1.Fufang Kangjiaolv Capsules Treat Anxiety in Rat Model of Chronic Restraint Stress via Microbiota-gut-brain Axis
Wenxin FAN ; Tingyue JIANG ; Yu WANG ; Ge ZHANG ; Yifan LU ; Mengmeng LIU ; Jiayuan LI ; Renzhi MA ; Jinli SHI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(4):95-107
ObjectiveTo observe the intervention effect of Fufang Kangjiaolv capsules on anxiety-like behaviors in the rat model of chronic restraint stress (CRS) and explore the mechanism underlying the anti-anxiety effect via the microbiota-gut-brain axis. MethodsRats were assigned into blank, model, positive drug (diazepam, 1 mg·kg-1), and low-, medium-, and high-dose (0.75, 1.5, 3 g·kg-1, respectively) Fufang Kangjiaolv capsules groups. After 14 days of administration, the elevated plus maze test, open field test, light and dark box test, and marble burying test were performed. Hematoxylin-eosin staining was employed to observe the pathological changes in the hippocampus and colon of rats, and Nissl staining was conducted to observe the damage of hippocampal neurons. The gut microbiota was analyzed by 16S rRNA gene sequencing. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was employed to determine the mRNA levels of zonula occludens-1 (ZO-1) and occludin in the colon of rats. The levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) in the colon, serum, and hippocampus were determined by enzyme-linked immunosorbent assay. Western blot was employed to determine the protein levels of ZO-1, occludin, nuclear factor-κB p65 (NF-κB p65) in the colon tissue and NF-κB p65 and brain-derived neurotrophic factor (BDNF) in the hippocampal tissue. ResultsCompared with the blank group, the model group showed reductions in the time and frequency ratio of rats entering the elevated plus maze, the time and frequency of rats entering the central area of the open field, the time of entering the open box, the times of passing through the light and dark box, and the number of unburied beads (P<0.05, P<0.01). Compared with the model group, Fufang Kangjiaolv capsules ameliorated the anxiety of the model rats to varying degrees, and the high-dose group had the best effect, with increases in the proportions of time and frequency of rats entering the open arm in the elevated plus maze (P<0.05), the number of rats entering the central area in the open field (P<0.05), the time of entering the open box, the times of passing through the light and dark boxes, and the number of unburied beads (P<0.01). Moreover, the high-dose group showed alleviated pathological damage of hippocampal neurons and colon. The results of 16S rRNA gene sequencing showed that the model group had increased relative abundance of Firmicutes, Deferribacterota, Romboutsia, and Phascolarctobacterium, while it had decreased relative abundance of Bavcteroidota and Lactobacillus. The drug administration groups showed increased relative abundance of Bavcteroidota, Bacteroides, norank f norank o Clostridia UCG-014, and Blautia and decreased relative abundance of Firmicutes and Deferribacterota. Compared with the blank group, the model group showed down-regulated protein and mRNA levels of ZO-1 and occludin in the colon (P<0.01), elevated levels of TNF-α, IL-6, and IL-β in the colon, serum, and hippocampus (P<0.01), up-regulated protein level of NF-κB p65 in the colon and hippocampus (P<0.01), and down-regulated protein level of BDNF in the hippocampus (P<0.05). Compared with the model group, high-dose Fufang Kangjiaolv capsules up-regulated the mRNA levels of ZO-1 and occludin in the colon (P<0.01), lowered the levels of TNF-α, IL-6, and IL-β in the colon, serum, and hippocampus (P<0.01), up-regulated the protein levels of ZO-1 (P<0.01) and occludin (P<0.05) in the colon, down-regulated the protein level of NF-κB p65 in the colon and hippocampus (P<0.05), and up-regulated the protein level of BDNF in the hippocampus. ConclusionFufang Kangjiaolv capsules can reduce the anxiety-like behaviors in the rat model of CRS by regulating the gut microbiota disturbance, up-regulating the expression of tight junction proteins in the colon, repairing intestinal mucosal mechanical barrier, and down-regulating NF-κB/BDNF signaling pathway, thereby reducing peripheral and central inflammation. This study proves the hypothesis that Fufang Kangjiaolv capsules play an anti-anxiety role via the microbiota-gut-brain axis, providing a new idea for further research.
2.Clinical Efficacy Evaluation of Tanreqing Injection Combined with Ceftazidime in Treatment of Phlegm Heat Obstructing Lung Syndrome in Acute Exacerbation of Chronic Obstructive Pulmonary Disease
Mengmeng ZHANG ; Qiao LI ; Qingyong XIONG ; Jiayao LI ; Linna XIE ; Jiasheng LU ; Zegeng LI
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(1):170-175
ObjectiveTo explore the effect of Tanreqing injection combined with Ceftazide on the clinical efficacy, lung function, and laboratory inflammatory index of patients suffering from phlegm heat obstructing lung syndrome in acute exacerbation of chronic obstructive pulmonary disease (AECOPD). MethodFrom June 2021 to June 2023, 76 patients diagnosed with phlegm heat obstructing lung syndrome in AECOPD were enrolled in the respiratory and critical medical department of Jieshou Hospital of Traditional Chinese Medicine. They were randomly divided into a control group and an observation group with 38 cases each. The control group used Ceftazidime intravenous drip and other conventional oxygen inhalation and antispasmodic treatment measures of western medicine. The observation group received Tanreqing injection intravenous drip based on the treatment of the control group, with a course of 10 days. The changes of laboratory indicators such as hs-CRP, calcitonin (PCT), and interleukin-6 (IL-6) before and after treatment were analyzed, and the improvement of forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), one second rate (FEV1/FVC), assessment and improvement of the British Medical Research Society’s dyspnea index (mMRC), self-evaluation test of chronic obstructive pulmonary disease patients (CAT), and traditional Chinese medicine syndrome score was compared. In addition, the total effective rate between the two groups after treatment was compared. ResultAfter treatment, the hs-CRP, PCT, IL-6, FEV1, FVC, FEV1/FVC, mMRC, CAT scores, and traditional Chinese medicine syndrome evaluation of both groups improved (P<0.01). After treatment, compared with the control group, the observation group showed more significant improvements in hs-CRP, PCT, IL-6, FEV1, FVC, FEV1/FVC, mMRC, CAT scores, and traditional Chinese medicine syndrome evaluation, and the difference was statistically significant (P<0.05,P<0.01). The total clinical effective rate of the control group was 86.84% (33/38), while that of the observation group was 94.74% (36/38). The therapeutic effect of the observation group was better than that of the control group (χ2=8.471, P<0.05). ConclusionTanreqing injection combined with Ceftazidime has obvious efficacy in the treatment of phlegm heat obstructing lung syndrome in AECOPD, which is better than the treatment of Ceftazidime antibiotics alone. It can reduce the risk of acute exacerbation, alleviate clinical symptoms, and delay the decline of lung function.
3.Study on the Risk Prediction Models of Overweight and Obesity in Medical Students
Xiaoyu LU ; Yuanli JIA ; Mengmeng LI
Chinese Journal of Health Statistics 2024;41(1):28-34
Objective To construct logistic regression,random forest and SVM models to predict the influencing factors of overweight and obesity in medical students,and the prediction performance of the three models was compared,so as to obtain the optimal model for the risk assessment of overweight and obesity.Methods Participants included 1 866 medical students from a city in Hebei Province from May to December 2020.The relevant data of overweight and obesity screening were collected through self-test questionnaire;three models of logistic regression,random forest and SVM are constructed by python.Results The test set showed that the accuracy of logistic regression,random forest and SVM models were 96.26%,98.66%and 98.13%respectively;the specificity were 99.77%,100%and 99.00%,respectively;and the AUC were 0.88,0.99 and 0.88 respectively.Random forest is the optimal prediction model;according to the random forest model results,subjective well-being,negative events and students'economic status are more than 10%of weight in the model.Conclusion Subjective well-being,negative events and students'economic status are the main factors affecting the incidence of overweight and obesity in medical students;the prediction performance of random forest model was better than logistic regression model and SVM model.
4.Analysis of the impact of bone quality on the accuracy of computer-aided design of implant guide plate
Yuxin QIAN ; Jian LI ; Jianlan ZHANG ; Shixuan ZHANG ; Yangqian GU ; Mengmeng LU ; Chunbo TANG
STOMATOLOGY 2024;44(7):508-514
Objective To explore the influence of different bone quality around the implant on the implantation accuracy,the com-puter-aided design of implant guide plate was used for patients with poor bone quality to evaluate its accuracy.Methods Retrospective analysis of relevant clinical data from 29 single-tooth implant patients with relatively poor bone quality meeting inclusion criteria was conducted.Using 3Shape Implant Studio software,implant plans were designed and fully guided digital templates were fabricated before surgery.Implantation was guided by the templates throughout,with torque and ISQ values recorded to evaluate the initial stability of the implant.Postoperative implant positions were reconstructed using CBCT images,and the three-dimensional deviation of implant place-ment was evaluated in conjunction with the preoperative design.Bone quality around the implants was also recorded and analyzed before and after surgery.Results In this study,digital guide plates were used in patients with poor bone quality,and the initial stability of implants was≥20 N·cm except for three cases.In cases of poor bone quality,the accuracy of the fully guided digital templates was as follows:cervix deviation(0.94±0.59)mm,apex deviation(1.40±0.81)mm and angle deviation 4.10°±2.99°.Bone quality had a greater impact on angle deviation(P<0.05).The higher the proportion of D3 bone was around the implant body 1/3,the smaller the deviation of neck,apex and angle was,while the higher the proportion of D5 bone,the greater the deviation of implantation.Conclu-sion For patients with poor bone quality,under the premise of restoration-oriented,the proportion of D3 bone around the implant can be increased by computer-aided design,and the initial stability of the implant can be improved by guiding the implantation with digital guide plate.Attention should be paid to the influence of bone on the angle deviation of implant during the application of guide plate.
5.Determination of tryptophan metabolite levels in serum and urine from adolescents with depression by liquid chromatogra-phy-tandem mass spectrometry
Mengmeng MA ; Xiaoming TENG ; Liu LU ; Zhihan YE ; Ming ZONG
Chinese Journal of Clinical Laboratory Science 2024;42(8):561-566
Objective To observe and compare the concentrations of tryptophan-kynurenine pathway metabolites in serum and urine of adolescents with depression individuals using liquid chromatography-tandem mass spectrometry(LC-MS/MS).Methods The major metabolites in this pathway,such as tryptophan(TRP),kynurenine(KYN),kynurenic acid(KYNA),and 3-hydroxykynurenine(3-HK)were quantitatively analyzed using isotope-labeled internal standards.The separation was achieved using a Shimadzu C18 col-umn with gradient elution of 0.2%aqueous acid and acetonitrile.The detection was performed within 7 minutes using positive ion mode and multiple reaction monitoring(MRM).The parameters,such as linear range and precision were evaluated to assess reliability of the method.Subsequently,this method was applied to detect and compare the results in the samples of serum and urine from 143 adoles-cents with depression and 110 healthy controls.Results Taking TRP as the example,the linear ranges for serum and urine were 0.54 to 107.84 μmol/L and 0.74 to 147.06 μmol/L,respectively.The intra-batch coefficient of variation(CV)was ≤6.3%,the inter-batch CV was ≤3.22%,and the total laboratory CV was ≤6.5%.The results showed the KYNA,KYN and TRP levels were lower in the de-pression group compared to the control group,while 3-HK levels were higher in the depression group with statistical significance(P<0.01).Apart from TRP,the levels of other metabolites were significantly higher in urine than those in serum,with statistical signifi-cance(P<0.01).Conclusion Compared to the results of serum,the concentrations of TRP metabolites,including KYN,KYNA and 3-HK were higher than those in urine.The concentrations of TRP-KP metabolites in urine,i.e.,KYN,KYNA and 3-HK were higher than those in serum,and the detection of TRP-KP metabolites in urine may offer a greater advantage because the urine collection process is non-invasive.
6.Undaria pinnatifida polysaccharides improves depression-like behavior of CUMS rats by reducing hippocampus oxidative stress
Mengmeng LU ; Yang ZHANG ; Fei LIN ; Xinyu CHEN ; Jianyu WANG ; Yuhe LIN ; Xiangjia YE ; Jiawen LI
Chinese Journal of Neuroanatomy 2024;40(2):145-152
Objective:To explore the effects of Undaria pinnatifida polysaccharides(UPPs)on depressive-like behavior,neurotransmitter content,oxidative stress,and the hypothalamus-pituitary-adrenal(HPA)axis in rats treated with chronic unpredictable mild stress(CUMS).Methods:A rat model of depression was prepared using the CUMS method,and rats were treated with normal saline(NS)or different doses of UPPs by gavage.The general condition of the rats was observed,and depressive-like behavior was detected by the open field test(OFT),sucrose preference test(SPT),and forced swimming test(FST).The activity or levels of 5-hydroxytryptamine(5-HT),dopamine(DA)and norepinephrine(NE),malondialdehyde(MDA),superoxide disidase(SOD)and catalase(CAT),adrenocorticotrop-ic hormore(ACTH),corticosterone(CORT)in the hippocampus or serum of rats were detected using commercial kits.Western Blot was used to detect the expression level of hippocampal glucocorticoid receptor(GR)protein,and hema-toxylin-eosin(HE)staining was used to observe the tissue structure of hippocampus of rats.Results:The depressive-like behavior of rats in the UPPs medium and high dose groups was significantly improved(P<0.05).In the UPPs high dose group,the contents of 5-HT,DA,and NE in the hippocampus of rats increased(P<0.05),while the con-tents of MDA in both serum and hippocampus decreased(P<0.05),and the activities of SOD and CAT increased(P<0.05).The contents of ACTH and CORT in serum decreased(P<0.05).In the UPPs medium dose group,the levels of hippocampal MDA and CAT,as well as serum SOD,ACTH,and CORT were improved(P<0.05).The expression level of GR protein in the hippocampus increased(P<0.05),and the pathological changes in the hipp-ocampal dentate gyrus were significantly improved.Conclusion:UPPs can alleviate depressive-like behavior in CUMS rats,and its mechanism may be related to increasing the content of monoamine neurotransmitters in the hippocampus,reducing oxidative stress damage,and HPA axis hyperfunction.
7.Correlation between CT-based arterial radiomics score and the neo-adjuvant treatment response of pancreatic cancer
Mengmeng ZHU ; Yun BIAN ; Chengwei CHEN ; Jian ZHOU ; Na LI ; Yifei GUO ; Ying LI ; Xiaohan YUAN ; Jieyu YU ; Jianping LU
Chinese Journal of Pancreatology 2024;24(3):190-197
Objective:To identify the relationship between the CT arterial radiomics score and the treatment response to neoadjuvant therapy for pancreatic cancer.Methods:The clinical data of 243 pancreatic cancer patients who received surgical resection after neo-adjuvant therapy in the First Affiliated Hospital of Naval Medical University from March 2017 to March 2023 were retrospectively analyzed. Based on the tumor regression grade (TRG), the patients were divided into good response group (TRG 0-1, n=30) and non-good response group (TRG 2-3, n=213). The clinical, radiological and pathological features were compared between two groups. Fully-automated segmentation tool was used for segmenting the arterial CT scan of pancreatic tumor before and after treatment. Python package was applied to extract the radiomics features of tumors after segmentation and the extracted features were reduced and chosen using the least absolute shrinkage and selection operator (Lasso) logistic regression algorithm. Lasso logistic regression formula was applied to calculate the arterial radiomics score. Univariate and multivariate logistic regression models were used to analyze the association between arterial radiomics score and treatment response to neoadjucant therapy. Receiver operating-characteristics (ROC) curve was drawn and area under curve (AUC), specificity, sensitivity and accuracy for evaluating the treatment response were calculated. The clinical usefulness of arterial radiomics score for diagnosing the response of neoadjuvant treatment for pancreatic cancer were determined by decision curve analysis (DCA) . Results:A total of 330 arterial radiomics CT features were obtained, and 9-selected arterial phase features associated with treatment response were determined after being reduced by the Lasso logistic regression algorithm. Univariate analysis showed that the arterial radiomics score, three-dimensional diameter after neoadjuvant therapy, pancreatic contour, T stage, N stage, Peri-pancreatic nerve invasion, lymph-vascular space invasion (LVSI) and invasion of duodenum were all associated with treatment response (all P value <0.05). Multivariate logistic regression analyses confirmed that arterial radiomics score was obviously associated with the neoadjuvant treatment response ( P<0.001). At the cut-off value of 1.93, AUC of the arterial radiomics score for diagnosing neoadjuvant treatment response was 0.92, and the specificity, sensitivity and accuracy was 86.7%, 84.5% and 84.8%. DCA demonstrated that when the percentage for predicting the treatment response by using the arterial radiomics score was >0.2, the patients could benefit from the application of arterial radiomics score for evaluating neoadjuvant therapy response. Conclusions:The arterial radiomics score was strongly correlated with the neoadjuvant treatment response of pancreatic cancer, and can accurately predict neoadjuant treatment efficacy.
8.Mechanism of action and research progress of vaccine adjuvants
Li ZHANG ; Chang LU ; Minghui AN ; Mengmeng WANG ; Xiaoyu ZONG ; Lin YU ; Zhuo-Ling RAN ; Jing SONG ; Huijie LI ; Jian GONG
Chinese Journal of Clinical Pharmacology and Therapeutics 2024;29(7):785-791
Vaccines are among the most effec-tive measures for preventing infectious diseases and play a crucial role in controlling the spread of these diseases.Adjuvants,serving as auxiliary com-ponents in vaccines,are indispensable in the vac-cine development process.Ideal adjuvants not only enhance the immune response,enabling the body to achieve optimal protective immunity but also play important roles in reducing the dosage of im-munogens and lowering vaccine production costs.To meet the demands of novel vaccines,many new types of adjuvants have been developed.However,there is still a lack of adjuvants that are safe,effec-tive,easy to prepare,highly pure,and suitable for a variety of vaccines in clinical settings.This article categorizes adjuvants and summarizes their mecha-nisms of action and characteristics,focusing on tra-ditional aluminum salt adjuvants and more modern lipid-based and nucleic acid-based adjuvants.The summary is based on a computer search of data-bases including PubMed,Embase,The Cochrane Li-brary,CNKI(China National Knowledge Infrastruc-ture),VIP Database,and Wanfang Database,using English search keywords such as Adjuvants,Vac-cine,Vaccine Adjuvant,aluminum salts,MF59,AS03,Toll-like receptor agonist,etc.,and corre-sponding Chinese search terms.The aim is to pro-vide references for the development and applica-tion of adjuvants.
9.Quantitative susceptibility mapping assessment of iron deposition in gray matter nuclei and the correlation with cognitive function in cerebral small vessel disease
Mengmeng FENG ; Yuan WANG ; Xiaoyi LIU ; Senhao ZHANG ; Fan YU ; Jie LU
Chinese Journal of Cerebrovascular Diseases 2024;21(9):595-602
Objective To evaluate iron deposition in gray matter nuclei in patients with cerebral small vessel disease(CSVD)based on quantitative susceptibility mapping(QSM)and to analyze its correlation with cognitive function.Methods Patients with CSVD attending the outpatient clinic in the Department of Neurology at Xuanwu Hospital of Capital Medical University from December 2016 to November 2022,and healthy controls recruited from previous studies in the Department of Radiology and Nuclear Medicine at Xuanwu Hospital of Capital Medical University from September 2022 to November 2022 were retrospectively consecutively collected.Baseline data of CSVD patients and healthy controls was collected and compared,including age,sex,past history(hypertension,diabetes,hyperlipidemia),smoking history,alcohol consumption history and Montreal cognitive assessment(MoCA)scale score.MRI of all CSVD patients and healthy controls were collected,including three-dimensional T1 weighted imaging,QSM,T2 weighted imaging,and fluid attenuated inversion recovery(FLAIR)sequence imaging.According to the MRI-related imaging features and CSVD total burden score,the patients were divided into mild CSVD(CSVD-m)group and severe CSVD(CSVD-s)group,and healthy controls were the control group.QSM was used to obtain the susceptibility values of gray matter nuclei for all CSVD patients and controls.One-way covariance analysis and Bonferroni correction were used to compare the gray matter nuclei susceptibility values among the three groups.Spearman correlation analysis was performed between susceptibility values of gray matter nuclei with statistically significant differences in susceptibility values and cognitive function.Results A total of 61 cases of CSVD patients were included,including 29 cases in the CSVD-s group and 32 cases in the CSVD-m group;32 healthy controls were included in the control group.(1)There was no statistically significant difference in age,sex,hypertension,diabetes,hyperlipidemia,smoking,and alcohol consumption between the CSVD-s group,CSVD-m group and control group(all P>0.05).The MoCA scale scores of the CSVD-s group and CSVD-m group were lower than those of the control group(25.0[22.5,27.5]points,27.0[25.0,29.0]points than 28.0[27.0,29.0]points,H=15.006,P<0.01).The difference in the imaging features distribution of cerebral microbleeds,white matter hyperintensity,and perivascular space among the CSVD-s group and the CSVD-m group was statistically significant(all P<0.05).(2)The differences in susceptibility values of the left putamen(F=4.790),pallidus(F=12.896),hippocampus(F=3.904)and the right putamen(F=36.278),pallidus(F=39.449),caudate nucleus(F=6.797),and thalamus(F=6.525)were statistically significant among the three groups(all P<0.05).After Bonferroni correction,the susceptibility values of the left putamen and pallidus and the right putamen,pallidus,caudate nucleus,and thalamus in the CSVD-s group were higher than those of the control group(all P<0.05);the susceptibility values of the left pallidus and the right pallidus,putamen,and thalamus in the CSVD-m group were higher than those of the control group(all P<0.01),and the left hippocampus was lower than that of the control group(P=0.045).(3)The susceptibility values of the bilateral putamen were significantly negatively correlated with MoCA scale score(left putamen:rs=-0.316,P=0.015;right putamen:rs=-0.316,P=0.014).Conclusion Abnormal iron metabolism occurs in gray matter nuclei of CSVD patients,and iron deposition in the putamen correlate with cognitive dysfunction.
10.Research progress on chemical composition and pharmacological effects of Bupleuri radix
Xiwen YANG ; Wenkai HU ; Xin JIANG ; Mengmeng ZHANG ; Qiuyue LIU ; Shumin LIU ; Fang LU
China Pharmacist 2024;28(11):507-522
Bupleuri radix is the dried root of Bupleuri radix or narrow-leaved Bupleuri radix of the umbelliferae family,and it is the most commonly used traditional Chinese medicine,which was first published in Shennong's Classic of Materia Medica.It has a variety of pharmacological effects such as anti-inflammatory,antioxidant,hepatoprotective,antitumor,antidepressant,et al.In the modern study,the extract of Bupleuri radix mainly includes a variety of chemical components such as Bupleuri radix saponin,flavonoids and volatile oil.By reviewing the relevant literature at home and abroad,this paper summarizes the research progress on the chemical composition and pharmacological effects of Bupleuri radix,and points out the future research direction to provide a certain reference basis for the subsequent research.

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