1.Mechanism of Zuogui Jiangtang Jieyu Prescription Against Damage to Hippocampal Synaptic Microenvironment via Suppressing GluR2/Parkin Signal-mediated Mitophagy in Rats with Diabetes-related Depression
Jian LIU ; Lin LIU ; Xiaoyuan LIN ; Wei LI ; Yuhong WANG ; Hui YANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(1):104-112
ObjectiveTo reveal the mechanism of Zuogui Jiangtang Jieyu prescription against damage to hippocampal synaptic microenvironment via suppressing glutamate receptor 2 (GluR2)/Parkin signal-mediated mitophagy in rats with diabetes-related depression (DD). MethodsEighty male SD rats underwent adaptive feeding for 5 days before the study. Ten rats were randomly assigned to the normal group. The model of DD rats was established with the rest by 2-week high-fat diet + streptozotocin (STZ) tail intravenous injection + 28 days of chronic unpredictable mild stress (CUMS) combined with isolation. The rats were randomly divided into a normal group, a model group, a GluR2 blocker group (5 μg·kg-1), a GluR2 agonist group (10 μg·kg-1), a metformin + fluoxetine group (0.18 g·kg-1 metformin + 1.8 mg·kg-1 fluoxetine), and high- and low-dose Zuogui Jiangtang Jieyu prescription groups (20.52 and 10.26 g·kg-1, respectively). The rats in the GluR2 blocker group and the GluR2 agonist group were continuously injected with CNQX and Cl-HIBO in the dentate gyrus of the hippocampus once a week starting from stress modeling, respectively, while the metformin + fluoxetine group and the high- and low-dose Zuogui Jiangtang Jieyu prescription groups were continuously given intragastric administration for 28 d at the same time of stress modeling. Depression-like behavior was evaluated by open field and forced swimming experiments. The levels of serum insulin and adenosine triphosphate (ATP) in hippocampus were detected by biochemical analysis. The levels of 5-hydroxytryptamine (5-HT) and dopamine (DA) in hippocampus were detected by enzyme-linked immunosorbent assay (ELISA). The autophagosomes of hippocampal neurons were observed by transmission electron microscopy. The morphology and structure of dendrites and spines of hippocampal neurons were evaluated by Golgi staining. Western blot detected the expression levels of GluR2 and Parkin proteins in hippocampus. The expression levels of GluR2, Parkin, regulating synaptic membrane exocytosis protein 3 (RIMS3), and postsynaptic density protein 95 (PSD95) in the dentate gyrus of the hippocampus were detected by immunofluorescence. ResultsCompared with the normal group, the model group exhibited reduced total activity distance in the open field and increased immobility time in forced swimming (P<0.01), lowered levels of serum insulin and ATP, 5-HT, and DA in hippocampus (P<0.01), increased autophagosomes of hippocampal neurons, significantly damaged morphology and structure of dendrites and spines of hippocampal neurons, decreased expression levels of GluR2, RIMS3, and PSD95 in hippocampus, and an increased Parkin expression level (P<0.05, P<0.01). Compared with the model group, the GluR2 blocker group and the GluR2 agonist group showed aggravation and alleviation of the above abnormal changes, respectively (P<0.05, P<0.01). The above depression-like behavior was significantly improved in the high- and low-dose Zuogui Jiangtang Jieyu prescription groups to different degrees. Specifically, the two groups saw elevated levels of serum insulin and ATP, 5-HT, and DA in hippocampus (P<0.05, P<0.01), restrained increase in autophagosomes and damage to morphology and structure of dendrites and spines of hippocampal neurons, up-regulated protein expression levels of GluR2, RIMS3, and PSD95, and down-regulated Parkin expression level (P<0.05, P<0.01). ConclusionZuogui Jiangtong Jieyu prescription can ameliorate the mitophagy-mediated damage to hippocampal synaptic microenvironment in DD rats, the mechanism of which might be related to the regulation of GluR2/Parkin signaling pathway.
2.Research Progress on the Correlation Between Mitophagy and Vascular Cognitive Impairment
Yan LIU ; Xingang DONG ; Xiaoyuan WANG ; Gege QI ; Yiqin REN ; Lianpeng ZHOU ; Hui LI ; Suqing ZHANG ; Weifeng LI
Medical Journal of Peking Union Medical College Hospital 2025;16(2):338-349
Vascular cognitive impairment (VCI), caused by cerebrovascular dysfunction, severely impacts the quality of life in the elderly population, yet effective therapeutic approaches remain limited. Mitophagy, a selective mitochondrial quality-control mechanism, has emerged as a critical focus in neurological disease research. Accumulating evidence indicates that mitophagy modulates oxidative stress, neuroinflammation, and neuronal apoptosis. Key signaling pathways associated with mitophagy—including PINK1/Parkin, BNIP3/Nix, FUNDC1, PI3K/Akt/mTOR, and AMPK—have been identified as potential therapeutic targets for VCI. This review summarizes the mechanistic roles of mitophagy in VCI pathogenesis and explores emerging therapeutic strategies targeting these pathways, aiming to provide novel insights for clinical intervention and advance the development of effective treatments for VCI.
3.Association Between Vitamin D Status and Insulin Resistance in Adolescents: A Cross-sectional Observational Study
Xiaoyuan GUO ; Yutong WANG ; Zhibo ZHOU ; Shi CHEN ; Mei ZHANG ; Bo BAN ; Ping LI ; Xinran ZHANG ; Qiuping ZHANG ; Kai YANG ; Hongbo YANG ; Hanze DU ; Hui PAN
Medical Journal of Peking Union Medical College Hospital 2025;16(3):577-583
To investigate the correlation between vitamin D nutritional status and insulin resistance in pubertal adolescents. This cross-sectional observational study employed convenience sampling to recruit 2021-grade(8th grade) students from Jining No.7 Middle School in Shandong Province on June 5, 2023. Data collection included questionnaires, physical examinations, and imaging assessments to obtain general information, secondary sexual characteristics development, and bone age. Venous blood samples were collected to measure fasting blood glucose(FBG), fasting insulin(FINS), homeostasis model assessment of insulin resistance(HOMA-IR), and 25-hydroxyvitamin D[25(OH)D] levels. Spearman correlation analysis and multivariate linear regression models were used to examine the associations between serum vitamin D levels and FBG, FINS, and HOMA-IR. The study included 168 pubertal adolescents[69 females(41.1%), 99 males(58.9%); mean age(13.27±0.46) years]. All participants had entered puberty based on sexual development assessment. Vitamin D deficiency was observed in 41 participants(24.4%), insufficiency in 109(64.9%), and sufficiency in 18(10.7%). The median HOMA-IR was 3.49(2.57, 5.14).Significant differences were found across vitamin D status groups for HOMA-IR [4.45(2.54, 6.62) Vitamin D deficiency/insufficiency is prevalent among pubertal adolescents, and serum vitamin D levels show a significant inverse association with insulin resistance. These findings suggest the potential importance of vitamin D status in metabolic health during puberty.
4.Body Composition Profiles and Associated Factors in Adolescents UndergoingLong-term Regular Exercise
Yutong WANG ; Xiaoyuan GUO ; Hanze DU ; Hui PAN ; Wei WANG ; Mei ZHANG ; Bo BAN ; Ping LI ; Xinran ZHANG ; Qiuping ZHANG ; Hongshuang SUN ; Rong LI ; Shi CHEN
Medical Journal of Peking Union Medical College Hospital 2025;16(3):591-597
To investigate body composition and associated factors in adolescents undergoing long-term regular sports training. This prospective longitudinal cohort study employed convenience sampling to recruit adolescents receiving structured athletic training at Jining Sports Training Center in June 2023. Baseline measurements included height, weight, body mass index (BMI), blood pressure, heart rate, waist circumference, and hip circumference. Questionnaires assessed sleep duration, screen time, and household income. Follow-up measurements in June 2024 repeated these assessments while adding bioelectrical impedance analysis for body composition (lean mass, skeletal muscle mass, fat mass, and body fat percentage). Linear regression models examined associations between training type (direct-contact vs. non-contact sports) and follow-up body fat percentage, BMI, and waist circumference as dependent variables, adjusting for covariates. The study included 110 adolescents (39 female, 71 male) with median age 13.21 years (IQR: 12.46-14.33). Participants comprised 65 direct-contact and 45 non-contact athletes. Baseline prevalence rates were 27.27% for overweight/obesity, 24.55% for elevated waist circumference, and 16.36% for elevated blood pressure. At follow-up, corresponding rates were 24.55%, 26.36%, and 13.64% respectively. The elevated blood pressure subgroup showed significantly higher waist circumference ( Despite regular athletic training, substantial proportions of adolescents exhibited overweight/obesity, abdominal obesity, and elevated blood pressure, warranting clinical attention. Training modality appears to influence body composition changes, with direct-contact sports associated with more favorable adiposity-related outcomes.
5.Application effect analysis of a horizontal endoscope storage cabinet in storage of flexible endoscopes
China Journal of Endoscopy 2024;30(1):47-51
Objective To explore the influence of different storage methods on flexible endoscope.Methods 500 compliant soft endoscopes in the endoscopy center of our hospital from January 2019 to January 2020 were selected as research objects.The endoscopes of the observation group were placed horizontally in the storage cabinet,while those of the control group were placed vertically in the storage cabinet.The effects of the two storage methods on bacterial colony number,quality qualified rate and quality of soft endoscopes were compared.Results The study found that the number of bacterial colonies in the flexible endoscope in the 2 h storage of the observation group was(10.27±2.22)cfu/piece and the control group was(13.18±1.33)cfu/piece,and the difference was not statistically significant(P>0.05);The number of bacterial colonies in the flexible endoscope in the 72 h of the observation group was(14.75±2.00)cfu/piece,and the control group was(223.28±17.07)cfu/piece,and the difference was statistically significant(P<0.05).The observed cost of consumables and labor were obliviously lower than those of the control group,there was statistical significance(P<0.05).Conclusion The flexible endoscope is placed horizontally in the designated storage cabinet,which can eliminate the daily morning pre-cleaning within 72 h,and will not increase the damage rate of endoscope.It is a clinically recommended storage method for endoscopes.
6.Effects of Jianpi Yichang Powder on Expressions of IL-1β and IL-18 of NLRP3 Signaling Pathway in Ulcerative Colitis Rats
Xiaoyuan LIN ; Kaiyang LI ; Jie GUAN ; Jiemin LIU
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(1):117-121
Objective To explore the effects of Jianpi Yichang Powder on the expressions of interleukin(IL)-1β and IL-18 of NLRP3 signaling pathway in ulcerative colitis(UC)model rats.Methods Ten rats were randomly selected from 40 SD rats as the normal group,and the other rats freely drank 5%dextran sulfate solution for 7 days to replicate UC rats model.The model rats were randomly divided into model group,sulfasalazine group and Jianpi Yichang Powder group,with 10 rats in each group.Jianpi Yichang Powder group and sulfasalazine group were given corresponding liquid medicine for gavage,and the normal and model groups were given equivalent volume distilled water for gavage for consecutive 14 d.The general status was observed,and the disease activity index(DAI)was scored,the contents of NLRP3,apoptosis-associated spotted proteins(ASC),and Caspase-1 in serum were detected by ELISA,the expressions of IL-1β and IL-18 protein and mRNA in colon tissue were detected by immunohistochemistry,Western blot and RT-PCR respectively.Results Compared with the normal group,the general status of the rats in model group was relatively worse,and DAI score significantly increased(P<0.01),the contents of NLRP3,ASC and Caspase-l in serum were significantly increased(P<0.01),the expressions of IL-1β and IL-18 protein and mRNA in colon tissue were significantly increased(P<0.01).Compared with the model group,the general status of the rats in Jianpi Yichang Powder group and sulfasalazine group were significantly improved,DAI score significantly decreased(P<0.01),the contents of NLRP3,ASC and Caspase-l in serum significantly reduced(P<0.05,P<0.01),and the expressions of IL-1β and IL-18 protein and mRNA in colon tissue significantly decreased(P<0.05,P<0.01).Conclusion Jianpi Yichang Powder can inhibit IL-1β and IL-18 expression of NLRP3 signaling pathway to reduce colon immune inflammatory damage,thus play a role in treating UC.
7.Research Progress in the Treatment of Ulcerative Colitis with Sishen Pills
Kaiyang LI ; Mei YANG ; Qi ZHAO ; Jing HUANG ; Xiaoyuan LIN ; Jiemin LIU ; Zhenfan GUO ; Hui SHI ; Yueyue YANG
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(3):180-185
Sishen Pills is a classic prescription for the treatment of spleen and kidney diarrhea,which has the effect of warming the kidney and the spleen,astringent intestine and antidiarrheal.In modern clinical application,the modified prescriptions based on Sishen Pills,combined with other treatments of TCM and integrated traditional Chinese and Western medicine are often used to treat ulcerative colitis with spleen-kidney yang deficiency syndrome,and the curative effect is remarkable.Experimental pharmacological studies have shown that Sishen Pills may achieve the purpose of ulcerative colitis by regulating the expression of related signaling pathway proteins,regulating inflammatory factors,inhibiting inflammatory response,regulating autophagy,regulating intestinal flora,improving intestinal mucosal permeability,repairing intestinal mucosal barrier,regulating cellular energy metabolism,anti-oxidative stress,regulating cellular immune function,etc.In this article,the research status of Sishen Pills in the treatment of ulcerative colitis was sorted out and summarized,in order to provide reference for further study of its mechanism and clinical application.
8.Effects of Electroacupuncture on Urodynamics and Expression of ERK/CREB/Bcl-2 Pathway in Spinal Cord of Rats with Neurogenic Bladder after Suprasacral Spinal Cord Injury
Ming XU ; Kun AI ; Yue ZHUO ; Qiong LIU ; Xiaomeng LIU ; Ya LI ; Xiaoyuan LUO ; Hong ZHANG
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(4):100-105
Objective To observe the effects of electroacupuncture at"Ciliao","Zhongji","Sanyinjiao"and"Dazhui"on urodynamics and expression of ERK/CREB/Bcl-2 pathway in spinal cord tissue of neurogenic bladder rats after suprasacral spinal cord injury.Methods Sixty female SD rats randomly selected 24 and divided into blank group and sham-operation group(12 rats in each group),the remaining 36 rats were subjected to surgical modeling.After modeling,rats were randomly divided into the model group and the electroacupuncture group,with 12 rats in each group.The electroacupuncture group received unilateral electroacupuncture stimulation at acupoints"Ciliao","Zhongji","Sanyinjiao",and"Dazhui"for 30 minutes each time,once a day,for 7 consecutive days.After administration,urodynamic testing was performed,HE staining was used to observe the morphology of bladder detrusor tissue,TUNEL method was used to detected apoptosis in spinal cord tissue,Western blot was used to detected expressions of p-ERK1/2,p-CREB,p-p90Rsk,CRE,Bcl-2,and Bax proteins in spinal cord tissue.Results Compared with the sham-operation group,the basal pressure,maximum pressure,and leakage point pressure of the bladder in the model group increased significantly(P<0.01),while the maximum capacity and compliance of the bladder decreased significantly(P<0.01);the structure of bladder smooth muscle cells was severely damaged and disorderly arranged,accompanied by a large amount of inflammatory cell infiltration;the apoptosis rate of spinal cord tissue cells significantly increased(P<0.01),and the expressions of p-ERK1/2,p-p90Rsk,p-CREB,CRE,and Bcl-2 proteins in spinal cord tissue were significantly decreased,while the expression of Bax protein significantly increased(P<0.01).Compared with the model group,the basal pressure,maximum pressure,and leakage point pressure of the bladder in the electroacupuncture group decreased significantly(P<0.05),while the maximum capacity and compliance of the bladder increased significantly(P<0.05,P<0.01);the integrity of bladder smooth muscle cells was enhanced,the degree of cell edema was reduced,and inflammatory cell infiltration was reduced;the apoptosis rate of spinal cord tissue cells was significantly reduced(P<0.05),and the expressions of p-ERK1/2,p-p90Rsk,p-CREB,CRE,and Bcl-2 proteins in spinal cord tissue significantly increased,while the expression of Bax protein was significantly decreased(P<0.05,P<0.01).Conclusion Electroacupuncture can promote the repair of bladder detrusor tissue in rats with neurogenic bladder model after suprasacral spinal cord injury,increase the maximum capacity and compliance of the bladder,alleviate the high pressure state in the bladder,and its mechanism is related to activating the ERK/CREB/Bcl-2 pathway,reducing secondary apoptosis of damaged neurons,effectively improving bladder innervation,and protecting bladder function.
9.Clinical characteristics and prognosis of brain metastasis in locally advanced rectal cancer
Ganbin LI ; Xiao ZHANG ; Chentong WANG ; Xiaoyuan QIU ; Guannan ZHANG ; Beizhan NIU ; Lai XU ; Junyang LU ; Bin WU ; Yi XIAO ; Guole LIN
Chinese Journal of Gastrointestinal Surgery 2024;27(10):1063-1068
Objective:To investigate the clinical characteristics of brain metastases after radical surgery for locally advanced rectal cancer (LARC).Methods:The clinical characteristics of LARC with brain metastases treated in the Department of General Surgery, Peking Union Medical College Hospital from 2013 to 2023 were retrospectively analyzed. The inclusion criteria were rectal adenocarcinoma within 15 cm of the anal verge and having undergone radical surgery, and the exclusion criterion was primary malignant tumor of the brain. The main outcomes were overall survival (OS), disease-free survival (DFS), and disease-specific overall survival (determined as the interval between occurrence of brain metastasis to death from any causes). The Kaplan–Meier method was used for survival analysis.Results:We identified 4500 patients with LARC, 20 (0.4%) of whom had brain metastases. The mean age of patients with brain metastases was 63.8±9.3 years. They comprised five women and 15 men. The brain was the first site of metastasis in four patients (20%) whereas 18 patients had heterochronous extracranial metastases before brain metastasis. Two patients also had multi-organ metastases. The most common manifestations of brain metastases were dizziness and headache (five patients, 25%), sudden onset of limb weakness (four, 20%), sudden speech impairment (two, 10%), and polyopia (two, 10%). The metastases were diagnosed during follow-up in three patients (15%). Four of the patients were asymptomatic (20%). Treatment approaches included surgical resection (six patients, 30%), chemoradiotherapy (nine, 45%), and palliative (five, 25%). The median follow-up time was 45.5 (4–112) months until October 2023. 1y-OS, 3y-OS, and 5y-OS were 95.0%, 62.9%, and 43.3%, respectively. 1y-DFS, 3y-DFS, and 5y-DFS were 55.0%, 25.0%, and 5.0%, respectively. With brain metastasis as the starting point, the median duration of survival was 16 (10.2–21.8) months.Conclusion:The incidence of brain metastasis is relatively low in patients with LARC, who often have multiple synchronous extracranial metastases. Brain metastases lack specific manifestations and more often occur in male patients. Surgical intervention or combined radiotherapy and chemotherapy may improve disease-specific survival to a certain extent. However, the overall prognosis remains poor.
10.Value of multimodal ultrasound parameters combined with peripheral blood lymphocyte-monocyte ratio in predicting recurrence and metastasis after radical breast cancer surgery
Xiaoyuan CHEN ; Jin LI ; Xiaoxia HOU
Chinese Journal of Endocrine Surgery 2024;18(5):648-651
Objective:To explore the value of multimodal ultrasound parameters combined with peripheral blood lymphocyte-monocyte ratio (LMR) in predicting recurrence and metastasis after radical breast cancer surgery.Methods:A total of 139 patients with breast cancer admitted to Northwest Women’s and Children’s Hospital from Jan. 2021 to Jan. 2022 were studied. The patients underwent postoperative multimodal ultrasonography and peripheral blood lymphocyte and monocyte examination. Patients were followed up for 2 years after surgery to evaluate postoperative recurrence and metastasis, and analyze the value of multimodal ultrasound parameters combined with LMR in predicting recurrence and metastasis of patients.Results:Among 139 patients, 32 recurrences and metastases occurred during 2-year follow-up; The peak systolic velocity (PSV), resistance index (RI), maximum lesion diameter, elasticity score, area under the curve (AUC) and peak intensity (PI) in patients with recurrent metastasis were higher than those without recurrent metastasis ( t=7.37, 4.75, 4.75, 5.46, 4.24, 5.22, P<0.05), and the LNR in patients with recurrent metastasis was lower. Pearson correlation analysis showed that PSV, RI, maximum lesion diameter, elasticity score, AUC, PI were negatively correlated with LMR ( r=-0.418, -0.502, -0.633, -0.526, -0.448, -0.482). P<0.05) ; The ROC curve showed that the AUC of PSV, RI, maximum lesion diameter, elasticity score, AUC, PI and LMR for predicting recurrence and metastasis were 0.852, 0.784, 0.791, 0.789, 0.615, 0.725 and 0.728, respectively, and the combined AUC value of each index was 0.992. Conclusions:The use of multimodal ultrasound parameters combined with LMR can improve the prediction value of recurrence and metastasis after radical breast cancer surgery.

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