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.Bioinformatics and Animal Experiments Reveal Mechanism of Shouhui Tongbian Capsules in Treating Constipation
Yong LIANG ; Qimeng ZHANG ; Bin GE ; Yang ZHANG ; Yu SHI ; Yue LU ; Hongxi ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(4):150-157
ObjectiveTo explore the mechanism of Shouhui Tongbian capsules in treating constipation based on the research foundation of its active components combined with network pharmacology and animal experiments. MethodsThe drug components were imported into SwissTargetPrediction to predict the targets of Shouhui Tongbian capsules, and constipation-related targets were collected from disease databases. A protein-protein interaction (PPI) network was constructed for the common targets shared by Shouhui Tongbian capsules and constipation to screen key targets, which was followed by gene ontology (GO) function and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses. A "bioactive component-target-pathway" network was constructed, and the core components of Shouhui Tongbian capsules in treating constipation were screened based on the topological parameters of this network. Molecular docking was employed to predict the binding affinity of core components to key targets. A mouse model of constipation was constructed to screen the key pathways and targets of the drug intervention in constipation. ResultsThe PPI network revealed six key constipation-related targets: protein kinase B (Akt1), B-cell lymphoma-2 (Bcl-2), glycogen synthase kinase-3β (GSK-3β), cyclooxygenase-2 (PTGS2), estrogen receptor 1 (ESR1), and epidermal growth factor receptor (EGFR). The KEGG pathway analysis showed that the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway was the most enriched. The topological parameter analysis of the "bioactive component-target-pathway" network screened out the top 10 core components: auranetin, isosinensetin, naringin, diosmetin, quercetin, apigenin, luteolin, hesperidin, isorhapontigenin, and chrysophanol. Molecular docking results showed that the 10 core components had strong binding affinity with the 6 key targets. Animal experiments showed that after intervention with different doses of Shouhui Tongbian capsules, the time to the first black stool excretion was reduced and the fecal water content and small intestine charcoal propulsion rate of mice were improved. After treatment with Shouhui Tongbian capsules, the colonic mucosal injury and glandular arrangement were alleviated, and the muscle layer thickness was increased. Western blot results showed that Shouhui Tongbian capsules recovered the expression of apoptosis-related molecules mediated by the PI3K/Akt pathway in the colonic tissue of constipated mice. Terminal-deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) results showed that the cell apoptosis rate of the colon significantly reduced after intervention with Shouhui Tongbian capsules. ConclusionThe results of network pharmacology and animal experiments confirmed that Shouhui Tongbian capsules can treat constipation through multiple targets and pathways. The capsules can effectively intervene in loperamide-induced constipation in mice by regulating the constipation indicators and reducing cell apoptosis in the colon tissue via activating the PI3K/Akt signaling pathway.
3.Application of progressive exercise training based on mMRC grading in respiratory rehabilitation for patients with chronic obstructive pulmonary disease in a primary healthcare setting
Tingting GE ; Chengyue ZHU ; Yanan ZHANG ; Zixuan ZHENG ; Jiannan LI ; Junqing LI ; Zhijun JIE ; Jindong SHI ; Hanwei ZHAO
Chinese Journal of Clinical Medicine 2025;32(4):578-584
Objective To explore the efficacy of progressive exercise training based on the modified Medical Research Council dyspnea scale (mMRC) grading in respiratory rehabilitation for patients with chronic obstructive pulmonary disease (COPD) at a primary healthcare setting. Methods A total of 106 patients with COPD admitted to Zhuanqiao Community Health Service Center in Shanghai from Aug.1, 2022 to Jul. 30, 2024 were selected as research subjects. They were randomly divided into a study group and a control group in a 1∶1 ratio, with 53 patients in each group. The control group received conventional treatment, while the study group received conventional treatment combined with progressive exercise training. After 4 weeks of continuous treatment, the changes in the 6-minute walk test (6MWT), COPD assessment test (CAT) score, mMRC grading, Global Initiative for Chronic Obstructive Lung Disease (GOLD) grading and pulmonary function were compared between the two groups. Results Patients in both groups showed improvements in 6MWT distance, CAT score, mMRC grading, GOLD grading, and pulmonary function compared to baseline (P<0.05). Moreover, the study group had better improvements in 6MWT distance, CAT score, mMRC grading, GOLD grading, and pulmonary function than the control group (P<0.05). Conclusions Conventional treatment combined with progressive exercise training based on mMRC grading can enhance the effect of respiratory rehabilitation in patients with COPD, particularly in improving pulmonary function and exercise tolerance.
4.Clinical observation on 5 cases of small intestinal bezoars with obstruction treated by oral double-balloon enteroscopy
Liangliang SHI ; Zhengchao LI ; Shuling HUANG ; Jing GE ; Yuqin TONG ; Yiyang ZHANG
Chinese Journal of Digestive Endoscopy 2024;41(6):484-486
To evaluate the safety and efficacy of oral double-balloon enteroscopy for small intestinal bezoars with obstruction, the clinical, endoscopic, imaging, pathological and surgical data of patients with small intestinal bezoars and obstruction treated in Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School from December 2021 to March 2023 were retrospectively analyzed. A total of 5 patients, all female, aged 52-83 years, were included. The clinical manifestation was mainly digestive tract obstruction. The diameter of bezoars was 30-50 mm. Three were located in the jejunum, one in the proximal ileum, and one at the jejuno-ileal junction. Three cases were diagnosed as having small intestinal bezoars by imaging examination before operation. All 5 patients achieved technical success. Four patients achieved clinical success, the symptoms of obstruction were completely relieved, and 1 patient was partially relieved due to malignant obstruction. No obvious complication occurred in 5 patients after operation. The follow-up time was 15-790 days, and there was no recurrence. The results showed that oral double-balloon enteroscopy for small intestinal bezoars was safe and effective, providing a new treatment for patients with small intestinal bezoars except for surgery.
5.Effectiveness and safety of narrow-band intense pulsed light on erythromelanosis follicularis faciei et colli
Hualing SHI ; Erjia ZHANG ; Yiping GE ; Mengli ZHANG ; Tong LIN
Chinese Journal of Medical Aesthetics and Cosmetology 2024;30(6):528-531
Objective:To evaluate the efficacy and safety of narrow-band intense pulsed light in the treatment of erythromelanosis follicularis faciei et colli (EFFC).Methods:The patients with EFFC, diagnosed at the Department of Cosmetic Laser Surgery, Hospital for Skin Disease, Chinese Academy of Medical Sciences, and Peking Union Medical College, from January 2017 to December 2022, were retrospectively evaluated. There were 28 patients, including 24 males and 4 females. They ranged in age from 15 to 35 (21.0±4.2) years. All patients received three sessions of narrow-band intense pulsed light treatments, with intervals of 1-2 months. A follow-up visit was completed 1-2 months after three treatments, and efficacy was evaluated. Two dermatologists assessed the clinical improvement in erythema, pigmentation, and follicular papules on a 4-point scale (0=0-25% improvement, 1=26%-50% improvement, 2=51%-75% improvement, and 3=76%-100% improvement). Adverse events were also recorded.Results:A total of 28 patients received three sessions of narrow-band intense pulsed light treatments and were followed-up. After three treatments, the mean improvement scores for erythema, follicular papules, and pigmentation were (2.02±0.65), (1.38±0.59) and (0.80±0.61) respectively. Among these patients, 67.9% (19/28) experienced over 50% improvement in erythema, 39.3% (11/28) showed over 50% improvement in follicular papules, and 7.1% (2/28) demonstrated over 50% improvement in pigmentation. No blisters and scars were formed.Conclusions:Narrow-band intense pulsed light is a safe and effective treatment for patients with EFFC, particularly for those presenting with erythema.
6.Application of the " three streams in one" integrated management based on dual code carriers in the whole lifecycle management of medical consumables
Qin ZHANG ; Hui ZHONG ; Xiaokun GAO ; Jian ZHANG ; Shancheng YU ; Feng SHI ; Wenjun GE ; Yue ZHUANG
Chinese Journal of Hospital Administration 2024;40(7):554-557
In order to improve the level of refined management of medical consumables, a hospital used radio frequency identification (RFID) technology to map the unique device identification barcode of medical devices to the supply-processing-distribution (SPD) code, generating a medical consumables RFID tag code with dual code carrier function and a unique serial number. The " three streams in one" mutual integration management mode of hospital information flow, material flow and financial flow was constructed, which realized the whole lifecycle traceability of medical consumables, effectively improved the intelligence and accuracy of inventory control, further optimized the integration function of medical consumables industry and finance, and provided strong data support for the decision-making analysis of hospital operation and management.
7.Research status of hand rehabilitation robots
Ge-Ge ZHANG ; Lian-Xin HU ; Ze-Feng WANG ; Shi-Jia HU ; Dan WANG ; Xin-Xin NI ; Hua-Jun WANG ; Shan-Qi GU
Chinese Medical Equipment Journal 2024;45(11):88-96
The current research status of different structures,driving modes and training modes of hand rehabilitation robots at home and abroad was introduced.The disadvantages of the existing hand rehabilitation robots were analyzed.It's pointed out hand rehabilitation robots in the future would involve in the combination of rigid and flexible wearing,new intelligent driving mode and multi-mode rehabilitation training.[Chinese Medical Equipment Journal,2024,45(11):88-96]
8.Mechanism of Elesclomol Induced Cuproptosis in Endometrial Cancer Cells
Shasha ZHANG ; Yingying SHI ; Chunxiang WU ; Ning GE
Herald of Medicine 2024;43(9):1393-1397
Objective To investigate the mechanism of copper ionophore elesclomol induced cuproptosis in endometrial cancer cells.Methods HEC-1-A cells were treated with different concentrations of copper ion carrier elesclomol and copper chloride.Cell proliferation was detected using a cell counting kit(CCK-8)assay.Enzyme-linked immunosorbent assay(ELISA)detected mitochondrial respiratory chain complexesⅠ,Ⅱ,Ⅲ,and IV.Quantitative real-time polymerase chain reaction(qRT-PCR)was used to detect mRNA expression.Western blotting and immunohistochemistry were used to detect protein expression.Results Adding elesclomol or copper chloride alone to HEC-1-A cells did not affect cell survival.However,the simultaneous addition of 50 nmol·L-1 elesclomol and 1 μmol·L-1 copper ions caused a significant decrease in cell survival(P<0.01).Elesclomol-induced HEC-1-A cell death does not involve the apoptosis mechanism.After treatment with 50 nmol·L-1 elesclomol and 1 μmol·L-1 copper ions in HEC-1-A cells,the levels of mitochondrial respiratory chain complexes Ⅰ,Ⅱ,and Ⅲsignificantly increased.After knocking down ferredoxin 1(FDX1),the cuproptosis in HEC-1-A cells was significantly inhibited(P<0.01).In addition,FDX1 was under-expressed in endometrial cancer tissues.Conclusion Elesclomol may promote cuproptosis in endometrial cancer cells through the FDX1/mitochondrial respiratory pathway.
9.Predictive value of controlling nutritional status score in the prognosis of patients with advanced diffuse large B-cell lymphoma
Huirong SHAN ; Xicheng CHEN ; Hao ZHANG ; Yuqing MIAO ; Fei WANG ; Yuye SHI ; Ling WANG ; Jingjing YE ; Ziyuan SHEN ; Wei SANG ; Hongfeng GE
Journal of Leukemia & Lymphoma 2024;33(2):104-109
Objective:To investigate the predictive value of controlling nutritional status (CONUT) score in the prognosis of patients with advanced diffuse large B-cell lymphoma (DLBCL).Methods:A retrospective case series study was performed. The clinical data of 654 patients newly diagnosed with advanced DLBCL diagnosed in 7 medical centers in Huaihai Lymphoma Working Group from October 2009 to January 2022 were retrospectively collected. All the patients received rituximab-based immune chemotherapy regimens. The patients were randomly assigned to the training set (458 cases) and the validation set (196 cases) in a 7:3 ratio. The clinicopathological data of patients were collected, and the CONUT score was calculated based on albumin, lymphocyte count, and total cholesterol. The optimal critical value of CONUT scote was determined by using MaxStat method. Kaplan-Meier method was used to draw survival curves; Cox proportional hazards model was used to make univariate analysis and multivariate analysis on the factors influencing overall survival (OS). The efficacy of CONUT score in combination with the International prognostic index (IPI) and an enhanced IPI (NCCN-IPI) in predicting OS was evaluated by using receiver operating characteristic (ROC) curves.Results:The median follow-up time of 654 patients was 38.1 months (95% CI: 35.3 months- 40.9 months), and the 5-year OS rate was 49.2%. According to the MaxStat method, the optimal critical value for CONUT score was determined to be 6 points. All the patients were classified into the normal nutritional status group (CONUT score ≤ 6 points, 489 cases) and the poor nutritional status group (CONUT score > 6 points, 165 cases). The results of the multivariate analysis showed that CONUT score > 6 points, male, lactate dehydrogenase >240 U/L, high white blood cell count, low hemoglobin level and age > 60 years were independent risk factors for OS of patients with advanced DLBCL (all P < 0.05). Patients in the poor nutritional status group (CONUT score > 6 points) had worse OS compared with that in the normal nutritional status group in the overall cohort of advanced DLBCL. Subgroup analysis revealed that among patients with Eastern Cooperative Oncology Group-performance status (ECOG PS) score < 2 points, IPI low-intermediate risk, IPI intermediate-high risk, NCCN-IPI low-intermediate risk, and NCCN-IPI intermediate-high risk, the patients in the poor nutritional status group (CONUT score > 6 points) had worse OS compared with that in the normal nutritional status group (CONUT score ≤ 6 points) (all P < 0.05). Conclusions:CONUT score has a certain value in the assessment of the prognosis of patients with advanced DLBCL, and its predictive efficacy is further improved when combined with IPI and NCCN-IPI.
10.Traditional Chinese Medicine in Treatment of Constipation Based on 5-HT Signaling Pathway: A Review
Yong LIANG ; Bin GE ; Yu SHI ; Yang ZHANG ; Hongxi ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(8):271-279
Chronic constipation (CC) is one of the most common functional gastrointestinal diseases. At present, the overall therapeutic effect of CC is still not satisfactory worldwide, which seriously affects the quality of life and social function of patients. The etiology and pathophysiological mechanism of constipation are still unclear. It involves comprehensive factors such as heredity, social psychology, diet, intestinal flora imbalance, intestinal motility disorder, visceral sensitivity change, pelvic floor muscle group dysfunction and enteric nervous system (ENS) disorder. Among them, the abnormal factors of the brain-gut-microbiome axis are particularly significant. The brain-gut-microbiome axis is a complex network of interactions between the intestine and the brain, integrating and coordinating the physiological functions and pathological processes of the gastrointestinal tract. Microorganisms in the intestinal lumen play an important role in it, and can communicate with the intestinal tract and the central nervous system through nerve, endocrine and immune pathways. As a key brain-gut peptide in the regulation pathway of the brain-gut-microbiome axis, 5-hydroxytryptamine (5-HT) is involved in the regulation of gastrointestinal motility, sensation and secretion. The abnormal conduction of the 5-HT signaling pathway is closely related to the occurrence and development of constipation. Traditional Chinese medicine(TCM) is a unique precious resource in China, which has good curative effects and safety. In recent years, it has received extensive attention in the treatment of constipation. TCM and active ingredients, acupuncture and massage specifically regulate 5-HT signal transmission, so that the expressions of related molecules tend to be suitable for individual disease state levels to effectively improve constipation symptoms, with unique advantages. Therefore, this study used ''constipation'', ''intestinal flora'', ''5-HT'', and ''traditional Chinese medicine'' as the keywords to search PubMed, China National Knowledge Infrastructure (CNKI) and other literature databases. The correlation between 5-HT and constipation as well as brain-gut-microbiome axis and the research progress of TCM intervention in the 5-HT signaling pathway in the treatment of constipation were reviewed in order to explore the potential therapeutic value of 5-HT system in this disease and provide references for subsequent research.

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