1.Mechanism of miR-21 targeting inhibition of the PTEN/AKT/mTOR pathway in ameliorating chronic renal fibrosis in mice
Jiao QI ; Shanshan XU ; Qige QI ; Yan MENG ; Jianrong ZHAO ; Liying ZHANG
Acta Universitatis Medicinalis Anhui 2026;61(2):217-224
ObjectiveTo investigate the mechanism through which miR‑21 improves chronic renal fibrosis in mice via targeted modulation of the phosphatase and tensin homolog (PTEN)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway. MethodsThirty‑two chronic kidney disease model mice were randomly divided into four groups (n=8 each group): model group, miR‑21 overexpression group, miR‑21 inhibition group, and miR‑21 inhibition + MK‑2206 group. Eight healthy mice were included as the control group. The miR‑21 overexpression, miR‑21 inhibition, and miR‑21 inhibition + MK‑2206 groups received tail‑vein injections of lentivirus (50 μL, 1×10⁸ TU per mouse) once weekly for three weeks. The control and model groups were injected with an equal volume of empty vector (LV‑NC). The miR‑21 inhibition + MK‑2206 group additionally received gavage of the AKT/mTOR pathway inhibitor MK‑2206 (480 mg/kg) once weekly for three weeks. The expressions of miR‑21, 24 h urinary protein, serum creatinine (Scr), blood urea nitrogen (BUN), and renal tissue levels of collagen Ⅰ, collagen Ⅲ, α‑smooth muscle actin (α‑SMA), and PTEN protein, as well as p‑AKT/AKT and p‑mTOR/mTOR ratios, were compared among groups. HE staining was used to observe pathological changes in renal tissue, and Masson staining was used to observe the degree of renal fibrosis. A dual‑luciferase assay was performed to verify the targeting relationship between miR‑21 and PTEN. ResultsCompared with the model group, miR‑21 expression in renal tissue increased in the miR‑21 overexpression group (P<0.05) and decreased in the miR‑21 inhibition group (P<0.05). Compared with the model group, the miR‑21 overexpression group showed increased 24 h urinary protein, Scr, BUN, and renal tissue expression of collagen Ⅰ, collagen Ⅲ, and α‑SMA (all P<0.05), while these indicators decreased in the miR‑21 inhibition group (P<0.05). Compared with the miR‑21 inhibition group, the miR‑21 inhibition + MK‑2206 group exhibited lower 24‑h urinary protein, Scr, BUN, and renal tissue expression of Collagen Ⅰ, Collagen Ⅲ, and α‑SMA (all P<0.05). Compared with the model group, the miR‑21 overexpression group showed decreased PTEN protein expression (P<0.05) and increased p‑AKT/AKT and p‑mTOR/mTOR ratios (P<0.05), while the miR‑21 inhibition group showed increased PTEN expression (P<0.05) and decreased p‑AKT/AKT and p‑mTOR/mTOR ratios (P<0.05). Compared with the miR‑21 inhibition group, the miR‑21 inhibition + MK‑2206 group had lower p‑AKT/AKT and p‑mTOR/mTOR ratios (P<0.05), with no significant difference in PTEN protein expression. HE and Masson staining showed normal kidney structure and almost no fibrosis in the control group. The model group exhibited glomerular enlargement, capillary loop adhesion, and focal fibrosis. The miR-21 overexpression group showed severe destruction of glomerular structure, accompanied by extensive fibrosis and renal tubular atrophy. The pathological changes and degree of fibrosis were alleviated in the miR-21 inhibition group. The miR-21 inhibition + MK-2206 group showed only mild pathological changes and mild fibrosis, with the interstitium being largely normal. Compared with PTEN-WT + NC mimics 1, the relative luciferase activity in the PTEN-WT + miR-21 mimics group decreased (P<0.001). There was no statistically significant difference in relative luciferase activity between PTEN-WT + NC mimics group and PTEN-MUT + miR-21 mimics group. ConclusionmiR‑21 may improve renal function indicators and alleviate renal fibrosis in chronic kidney disease mice via targeted modulation of PTEN and subsequently inhibiting the AKT/mTOR pathway.
2.Research progress on strategies for toxicity reduction and efficacy enhancement of triptolide
Xiaoqing ZHENG ; Ying DING ; Shanshan XU ; Long WANG ; Shanshan HAN ; Yaping XING ; Meng ZHANG ; Wenhao LI
China Pharmacy 2026;37(11):1496-1501
Triptolide (TP), the core active component of the traditional Chinese medicine Tripterygium wilfordii , exhibits remarkable pharmacological activities including anti-inflammatory, immunosuppressive and anti-tumor effects, and holds broad application prospects in the treatment of major diseases such as autoimmune diseases and malignant tumors. However, TP has a narrow therapeutic window and causes multi-organ toxicities including liver, kidney and reproductive toxicities, which severely restrict its safe clinical application and new drug development. Therefore, toxicity reduction and efficacy enhancement has become a core scientific problem urgently to be solved in this field. This paper systematically reviews the four core strategies for TP toxicity reduction and efficacy enhancement, including structural modification, dosage form improvement, herbal compatibility, and external therapies of traditional Chinese medicine. Among them, structural modification optimizes the toxic and efficacy characteristics of TP from the molecular structure level, with typica l derivatives including (5 R )-5-hydroxy triptolide, ZT01, PG490-88, etc. Dosage form modification achieves toxicity reduction and efficacy enhancement via targeted and sustained-controlled drug release of diverse delivery systems. It includes triptolide preparations such as nanoparticles, liposomes, microemulsion gels and liquid crystals, possessing favorable clinical transformation potential. The herbal compatibility and external therapies of traditional Chinese medicine conform to the holistic view of traditional Chinese medicine and have a profound clinical application foundation, but their mechanisms of action are insufficiently elucidated, and they lack unified standardized specifications and high-quality evidence-based proof. In the future, we should rely on multi-omics technology to elucidate the toxic and efficacy mechanisms, integrate technologies to optimize preparations, improve the evaluation system and promote clinical transformation.
3.Effect of macrophage lipolysis-stimulated lipoprotein receptor deficiency on a mouse model of metabolic dysfunction-associated steatohepatitis
Hang MENG ; Qianfeng JIA ; Shanshan DU ; Jiashu XU ; Yongfeng GONG ; Cai MA
Journal of Clinical Hepatology 2026;42(9):2093-2105
ObjectiveTo investigate whether macrophage lipolysis-stimulated lipoprotein receptor (LSR) deficiency affects the progression of metabolic dysfunction-associated steatohepatitis (MASH) by activating the Yes-associated protein (YAP) signaling pathway. MethodsMale wild-type (WT) mice and macrophage-specific Lsr knockout (LsrMφKO, KO) mice, with an age of 8 weeks and similar body weights, were selected and fed with a normal diet, a high-fat diet (HFD), or a high-fat high-cholesterol (HFHC) diet for 30 weeks. HE staining and oil red O staining were used to evaluate liver pathological changes; immunofluorescent staining was used to measure the expression levels of F4/80 and α-smooth muscle actin; RT-qPCR and Western blot were used to measure the levels of markers associated with lipid metabolism, inflammation, and fibrosis. Bone marrow transplantation rescue experiments (WT→KO vs KO→KO groups) were conducted to explore the functional role of LSR in macrophages. At the cellular level, hepatic macrophages were isolated from WT and KO mice to measure the expression levels of YAP signaling pathway-related proteins and their downstream target genes, and in addition, these cells were treated in vitro with verteporfin (VP), a specific inhibitor of YAP, to verify the regulatory effect of this pathway on the expression of inflammatory factors. The independent samples t-test was used for comparison of normally distributed measurement data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed measurement data. ResultsUnder the condition of normal diet, there were no significant differences in hepatic indicators between WT and KO mice. KO mice fed an HFD or HFHC diet showed a significant increase in hepatic lipid droplet accumulation, accompanied by lipid metabolism disorder and significant increases in the levels of indicators associated with inflammation and fibrosis (P<0.05). Bone marrow transplantation experiments confirmed that compared with the KO→KO group, the WT→KO group had significant alleviation of liver injury (P<0.05). Mechanistic studies showed that there were significant reductions in the levels of phosphorylated large tumor suppressor kinase 1 (LATS1) and phosphorylated YAP and significant increases in the expression levels of total YAP protein and its downstream target genes in hepatic macrophages of KO mice (P<0.05). In vitro VP intervention significantly inhibited the expression levels of inflammatory factors in hepatic macrophages isolated from KO mice (P<0.05). ConclusionMacrophage LSR deficiency activates the YAP signaling pathway by inhibiting LATS1/2 kinase activity and promotes the expression of inflammatory factors, thereby accelerating the progression of liver injury in a mouse model of MASH.
4.Application of three-dimensional arterial spin labeling MR imaging to quantify changes in hippocampal perfusion before and after radiotherapy for brain metastases
Rui LIU ; Guanzhong GONG ; Shanshan DU ; Kangning MENG ; Ruozheng WANG ; Yong YIN
Chinese Journal of Medical Physics 2025;42(2):148-153
Objective To retrospectively analyze the changes in cerebral blood flow(CBF)of hippocampus before and after radiotherapy(RT)and to explore its relationship with dose for providing a feasible approach for dynamically monitoring hippocampal response after whole brain radiation therapy in patients with brain metastases(BMs).Methods A retrospective analysis was conducted on magnetic resonance(MR)images from 43 BMs patients before and after RT,including T1-weighted imaging(T1WI)and three-dimensional arterial spin labeling(3D-ASL)imaging.Manual segmentation of the hippocampal structures was performed on T1WI to determine hippocampal volume,while CBF within the hippocampus was derived from 3D-ASL images.Patients were categorized into different groups according to the time interval between two MR scans and the dose received by the hippocampus,namely short time interval[<30 d,with an average of(19.74±7.15)d]≤1 Gy,1-30 Gy and≥30 Gy groups;long time interval[>3 months,with an average of(495.50±226.06)d]≤1 Gy,1-30 Gy and≥30 Gy groups.The patterns of changes in hippocampal CBF and volume,as well as the dose-effect relationship following RT were analyzed.Results(1)A total of 86 hippocampi were enrolled,showing reductions of 8.32%in minimum CBF(CBF-min),7.31%in maximum CBF(CBF-max),8.09%in mean CBF(CBF-mean),and 4.11%in hippocampal volume after RT(P<0.05).The decrease rates of CBF-min,CBF-max and CBF-mean were 6.33%,7.01%and 8.23%higher than the reduction rate of hippocampal volume,respectively.(2)With a brief interval between two MR simulation localization scans,hippocampal CBF in the groups receiving≤1 Gy and 1-30 Gy exhibited an increase,with the increase rate positively correlated to the radiation dose absorbed by the hippocampus.Conversely,in the group receiving≥30 Gy,hippocampal CBF decreased.The variations in the rate of hippocampal CBF change across the dose groups were statistically significant,except when comparing≤1 Gy and 1-30 Gy groups(P<0.05).Additionally,the hippocampal volume in all 3 dose groups experienced a slight increase,with the growth rate also positively correlated to the radiation dose received by the hippocampus;however,these differences were not statistically significant(P>0.05).(3)With a long interval between MR simulation localization scans,both hippocampal CBF and volume in all 3 dose groups demonstrated decreasing trends,with the decrease rate positively correlated to the radiation dose received by the hippocampus.Statistically significant differences in the rate of CBF change were noted among the dose groups,except for the comparison between≤1 Gy and 1-30 Gy groups(P<0.05).The reduction rate of hippocampal volume across 3 dose groups was statistically significant(P<0.05).Conclusion The reduction in hippocampal CBF following RT in BMs patients is more sensitive than the reduction in hippocampal volume,exhibiting a pronounced dependence on both time and radiation dose.Consequently,CBF changes should be employed as a standard bioindicator for monitoring the response to hippocampal RT and predicting radiological injuries after whole brain radiotherapy in BMs patients.
5.Evaluating the relationship between glucose metabolic status and neonatal weight by using regression discontinuity analysis
Ran ZHANG ; Shanshan HOU ; Junfeng MA ; Ying MENG ; Mingyuan JIAO
Chinese Journal of Clinical Laboratory Science 2025;43(8):591-595
Objective To explore relationship between glucose metabolism and neonatal weight in high-risk gestational diabetes melli-tus(GDM).Method A retrospective study was conducted on 779 pregnant women who underwent prenatal examinations at Tongzhou Maternity and Child Health Care Hospital in Beijing from March to June 2022.The data on pre-pregnancy weight,mid-and late-preg-nancy glycated albumin(GA)and glycated hemoglobin(HbA1c),pre-delivery weight,gestational weight gain,and neonatal birth weight were collected.A GDM risk assessment model was established using multivariate logistic regression to classify pregnant women into high-risk and low-risk groups for GDM,followed by separate management strategies.Regression discontinuity(RD)analysis was applied to evaluate the relationship between gestational glucose metabolism status and neonatal birth weight.Results Among the 779 pregnant women,the overall incidence of macrosomia was 7.32%.The high-risk GDM group exhibited significantly higher pre-pregnan-cy weight,late-pregnancy HbA1c,and GA levels compared to the low-risk group(all P<0.001).Neonatal birth weight in the high-risk group was significantly higher than that in the low-risk group(P<0.05),with a significantly increased macrosomia incidence(13.55%vs 5.77%,P<0.05).RD analysis revealed a jump reduction of 199.59 g(P=0.029)in neonatal birth weight at the risk score thresh-old.Conclusion Lifestyle glucose metabolism management in high-risk GDM pregnant women may effectively reduce neonatal birth weight,mitigated the trend of excessive gestational weight gain,and improved late-pregnancy HbA1c and GA levels,providing evi-dence-based support for maternal and child health services.
6.Clinical efficacy and safety of a domestic calcipotriol/betamethasone dipropionate ointment in the treatment of stable plaque psoriasis: a multicenter, randomized, double-blind, controlled study
Lixin XIA ; Guang XIANG ; Qingchun DIAO ; Kun HUANG ; Shoumin ZHANG ; Shanshan LI ; Yumei LI ; Zhiqiang SONG ; Qing SUN ; Xiumin YANG ; Meng PAN ; Yuling SHI ; Shuping GUO ; Huiping WANG ; Tiechi LEI ; Xiaoyong ZHOU ; Songmei GENG ; Suchun HOU ; Juan SU ; Yong CUI ; Rixin CHEN ; Yanyan FENG ; Hongxia FENG ; Rushan XIA ; Zudong MENG ; Fang YIN ; Jingjing WANG ; Xinghua GAO
Chinese Journal of Dermatology 2025;58(11):1020-1026
Objective:To evaluate the clinical equivalence between a domestic calcipotriol/betamethasone dipropionate ointment and the originator product in the treatment of stable plaque psoriasis.Methods:A multicenter, randomized, double-blind, three-arm, parallel-group, active- and placebo-controlled study was conducted, and 449 patients aged 18 - 65 years with stable plaque psoriasis were enrolled from 25 hospitals (such as the First Affiliated Hospital of China Medical University). Eligible patients had a baseline physician's global assessment (PGA) score of ≥ 3 points, baseline body surface area (BSA) involvement of 5% - 30%, and a target lesion psoriasis area and severity index (TL-PASI) for plaque elevation of ≥ 3 points. Participants were randomly assigned in a 2:2:1 ratio to the test group ( n = 179), reference group ( n = 180), and placebo group ( n = 90), and applied the domestic calcipotriol/betamethasone dipropionate ointment, originator product, and ointment base respectively, once daily in the evening for 4 weeks. Efficacy and safety were assessed at weeks 1, 2, and 4. The primary efficacy endpoints were the treatment success rates and clinical success rates in each group at week 4. The per-protocol set (PPS) was used for the primary efficacy analysis, and the intention-to-treat (ITT) set for supplementary efficacy analysis. Equivalence between the test and reference preparations was tested using the Cochran-Mantel-Haenszel method adjusted for randomization strata. Superiority of the test and reference preparations over the placebo was also tested. Measurement data were compared among the 3 groups using analysis of variance or non-parametric tests, while treatment success rates, clinical success rates, and incidence rates of adverse reactions were compared using the chi-square test. Results:The ITT, PPS, and safety sets included 447, 420, and 448 patients, respectively. In the ITT set, patients were aged 43.6 ± 12.8 years, including 320 (71.6%) males and 127 (28.4%) females, and the disease duration was 11.21 ± 9.05 years; 316 (70.7%) had a PGA score of 3 points and 131 (29.3%) had a PGA score of 4 - 5 points. No significant differences in the baseline characteristics (including age, sex, disease duration and disease severity) were observed among the 3 groups (all P > 0.05). Based on the PPS analysis, the treatment success rates were 57.9% (99/171) in the test group, 50.3% (86/171) in the reference group, and 7.7% (6/78) in the placebo group, and the clinical success rates were 57.9% (99/171), 50.3% (86/171), and 10.3% (8/78), respectively; both the test and reference groups were superior to the placebo group in both treatment and clinical success rates (all P < 0.001) ; the rate differences for treatment success (90% confidence interval [ CI]: -1.3% - 16.4%) and clinical success (90% CI: -1.3% - 16.3%) between the test and reference groups were entirely within the pre-defined equivalence margin (-20% - 20%). Subgroup analyses by baseline PGA scores: for patients with a baseline PGA score of 3 points, the treatment success rates in the test, reference, and placebo groups were 60.8% (73/120), 52.1% (62/119), and 11.1% (6/54), respectively, and the corresponding clinical success rates were 61.7% (74/120), 53.8% (64/119), and 13% (7/54), respectively; the test and reference groups did not differ significantly in treatment or clinical success rates (both P > 0.05), but both showed higher success rates than the placebo group (all P < 0.001) ; the results of statistical comparisons among the 3 groups in patients with a baseline PGA score of 4 - 5 points were consistent with those observed in patients with a baseline PGA score of 3 points. The percentage reductions in PGA and TL-PASI scores from baseline to weeks 1, 2, and 4 showed significant differences among the 3 groups, which were significantly higher in the test and reference groups than in the placebo group (all P < 0.001), but did not differ between the test and reference groups (all P > 0.05). The primary adverse reactions were local skin reactions, such as pruritus, pain, and erythema. The incidence rates of adverse reactions were 8.9% (16/179) in the test group, 7.3% (13/179) in the reference group, and 7.8% (7/90) in the placebo group, with no significant difference among the 3 groups ( P > 0.05) . Conclusions:The domestic calcipotriol/betamethasone dipropionate ointment demonstrated clinical equivalence to the originator product in the treatment of stable plaque psoriasis, and the two agents exhibited comparable efficacy for patients with varying degrees of disease severity, and were comparable in the speed and degree of clinical improvement, with similar favorable safety profiles.
7.Exploration of epidemiological characteristics of multidrug-resistant organisms among burn wound patients and prevention and control strategies based on worldwide database for nosocomial outbreaks
Jiao SHAN ; Wei HUAI ; Shanshan MENG ; Meng JIN ; Xiaoyuan BAO ; Yulong CAO ; Hong LI ; Hui CHEN
Chinese Journal of Nosocomiology 2025;35(17):2592-2596
OBJECTIVE To investigate the epidemiological characteristics of hospital-associated infections caused by multidrug-resistant organisms(MDROs)among the burn wound patients so as to provide bases for taking tar-geted control measures.METHODS A systematic search was conducted in the worldwide database for nosocomial outbreaks,PubMed and CNKI databases so as to summarize and analyze the data regarding to outbreaks of MDROs hospital-associated infections among burn wound patients.RESULTS A total of 61 incidents of MDROs hospital-associated infections outbreaks among the burn wound patients were included,involving 2 293 patients from 21 countries and regions,50(81.97%)of which were reported for the infection sites or colonization sites in-volving burn wound,12(19.67%)involving the respiratory tract,10(16.39%)involving the bloodstream infec-tions.Methicillin-resistant Staphylococcus aureus(28 incidents,45.90%)was dominant among the pathogens causing the infections,followed by multidrug-resistant Acinetobacter baumannii(17 incidents,27.87%)and multidrug-resistant Pseudomonas aureus(9 incidents,14.75%).52 incidents(82.25%)of outbreaks were reported the contact as the major transmission mode.The suspected sources of the outbreaks included the patients(37 incidents,28.46%),health care workers(30 incidents,23.08%),ward environments(28 incidents,21.54%),medical equipments(19 incidents,30.56%),drainage systems(6 incidents,4.62%).The major pre-vention and control measures included environmental cleaning and disinfection,screening of colonization in patients and health care workers,isolation of patients with infections and hand hygiene;8 incidents were taken the measure of closing the ward.CONCLUSIONS The outbreaks of MDROs infections in the burn wound patients are mostly associated with the high frequently contact environments,medical equipments and hand hygiene of health care workers.In view of the peculiarities of the burn wound patients,it is feasible to take the targeted measures based on the summarized prevention and control combinations for MDROs so as to prevent the outbreak of hospital-asso-ciated infections.
8.Ginsenosides targeting P-glycoprotein enhance the inhibitory effect of paclitaxel on colon cancer
Xiaohui ZHU ; Yuanyuan ZHAO ; Nanxi LI ; Jinnan GUO ; Yunfei TIAN ; Huiting ZHAI ; Shanshan WANG ; Dexuan YANG ; Guifang DOU ; Suxiang FENG ; Zhiyun MENG
Chinese Journal of Pharmacology and Toxicology 2025;39(2):89-99
OBJECTIVE To investigate the effects of ginsenosides as P-glycoprotein(P-gp)substrates in combination with paclitaxel on the proliferation and migration of colon cancer Caco-2 cells.METHODS Bio-layer interferometry(BLI)technology was used to detect the constants of ginsenosides and P-gp.Network molecular docking was adopted to predict the binding affinity energy of ginsenosides and P-gp.Caco-2 cells were divided into paclitaxel 0,6.25,12.5,25,50,100 and 200 mg·L-1 groups,ginsenoside Rg3 0,6.25,12.5,25,50,100 and 200 mg·L-1 groups,and paclitaxel 5 mg·L-1+ginsenoside Rg3 0,25,50,100 and 200 mg·L-1 groups.After 48 h of incubation,the growth inhibition rate of Caco-2 cells was detected by MTT assay,and the interaction between the two drugs was quantitatively evaluated using the"one-belt,one-line"modle.Caco-2 cells were divided into the cell control group,paclitaxel 5 mg·L-1 group,ginsenoside Rg3 50 and 100 mg·L-1 groups,and paclitaxel 5 mg·L-1+ginsenoside Rg3 50 and 100 mg·L-1 groups.After 24 h of incubation,the proliferation and migration ability of the cells were detected by colony assay and Transwell migration assay.Caco-2 cells were then divided into the cell control group,quinidine 12.5 mg·L-1 group,and ginsenoside Rg3 6.25 and 12.5 mg·L-1 groups.After 4 h of incubation,the expression levels of P-gp and total protein were detected by ELISA.RESULTS The affinity constants of ginsenoside Rb1,Rg3,Rg5 with P-gp were all less than 10-3 mol·L-1,while that of ginsenoside CK with P-gp was 10-2 mol·L-1.There was no typical binding dissociation curve between ginsenoside Re and P-gp.The absolute binding affinities of ginsenosides Rg3 and Rg5 to P-gp were determined to be 8.5 kcal·mol-1 and 7.6 kcal·mol-1,respectively.Ginsenosides mixed with PTX 5 mg·L-1 inhibited the growth of colon cancer cells through synergy and addition,and the dose range of the syner-gistic effect was[0+5,43.15+5]mg·L-1;[164.51+5,200+5]mg·L-1,the additive effect dose ranged from[43.15+5,164.51+5]mg·L-1.The combination of the two drugs could significantly reduce the proliferation and migration ability of Caco-2 cells(P<0.01).The ELISA results showed a decrease in total protein and P-gp content in both the ginsenoside and quinidine groups(P<0.05).CONCLUSION Ginsenoside bind to and inhibit the activity of P-gp,synergizing with paclitaxel to reduce the proliferative and migratory abili-ties of Caco-2 cells.The combination of ginsenosides and paclitaxel enhances the sensitivity of Caco-2 cells to paclitaxel induced inhibition.The combined use of these two substances is expected to achieve better anticancer effects compared to paclitaxel alone.
9.Analysis of the current status and influencing factors of cognitive function and sleep quality of elderly people in Shanghai community
Yanli ZHANG ; Meng WANG ; Xuechun WANG ; Shanshan HUANG ; Jiaoqi REN ; Houguang ZHOU
Chinese Journal of Clinical Medicine 2025;32(1):58-64
Objective To analyze the cognitive function and sleep quality of the elderly in Shanghai community, and explore the related influencing factors. Methods A stratified cluster random sampling method was used to select 8 community health centers in Shanghai for a questionnaire survey, including 3 677 elderly individuals who completed the “Comprehensive Health Status Survey of Elderly Residents in Shanghai” from September 2023 to November 2023. Basic information of the elderly was collected, including age, gender, education level, smoking, drinking, mahjong playing behavior, and exercise habits. The Pittsburgh sleep quality index (PSQI) was used to assess the sleep quality of the elderly, subjective cognitive decline (SCD) self-assessment questionnaire and Mini-Mental State Examination (MMSE) were used to evaluate cognitive function, while the Hamilton Anxiety Scale (HAMA) and patient health questionnaire-9 (PHQ-9) were used to assess anxiety and depression levels, and the mini nutritional assessment (MNA) was used to evaluate nutritional status. According to the MMSE scores, the elderly were divided into three groups: no cognitive impairment (MMSE ≥ 27), mild cognitive impairment (MMSE 21-26), and moderate to severe cognitive impairment (MMSE ≤ 20). The general data, lifestyle habits, and scale scores of the three groups were compared. Ordered logistic regression was used to analyze the influencing factors of sleep quality. Results There were statistically significant differences in age, gender, waist circumference, body mass index (BMI), education level, pet ownership, smoking, drinking, mahjong playing behavior, exercise habits, and scale scores among the three groups (P<0.05). Logistic regression analysis showed that age, waist circumference, gender, drinking habits, mahjong playing behavior, and chronic comorbidities are influencing factors for the PSQI grading in the elderly (P<0.05). The MMSE score (OR=1.037, P=0.001), SCD score (OR=1.123, P<0.001), HAMA score (OR=1.183, P<0.001), PHQ-9 score (OR=1.249, P<0.001) are positive influencing factors for PSQI grading, while the MNA score is a negative influencing factor (OR=0.960, P=0.037). Conclusions Advanced age, female gender, low education level, no pet ownership, no mahjong playing behavior, no exercise habits, and poor sleep quality are risk factors for cognitive impairment in the elderly. Advanced age, female gender, no mahjong playing behavior and poor nutritional status are influencing factors for poor sleep quality in the elderly, and severe comorbidities, anxiety, depression, and subjective decline in cognitive function all affect sleep quality.
10.Effect of pomegranate peel polyphenols on the malignant biological behavior of colon cancer cells by regulat-ing the miR-138-5p/HIF-1α pathway
Hongyan BIAN ; Shu ZHANG ; Shanshan MENG ; Ying WEI
The Journal of Practical Medicine 2025;41(5):676-682
Objective To investigate the impact of pomegranate peel polyphenols(PPP)on the malignant biological behavior of colon cancer cells through modulation of the miR-138-5p/hypoxia-inducible factor-1α(HIF-1α)pathway.Methods Quantitative real-time PCR(qRT-PCR)was employed to measure the expression levels of miR-138-5p and HIF-1α mRNA in the normal colon epithelial cell line FHC and three colorectal cancer cell lines:SW480,HCT116,and Caco-2.SW480 cells were divided into six groups:a blank control group,a negative control(mimics NC)group,a miR-138-5p mimics group,three different concentrations of PPP treatment groups(0.5 mg/mL,1 mg/mL,and 2 mg/mL),a PPP+inhibitor NC group at 2 mg/mL,and a PPP+miR-138-5p inhibitor group at 2 mg/mL.The effects on cell proliferation,invasion,and migration,as well as changes in apoptosis and related proteins including B-cell lymphoma 2(Bcl-2),migration invasion enhancer 1(MIEN1),and Cyclin D1,were evaluated separately.Additionally,the targeting relationship between miR-138-5p and HIF-1α was validated.The expression levels of miR-138-5p,HIF-1α mRNA,and protein were assessed in each experimental group.Results The expression levels of miR-138-5p were highest in FHC cells and lowest in SW 480 cells,while the expression levels of HIF-1α mRNA showed an opposite trend,being lowest in FHC cells and highest in SW 480 cells(P<0.05).Compared with the control group,different concentrations of PPP significantly promoted cell apoptosis,upregulated miR-138-5p expression,inhibited cell proliferation,invasion,and migration,and downregulated the expression of HIF-1α mRNA,Bcl-2,MIEN1,CyclinD1,and HIF-1α protein,with significant differences between groups(P<0.05).Compared with the mimics NC group,the miR-138-5p mimics group significantly enhanced cell apoptosis,upregulated miR-138-5p expression,inhibited cell proliferation,invasion,and migration,and downregulated the expression of HIF-1α mRNA,Bcl-2,MIEN1,CyclinD1,and HIF-1α protein(P<0.05).Compared with the 2 mg/mL PPP+inhibitor NC group,the 2 mg/mL PPP+miR-138-5p inhibitor group significantly suppressed cell apoptosis,downregulated miR-138-5p expression,promoted cell proliferation,invasion,and migration,and upregulated the expression of HIF-1α mRNA,Bcl-2,MIEN1,CyclinD1,and HIF-1α protein(P<0.05).These results indicate a targeted relationship between miR-138-5p and HIF-1α(P<0.05).Conclusion PPP inhibits the malignant biological behavior of colon cancer cells through upregulation of the miR-138-5p/HIF-1α pathway.

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