influences the distribution of amyloid precursor protein (APP) in the trans-Golgi network (TGN), endolysosomal system, and cell membranes and to reveal the effects of SV2A on APP amyloid degradation.
METHODS:
Colocalization analysis of APP with specific tagged proteins in the TGN, ensolysosomal system, and cell membrane was performed to explore the effects of SV2A on the intracellular transport of APP. APP, β-site amyloid precursor protein cleaving enzyme 1 (BACE1) expressions, and APP cleavage products levels were investigated to observe the effects of SV2A on APP amyloidogenic processing.
RESULTS:
APP localization was reduced in the TGN, early endosomes, late endosomes, and lysosomes, whereas it was increased in the recycling endosomes and cell membrane of SV2A-overexpressed neurons. Moreover, Arl5b (ADP-ribosylation factor 5b), a protein responsible for transporting APP from the TGN to early endosomes, was upregulated by SV2A. SV2A overexpression also decreased APP transport from the cell membrane to early endosomes by downregulating APP endocytosis. In addition, products of APP amyloid degradation, including sAPPβ, Aβ 1-42, and Aβ 1-40, were decreased in SV2A-overexpressed cells.
CONCLUSION
These results demonstrated that SV2A promotes APP transport from the TGN to early endosomes by upregulating Arl5b and promoting APP transport from early endosomes to recycling endosomes-cell membrane pathway, which slows APP amyloid degradation.
Amyloid beta-Protein Precursor/genetics*
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Membrane Glycoproteins/genetics*
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Animals
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Protein Transport
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Nerve Tissue Proteins/genetics*
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Humans
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Mice
;
Endosomes/metabolism*
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trans-Golgi Network/metabolism*
8.Deciphering Virulence Factors of Hyper-Virulent Pseudomonas aeruginosa Associated with Meningitis.
Li Ling XIE ; Shuo LIU ; Yu Fan WANG ; Ming Chun LI ; Zhen Hua HUANG ; Yue MA ; Qi Lin YU
Biomedical and Environmental Sciences 2025;38(7):856-866
OBJECTIVE:
Pseudomonas aeruginosa( P. aeruginosa) is a prevalent pathogenic bacterium involved in meningitis; however, the virulence factors contributing to this disease remain poorly understood.
METHODS:
The virulence of the P. aeruginosa A584, isolated from meningitis samples, was evaluated by constructing in vitro blood-brain barrier and in vivo systemic infection models. qPCR, whole-genome sequencing, and drug efflux assays of A584 were performed to analyze the virulence factors.
RESULTS:
Genomic sequencing showed that A584 formed a phylogenetic cluster with the reference strains NY7610, DDRC3, Pa58, and Pa124. Its genome includes abundant virulence factors, such as hemolysin, the Type IV secretion system, and pyoverdine. A584 is a multidrug-resistant strain, and its wide-spectrum resistance is associated with enhanced drug efflux. Moreover, this strain caused significantly more severe damage to the blood-brain barrier than the standard strain, PAO1. qPCR assays further revealed the downregulation of the blood-brain barrier-associated proteins Claudin-5 and Occludin by A584. During systemic infection, A584 exhibited a higher capacity of brain colonization than PAO1 (37.1 × 10 6 CFU/g brain versus 2.5 × 10 6 CFU/g brain), leading to higher levels of the pro-inflammatory factors IL-1β and TNF-α.
CONCLUSION
This study sheds light on the virulence factors of P. aeruginosa involved in meningitis.
Pseudomonas aeruginosa/genetics*
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Virulence Factors/metabolism*
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Animals
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Virulence
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Mice
;
Pseudomonas Infections/microbiology*
;
Blood-Brain Barrier/microbiology*
;
Humans
;
Female
9.A study on the correlation between oral health status and cognitive impairment in elderly population.
Lisheng XU ; Fan LIU ; Jingyi WEI ; Xin ZHENG ; Xiaoying LI ; Ling ZHANG
West China Journal of Stomatology 2025;43(2):220-226
OBJECTIVES:
This cross-sectional study aims to explore the association between oral health status and cognitive function in Chinese elderly individuals.
METHODS:
The survey participants were composed of elderly people aged≥60 who were admitted to West China Hospital of Stomatology, Sichuan University from August 2022 to March 2024. They were divided into a cognitive impairment (CI) group and a healthy control (HC) group according to the Montreal Cognitive Assessment (MoCA) score. General information and oral health indicators of all elderly people were collected. Independent sample t-test and chi-square test were used for inter-group comparison, and multiple linear regression model was applied for multivariate analysis of MoCA scores.
RESULTS:
A total of 402 elderly people were included in the study, and the number of remaining teeth in the CI group was significantly lower than that in the HC group. The decayed, missing, filled teeth index, debris index-simplified, gingival index, probing depth (PD), and clinical attachment loss in the CI group were all significantly higher than those in the HC group. There was no difference in denture wearing between the two groups. The results of multiple linear regression showed that there was a correlation between the number of remaining teeth and PD and MoCA scores after correcting for confounding factors.
CONCLUSIONS
Elderly individuals with CI have more prominent oral health issues compared to those with normal cognitive function. There may be a bidirectional relationship between the number of remaining teeth, PD, and cognitive function in elderly people.
Humans
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Oral Health
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Aged
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Cross-Sectional Studies
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Cognitive Dysfunction/epidemiology*
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Male
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Female
;
China/epidemiology*
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Middle Aged
;
Linear Models
;
Aged, 80 and over
;
Periodontal Index
;
Cognition
10.Effect of miR-185-5p expression on myocardial metabolic abnormalities mediated by inflammatory response in patients with CHF
Ling LI ; Haichao FAN ; Junhong LIU
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2025;27(8):1026-1029
Objective To investigate the role of miR-185-5p expression changes in inducing myo-cardial metabolic abnormalities mediated by inflammatory responses in patients with chronic heart failure(CHF).Methods A total of 228 CHF patients treated in our department from June 2022 to June 2024 were prospectively enrolled and served as observation group,and another 108 healthy individuals taking physical examinations were subjected as the control group.Cardioechography was used to detect ejection time,fractional shortening,stroke volume,left ventricular mass index(LVMI),left ventricular end-diastolic diameter(LVEDD),left ventricular ejection fraction(LVEF),and left ventricular end-systolic diameter(LVESD).Then LV circumferential end-systolic wall stress(CESS)and MEE were calculated.The levels of IL-6,CRP,and TNF-α were detected with ELISA.Results The expression of miR-185-5p was significantly lower,and the levels of IL-6,CRP,and TNF-α were obviously higher in the observation group than the control group(P<0.01).MiR-185-5p was negatively correlated with IL-6,CRP and TNF-α levels(r=-0.765,-0.558,-0.693,P<0.01);MEE was negatively correlated with miR-185-5p(r=-0.594,P<0.01)and positively with IL-6,CRP and TNF-α levels(r=0.712,0.684,0.559,P<0.01).Multivariate logistic regression analysis showed that ejection time,fractional shortening,stroke volume,LVEF,and miR-185-5p were independent protective factors for MEE,while LVMI,LVESD,LVEDD,CESS,IL-6,CRP,and TNF-α were independent risk factors for MEE(P<0.05,P<0.01).Conclusion Low expression of miR-185-5p is associated with myocardial metabolic abnormalities mediated by inflammatory responses in CHF patients.

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