1.Mechanism of Congrong Zonggan Capsules in Improving Neuroinflammation and Cognitive Impairment in 5×FAD Mice Based on NF-κB/NLRP3 Signaling Pathway
Yanru ZHOU ; Xinru GU ; Yuru LIU ; Shun ZHANG ; Yaozhong LYU ; Zhenzhong WANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(10):130-138
ObjectiveTo investigate the effects of Congrong Zonggan capsules (CRZG) on cognitive impairment in the Alzheimer's disease (AD) model of mice and its related mechanisms. MethodsSPF grade 4-week-old 5×FAD mice were divided into a model group, low-dose CRZG (0.819 g·kg-1) and high-dose CRZG (1.638 g·kg-1) groups, and Donepezilepezil hydrochloride group (2 mg·kg-1), with eight mice in each group. Eight C57 mice with the same background were set as the normal group. After one week of adaptive feeding, mice were orally administered continuously for six months. On the 5th month of drug administration, Y maze, new object recognition, and Morris water maze tests were conducted separately. After administration, mouse brain tissue was taken, and the levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in brain tissue were detected by enzyme-linked immunosorbent assay (ELISA). Immunofluorescence (IF) was used to detect the expression of small glial cell markers Iba1, astrocyte markers GFAP, and amyloid protein 1-42 (Aβ1-42) in the hippocampus of the brain tissue. The hematoxylin-eosin (HE) staining was used to detect pathological changes in the hippocampus of brain tissue. Western blot was used to detect the expression of nuclear factor-κB (NF-κB) p65, NOD-like receptor protein 3 (NLRP3), cleaved Caspase-1, apoptosis-associated speck-like protein containing a CARD (ASC), and other proteins in the brain tissue. ResultsCompared with those in the normal group, the mice in the model group had obvious cognitive impairment. The spontaneous alternation rate of the Y maze was decreased, and the discrimination index of novel object recognition was decreased significantly (P<0.01). The escape latency in the water maze was shortened significantly (P<0.01). The contents of IL-6 and TNF-α in brain tissue were increased. The fluorescence levels of Iba1 and Aβ1-42 in the hippocampus were significantly increased (P<0.01). There was a significant increase in neuronal lesions, neuronal atrophy, loose arrangement of tissue structure, and abnormal erythrocyte aggregation in the hippocampus. The protein expressions of p-NF-κB p65/NF-κB p65, cleaved Caspase-1, ASC, IL-6, and IL-1β were significantly increased (P<0.05, P<0.01). Compared with the model group, the spontaneous alternation rate and discrimination index of the high-dose CRZG group were increased significantly (P<0.01), and the escape latency was shortened significantly (P<0.05, P<0.01). The content of IL-6 decreased in the brain, and that of TNF-α dropped significantly (P<0.01). The expression of Iba1 protein and Aβ1-42 in the hippocampus decreased significantly (P<0.05, P<0.01). The hippocampal neurons were densely arranged, and the pyramidal nuclei were clear and centered. The abnormal aggregation of red blood cells was alleviated. The value of p-NF-κB/NF-κB proteins and the expression of ASC, cleaved Caspase-1, IL-6, and IL-1β were significantly decreased (P<0.05, P<0.01). ConclusionCRZG can effectively improve cognitive impairment in 5×FAD mice with Alzheimer's disease, and its mechanism may be related to the regulation of the NF-κB/NLRP3 pathway to reduce the abnormal activation of microglia and inhibit neuroinflammation.
2.Effect of Zishen Tongguan Formula on "Gut-prostate" Axis of Rats with Chronic Non-bacterial Prostatitis Based on 16S rDNA Sequencing
Xiran LI ; Mengjiao CHEN ; Kaiping ZOU ; Chenguang ZHAO ; Xingbin DAI ; Xiaoqing ZHANG ; Shun LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):63-71
ObjectiveBased on the theory of "gut-prostate" axis, this study explored the effects and mechanisms of Zishen Tongguan formula and Cinnamomi Cortex in the formula in treating rats with chronic non-bacterial prostatitis(CNP) by detecting the levels of inflammatory factors, and the composition and structure of intestinal flora in CNP rats. MethodsEight out of 42 SD rats were randomly selected as the normal group, and the remaining rats were injected with carrageenan to prepare the CNP model. After successful modeling, 32 rats were randomly divided into the model group, Ningmitai capsule group(0.50 g·kg-1), Zishen Tongguan formula group(2.00 g·kg-1), and the Phellodendri Chinensis Cortex-Anemarrhenae Rhizoma pair group(PCC-AR group, 2.00 g·kg-1), with 8 rats in each group. The administered groups were given the corresponding medicinal solution by gavage, and the normal and model groups were intragastrically administered with an equal volume of normal saline, once a day for 14 consecutive days. The prostate tissues of rats were collected and subjected to hematoxylin-eosin(HE) staining and Masson staining to observe the pathological changes of the tissues in each group. Enzyme-linked immunosorbent assay(ELISA) was used to detect the levels of related inflammatory factors in rat serum, and 16S rDNA sequencing was used to analyze the abundance and diversity changes of gut microbiota before and after administration, and species difference analysis was performed. ResultsAll the administered groups could alleviate the inflammatory symptoms of CNP rats, increase the expression levels of anti-inflammatory factors and decrease the expression levels of pro-inflammatory factors, with the most sIgnificant effect observed in the Zishen Tongguan formula group. Compared with the normal group, the expression levels of interleukin(IL)-8, hypersensitive C-reactive protein(hs-CRP), immunoglobulin(Ig)M, secretory IgA (sIgA), and inducible nitric oxide synthase(iNOS) were sIgnificantly increased in the model group(P<0.01). Compared with the model group, the expression levels of the above inflammatory factors in all administered groups were significantly reduced(P<0.01). When compared with the PCC-AR group, the Zishen Tongguan formula group showed a significant decrease in transforming growth factor(TGF)-β1 expression level(P<0.05) and a significant increase in IgM expression level(P<0.01). The results of gut microbiota analysis showed that, compared with the PCC-AR group, at the order level, the Zishen Tongguan formula group significantly reduced the relative abundance of conditional pathogens such as Bacteroidales, Acidaminococcales, Rhodospirillales, Clostridiales, and Elusimicrobiales(P<0.01). And at the genus level, the Zishen Tongguan formula group significantly decreased the relative abundance of pathogenic microbiota such as Lachnospira and Bacteroides(P<0.01) and significantly increased the relative abundances of beneficial microbiota such as Ruminococcus and Lactobacillus(P<0.01). ConclusionZishen Tongguan formula can reduce the level of harmful intestinal bacteria, increase the level of beneficial intestinal bacteria, down-regulate the expression of serum inflammatory factors, and the small amount of Cinnamomi Cortex in the formula may play a key role in the treatment of CNP with this formula.
3.Effect of Zishen Tongguan Formula on "Gut-prostate" Axis of Rats with Chronic Non-bacterial Prostatitis Based on 16S rDNA Sequencing
Xiran LI ; Mengjiao CHEN ; Kaiping ZOU ; Chenguang ZHAO ; Xingbin DAI ; Xiaoqing ZHANG ; Shun LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):63-71
ObjectiveBased on the theory of "gut-prostate" axis, this study explored the effects and mechanisms of Zishen Tongguan formula and Cinnamomi Cortex in the formula in treating rats with chronic non-bacterial prostatitis(CNP) by detecting the levels of inflammatory factors, and the composition and structure of intestinal flora in CNP rats. MethodsEight out of 42 SD rats were randomly selected as the normal group, and the remaining rats were injected with carrageenan to prepare the CNP model. After successful modeling, 32 rats were randomly divided into the model group, Ningmitai capsule group(0.50 g·kg-1), Zishen Tongguan formula group(2.00 g·kg-1), and the Phellodendri Chinensis Cortex-Anemarrhenae Rhizoma pair group(PCC-AR group, 2.00 g·kg-1), with 8 rats in each group. The administered groups were given the corresponding medicinal solution by gavage, and the normal and model groups were intragastrically administered with an equal volume of normal saline, once a day for 14 consecutive days. The prostate tissues of rats were collected and subjected to hematoxylin-eosin(HE) staining and Masson staining to observe the pathological changes of the tissues in each group. Enzyme-linked immunosorbent assay(ELISA) was used to detect the levels of related inflammatory factors in rat serum, and 16S rDNA sequencing was used to analyze the abundance and diversity changes of gut microbiota before and after administration, and species difference analysis was performed. ResultsAll the administered groups could alleviate the inflammatory symptoms of CNP rats, increase the expression levels of anti-inflammatory factors and decrease the expression levels of pro-inflammatory factors, with the most sIgnificant effect observed in the Zishen Tongguan formula group. Compared with the normal group, the expression levels of interleukin(IL)-8, hypersensitive C-reactive protein(hs-CRP), immunoglobulin(Ig)M, secretory IgA (sIgA), and inducible nitric oxide synthase(iNOS) were sIgnificantly increased in the model group(P<0.01). Compared with the model group, the expression levels of the above inflammatory factors in all administered groups were significantly reduced(P<0.01). When compared with the PCC-AR group, the Zishen Tongguan formula group showed a significant decrease in transforming growth factor(TGF)-β1 expression level(P<0.05) and a significant increase in IgM expression level(P<0.01). The results of gut microbiota analysis showed that, compared with the PCC-AR group, at the order level, the Zishen Tongguan formula group significantly reduced the relative abundance of conditional pathogens such as Bacteroidales, Acidaminococcales, Rhodospirillales, Clostridiales, and Elusimicrobiales(P<0.01). And at the genus level, the Zishen Tongguan formula group significantly decreased the relative abundance of pathogenic microbiota such as Lachnospira and Bacteroides(P<0.01) and significantly increased the relative abundances of beneficial microbiota such as Ruminococcus and Lactobacillus(P<0.01). ConclusionZishen Tongguan formula can reduce the level of harmful intestinal bacteria, increase the level of beneficial intestinal bacteria, down-regulate the expression of serum inflammatory factors, and the small amount of Cinnamomi Cortex in the formula may play a key role in the treatment of CNP with this formula.
4.The safety and feasibility of laparoscopic indocyanine green fluorescence mapping during sentinel node navigational surgery for early gastric cancer
Chunguang GUO ; Zefeng LI ; Tongbo WANG ; Xiaojie ZHANG ; Chongyuan SUN ; Hu REN ; Yong LIU ; Lizhou DOU ; Shun HE ; Yueming ZHANG ; Guiqi WANG ; Dongbing ZHAO
Chinese Journal of General Surgery 2024;39(10):770-775
Objective:To evaluate the safety and feasibility of the laparoscopic indocyanine green (ICG) fluorescence imaging during the sentinel node navigational surgery for the early gastric cancer.Methods:Patients with <4 cm early gastric cancer were chosen. 0.5 ml ICG (2.5 mg/ml) was preoperatively injected into submucosa around the lesion in four points by the endoscopy. The sentinel lymph node basin including the stained tissue and lymph node (LN) were completely resected guided by the fluorescence mapping under ICG laparoscopy. The specimen was inspected by frozen pathology section. The radical gastrectomy was dependent on the pathology result.Result:Between 2019 and 2021, a total of 18 patients were included in the final analysis. Most tumors (16/18) located in the middle or distal stomach. Median tumor size was 2.0 cm. Lymph vessel invasion was revealed in five cases and perineural invasion in three cases. According to AJCC tumor grading system, tumor depth was classified as Tis in 2 cases, T1a in 5 cases and T1b in 11 cases. Lymph node metastasis (LNM) was revealed in four patients (4/18, 22%). Median sentinel lymph node basins per patient were 2 (range, 1-5). An average 6 (range, 2-13) LNs were harvested in each case, including 6 (1-13) ICG stained LNs and 1 (0-5) non stained LNs. All of four LNM patients were detected by sentinel node navigational surgery. The rate of the sensitivity and accuracy were 100% and 100%, respectively. The median follow-up for the entire group was 58.3 months (0.3-59.9 months), with no recurrence or metastasis observed in any patient.Conclusion:The sensitivity and accuracy of the laparoscopic indocyanine green fluorescence imaging during the sentinel node navigational surgery were satisfactory.
5.Review of conductivity reconstruction methods based on magneto-acoustic coupling effects
Yu-Hui NIE ; Zhi-Peng LIU ; Tao YIN ; Shun-Qi ZHANG
Chinese Medical Equipment Journal 2024;45(7):94-104
The theoretical foundations of the forward and inverse problems of two conductivity imaging methods based on magneto-acoustic coupling effects,including magneto-acoustic tomography(MAT)and magneto-acousto-electrical tomogra-phy(MAET),were introduced.The research progress of the conductivity reconstruction methods with different imaging strate-gies was reviewed.The problems of the conductivity reconstruction methods based on magnetoacoustic coupling effects were analyzed in terms of acoustic source model construction,reconstruction algorithm and imaging speed,and the future develop-ment directions were pointed out.[Chinese Medical Equipment Journal,2024,45(7):94-104]
6.Current situation,problems and suggestions of medical simulation technology for mobile medical service detachment training
Jun-Xiang HUANG ; Pei-Yuan XIN ; Yong-Shun ZHANG ; Zheng-Yu LIU ; Ke FANG ; Zhou LU
Chinese Medical Equipment Journal 2024;45(10):88-92
The current situation of medical simulation technology was introduced when applied in medical service of foreign armies.The current situation and problems of medical simulation technology in mobile medical service detachment training of the PLA were described.Some suggestions were put forward including completing medical simulation management system,optimizing personnel managment and training mode and promoting standardization and modular construction of medical simulation system.References were provided for enhancing combat-oriented training and medical service support capability of levels of medical service institutions and mobile medical service detachment of the PLA.[Chinese Medical Equipment Journal,2024,45(10):88-92]
7.Emerging role of Jumonji domain-containing protein D3 in inflammatory diseases
Li XIANG ; Chen RU-YI ; Shi JIN-JIN ; Li CHANG-YUN ; Liu YAN-JUN ; Gao CHANG ; Gao MING-RONG ; Zhang SHUN ; Lu JIAN-FEI ; Cao JIA-FENG ; Yang GUAN-JUN ; Chen JIONG
Journal of Pharmaceutical Analysis 2024;14(9):1282-1300
Jumonji domain-containing protein D3(JMJD3)is a 2-oxoglutarate-dependent dioxygenase that specif-ically removes transcriptional repression marks di-and tri-methylated groups from lysine 27 on histone 3(H3K27me2/3).The erasure of these marks leads to the activation of some associated genes,thereby influencing various biological processes,such as development,differentiation,and immune response.However,comprehensive descriptions regarding the relationship between JMJD3 and inflammation are lacking.Here,we provide a comprehensive overview of JMJD3,including its structure,functions,and involvement in inflammatory pathways.In addition,we summarize the evidence supporting JMJD3's role in several inflammatory diseases,as well as the potential therapeutic applications of JMJD3 inhibitors.Additionally,we also discuss the challenges and opportunities associated with investigating the functions of JMJD3 and developing targeted inhibitors and propose feasible solutions to provide valuable insights into the functional exploration and discovery of potential drugs targeting JMJD3 for inflammatory diseases.
8.Progress in impact of interaction between Treponema pallidum and ma-ternal-fetal interface cells on pregnancy outcomes
Shaobin HUANG ; Shun XIONG ; Zhaoping LIU ; Xiaohong ZHANG ; Feijun ZHAO
Chinese Journal of Pathophysiology 2024;40(2):351-357
Treponema pallidum(Tp),a common sexually transmitted pathogen,can infect the fetus via pla-cental vertical transmission,leading to congenital syphilis(CS).This infection results in adverse pregnancy outcomes,such as stillbirth,miscarriage,preterm birth,and fetal growth restriction.However,the exact pathogenesis remains un-clear.Studies indicate that patients with early syphilis primarily exhibit pro-inflammatory immune responses.The Tp has been proven to induce dysfunction in various immune cells and abnormal expression of cytokines,potentially disrupting im-mune tolerance homeostasis and leading to adverse pregnancy outcomes.Grounded in the current understanding of CS and maternal-fetal immunology by scholars both domestically and internationally,this paper provides a comprehensive review of the potential mechanisms of Tp interacting with the cells of the maternal-fetal interface,ultimately leading to adverse pregnancy outcomes.It summarizes the pathogenesis characteristics,clinical manifestations,and maternal-fetal immune responses of CS.
9.Bioequivalence study of buspirone hydrochloride tablets in Chinese healthy subjects
Ping LU ; Rui WANG ; Hui-Hui WU ; Hai-Yan LIU ; Ge-Fei HE ; Shun-Zhi ZHANG ; Wei WU
The Chinese Journal of Clinical Pharmacology 2024;40(5):723-727
Objective To study the pharmacokinetic characteristics of buspirone hydrochloride tablets in healthy adult populations under conditions of fasting and postprandial administration.Methods A single-center,randomized,three-cycle partially repeated crossover trial design was adopted,and 36 subjects were enrolled on fasting/postprandial,one tablet of the test preparation was taken in one cycle,one tablet of reference preparation(5 mg of buspirone tablets)was taken once in each of 2 cycles,the drug concentration of buspirone in plasma was determined by liquid chromatography-tandem mass spectrometry,and the pharmacokinetic parameters were calculated by WinNonlin software.Results Main pharmacokinetics of buspirone after oral administration of test and reference preparations in fasting group,the Cmax was(285.72±286.08)and(308.94±341.03)pg·mL-1;AUC0-t were(577.09±491.10)and(618.62±642.56)pg·mL-1·h;AUC0-∞ were(586.85±510.04)and(655.92±687.95)pg·mL-1·h;tmax was 0.75(0.33-4.00)and 0.75(0.33-1.75)h.Main pharmacokinetics of buspirone after oral administration of test and reference preparations in the postprandial group,the Cmax were(676.36±603.64)and(760.33±610.27)pg·mL-1;AUC0-t were(1 755.58±1 001.69)and(1 743.00±1 073.33)pg·h·mL-1;AUC0-∞ were(1 839.97±1 044.60)and(1 818.00±1 106.95)pg·mL-1·h;tmax was 1.25(0.25-4.50)and 1.00(0.25-3.50)h.The 90%confidence intervals of the AUC0-t and AUC0-∞ geometric mean ratios of the test preparation and the reference preparation in the fasting test and the postprandial test all fell between 80.00%and 125.00%,and the 95%upper confidence limit of of Cmax was ≤0 and geometric mean ratios point estimates fall between 80.00%and 125.00%.Conclusion Two kinds of buspirone hydrochloride are bioequivalent in Chinese healthy adult subject.
10.Knockout SQLE in melanoma cells potentiates anti-tumor immunity via improving CD8+T cell infiltration in tumor microenvironment
Yao DING ; Wen LIU ; Yiran LIAO ; Shun LEI ; Yan ZHANG ; Yezi CHEN ; Yi GONG ; Qizhao HUANG
Acta Universitatis Medicinalis Anhui 2024;59(8):1315-1322
Objective To investigate the role of squalene epoxidase(SQLE)knockout in anti-tumor effect vial im-proving CD8+T cell infiltration in melanoma tumor microenvironment.Methods Both immunodeficient and immu-nocompetent mice were inoculated with SQLE knockout B16F10 cells to determine the cell-autonomous and non-au-tonomous regulation of malignancy.Antibody blockade,Luminex multiplex assays,and flow cytometry were em-ployed to explore the impact of SQLE gene knockout on the secretion of cytokines/chemokines and immune cell in-filtration.Bioinformatics analysis was conducted to validate the correlation between SQLE expression and immune infiltration as well as clinical prognosis in melanoma patients.Results Compared with immunodeficient mice,SQLE knockout significantly inhibited melanoma proliferation in immunocompetent mice and prolonged their surviv-al.SQLE knockout induced the secretion of cytokines and chemokines from tumor cells,improved CD8+T cell in-filtration in the tumor microenvironment,thereby potentiating anti-tumor immunity.Bioinformatics analysis sugges-ted a significant correlation between SQLE and its corresponding immune infiltration markers with the prognosis of melanoma patients.Conclusion SQLE regulates anti-tumor immunity by controlling cytokines and chemokines re-leasing in tumor microenvironment,thus holding promise as a novel tumor immunotherapy target and efficacy predic-tion molecular indicator.


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