1.Total Flavonoids from Cuscutae Semen Inhibit Depression in CUMS Mice via UCP2/TXNIP/NLRP3 Signaling Pathway
Andong SONG ; Guohua LI ; Bo YUAN ; Menghui JIA ; Zhantao LI ; Xiaoli WANG ; Long WANG ; Huiling FU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):109-119
ObjectiveTo investigate the antidepressant effects and mechanisms of total flavonoids from Cuscutae Semen (TFCC) in the mouse model of chronic unpredictable mild stress (CUMS). MethodsFifty male 4-week-old ICR mice were randomized into five groups (n=10 per group): blank control, model, Cuscutae Semen decoction (10.2 g·kg-1·d-1), paroxetine (2.6 mg·kg-1·d-1), and TFCC (173.2 mg·kg-1·d-1). The other groups except the blank control group underwent chronic unpredictable mild stress (CUMS) for 4 weeks. Behavioral assessments were conducted post-modeling. Then, the model group received distilled water (10 mL·kg-1·d-1), while treatment groups were administrated with respective agents via oral gavage (10 mL·kg-1) for 4 weeks. Depression-like behaviors were evaluated by the sucrose preference test (SPT), forced swimming test (FST), and tail suspension test (TST). Hippocampal neuronal morphology was observed via hematoxylin-eosin staining, and apoptosis in the brain tissue was assessed via terminal- deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL). Enzyme-linked immunosorbent assay (ELISA) was employed to measure the hippocampal levels of inflammatory cytokines [interleukin (IL)-1β, IL-6, and TNF-α)] and neurotransmitters [5-hydroxytryptamine (5-HT), dopamine (DA), and brain-derived neurotrophic factor (BDNF)], while the reactive oxygen species (ROS) levels were quantified via the DCFH-DA probe. Real-time PCR was performed to measure the mRNA levels of NOD-like receptor protein 3 (NLRP3), apoptosis-associated Speck-like protein containing a CARD (ASC), cysteinyl aspartate-specific proteinase-1 (Caspase-1), IL-1β, and inducible nitric oxide synthase (iNOS). Western blot was employed to evaluate the protein levels of NLRP3, ASC, Caspase-1, uncoupling protein 2 (UCP2), and thioredoxin-interacting protein (TXNIP). ResultsCompared with the blank control group, the model group exhibited weight loss (P<0.01), reduced sucrose preference (P<0.01), prolonged immobility time in FST and TST (P<0.01), neuron disarrangement with nuclear pyknosis in hippocampal CA3 region, increased apoptosis in the brain tissue, elevated levels of IL-1β, IL-6, and TNF-α (P<0.01), declined levels of 5-HT, DA, and BDNF (P<0.01), increased ROS accumulation (P<0.01), upregulated mRNA levels of NLRP3, ASC, Caspase-1, IL-1β, and iNOS (P<0.01), down-regulated protein level of UCP2 (P<0.01), and up-regulated protein levels of NLRP3, ASC, Caspase-1, and TXNIP (P<0.01). Compared with the model group, the interventions restored sucrose preference (P<0.01), shortened immobility time (P<0.01), repaired hippocampal neuronal structure, reduced apoptosis, lowered the levels of inflammatory cytokines (P<0.01), restored the levels of neurotransmitters (P<0.01), alleviated ROS accumulation (P<0.01), downregulated the mRNA levels of NLRP3, ASC, Caspase-1, IL-1β, and iNOS (P<0.01), upregulated the protein level of UCP2 (P<0.01), and reduced the protein levels of NLRP3, ASC, Caspase-1, and TXNIP (P<0.01). Moreover, TFCC outperformed Cuscutae Semen decoction in ameliorating depressive behaviors. TFCC excelled in neuronal repair, neurotransmitter regulation, anti-inflammatory effects, and modulation of the UCP2/TXNIP/NLRP3 pathway (P<0.05). ConclusionTFCC modulates the hippocampal UCP2/TXNIP/NLRP3 pathway to inhibit inflammasome activation, reduce oxidative stress, restore neurotransmitters, thus suppressing neuronal apoptosis and promoting the rearrangement and morphology recovery of hippocampal cells. It outperforms Cuscutae Semen decoction in the antidepressant efficacy.
2.Total Flavonoids from Cuscutae Semen Inhibit Depression in CUMS Mice via UCP2/TXNIP/NLRP3 Signaling Pathway
Andong SONG ; Guohua LI ; Bo YUAN ; Menghui JIA ; Zhantao LI ; Xiaoli WANG ; Long WANG ; Huiling FU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):109-119
ObjectiveTo investigate the antidepressant effects and mechanisms of total flavonoids from Cuscutae Semen (TFCC) in the mouse model of chronic unpredictable mild stress (CUMS). MethodsFifty male 4-week-old ICR mice were randomized into five groups (n=10 per group): blank control, model, Cuscutae Semen decoction (10.2 g·kg-1·d-1), paroxetine (2.6 mg·kg-1·d-1), and TFCC (173.2 mg·kg-1·d-1). The other groups except the blank control group underwent chronic unpredictable mild stress (CUMS) for 4 weeks. Behavioral assessments were conducted post-modeling. Then, the model group received distilled water (10 mL·kg-1·d-1), while treatment groups were administrated with respective agents via oral gavage (10 mL·kg-1) for 4 weeks. Depression-like behaviors were evaluated by the sucrose preference test (SPT), forced swimming test (FST), and tail suspension test (TST). Hippocampal neuronal morphology was observed via hematoxylin-eosin staining, and apoptosis in the brain tissue was assessed via terminal- deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL). Enzyme-linked immunosorbent assay (ELISA) was employed to measure the hippocampal levels of inflammatory cytokines [interleukin (IL)-1β, IL-6, and TNF-α)] and neurotransmitters [5-hydroxytryptamine (5-HT), dopamine (DA), and brain-derived neurotrophic factor (BDNF)], while the reactive oxygen species (ROS) levels were quantified via the DCFH-DA probe. Real-time PCR was performed to measure the mRNA levels of NOD-like receptor protein 3 (NLRP3), apoptosis-associated Speck-like protein containing a CARD (ASC), cysteinyl aspartate-specific proteinase-1 (Caspase-1), IL-1β, and inducible nitric oxide synthase (iNOS). Western blot was employed to evaluate the protein levels of NLRP3, ASC, Caspase-1, uncoupling protein 2 (UCP2), and thioredoxin-interacting protein (TXNIP). ResultsCompared with the blank control group, the model group exhibited weight loss (P<0.01), reduced sucrose preference (P<0.01), prolonged immobility time in FST and TST (P<0.01), neuron disarrangement with nuclear pyknosis in hippocampal CA3 region, increased apoptosis in the brain tissue, elevated levels of IL-1β, IL-6, and TNF-α (P<0.01), declined levels of 5-HT, DA, and BDNF (P<0.01), increased ROS accumulation (P<0.01), upregulated mRNA levels of NLRP3, ASC, Caspase-1, IL-1β, and iNOS (P<0.01), down-regulated protein level of UCP2 (P<0.01), and up-regulated protein levels of NLRP3, ASC, Caspase-1, and TXNIP (P<0.01). Compared with the model group, the interventions restored sucrose preference (P<0.01), shortened immobility time (P<0.01), repaired hippocampal neuronal structure, reduced apoptosis, lowered the levels of inflammatory cytokines (P<0.01), restored the levels of neurotransmitters (P<0.01), alleviated ROS accumulation (P<0.01), downregulated the mRNA levels of NLRP3, ASC, Caspase-1, IL-1β, and iNOS (P<0.01), upregulated the protein level of UCP2 (P<0.01), and reduced the protein levels of NLRP3, ASC, Caspase-1, and TXNIP (P<0.01). Moreover, TFCC outperformed Cuscutae Semen decoction in ameliorating depressive behaviors. TFCC excelled in neuronal repair, neurotransmitter regulation, anti-inflammatory effects, and modulation of the UCP2/TXNIP/NLRP3 pathway (P<0.05). ConclusionTFCC modulates the hippocampal UCP2/TXNIP/NLRP3 pathway to inhibit inflammasome activation, reduce oxidative stress, restore neurotransmitters, thus suppressing neuronal apoptosis and promoting the rearrangement and morphology recovery of hippocampal cells. It outperforms Cuscutae Semen decoction in the antidepressant efficacy.
3.Targeting AMPK related signaling pathways: A feasible approach for natural herbal medicines to intervene non-alcoholic fatty liver disease.
Yongqing CAI ; Lu FANG ; Fei CHEN ; Peiling ZHONG ; Xiangru ZHENG ; Haiyan XING ; Rongrong FAN ; Lie YUAN ; Wei PENG ; Xiaoli LI
Journal of Pharmaceutical Analysis 2025;15(1):101052-101052
Non-alcoholic fatty liver disease (NAFLD) is a metabolic disease characterized by abnormal deposition of lipid in hepatocytes. If not intervened in time, NAFLD may develop into liver fibrosis or liver cancer, and ultimately threatening life. NAFLD has complicated etiology and pathogenesis, and there are no effective therapeutic means and specific drugs. Currently, insulin sensitizers, lipid-lowering agents and hepatoprotective agents are often used for clinical intervention, but these drugs have obvious side effects, and their effectiveness and safety need to be further confirmed. Adenosine monophosphate (AMP)-activated protein kinase (AMPK) plays a central role in maintaining energy homeostasis. Activated AMPK can enhance lipid degradation, alleviate insulin resistance (IR), suppress oxidative stress and inflammatory response, and regulate autophagy, thereby alleviating NAFLD. Natural herbal medicines have received extensive attention recently because of their regulatory effects on AMPK and low side effects. In this article, we reviewed the biologically active natural herbal medicines (such as natural herbal medicine formulas, extracts, polysaccharides, and monomers) that reported in recent years to treat NAFLD via regulating AMPK, which can serve as a foundation for subsequent development of candidate drugs for NAFLD.
4.Impact of FASN-enriched EVs on endothelial cell function in obstructive sleep apnea hypopnea syndrome.
Yuan TIAN ; Dan ZHANG ; Huaian YANG ; Xiaoli ZHANG ; Shengqun XU
Journal of Pharmaceutical Analysis 2025;15(5):101251-101251
Endothelial dysfunction is a key factor linking obstructive sleep apnea hypopnea syndrome (OSAHS) with cardiovascular diseases. In this study, we used advanced proteomics and metabolomics approaches to investigate the impact of extracellular vesicles (EVs) derived from the serum of OSAHS patients on endothelial function. Our multi-omics analysis identified dysregulated pathways related to fatty acid metabolism, apoptosis regulation, and inflammatory responses, highlighting fatty acid synthase (FASN) as a crucial player in OSAHS-induced endothelial dysfunction. Both in vitro and in vivo experiments demonstrated that FASN-enriched EVs impair endothelial cell viability and disrupt metabolic homeostasis, offering new insights for the development of targeted therapies for cardiovascular complications associated with OSAHS.
5.Meta-analysis of hydrocortisone in the treatment of severe community-acquired pneumonia.
Xue GU ; Penglei YANG ; Lina YU ; Jun YUAN ; Zhou YUAN ; Xiaoli ZHANG ; Lianxin CHEN ; Ying ZHANG ; Jikuan HU ; Yu HUANG ; Qihong CHEN
Chinese Critical Care Medicine 2025;37(6):542-548
OBJECTIVE:
To explore whether hydrocortisone can improve the prognosis of patients with severe community-acquired pneumonia (sCAP) by Meta-analysis.
METHODS:
Randomized controlled trial (RCT) on hydrocortisone in the treatment of sCAP were extracted from the database including PubMed, Cochrane library, Web of Science, and Embase, and the search time was up to April 29, 2023. The patients in the standard treatment group received standard treatment such as antibiotics and supportive care, while those in the hydrocortisone group received hydrocortisone treatment on the basis of standard treatment. Meta-analysis was used to compare the mortality, duration of mechanical ventilation, mechanical ventilation rate and incidence of adverse reactions (hyperglycemia, gastrointestinal bleeding, secondary infection) between the two groups. The risk of literature bias was assessed. The studies that might have publication bias were corrected by the subtraction and complementation method. At the same time, trial sequential analysis (TSA) was conducted.
RESULTS:
A total of 5 RCTs involving 1 031 patients were finally enrolled, including 494 patients in the standard treatment group and 537 patients in the hydrocortisone group. Among the 5 studies, the research site of 2 studies was in the mixed ward. Considering the inclusion characteristics of the study population, there was doubt whether its research object was sCAP patients, which might have a certain impact on the results and introduce potential bias. Meta-analysis showed that the mortality in the hydrocortisone group was significantly lower than that in the standard treatment group [6.0% vs. 14.0%; odds ratio (OR) = 0.38, 95% confidence interval (95%CI) was 0.25-0.59, P < 0.01; I2 = 9%]. The studies that were asymmetric were corrected by the reduction and supplementation method. Even after filling the missing studies, hydrocortisone could still reduce the death risk of the patient (OR = 0.49, 95%CI was 0.32-0.73, P < 0.01; I2 = 31%). TSA showed that the average mortality of the standard treatment group was about 14.0%, and that of the hydrocortisone group was about 6.0%, with a relative risk reduction (RRR) = 57%. The calculated sample size was 699 cases, and the actual sample size was 1 031 cases. The actual sample size exceeded the required sample size, and the Z-curve crossed the O'Brien-Fleming boundary and the curve corresponding to P = 0.05, it meant that hydrocortisone could effectively reduce the mortality of sCAP. Compared with the standard treatment group, no statistical difference in the duration of mechanical ventilation was found in the hydrocortisone group [mean difference (MD) = -3.26, 95%CI was -6.72-0.21, P = 0.07; I2 = 0%], but the 8-day mechanical ventilation rate was significantly lowered (19.5% vs. 55.4%; OR = 0.24, 95%CI was 0.12-0.45, P < 0.01; I2 = 0%), and also no significantly difference was found in the incidence of hyperglycemia (54.3% vs. 44.6%, OR = 1.26, 95%CI was 0.56-2.84, P = 0.58; I2 = 61%), gastrointestinal bleeding (2.5% vs. 3.6%; OR = 0.70, 95%CI was 0.34-1.46, P = 0.34; I2 = 0%) and secondary infection (9.2% vs. 11.5%; OR = 0.46, 95%CI was 0.06-3.35, P = 0.45; I2 = 53%).
CONCLUSION
Hydrocortisone can reduce the mortality rate of sCAP patients, decrease their need for mechanical ventilation, and does not increase the risk of hyperglycemia, gastrointestinal bleeding, or secondary infections.
Humans
;
Hydrocortisone/therapeutic use*
;
Community-Acquired Infections/drug therapy*
;
Pneumonia/drug therapy*
;
Randomized Controlled Trials as Topic
;
Respiration, Artificial
;
Community-Acquired Pneumonia
6.Identification of anti-Jra antibodies by serology and mass spectrometry
Zhifa LING ; Xiaoli ZENG ; Xuewen YUAN ; Wei SHEN
Chinese Journal of Blood Transfusion 2024;37(7):827-830
Objective To report the antibody specific identification process of a pregnant woman who had no history of blood transfusion but presented high-frequency anti-Jra antibodies.Methods Antibody screening and identification were performed by saline and indirect Coomb's technique(microcolumn gel card,PEG).ABO,Rh and other blood group anti-gens were identified by saline.Further antibody identification tests were performed by the reaction between cells treated with various enzymes and patient plasma.Jra antigen was identified by human anti-Jraantibody.JR blood type genotyping was per-formed by MALDI-TOF mass spectrometry detection system.Antibody titer in serum was tested.Results The patient′s blood type was O with RhD(+)and CcDEe.The plasma reacted negatively with antibody screening and identification cells by saline,but positively by indirect globulin test.The self-control was negative.The patient′s Jraantigen was negative in sero-logical tests and mass spectrometry blood type genotyping.Mass spectrometry revealed a homozygous nonsense mutation(c.376C>T)in exon4.The anti-Jra antibody titer was1∶2.Conclusion The patient developed high-frequency anti-Jraantibod-ies during pregnancy.
7.Role of BRAF gene mutation detection in thyroid nodules in guiding total thyroid cancer surgery
Jie LIU ; Wenqing CAI ; Dongxu YUAN ; Xiaoli LIU
International Journal of Surgery 2024;51(5):349-354
Thyroid carcinoma is a common malignant tumor of the endocrine system and its incidence has increased significantly in recent years. Surgery is the most important initial treatment for thyroid cancer, but total thyroidectomy increases the risk of postoperative hyponatremia and recurrent laryngeal nerve injury while prolonging the disease-free survival of patients, decreasing the risk of disease recurrence and reducing residual lesions. Therefore, how to make the best surgical decision based on preoperative findings is still controversial. V-raf murine sarcoma viral oncogene homolog B1 ( BRAF), as one of the common genetic mutations in thyroid malignant tumors, is closely related to the degree of malignancy and prognosis of the tumor. Preoperative BRAF gene testing can help determine the aggressive pathological features of thyroid tumors and provide scientific guidance for clinicians to decide the scope of surgical resection.This article reviews the guiding role of BRAF gene mutation detection results in total thyroid cancer resection.
8.Analysis of clinical and electrophysiological characteristics of selective serotonin reuptake inhibitor drug-associated hypereye movement during non-rapid eye movement sleep
Min LI ; Na YUAN ; Xiaoli WANG ; Yonghong LIU
Journal of Chinese Physician 2024;26(10):1483-1487
Objective:To investigate the clinical and electrophysiological characteristics of 7 patients with non-rapid eye movement (NREM) sleep induced by selective serotonin reuptake inhibitor (SSRI).Methods:The clinical and electrophysiological data of 7 patients with SSRI drug-related NREM excessive eye movement admitted to Sleep Center, Department of Neurology, the First Affiliated Hospital of Air Force Medical University, from June 2021 to May 2022 were summarized.Results:Seven patients ranged in age from 10 to 76 years (median 34 years), and four were female. Four patients were diagnosed with anxiety and depression, and three patients were diagnosed with narcolepsy (one patient was comorbidized with periodic limb movement disorder). Sertraline was used in 4 patients, fluoxetine in 1 patient, escitalopram in 1 patient, and paroxetine hydrochloride in 1 patient. SSRI drug-related excessive eye movement in NREM stage was detected in all patients, which was characterized by coexistence of slow eye movement and fast eye movement, and eye movement density in stage 1 was greater than that in stage 2. All patients had sleep structure disorder, increased proportion of NREM phase 1 sleep and a large number of micro-awakenings.Conclusions:During SSRI drug use, some patients have characteristic abnormal eye movement in NREM, mostly in NREM 1 and 2 sleep, which should be distinguished from normal rapid eye movement (REM) sleep.
9.Clinical efficacy of adjunctive perampanel in focal epilepsy patients≥12 years old
Xiaoli SHI ; Lixia LI ; Yanting LU ; Lang SHEN ; Xiangru LU ; Jinou ZHENG ; Yuan WU ; Lu YU
Chinese Journal of Neuromedicine 2024;23(1):48-54
Objective:To evaluate the clinical efficacy, tolerability and safety of adjunctive perampanel in focal epilepsy patients≥12 years old.Methods:One hundred and nineteen focal epilepsy patients≥12 years old accepted adjunctive perampanel in Department of Neurology, First Affiliated Hospital of Guangxi Medical University from July 2020 to December 2022 were chosen. At 1-3 months, 4-6 months, 7-9 months and 10-12 months after adjunctive perampanel, seizure frequency changes every 28 d, medication retention rate and adverse reactions were recorded to evaluate the clinical efficacy (a reduction in seizure frequency≥50% from baseline was defined as overall valid treatment), tolerability and safety of adjunctive perampanel. According to efficacy results after adjunctive perampanel of 4-6 months (short-term) and 10-12 months (long-term), these patients were divided into valid group and invalid group; and the influencing factors for short-term and long-term efficacy were analyzed.Results:At 1-3, 4-6, 7-9, 10-12 months after adjunctive perampanel, reduction in seizure frequency every 28 d was 66.7% (24.3%, 97.2%), 77.5% (48.6%, 100%), 94.6% (50%, 100%), 100% (70.9%, 100%), enjoying overall valid rate of 60.2% (59/98), 75.0% (7/76), 78.9% (45/57), 86.5% (32/37). The retention rate at 3, 6, 9 and 12 months after adjunctive perampanel was 85.2% (98/115), 67.9% (76/112), 54.3% (57/105), 41.1% (37/90). Adverse reactions were reported in 33 patents (27.7%), mainly with dizziness and secondly with mental symptoms. After short-term and long-term adjunctive perampanel, no significant difference was noted in gender, initial age of adjunctive perampanel, course of disease, etiology, EEG results, imaging results, number and type of combined anti-seizure drugs, or maximum dose of pirampanel between the valid group and invalid group ( P>0.05). Conclusion:Perampanel has good efficacy, tolerability and safety in adolescents and adults≥12 years old with focal epilepsy; no clear influencing factors for pirampanel valid treatment is found so far.
10.Prevalence and factors related to overweight, obesity and hypertension comorbidities among primary and secondary school students in Ningxia
WEI Rong, LI Yuan, MA Ning, WANG Xiaoli, JIN Yanan,MA Fang,YANG Yi,CHEN Yaogeng
Chinese Journal of School Health 2024;45(12):1807-1810
Objective:
To explore the prevalence and related factors of overweight, obesity and hypertension comorbidities among children and adolescents in Ningxia, so as to provide a scientific basis for effective early health intervention in children and adolescents.
Methods:
From September 2021 to June 2022, a total of 4 577 students aged 9-16 were selected from Jinfeng District of Yinchuan City, Shapotou District of Zhongwei City, Yanchi County of Wuzhong City and Pingluo County of Shizuishan City in Ningxia by multi stage cluster random sampling method for questionnaire survey and physical measurement. The influencing factors of overweight, obesity and hypertension comorbidities in children and adolescents were investigated by Chi square test and multivariate unconditioned Logistic regression analysis with weighted complex sampling design.
Results:
The prevalence of overweight and obesity among primary and secondary school students in Ningxia was 22.87%, the prevalence of hypertension was 1.30%, and the comorbity rate of overweight, obesity and hypertension was 1.07%. Multivariate Logistic regression analysis showed that students aged 13-16 ( OR =15.66,95% CI =3.84-63.96, P <0.05) were more likely to suffer from overweight, obesity and hypertension than students aged 9-12. The students of insufficient sleep duration ( OR =5.47, 95% CI =1.73-17.33, P <0.05) had higher levels of overweight, obesity and hypertension comorbidities than those of adequate sleep duration. Students who had breakfast 1 to 7 times a week ( OR =0.08, 95% CI =0.02-0.37) had lower incidence than those who had breakfast once a week ( P <0.05).
Conclusions
Age, sleep time and breakfast frequency are all related factors of overweight, obesity and hypertension co morbidity among primary and secondary school students in Ningxia. Close attention should be paid to students aged 9-12 years with insufficient sleep time and fasting in the morning, and carry out scientific education and prevention and control interventions should be carried out.


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