1.Mahoniae Caulis Alkaloids Ameliorate Depression by Regulating Synaptic Plasticity via cAMP Pathway
Junhui HE ; Chunlian JIA ; Kedao LAI ; Guili ZHOU ; Rongfei ZHOU ; Yi LI ; Dongmei LI ; Jiaxiu XIE ; Guining WEI ; Juying ZHOU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):132-140
ObjectiveTo explore the mechanisms associated with Mahoniae Caulis alkaloids (MA) in ameliorating depression by network pharmacology, molecular docking, and animal experiments. MethodsThe component targets of MA were obtained through Swiss Target Prediction and TCMIP database. The depression targets were collected through TCMIP, Genecards, HPO, DrugBank and OMIM database. The depression targets were collected through TCMIP, Genecards, HPO, DrugBank and OMIM database. Protein-protein interaction (PPI) network was constructed by protein interaction analysis (STRING) database. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed through Bioinformatics (DAVID) database. The docking of components and targets was performed by AGFR. The mouse model of depression was established by intraperitoneal injection of corticosterone (CORT) once a day for 35 consecutive days. Sixty mice were randomly allocated into control (0.9% normal saline), model (CORT, 20 mg·kg-1), positive control (fluoxetine hydrochloride, 3.6 mg·kg-1), and MA (10, 5, and 2.5 mg·kg-1) groups. Each group was administrated with corresponding medicine or normal saline once a day for 28 consecutive days. The depression-like behavior of mice was observed. The pathological changes of prefrontal cortex in mice were observed by hematoxylin-eosin staining. Terminal deoxynucleotidyl dUTP transferase nick end labeling (TUNEL) was employed to observe the apoptosis of neurons in the prefrontal cortex. Enzyme-linked immunosorbent assay was employed to assess the serum levels of brain-derived neurotrophic factor (BDNF), dopamine (DA), 5-hydroxytryptamine (5-HT), and norepinephrine (NE) in mice. The mRNA levels of cyclic adenosine monophosphate (cAMP) pathway-related factors and inflammatory factors were determined by Real-time PCR. Western blot was employed to determine the expression of cAMP pathway-related factors and connexin 43 (Cx43). ResultsA total of 434 component targets and 545 depression targets were obtained, including 84 common targets, among which 10 core targets were screened out. GO analysis predicted 34 biological processes, 15 cell components, and 11 molecular functions. The KEGG pathways were mainly related to gap junction and cAMP signaling pathway. The core components had good binding affinity with the core targets. The results of animal experiments showed that compared with the control group, CORT prolonged the immobility time of mice in forced swimming and tail suspension tests (P<0.01), lowered the serum levels of NE, BDNF, and 5-HT (P<0.05), up-regulated the mRNA levels of nuclear factor-κB (NF-κB) and interleukin-6 (IL-6) in the brain tissue (P<0.05), and down-regulated the mRNA levels of cyclic adenosine monophosphate effector binding protein (CREB) and BDNF (P<0.05) and the protein levels of protein kinase (PRKACA), phosphorylation (p)-CREB/CREB, BDNF, and Cx43 (P<0.05) in the brain tissue. Compared with the model group, high-dose MA reduced the immobility time of mice in forced swimming (P<0.05) and tail suspension (P<0.01) tests, raised the serum levels of NE, BDNF, and 5-HT (P<0.01), down-regulated the mRNA level of NF-κB (P<0.01), and up-regulated the mRNA level of BDNF (P<0.01) and protein levels of PRKACA, p-CREB/CREB, BDNF, and Cx43 (P<0.05). ConclusionMA alleviates the CORT-induced depressive behavior of mice. It may play an antidepressant role by regulating cAMP signaling pathway and gap junction pathway, improving synaptic plasticity and gap junction function, and reducing neuroinflammation.
2.Mahoniae Caulis Alkaloids Ameliorate Depression by Regulating Synaptic Plasticity via cAMP Pathway
Junhui HE ; Chunlian JIA ; Kedao LAI ; Guili ZHOU ; Rongfei ZHOU ; Yi LI ; Dongmei LI ; Jiaxiu XIE ; Guining WEI ; Juying ZHOU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):132-140
ObjectiveTo explore the mechanisms associated with Mahoniae Caulis alkaloids (MA) in ameliorating depression by network pharmacology, molecular docking, and animal experiments. MethodsThe component targets of MA were obtained through Swiss Target Prediction and TCMIP database. The depression targets were collected through TCMIP, Genecards, HPO, DrugBank and OMIM database. The depression targets were collected through TCMIP, Genecards, HPO, DrugBank and OMIM database. Protein-protein interaction (PPI) network was constructed by protein interaction analysis (STRING) database. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed through Bioinformatics (DAVID) database. The docking of components and targets was performed by AGFR. The mouse model of depression was established by intraperitoneal injection of corticosterone (CORT) once a day for 35 consecutive days. Sixty mice were randomly allocated into control (0.9% normal saline), model (CORT, 20 mg·kg-1), positive control (fluoxetine hydrochloride, 3.6 mg·kg-1), and MA (10, 5, and 2.5 mg·kg-1) groups. Each group was administrated with corresponding medicine or normal saline once a day for 28 consecutive days. The depression-like behavior of mice was observed. The pathological changes of prefrontal cortex in mice were observed by hematoxylin-eosin staining. Terminal deoxynucleotidyl dUTP transferase nick end labeling (TUNEL) was employed to observe the apoptosis of neurons in the prefrontal cortex. Enzyme-linked immunosorbent assay was employed to assess the serum levels of brain-derived neurotrophic factor (BDNF), dopamine (DA), 5-hydroxytryptamine (5-HT), and norepinephrine (NE) in mice. The mRNA levels of cyclic adenosine monophosphate (cAMP) pathway-related factors and inflammatory factors were determined by Real-time PCR. Western blot was employed to determine the expression of cAMP pathway-related factors and connexin 43 (Cx43). ResultsA total of 434 component targets and 545 depression targets were obtained, including 84 common targets, among which 10 core targets were screened out. GO analysis predicted 34 biological processes, 15 cell components, and 11 molecular functions. The KEGG pathways were mainly related to gap junction and cAMP signaling pathway. The core components had good binding affinity with the core targets. The results of animal experiments showed that compared with the control group, CORT prolonged the immobility time of mice in forced swimming and tail suspension tests (P<0.01), lowered the serum levels of NE, BDNF, and 5-HT (P<0.05), up-regulated the mRNA levels of nuclear factor-κB (NF-κB) and interleukin-6 (IL-6) in the brain tissue (P<0.05), and down-regulated the mRNA levels of cyclic adenosine monophosphate effector binding protein (CREB) and BDNF (P<0.05) and the protein levels of protein kinase (PRKACA), phosphorylation (p)-CREB/CREB, BDNF, and Cx43 (P<0.05) in the brain tissue. Compared with the model group, high-dose MA reduced the immobility time of mice in forced swimming (P<0.05) and tail suspension (P<0.01) tests, raised the serum levels of NE, BDNF, and 5-HT (P<0.01), down-regulated the mRNA level of NF-κB (P<0.01), and up-regulated the mRNA level of BDNF (P<0.01) and protein levels of PRKACA, p-CREB/CREB, BDNF, and Cx43 (P<0.05). ConclusionMA alleviates the CORT-induced depressive behavior of mice. It may play an antidepressant role by regulating cAMP signaling pathway and gap junction pathway, improving synaptic plasticity and gap junction function, and reducing neuroinflammation.
3.Stem cell therapy for premature ovarian insufficiency: a review of clinical evidence and therapeutic strategies.
Journal of Zhejiang University. Medical sciences 2025;():1-10
Premature ovarian insufficiency (POI), characterized by the decline of ovarian function before age 40, significantly compromises fertility and long-term health of patients. Stem cell therapy has emerged as a promising approach for POI. This review synthesizes clinical evidence from studies utilizing cells sourced from adult tissues (e.g., adipose derived mesenchymal stem cells, bone marrow mesenchymal stem cells, peripheral blood stem cells) and perinatal tissues (e.g., human amniotic epithelial cells, umbilical cord-derived mesenchymal stem cells). Evidence suggests that stem cell transplantation can improve ovarian reserve, reflected by reduced follicle-stimulating hormone levels and increased estradiol and anti-Müllerian hormone levels, with some patients resuming menstruation and achieving pregnancy. However, treatment efficacy is influenced by patient-specific factors and clinical protocols. Optimizing stem cell transplantation protocols is pivotal for enhancing their clinical efficacy and safety. This article elaborates on key optimization strategies, including transplantation timing, delivery routes, and combination therapies, proposing that early intervention and personalized regimens may improve outcomes. We also discuss patient benefits (such as pregnancy outcomes and quality of life) and treatment safety. Future research should focus on refining personalized strategies, investigating the therapeutic potential of stem cell-derived agents, and establishing long-term follow-up, thereby advancing POI therapy toward precision medicine and standardized application.
4.Simultaneous determination of sucrose and mannitol by HPLC-ELSD in meningococcal polysaccharide vaccine
Gang HE ; Dongmei ZHOU ; Yueyue LAI ; Qian HUANG ; Qian WANG ; Siqin CAI ; Gongxiao WANG ; Fang HUANG
Drug Standards of China 2025;26(4):424-429
Objective:To establish a high performance liquid chromatography-evaporative light scattering detector(HPLC-ELSD)technique for simultaneous determining the content of excipients sucrose and mannitol in meningo-coccal polysaccharide vaccine.Methods:Using NanoChrom Sugar-10Ca analytical column(300 mm × 7.8 mm)and HPLC system(Agilent 1260).With purified water as the mobile phase,a flow rate of 0.5 mL·min-1,column temperature was 80 ℃,and the injection volume was 50 μL.The evaporative light detector was based on nitrogen.The carrier gas flow rate is 3.2 L·min-1,the temperature of drift tube was 1 10 ℃,the gain value was 1,and the impactor was"mode 1".This assay was subsequently validated for its system suitability,specificity,repeatability,intermediate precision and linearity,and accuracy.The established method was used to assay the contents of the sucrose and mannitol in four batches of meningococcal polysaccharide vaccine.Results:The estab-lished HPLC-ELSD method showed good systemic suitability.Specificity validation showed that there was no inter-ference peak in the blank solvent;the separation of the target peaks between sucrose and mannitol was>2.0.The relative standard deviations(RSD)value of peak area of sucrose and mannitol in six tests were 0.44%and 0.38%,respectively.RSD of intermediate precision of both sucrose and mannitol were lower than 2.00%,indica-ting that the precision of high performance liquid chromatography instrument was well.The linear range of two excipients were 12.5-150.0 μg·mL-1(R2>0.99,respectively).The recovery rate of sucrose and mannitol were 95.74%-99.33%,94.37%-98.85%,respectively.There was no significant difference in the contents of sucrose and mannitol in 4 batches of meningococcal polysaccharide vaccine.Conclusion:The HPLC-ELSD method showed good specificity,precision,linearity and accuracy,and the test results were stable and reliable,so that it is suitable for simultaneous determination of sucrose and mannitol contents of meningococcal polysaccharide injections.
5.Current status and risk factors for hospital-acquired rhinosinusitis in Neurocritical Care Unit patients
Qiong CHEN ; Qindi ZHANG ; Dongmei WANG ; Man YANG ; Linyan LAI ; Daihong CHENG ; Xiaoxian HUANG ; Xiaoyan LIAO
Chinese Journal of Modern Nursing 2025;31(16):2231-2235
Objective:To explore the current status of hospital-acquired rhinosinusitis (HAR) in Neurocritical Care Unit (NCU) patients and to analyze its risk factors.Methods:From January 2021 to December 2022, 819 NCU patients of Nanfang Hospital, Southern Medical University were selected by whole population sampling method, of which 125 patients met the inclusion and exclusion criteria for analysis. Patients were categorized into HAR group ( n=69) and non-HAR group ( n=56) based on the occurrence of HAR. Differences in demographic and clinical data of the two groups of patients were compared. Logistic regression analysis was used to explore the risk factors for the HAR in patients. Results:HAR occurred in 69 NCU patients, with an incidence of 55.2% (69/125) . There were statistically significant differences in gender, smoking history, Glasgow Coma Scale score on admission, whether or not there was pneumonia, whether or not a nasogastric tube was indwelt before the occurrence of HAR, whether or not tracheal intubation was performed before the occurrence of HAR, whether or not mechanical ventilation was conducted before the occurrence of HAR, whether or not tracheotomy was performed, and the length of NCU stay between patients in HAR group and non-HAR group ( P<0.05) . Logistic regression analysis showed that indwelling nasogastric tube before the occurrence of HAR, failure to quit smoking before admission, and prolonged NCU stay were risk factors for HAR ( OR=6.291, 3.976, 1.089; P<0.05) . Conclusions:NCU patients have a high incidence of HAR, and indwelling nasogastric tube, failure to quit smoking before admission, and prolonged NCU stay are risk factors for HAR in NCU patients.
6.Risk factors for postoperative secondary hydrocephalus in patients with severe craniocerebral injury and construction of nomogram risk model
Yanling LAI ; Dongmei CAI ; Jingjing ZHUO ; Hao LI ; Wenhui LI
Journal of Clinical Medicine in Practice 2025;29(1):94-97,117
Objective To explore the risk factors for postoperative secondary hydrocephalus in patients with severe craniocerebral injury and construct a nomogram prediction model.Methods A total of 360 patients with severe craniocerebral injury were selected as the study subjects,and divided into hydrocephalus group(n=34)and non-hydrocephalus group(n=326)based on the occurrence of postoperative secondary hydrocephalus.Logistic regression analysis was used to screen for risk fac-tors of postoperative secondary hydrocephalus.A nomogram model for predicting postoperative second-ary hydrocephalus in patients with severe craniocerebral injury was constructed based on the identified risk factors,and its predictive performance was validated.Results Among the 360 patients,34 de-veloped secondary hydrocephalus after surgery,with an incidence rate of 9.44%(34/360).Logistic regression analysis revealed that intracranial infection,ventricular hemorrhage,midline shift ≥12 mm,preoperative Glasgow Coma Scale(GCS)score of 3 to 5,decompressive craniectomy and dura mater o-pening were independent risk factors for postoperative secondary hydrocephalus in patients with severe traumatic brain injury(P<0.05).The concordance index of the nomogram model constructed based on these risk factors was 0.874,and the area under the curve was 0.831.Conclusion The nomogram model constructed in this study based on factors such as intracranial infection,ventricular hemorrhage,midline shift,preoperative GCS score,decompressive craniectomy and dura mater opening,effectively predicts risk of postoperative secondary hydrocephalus in patients with severe traumatic brain injury.This model has clinical significance for early prevention and treatment.
7.Simultaneous determination of sucrose and mannitol by HPLC-ELSD in meningococcal polysaccharide vaccine
Gang HE ; Dongmei ZHOU ; Yueyue LAI ; Qian HUANG ; Qian WANG ; Siqin CAI ; Gongxiao WANG ; Fang HUANG
Drug Standards of China 2025;26(4):424-429
Objective:To establish a high performance liquid chromatography-evaporative light scattering detector(HPLC-ELSD)technique for simultaneous determining the content of excipients sucrose and mannitol in meningo-coccal polysaccharide vaccine.Methods:Using NanoChrom Sugar-10Ca analytical column(300 mm × 7.8 mm)and HPLC system(Agilent 1260).With purified water as the mobile phase,a flow rate of 0.5 mL·min-1,column temperature was 80 ℃,and the injection volume was 50 μL.The evaporative light detector was based on nitrogen.The carrier gas flow rate is 3.2 L·min-1,the temperature of drift tube was 1 10 ℃,the gain value was 1,and the impactor was"mode 1".This assay was subsequently validated for its system suitability,specificity,repeatability,intermediate precision and linearity,and accuracy.The established method was used to assay the contents of the sucrose and mannitol in four batches of meningococcal polysaccharide vaccine.Results:The estab-lished HPLC-ELSD method showed good systemic suitability.Specificity validation showed that there was no inter-ference peak in the blank solvent;the separation of the target peaks between sucrose and mannitol was>2.0.The relative standard deviations(RSD)value of peak area of sucrose and mannitol in six tests were 0.44%and 0.38%,respectively.RSD of intermediate precision of both sucrose and mannitol were lower than 2.00%,indica-ting that the precision of high performance liquid chromatography instrument was well.The linear range of two excipients were 12.5-150.0 μg·mL-1(R2>0.99,respectively).The recovery rate of sucrose and mannitol were 95.74%-99.33%,94.37%-98.85%,respectively.There was no significant difference in the contents of sucrose and mannitol in 4 batches of meningococcal polysaccharide vaccine.Conclusion:The HPLC-ELSD method showed good specificity,precision,linearity and accuracy,and the test results were stable and reliable,so that it is suitable for simultaneous determination of sucrose and mannitol contents of meningococcal polysaccharide injections.
8.Current status and risk factors for hospital-acquired rhinosinusitis in Neurocritical Care Unit patients
Qiong CHEN ; Qindi ZHANG ; Dongmei WANG ; Man YANG ; Linyan LAI ; Daihong CHENG ; Xiaoxian HUANG ; Xiaoyan LIAO
Chinese Journal of Modern Nursing 2025;31(16):2231-2235
Objective:To explore the current status of hospital-acquired rhinosinusitis (HAR) in Neurocritical Care Unit (NCU) patients and to analyze its risk factors.Methods:From January 2021 to December 2022, 819 NCU patients of Nanfang Hospital, Southern Medical University were selected by whole population sampling method, of which 125 patients met the inclusion and exclusion criteria for analysis. Patients were categorized into HAR group ( n=69) and non-HAR group ( n=56) based on the occurrence of HAR. Differences in demographic and clinical data of the two groups of patients were compared. Logistic regression analysis was used to explore the risk factors for the HAR in patients. Results:HAR occurred in 69 NCU patients, with an incidence of 55.2% (69/125) . There were statistically significant differences in gender, smoking history, Glasgow Coma Scale score on admission, whether or not there was pneumonia, whether or not a nasogastric tube was indwelt before the occurrence of HAR, whether or not tracheal intubation was performed before the occurrence of HAR, whether or not mechanical ventilation was conducted before the occurrence of HAR, whether or not tracheotomy was performed, and the length of NCU stay between patients in HAR group and non-HAR group ( P<0.05) . Logistic regression analysis showed that indwelling nasogastric tube before the occurrence of HAR, failure to quit smoking before admission, and prolonged NCU stay were risk factors for HAR ( OR=6.291, 3.976, 1.089; P<0.05) . Conclusions:NCU patients have a high incidence of HAR, and indwelling nasogastric tube, failure to quit smoking before admission, and prolonged NCU stay are risk factors for HAR in NCU patients.
9.Construction of nomogram prediction model for risk of mild cognitive impairment in elderly people
Dongmei HUANG ; Huiqiao HUANG ; Jinjin WEI ; Caili LI ; Yanfei PAN ; Lichong LAI ; Shujie LONG
Chongqing Medicine 2024;53(11):1630-1635
Objective To construct a nomogram prediction model for the risk of mild cognitive impair-ment (MCI) in elderly people aged ≥ 60-year-old.Methods A total of 502 elderly permanent residents in Guangxi were selected as the research subjects by the multi-stage stratified random sampling method,and the general situation questionnaire and the Beijing edition of MoCA-BJ scale were used to investigate the elderly people,and their anthropometric indicators were collected.The minimum absolute shrinkage rate and selection operator (LASSO) regression were used to screen the characteristic variables.The MCI risk nomogram pre-diction model was constructed.The receiver operating characteristic (ROC) curve and calibration curve were adopted to conduct the fitting effect test on the prediction model.Results Among the 502 elderly people,244 cases (46.04%) had the normal cognition and 258 cases (48.68%) had MCI.The logistic regression analysis showed that the age,education background,month income,children support,calf circumference,BMI and body fat index were the influencing factors of MCI in the elderly people,and the nomogram prediction model of the MCI risk in the elderly people was constructed by these seven variables.The area under the ROC curve (AUC) of the model was 0.790 (95%CI:0.750-0.829),the sensitivity was 0.64,the specificity was 0.62,the C-index index was 0.790,and the model fitting x2=8.111,P=0.454,the predictive value was basically consistent with the actual value.Conclusion The nomogram prediction model of MCI risk in the elderly peo-ple is successfully constructed with good predictive effect.
10.Comparative study on nomogram and machine learning algorithms for predicting dental caries in middle-aged and elderly people
Lichong LAI ; Faye WEI ; Dongmei HUANG ; Xiaoying CAO ; Jie PENG ; Xiaoling FENG ; Huiqiao HUANG
Chongqing Medicine 2024;53(14):2130-2137
Objective To compare the efficiency of nomogram and different machine learning algo-rithms for constructing the dental caries predictive models for middle-aged and elderly people.Methods The multi-stage stratified random sampling method was used to select 510 middle-aged and elderly people from Nanning City,Guigang City and Chongzuo City as the research subjects for conducting the questionnaire sur-vey and oral cavity examination.The univariate analysis and Lasso regression were used to screen the related variables,and the multivariate logistic regression analysis was used to determine the final independent influen-cing factors.Based on the salient features,the nomogram predictive model was established,and the seven ma-chine learning algorithms,including linear discriminant analysis (LDA),partial least squares (PLS),range Doppler algorithm (RDA),generalized linear models (GLM),random forest (RF),support vector machine (SVM) kernel function (SVM-Radial),and SVM linear kernel function (SVM-Linear),were used to construct the seven kinds of dental caries risk predictive models.The area under the receiver operating characteristic (ROC) curve (AUC) was adopted to evaluate the predictive performance of various models and the predictive performance of models constructed using different variable screening methods.Results The detection rate of dental caries in middle-aged and elderly people was 71.18%.After feature screening,the five predictive factors were ultimately retained,which were the age (OR=0.945,95%CI:0.917-0.973),brushing frequency (OR=0.688,95%CI:0.475-0.997),whether having teeth cleaning in the past one year (OR=0.303,95%CI:0.103-0.890),number of remaining teeth (OR=1.062,95%CI:1.038-1.087) and oral health assess-ment tool (OHAT) score (OR=1.363,95%CI:1.234-1.505).The results of comparison of various models showed that the predictive model constructed by the RF algorithm performed the best,the median of AUC was 0.747,followed by the nomogram,and the median of AUC was 0.733.The median of AUCs in the predic-tion model constructed by single factor+Lasso+multivariate logistic (Lasso+logistic) screening independent variables were higher than those constructed by RF algorithm screening independent variables.ConclusionBased on Lasso+logistic screening variables,RF provide more reliable predictive efficiency in predicting dental caries in middle-aged and elderly people than nomogram and the other machine learning algorithms.

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