1.Huanglian Jiedutang Improves Cognitive Impairment after Schemic Stroke by Regulating Neuron via NF-κB Signaling Pathway
Mengying SUN ; Lizhen WANG ; Tong LI ; Leilei WANG ; Shiyan JIA ; Tingting WANG ; Yanwen YANG ; Kaiqiang SI ; Youxiang CUI ; Zhilong LIU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(11):68-76
ObjectiveTo investigate the effects of Huanglian Jiedutang (HLJDT) on cognitive function in mice with ischemic stroke (IS) and to elucidate whether its neuroprotective effects are mediated by inhibition of the nuclear factor-κB (NF-κB) signaling pathway and subsequent suppression of NF-κB-regulated neuronal apoptosis. MethodsAn IS model was established using middle cerebral artery occlusion (MCAO). Sixty C57BL/6J mice were randomly assigned to five groups (n =12 per group), i.e., sham operation, model, HLJDT low-dose (3.9 g·kg-1·d-1), HLJDT high-dose (7.8 g·kg-1·d-1), and Ginkgo biloba extract (GBE, 31.2 mg·kg-1·d-1). Post-operatively, neurological deficit scores (Longa score), cerebral infarct volume assessed by 2,3,5-triphenyltetrazolium chloride (TTC) staining, and brain water content were evaluated. Learning and memory were assessed using new object recognition (NOR) and fear conditioning (FC) tests. Hippocampal pathology was examined via hematoxylin and eosin (HE) staining. Immunofluorescence detected expression of glial fibrillary acidic protein (GFAP, astrocyte marker), cellular oncogene Fos (c-Fos, neuronal activation marker), and glutamate decarboxylase 65 (GAD65). Western blot measured nuclear factor-κB inhibitor protein α (IκBα), phosphorylated IκBα (p-IκBα), NF-κB p65, phosphorylated NF-κB p65 (p-NF-κB p65), ionic calcium binding adapter molecule 1 (Iba-1), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and apoptosis-related proteins, such as cleaved cysteinyl aspartate-specific protease 3 (Caspase-3), B-cell lymphoma 2 (Bcl-2), and Bcl-2-associated X protein (Bax). Real-time quantitative PCR (Real-time PCR) was used to assess mRNA levels of Iba-1, TNF-α, IL-1β, NF-κB p65, cleaved Caspase-3, Bax, and Bcl-2. ResultsCompared with the sham group, the model group exhibited significantly increased neurological deficit scores, brain water content, and cerebral infarct volume (P<0.01). Hippocampal CA1 neurons were disorganized, showing nuclear pyknosis and karyolysis. NOR exploration time and FC freezing time were significantly reduced (P<0.01). GFAP and c-Fos expression were increased, while GAD65 expression was decreased (P<0.01). Cleaved Caspase-3 and Bax were upregulated, Bcl-2 was downregulated, and the Bax/Bcl-2 ratio was elevated (P<0.01). Expression levels of p-IκBα, p-NF-κB p65, IL-1β, TNF-α, and Iba-1 were significantly increased (P<0.01). Compared with the model group, HLJDT high-dose, low-dose, and GBE groups showed significant improvements in all parameters (P<0.01). Among them, the HLJDT high-dose group showed the most pronounced neuronal structural recovery and superior performance in NOR and FC tests (P<0.01). In this group, GFAP and c-Fos decreased, GAD65 increased (P<0.01), apoptosis-related protein expression was reversed, and NF-κB signaling and related inflammatory factor expression were suppressed (P<0.01). ConclusionHLJDT ameliorates cognitive dysfunction in mice after IS, potentially by inhibiting the NF-κB signaling pathway, thereby reducing neuroinflammation and hippocampal neuronal apoptosis.
2.A Mouse Model and Mechanism Study of Premature Ovarian Insufficiency Induced by Different Concentrations of Cyclophosphamide
Leilei GONG ; Xiaoxia WANG ; Xuewei FENG ; Xinlei LI ; Han ZHAO ; Xueyan ZHANG ; Xin FENG
Laboratory Animal and Comparative Medicine 2025;45(4):403-410
ObjectiveTo observe and compare the effects of different concentrations of cyclophosphamide (CTX) in inducing premature ovarian insufficiency (POI) model in mice and investigate the mechanism of injury. MethodsThirty-two 6~8-week-old female C57BL/6J mice were randomly divided into four groups (n=8 per group) using a weight-based block randomization method. The POI model was established via a single intraperitoneal injection of 75 mg/kg cyclophosphamide (CTX), 120 mg/kg CTX, 120 mg/kg CTX + 12 mg/kg Busulfan, or an equivalent volume of normal saline (control). Ovarian coefficients, serum estradiol (E2) and follicle-stimulating hormone (FSH) levels were measured. Western blotting was performed to assess changes in ovarian expression levels of NAD-dependent deacetylase sirtuin-5 (SIRT5) and forkhead box O3a (FOXO3a) under different modeling conditions. After determining the optimal CTX concentration for modeling, an additional forty 6~8-week-old femal C57BL/6J mice were randomly divided into five groups (n=8 per group) using a weight-based block randomization method: saline control, 120 mg/kg CTX sampling at 1, 2, 7, or 14 days after modeling. Western blotting was used to evaluate temporal changes of ovarian SIRT5 and FOXO3a protein expression. ResultsCompared with the saline control, all concentrations of CTX (75 mg/kg CTX, 120 mg/kg CTX) and 120 mg/kg CTX + 12 mg/kg Busulfan induced POI injury in mice. The 120 mg/kg CTX group exhibited smaller changes in ovarian coefficients (P<0.001) and E2 levels (P<0.05), whereas the 120 mg/kg CTX + 12 mg/kg Busulfan group showed rough and reduced luster fur, sluggish response and was in the worst state. Compared with the saline control group, FOXO3a expression was significantly down-regulated (P<0.05), while SIRT5 remained unchanged in the 75 mg/kg CTX group (P>0.05). In contrast, both SIRT5 (P<0.05) and FOXO3a (P<0.05) were significantly down-regulated in the 120 mg/kg CTX group. Further analysis revealed that on day 2 and 7 after 120 mg/kg CTX modeling, the expressions of SIRT5 (P<0.01) and FOXO3a (P<0.001) were significantly down-regulated, with the largest decrease observed on day 7 (SIRT5, P<0.000 1; FOXO3a, P<0.000 1). ConclusionOvarian injury in the POI model induced by 120 mg/kg CTX is milder than that in the POI model induced by 75 mg/kg CTX. Moreover, the expression changes of SIRT5 and FOXO3a are most significant on day 7 after modeling induced by 120 mg/kg CTX, which may be related to the inhibition of the SIRT5-FOXO3a signaling pathway.
3.The impact of postpartum depression on maternal responsiveness in infant care
Shuzhen LI ; Fang WANG ; Ke WANG ; Su LIU ; Qian WEI ; Qing YANG ; Leilei LIU ; Huijing SHI
Shanghai Journal of Preventive Medicine 2025;37(3):271-275
ObjectiveTo analyze the impact of maternal postpartum depression (PPD) at 2 months postpartum on caregiving for infants aged2 to 24 months, and to provide a scientific basis for future maternal and infant healthcare services. MethodsBased on the Shanghai Maternal-Child Pairs Cohort, 1 060 mother-child pairs were selected from those fully participating in follow-up visits at 2, 6, 12, and 24 months postpartum. Pregnancy and childbirth-related information was collected using standardized questionnaire surveys and hospital obstetric and maternity records. The Edinburgh postpartum depression scale was used to assess the maternal postpartum depressive symptoms at 2 months postpartum. At 2, 6, 12, and 24 months postpartum, questionnaire survey was used to evaluate the maternal responsiveness in caregiving and the provision of early learning opportunities for infants. Scores for responsive caregiving and early learning opportunities at 2, 6, 12, and 24 months were grouped based on the 25th percentile (P25) of total scores. The mixed-effects model was used to analyze the longitudinal impact of maternal postpartum depression at 2 months on the caregiving of 2 to 24-month-old infants. ResultsThe longitudinal results from the mixed-effects model did not show an impact of maternal PPD on infant responsive caregiving within 12 months and early learning opportunities within24 months. However, cross-sectional analysis revealed that, compared to the non-PPD group, the risk of low responsive caregiving at 2 months in the PPD group was 93% higher (OR=1.931, 95%CI: 1.113‒3.364, P=0.019). The risks for low provision of early learning opportunities at2 months and 24 months increased by 59% (OR=1.589, 95%CI: 1.082‒2.324, P=0.017) and 60% (OR=1.598, 95%CI:1.120‒2.279, P=0.010), respectively. ConclusionMaternal postpartum depression increases the risk of low responsive caregiving at 2 months, but its long-term effects warrant further research.
4.Erratum: Author correction to "PRMT6 promotes tumorigenicity and cisplatin response of lung cancer through triggering 6PGD/ENO1 mediated cell metabolism" Acta Pharm Sin B 13 (2023) 157-173.
Mingming SUN ; Leilei LI ; Yujia NIU ; Yingzhi WANG ; Qi YAN ; Fei XIE ; Yaya QIAO ; Jiaqi SONG ; Huanran SUN ; Zhen LI ; Sizhen LAI ; Hongkai CHANG ; Han ZHANG ; Jiyan WANG ; Chenxin YANG ; Huifang ZHAO ; Junzhen TAN ; Yanping LI ; Shuangping LIU ; Bin LU ; Min LIU ; Guangyao KONG ; Yujun ZHAO ; Chunze ZHANG ; Shu-Hai LIN ; Cheng LUO ; Shuai ZHANG ; Changliang SHAN
Acta Pharmaceutica Sinica B 2025;15(4):2297-2299
[This corrects the article DOI: 10.1016/j.apsb.2022.05.019.].
5.Effect of Helicobacter pylori induced mitochondrial unfolded protein response on gastric cancer cell proliferation
Jili Chen ; Leilei Li ; Yuanjia Chen ; Yan Zhao ; Yuan Xie ; Jianjiang Zhou
Acta Universitatis Medicinalis Anhui 2025;60(2):300-306
Objective :
To explore the mechanism of proliferation of gastric cancer cells induced byHelicobacter pylori(Hp) from the perspective of the mitochondrial unfolded protein response(UPRMT).
Methods :
C57BL6/J mice, human gastric cancer cells AGS and SGC-7901 cells were infected with Hp, mitochondrial proteins were extracted, and the expressions of UPRMT, including activation of transcription factor 5(ATF5), heat shock protein 60(mtHSP60), heat shock protein 70(mtHSP70) and mitochondrial protease(ClpP), were detected by Western blot. Immunohistochemistry was used to locate the expression sites of 4 proteins in mouse gastric tissue. AGS and SGC-7901 cells were infected with Hp, and cell proliferation was detected by RTCA and CCK-8. Finally, the expression of four indexes in gastric cancer tissues was analyzed by TCGA samples in the UALCAN database.
Results :
Hp infection could significantly promote the expression of ATF5, mtHSP60, mtHSP70 and ClpP in the mitochondria of gastric epithelial cells of C57BL6/J mice, AGS and SGC-7901 cells, and promote the proliferation of gastric cancer cells. When compared to normal gastric tissues in TCGA samples, ATF5, mtHSP60, mtHSP70, and ClpP were highly expressed in gastric cancer tissues, with statistically significant difference(allP<0.01).
Conclusion
Hp infection can induce UPRMTin gastric epithelial cells and gastric cancer cells, which in turn promotes cell proliferation.
6.Exploring the criteria for assessing hypoxemia in patients with obstructive sleep apnea from the standpoint of hypertension
Leilei YU ; Shizhen ZOU ; Yuanyuan JIA ; Rong ZHANG ; Jinrang LI
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2025;60(4):441-446
Objective:To determine appropriate cutoff values for evaluating hypoxemia severity in patients with obstructive sleep apnea (OSA).Methods:This cross-sectional study selected data from 1, 781 young patients with obstructive sleep apnea (OSA) who underwent polysomnography in the Department of Otorhinolaryngology Head and Neck Surgery of the Sixth Medical Center of PLA General Hospital from January 2015 to June 2023. The cohort included 1, 604 males and 177 females, with a mean age of (32.6±5.3) years. The relationship between the minimum arterial oxygen saturation (MSaO 2) and the prevalence of hypertension in this population was investigated. Subjects were categorized into seven groups based on MSaO 2 levels: Group 1 (MSaO 2≥90%), Group 2 (85%≤MSaO 2<90%), Group 3 (80%≤MSaO 2<85%), Group 4 (75%≤MSaO 2<80%), Group 5 (70%≤MSaO 2<75%), Group 6 (65%≤MSaO 2<70%), and Group 7 (MSaO 2<65%). The prevalence of hypertension in each group was statistically analyzed, and the chi-square test was used to identify significant differences in hypertension prevalence. The diagnostic performance of the new versus traditional grouping methods was evaluated using receiver operating characteristic (ROC) curve analysis. Results:Among the 1, 781 OSA patients, 915 had hypertension. The prevalence of hypertension in Groups 1 to 7 was 27.8%, 42.4%, 52.2%, 54.1%, 59.5%, 70.5%, and 75.4%, respectively. Significant differences in hypertension prevalence were observed between Group 1 and other groups, Group 2 and Groups 5-7, Group 3 and Groups 6-7, and Group 4 and Group 7( χ2=187.94, P<0.001). After merging the groups based on MSaO 2 thresholds of≥90%, 90%>MSaO 2≥85%, 85%>MSaO 2≥75%, and MSaO 2<75%, the prevalence of hypertension in the new groups was 27.8%, 42.4%, 53.0%, and 71.2%, respectively, with significant differences between adjacent groups( χ2=178.99, P<0.001). ROC curve analysis revealed that the area under the curve (AUC) for the new grouping method (0.676) was higher than that for the original grouping method (0.664). Conclusions:As hypoxemia severity increases in OSA, so does the prevalence of comorbid hypertension. Using MSaO 2 cutoff values of 90%, 85%, and 75% to categorize hypoxemia severity appears more appropriate compared to the existing guideline values of 90%, 85%, and 80%.
7.Study on the characteristics of laryngopharyngeal reflux events in patients with obstructive sleep apnea
Lianlian LIU ; Jinrang LI ; Zhi LIU ; Chun ZHANG ; Leilei YU ; Yuanyuan JIA ; Rong ZHANG
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2025;60(8):875-881
Objective:To study the characteristics of laryngopharyngeal reflux (LPR) events in patients with obstructive sleep apnea (OSA).Methods:This cross-sectional study analyzed OSA patients who were admitted in the Department of Otolaryngology-Head and Neck Surgery, the Sixth Medical Center of the Chinese PLA General Hospital between November 2020 to July 2023[OSA group, 52 males, 6 females, aged 23-69 (41.22±11.42) years], and non-OSA patients admitted during the same period serve as the control group[non-OSA group, 40 males, 1 female, aged 21-68 (45.12±11.30) years]. All participants completed the Reflux Symptom Index (RSI), Reflux Finding Score (RFS) scale, and 24-hour Hypopharyngeal Esophageal Multichannel Intraluminal Impedance-pH (HEMII-pH) monitoring. LPR events were categorized based on their physical composition-liquid, gas, or gas-liquid mixed, according to the change of impedance values; and further classified by pH levels as acidic, weakly acidic, or alkaline. Differences in LPR events physical properties and the time trends of LPR events between the two groups were compared. Group comparisons were performed using t-test or Mann-Whitney U-test. Analyses were conducted using Pearson, Spearman, or Kendall′s tau-b correlation analysis. Categorical data were analyzed using chi-square test. Results:A total of 99 patients were enrolled, including 58 with OSA and 41 without OSA. Of these, 88.89% (88/99) met the diagnostic criteria for laryngopharyngeal reflux disease (LPRD). In LPRD patients, the median proportion of non gas reflux events and the number of alkaline reflux were significantly higher in the OSA with LPRD group than in the non OSA with LPRD group (70.00% vs 36.36%, 0 vs 0, Z-values respectively -3.373, -3.134, P<0.01). Liquid reflux proportion and the number of both liquid and mixed reflux events showed a positive correlation with the apnea-hypopnea index (AHI) ( r-values respectively 0.304, 0.326, 0.268, P<0.05), while the gas reflux constituent ratio was inversely correlated with AHI ( r=-0.358, P<0.01). The frequency and proportion of nocturnal reflux events showed a positive correlation with AHI ( r-values respectively 0.250, 0.211, P<0.05). A significantly higher proportion of OSA with LPRD group experienced both daytime and nighttime reflux compared to non OSA with LPRD group (66.67% vs 38.71%, P<0.05). In LPRD patients, over 50% of all LPR events occurred within 3 hours after each of the three main meals. Conclusions:In OSA with LPRD patients, LPR events are predominantly non gas in nature. OSA with LPRD patients exhibits a higher proportion and frequency of nocturnal reflux events and a greater number of alkaline reflux episodes compared to non OSA with LPRD patients.
8.Prediction model and verification of sperm DNA fragments based on traditional Chinese medicine syndrome and semen quality-related parameters
Chao ZHOU ; Guangyu YU ; Shaohua YANG ; Leilei GAO ; Zhen JIN ; Yueyuan JIANG ; Huan LI
Chinese Journal of Tissue Engineering Research 2025;29(13):2661-2668
BACKGROUND:The combination of traditional Chinese medicine syndrome and semen quality-related parameters can jointly predict the occurrence of abnormal increase in sperm DNA fragmentation index (DFI) and draw a column chart,which can significantly improve clinical practicality and application efficiency,provide a basis for comprehensive evaluation of semen quality in clinical practice,take active intervention measures to improve clinical outcomes,and formulate personalized medical plans.OBJECTIVE:To explore the prediction model and verification of sperm DNA fragments based on traditional Chinese medicine syndrome and semen quality-related parameters.METHODS:Retrospective analysis was made on 420 infertile patients who received traditional Chinese medicine syndrome diagnosis and sperm DNA fragment rate examination in the Department of Traditional Chinese Medicine Andrology,Nanxishan Hospital of Guangxi Zhuang Autonomous Region from July 2019 to July 2021.According to the Manual of Human Semen Examination and Treatment Laboratories (6th Edition),137 patients with sperm DFI>30% were included in the group of abnormally high sperm DFI,and 283 patients with sperm DFI ≤ 30% were taken as the control group.First,univariate analysis was used to screen the influencing factors of the abnormal increase of sperm DFI.Then,the best matching factor was selected by using the collinearity problem of LASSO correction factors.Then,it was included in the multifactor forward stepwise logistic regression to find out its independent influencing factors and draw a nomogram.Finally,the receiver operating characteristic curve,calibration curve,decision curve analysis and clinical impact curve were used to verify the differentiation and accuracy of the prediction model and its clinical application effectiveness.RESULTS AND CONCLUSION:(1) The results of the univariate analysis showed that age,body mass index,forward motion rate,total sperm motility,sperm concentration,sperm morphology,kidney yang deficiency syndrome,damp heat downpour syndrome,and kidney sperm deficiency syndrome were the influencing factors for the abnormal increase of sperm DFI (P<0.05).(2) The best matching factors further screened by LASSO regression were age,body mass index,total sperm motility,sperm concentration,sperm morphology,kidney yang deficiency syndrome,damp heat downpour syndrome,and kidney essence deficiency syndrome (P<0.05).(3) Multifactor forward stepwise Logistic regression showed that age,body mass index,sperm concentration,total sperm motility,damp heat downpour syndrome,and kidney yang deficiency syndrome were six independent factors that caused the abnormal increase in sperm DFI.(4) Receiver operating characteristic curve showed that the area under the curve of the model group was 0.760(0.713,0.806),and the area under the curve of the validation group was 0.745(0.714,0.776).It showed that the prediction model had good discrimination.(5) The average absolute error of the calibration curve was 0.040,and the Hosmer Lemeshow test (P>0.05),suggesting that there was no significant statistical difference between the probability of the abnormal increase in DFI of spermatozoa predicted by the model and the probability of the abnormal increase in DFI of spermatozoa actually occurred,which confirmed that the model had good accuracy.(6) Decision curve analysis and clinical impact curve showed that the model group and validation group had the maximum clinical net benefit when the threshold probability values were (0.08-0.84) and (0.09-0.78) respectively,and had good clinical application efficiency within the threshold probability range.(7) These findings conclude that age,body mass index,sperm concentration,total sperm viability,damp heat downpour syndrome and kidney yang deficiency syndrome are independent factors that cause the abnormal increase in sperm DFI.The nomogram of the clinical prediction model constructed by them has good clinical prediction value and clinical application efficiency,and can provide the basis for comprehensive clinical evaluation of semen quality and individualized medical service.
9.Characteristics analysis of OSA patients in different age groups based on 10 years of PSG monitoring
Lili PENG ; Jinrang LI ; Zhi LIU ; Chun ZHANG ; Shizhen ZOU ; Wei YUAN ; Leilei YU ; Yuanyuan JIA
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2025;60(9):1127-1133
Objective:A retrospective analysis was conducted on the clinical characteristics and polysomnography (PSG) features of patients with obstructive sleep apnea (OSA) of different ages.Methods:From January 2015 to March 2024, the patients who underwent overnight PSG monitoring at the Sleep Respiratory Disease Diagnosis and Treatment Center, Department of Otolaryngology, Head and Neck Surgery, Sixth Medical Center of the PLA General Hospital were sequentially enrolled.A total of 4 396 patients[aged from 18 to 97(46.04±12.60)years] with OSA who met the criteria were finally enrolled and divided into the youth group (18-44 years old, n=2 099), middle-aged group (45-59 years old, n=1 641), and elderly group (≥60 years old, n=656).The differences in general condition, Epworth sleepiness Scale (ESS) score, rapid eye movement sleep (REM) sleep time in total sleep time, micro-awakening index, apnea hypopnea index (AHI), minimum oxygen saturation at night (LSpO 2), oxygen hypoxia index (ODI) and so on were compared.Multivariate Logistic regression was used to analyze the relationship between age stratification and different severity of OSA (mild 5≤AHI≤15, moderate 15
10.Exploration on the Onset of Acute Lymphoblastic Leukemia in Children Based on the Five-Circuit and Six-Qi Theory
Yunyun SUN ; Liang LI ; Leilei CHU ; Ke YANG ; Zhexiu JIANG ; Tian LIU ; Jianmin ZHANG ; Jian PAN ; Yanfang TAO
Journal of Guangzhou University of Traditional Chinese Medicine 2025;42(1):32-38
Objective To explore the five-circuit and six-qi features of birth time and onset time of children with acute lymphoblastic leukemia(ALL).Methods A total of 877 cases of children with ALL from Children's Hospital of Soochow University from June 2021 to February 2023 were collected,and their five-circuit and six-qi features of birth time and onset time were analyzed.And then the correlation of five-circuit and six-qi features of birth time and onset time with ALL was explored preliminarily,and the pathogenic characteristics of congenital factors and acquired pathogenic factors were revealed.Results(1)The children who were born in the year with the heavenly stems being bing(the 3rd of the ten heavenly stems)and ding(the 4th of the ten heavenly stems)and with the earthly branches being shen(the 8th of the twelve earthly branches)and you(the 9th of the twelve earthly branches)are prone to suffer from ALL,and the birth year of children with ALL had the five-circuit and six-qi features of the joining of guest circuit with dominant circuit being rebellious.ALL is commonly seen in the year with the heavenly stems being geng(the 7th of the ten heavenly stems)and xin(the 8th of the ten heavenly stems)and with the earthly branches being zi(the 1st of the twelve earthly branches)and chou(the 2nd of the twelve earthly branches),and the onset year of ALL in children had the five-circuit and six-qi features of the yearly circuit being gold-circuit and water-circuit,sitian-zaiquan yearly circuit qi being shaoyin monarch-fire with yangming dryness-gold,taiyin damp-earth with taiyang cold-water,and the qi-circuit assimilation relationship being celestial correspondence,same celestial correspondence,celestial correspondence in convergent year,disharmony,mildly-rebellious,and celestial restriction.Conclusion Gold-dryness and water-cold are the congenital factors and acquired pathogenic factors of ALL.The onset of ALL in children is closely related to qi insufficiency and qi stagnation of wood and fire in five-circuit and six-qi theory.


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