1.Mechanisms of Sini San in Regulation of Gut Microbiota Against Depression and Liver Injury in CUMS Rats
Junling LI ; Yan ZHANG ; Lei WANG ; Fang QI ; Zhenzhen CHEN ; Tianxing CHEN ; Yuhang LIU ; Xueying WANG ; Xianwen TANG ; Yubo LI
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):33-40
ObjectiveTo explore the efficacy and mechanisms of Sini San in the treatment of depression and liver injury based on gut microbiota. MethodsThirty-two male Sprague-Dawley (SD) rats were randomly divided into a normal group, model group (M), Sini San group (MS, 2.5 g·kg-1), and fluoxetine group (MF, 2 mg·kg-1). Except for the normal group, rats in the other three groups were subjected to chronic unpredictable mild stress (CUMS). After 8 weeks, the open-field test and sucrose preference test were conducted. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum corticosterone (CORT), adrenocorticotropic hormone (ACTH), corticotropin-releasing factor (CRF), lipopolysaccharide (LPS), Zonulin, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), γ-aminobutyric acid (GABA) levels in the hippocampus and prefrontal cortex, and brain-derived neurotrophic factor (BDNF) levels in the hippocampus. Real-time quantitative polymerase chain reaction (Real-time PCR) was used to detect hippocampal BDNF mRNA expression. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were measured using the ultraviolet lactate dehydrogenase method. The ultrastructure of the intestinal epithelium was observed by electron microscopy, and gut microbiota in rat feces were analyzed using 16S rDNA high-throughput sequencing. ResultsCompared with the normal group, the sucrose preference of rats in the model group was significantly reduced (P0.01), whereas it was significantly increased in the Sini San group compared with the model group (P0.05). Compared with the normal group, hippocampal GABA protein levels and BDNF mRNA expression in the model group were significantly decreased (P0.05), and compared with the model group, both were significantly increased in the Sini San group (P0.05, P0.01). Compared with the normal group, serum LPS and Zonulin levels in the model group were significantly increased (P0.05, P0.01), and compared with the model group, Zonulin levels in the Sini San group were significantly decreased (P0.05). No obvious changes were observed in the ultrastructure of the jejunal mucosa among groups. Compared with the normal group, widened and blurred tight junctions, sparse and shortened microvilli, and mitochondrial swelling with cristae disruption in epithelial cells were observed in the ileal and colonic mucosa of the model group, which were markedly improved in the Sini San and fluoxetine groups. The results of 16S rDNA high-throughput sequencing showed that Sini San improved CUMS-induced dysbiosis of Bacteroidetes and Proteobacteria. Correlation analysis indicated that Bacteroidetes and Proteobacteria were significantly correlated with depression-related indicators, liver function, and intestinal mucosal permeability. ConclusionSini San exerts antidepressant and hepatoprotective effects by improving Bacteroidetes and Proteobacteria and inhibiting the increase in intestinal mucosal permeability in CUMS rats.
2.Mechanisms of Sini San in Regulation of Gut Microbiota Against Depression and Liver Injury in CUMS Rats
Junling LI ; Yan ZHANG ; Lei WANG ; Fang QI ; Zhenzhen CHEN ; Tianxing CHEN ; Yuhang LIU ; Xueying WANG ; Xianwen TANG ; Yubo LI
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):33-40
ObjectiveTo explore the efficacy and mechanisms of Sini San in the treatment of depression and liver injury based on gut microbiota. MethodsThirty-two male Sprague-Dawley (SD) rats were randomly divided into a normal group, model group (M), Sini San group (MS, 2.5 g·kg-1), and fluoxetine group (MF, 2 mg·kg-1). Except for the normal group, rats in the other three groups were subjected to chronic unpredictable mild stress (CUMS). After 8 weeks, the open-field test and sucrose preference test were conducted. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum corticosterone (CORT), adrenocorticotropic hormone (ACTH), corticotropin-releasing factor (CRF), lipopolysaccharide (LPS), Zonulin, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), γ-aminobutyric acid (GABA) levels in the hippocampus and prefrontal cortex, and brain-derived neurotrophic factor (BDNF) levels in the hippocampus. Real-time quantitative polymerase chain reaction (Real-time PCR) was used to detect hippocampal BDNF mRNA expression. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were measured using the ultraviolet lactate dehydrogenase method. The ultrastructure of the intestinal epithelium was observed by electron microscopy, and gut microbiota in rat feces were analyzed using 16S rDNA high-throughput sequencing. ResultsCompared with the normal group, the sucrose preference of rats in the model group was significantly reduced (P<0.01), whereas it was significantly increased in the Sini San group compared with the model group (P<0.05). Compared with the normal group, hippocampal GABA protein levels and BDNF mRNA expression in the model group were significantly decreased (P<0.05), and compared with the model group, both were significantly increased in the Sini San group (P<0.05, P<0.01). Compared with the normal group, serum LPS and Zonulin levels in the model group were significantly increased (P<0.05, P<0.01), and compared with the model group, Zonulin levels in the Sini San group were significantly decreased (P<0.05). No obvious changes were observed in the ultrastructure of the jejunal mucosa among groups. Compared with the normal group, widened and blurred tight junctions, sparse and shortened microvilli, and mitochondrial swelling with cristae disruption in epithelial cells were observed in the ileal and colonic mucosa of the model group, which were markedly improved in the Sini San and fluoxetine groups. The results of 16S rDNA high-throughput sequencing showed that Sini San improved CUMS-induced dysbiosis of Bacteroidetes and Proteobacteria. Correlation analysis indicated that Bacteroidetes and Proteobacteria were significantly correlated with depression-related indicators, liver function, and intestinal mucosal permeability. ConclusionSini San exerts antidepressant and hepatoprotective effects by improving Bacteroidetes and Proteobacteria and inhibiting the increase in intestinal mucosal permeability in CUMS rats.
3.Caffeic acid-vanadium nanozymes treat skin flap ischemia-reperfusion injury through macrophage reprogramming and the upregulation of X-linked inhibitors of apoptotic proteins.
Xinyu ZHAO ; Jie SHAN ; Hanying QIAN ; Xu JIN ; Yiwei SUN ; Jianghao XING ; Qingrong LI ; Xu-Lin CHEN ; Xianwen WANG
Acta Pharmaceutica Sinica B 2025;15(1):592-610
Ischemia-reperfusion (I/R) injury following skin flap transplantation is a critical factor leading to flap necrosis and transplant failure. Antagonizing inflammatory responses and oxidative stress are regarded as crucial targets for mitigating reperfusion injury and enhancing flap survival. In this study, caffeic acid-vanadium metal polyphenol nanoparticles (CA-V NPs) were prepared for the treatment of skin flap ischemia and reperfusion. This study was conducted using a one-step method to prepare new types of CA-V NPs with uniform sizes and stable structures. In vitro, the CA-V NPs exhibited CAT-like and SOD-like activities and could effectively scavenge ROS, generate oxygen, and alleviate oxidative stress. In the H2O2-induced cellular oxidative stress model, CA-V NPs effectively reduced ROS levels and inhibited apoptosis through the XIAP/Caspase-3 pathway. In the cellular inflammation model induced by LPS combined with IFN-γ, CA-V NPs reprogrammed macrophage polarization toward the M2 phenotype and reduced inflammatory responses by reducing the expression of the chemokines CCL4 and CXCL2. In addition, animal experiments have shown that CA-V NPs can alleviate oxidative stress in skin flap tissues, inhibit apoptosis, promote angiogenesis, and ultimately improve the survival rate of skin flaps. CA-V NPs provide a new target and strategy for the treatment of flap I/R injury.
4.Identification of Dalbergia odorifera and Its Counterfeits by HS-GC-MS
Li ZHAO ; Xiaowei MENG ; Jiarong LI ; Qing ZHU ; Xianwen WEI ; Ronghua LIU ; Lanying CHEN
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(2):156-163
ObjectiveTo screen the differential markers by analyzing volatile components in Dalbergia odorifera and its counterfeits, in order to provide reference for authentication of D. odorifera. MethodThe volatile components in D. odorifera and its counterfeits were detected by headspace gas chromatography-mass spectrometry(HS-GC-MS), and the GC conditions were heated by procedure(the initial temperature of the column was 50 ℃, the retention time was 1 min, and then the temperature was raised to 300 ℃ at 10 ℃ for 10 min), the carrier gas was helium, and the flow rate was 1.0 mL·min-1, the split ratio was 10∶1, and the injection volume was 1 mL. The MS conditions used electron bombardment ionization(EI) with the scanning range of m/z 35-550. The compound species were identified by database matching, the relative content of each component was calculated by the peak area normalization method, and principal component analysis(PCA), orthogonal partial least squares-discrimination analysis(OPLS-DA) and cluster analysis were performed on the detection results by SIMCA 14.1 software, and the differential components of D. odorifera and its counterfeits were screened out according to the variable importance in the projection(VIP) value>2 and P<0.05. ResultA total of 26, 17, 8, 22, 24 and 7 volatile components were identified from D. odorifera, D. bariensis, D. latifolia, D. benthamii, D. pinnata and D. cochinchinensis, respectively. Among them, there were 11 unique volatile components of D. odorifera, 6 unique volatile components of D. bariensis, 3 unique volatile components of D. latifolia, 6 unique volatile components of D. benthamii, 8 unique volatile components of D. pinnata, 4 unique volatile components of D. cochinchinensis. The PCA results showed that, except for D. latifolia and D. cochinchinensis, which could not be clearly distinguished, D. odorifera and other counterfeits could be distributed in a certain area, respectively. The OPLS-DA results showed that D. odorifera and its five counterfeits were clustered into one group each, indicating significant differences in volatile components between D. odorifera and its counterfeits. Finally, a total of 31 differential markers of volatile components between D. odoriferae and its counterfeits were screened. ConclusionHS-GC-MS combined with SIMCA 14.1 software can systematically elucidate the volatile differential components between D. odorifera and its counterfeits, which is suitable for rapid identification of them.
5.Identification of Dalbergiae Odoriferae Lignum and Its Counterfeits by 1H-NMR Combined with Multivariate Statistical Analysis
Xianwen WEI ; Lanying CHEN ; Xiaowei MENG ; Qing ZHU ; Honghua YU ; Qiwan ZHENG ; Jiahui REN ; Lihua LIN ; Ronghua LIU
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(13):173-179
ObjectiveTo establish the identification method of Dalbergiae Odoriferae Lignum(DOL) and its counterfeits by nuclear magnetic resonance hydrogen spectrum(1H-NMR) combined with multivariate statistical analysis. Method1H-NMR spectra of DOL and its counterfeits were obtained by NMR, and the full composition information was established and transformed into a data matrix, and the detection conditions were as follows:taking dimethyl sulfoxide-d6(DMSO-d6) containing 0.03% tetramethylsilane(TMS) as the solvent, the constant temperature at 298 K(1 K=-272.15 ℃), pulse interval of 1.00 s, spectrum width of 12 019.23 Hz, the scanning number of 16 times, and the sampling time of 1.08 s. Similarity examination and hierarchical cluster analysis(HCA) were performed on the data matrix of DOL and its counterfeits, and orthogonal partial least squares-discriminant analysis(OPLS-DA) was used to analyze the data matrix and identify the differential components between them. In the established OPLS-DA category variable value model, the category variable value of DOL was set as 1, and the category variable value of the counterfeits was set as 0, and the threshold was set as ±0.3, in order to identify the commercially available DOL. The OPLS-DA score plot was used to determine the types of counterfeits in commercially available DOL, and it was verified by thin layer chromatography(TLC). ResultThe results of similarity analysis and HCA showed that there was a significant difference between DOL and its counterfeits. OPLS-DA found that the differential component between DOL and its counterfeits was trans-nerolidol. The established category variable value model could successfully identify the authenticity of the commercially available DOL. The results of the OPLS-DA score plot showed that there were heartwood of Dalbergia pinnata and D. cochinchinensis in the commercially available DOL, and were consistent with the TLC verification results. ConclusionThere is a phenomenon that heartwood of D. pinnata and D. cochinchinensis are sold as DOL in the market. 1H-NMR combined with multivariate statistical analysis can effectively distinguish DOL and its counterfeits, which can provide a reference for the identification of them.
6.Assessment of conventional magnetic resonance morphological measurements in diagnosis and differential diagnosis of progressive supranuclear paralysis
Tieyu WU ; Chuan LI ; Yue JIAO ; Juan LI ; Tong WU ; Shangpei WANG ; Xianwen CHEN
Chinese Journal of Geriatrics 2023;42(2):188-195
Objective:To study the features as well as the diagnosis and differential diagnosis values by conventional MRI morphometrics in different clinical subtypes of progressive supranuclear palsy(PSP).Methods:Forty five patients with PSP were included, comprising three PSP subtypes: 15 cases of Richardson's syndrome(PSP-RS), 15 cases of Parkinson's syndrome(PSP-P)and 15 cases of progressive frozen gait(PSP-PFG). In addition, three control groups were established: 15 cases of multiple system atrophy-Parkinson's syndrome(MSA-P), 30 cases of primary Parkinson's disease(PD)and 40 healthy controls(HC). Midbrain area-to-Pons area ratio(M/P), Magnetic Resonance Parkinsonism Index(MRPI, MRPI2.0), width ratio of middle cerebellar peduncle to superior cerebellar peduncle(MCP/SCP), Midbrain-to-Pons ratio(MTPR), Angle of cerebral peduncle(A cp), third ventricle width/frontal horns width ratio(V 3rd/FH), and Humming bird sign rating scale(HBS-RS)scores were calculated.Diagnostic sensitivity and specificity were performed by ROC curve to assess the accuracy of these imaging indicators in the diagnosis and differential diagnosis of PSP and its subtypes. Results:The MRPI, MRPI2.0, MCP/SCP and HBS-RS scores were significantly higher in PSP group than in other control groups( H=69.351, 66.776, 33.926 and 84.694, all P<0.05), while M/P and MTPR were significantly lower in PSP group than in other control groups(H=60.101 and 77.276, all P<0.05). PSP group also had higher V 3rd/FH compared with PD or HC group( F=17.168, P<0.05), but not with MSA-P group( Z=-1.602, P>0.05). The above differences also existed between each PSP subgroup and control groups.Among PSP subgroups, PSP-PFG subgroup had a larger A cp than did PSP-RS( Z=-2.510, P<0.05), and had higher HBS-RS score than did PSP-P group( Z=-2.380, P<0.05). No significant differences in other MRI morphometric indexes were identified among PSP subtypes.The M/P, MRPI, MTPR, MRPI2.0, HBS-RS score showed good accuracy in diagnosing PSP and its each subgroup, with HBS-RS score being the most accurate indicator, when the cutoff value was 2, the AUC values were all higher than 0.99, and the sensitivity and specificity were all above 90%.PSP and its subtypes were best distinguished from MSA-P by MRPI, when the cutoff value was 9.94, the AUC values were all higher than 0.90, with the sensitivity of 100% and specificity of 86.67%.PSP and its subtypes were best distinguished from PD by MTPR, AUC values were all above 0.95, with slightly different cutoff values.Almost all the morphological measurement parameters failed to show significant sensitivity and specificity in discriminating subtypes of PSP.The sensitivity and specificity of almost all MRI morphometry indicators in differentiating different subtypes of PSP are not high. Conclusions:MRI morphometrics have a high value both in the diagnosis of PSP and its subtypes, and also in specific application fields.MRI morphometrics have a limited value in discriminating PSP subtypes.
7.Analysis of 5 ischemic stroke patients caused by pulmonary arteriovenous fistula
Lulu ZHENG ; Xianwen WANG ; Xu ZHONG ; Tingting WU ; Xiaobin CHEN
Chinese Journal of Neurology 2023;56(6):661-665
Objective:To investigate the correlation between pulmonary arteriovenous fistula (PAVF) and ischemic stroke, and to improve the diagnosis and treatment of embolic strokes of undetermined source.Methods:Five patients with ischemic stroke caused by PAVF admitted to Xiangya Hospital of Central South University from January 2017 to December 2020 were collected. The diagnosis, treatment and prognosis of stroke caused by PAVF were summarized based on literature review.Results:Among the 5 patients, 1 is male and 4 are females, with age of (34.4±9.3) years. Weakness of unilateral limb, slurred speech, vision changes, drooping eyelids, etc., were the first manifestations of stroke. The location of cerebral infarction was indefinite. In this study, 5 patients were all isolated PAVF, including 3 cases of left lower lung, 1 case of left upper lung and 1 case of right lower lung. All 5 patients underwent interventional therapy, were followed-up for 6 months and 12 months after surgery, and none of them had a new stroke attack, and only 1 case had recanalization of PAVF.Conclusions:PAVF is a rare vascular lesion, stroke caused by which is even rarer, with a lack of specificity in clinical manifestations. For young patients with unexplained embolic stroke, if the stroke has a sudden onset, the anterior and posterior circulation can be involved, and multiple vascular distribution regions are often involved, and it is difficult to find a clear emboli basis, with manifestations such as hypoxemia, PAVF should be considered. Percutaneous catheter intervention for PAVF is safe and effective, and is the preferred method for the treatment of PAVF.
8.The interaction between polyphyllin I and SQLE protein induces hepatotoxicity through SREBP-2/HMGCR/SQLE/LSS pathway
Zhiqi LI ; Qiqi FAN ; Meilin CHEN ; Ying DONG ; Farong LI ; Mingshuang WANG ; Yulin GU ; Simin GUO ; Xianwen YE ; Jiarui WU ; Shengyun DAI ; Ruichao LIN ; Chongjun ZHAO
Journal of Pharmaceutical Analysis 2023;13(1):39-54
Polyphyllin Ⅰ(PPⅠ)and polyphyllin Ⅱ(PⅡ)are the main active substances in the Paris polyphylla.However,liver toxicity of these compounds has impeded their clinical application and the potential hepatotoxicity mechanisms remain to be elucidated.In this work,we found that PPⅠ and PⅡ exposure could induce significant hepatotoxicity in human liver cell line L-02 and zebrafish in a dose-dependent manner.The results of the proteomic analysis in L-02 cells and transcriptome in zebrafish indicated that the hepa-totoxicity of PPⅡ and PⅡwas associated with the cholesterol biosynthetic pathway disorders,which were alleviated by the cholesterol biosynthesis inhibitor lovastatin.Additionally,3-hydroxy-3-methy-lglutaryl CoA reductase(HMGCR)and squalene epoxidase(SQLE),the two rate-limiting enzymes in the choles-terol synthesis,selected as the potential targets,were confirmed by the molecular docking,the over-expression,and knockdown of HMGCR or SQLE with siRNA.Finally,the pull-down and surface plasmon resonance technology revealed that PPⅠ could directly bind with SQLE but not with HMGCR.Collectively,these data demonstrated that PPⅠ-induced hepatotoxicity resulted from the direct binding with SQLE protein and impaired the sterol-regulatory element binding protein 2/HMGCR/SQLE/lanosterol synthase pathways,thus disturbing the cholesterol biosynthesis pathway.The findings of this research can contribute to a better understanding of the key role of SQLE as a potential target in drug-induced hepatotoxicity and provide a therapeutic strategy for the prevention of drug toxic effects with similar structures in the future.
9.Efficacy of ultrasound-guided closed reduction in the treatment of supracondylar fractures of the humerus in children
Xianwen MA ; Dijia CHEN ; Ben MA
Chinese Journal of Primary Medicine and Pharmacy 2023;30(8):1194-1198
Objective:To investigate the clinical efficacy of ultrasound-guided closed reduction and percutaneous Kirschner wire fixation in the treatment of supracondylar fractures of the humerus in children.Methods:The clinical data of 78 children with Gartland type II and type III straight-type supracondylar fractures of the humerus who received treatment in The First Affiliated Hospital of Anhui Medical University from October 2019 to October 2022 were retrospectively analyzed. These children were divided into an observation group ( n = 38) and a control group ( n = 40) according to different treatment methods. The observation group was subjected to ultrasound-guided closed reduction and percutaneous Kirschner wire fixation. The control group was given C-arm fluoroscopy-guided closed reduction and percutaneous Kirschner wire fixation. Mayo elbow performance score (MEPS), clinical healing time, operative time, and the incidence of intraoperative complications such as vascular and nerve injury were compared between the two groups. Results:Both groups of children achieved closed reduction without open reduction. The operative time in the observation group was (30.68 ± 5.45) minutes, which was significantly shorter than (40.54 ± 5.78) minutes in the control group ( t = 2.30, P < 0.05). The healing time of the fracture in the observation and control groups was (32.73 ± 4.56) days and (36.47 ± 6.24) days, respectively, and there was no significant difference between the two groups ( P > 0.05). The range of joint motion and elbow hyperextension angle range in the observation group were (148.78 ± 3.81)° and (8.72 ± 8.92)°, respectively, and they were (147.24 ± 4.36)° and (7.98 ± 8.86)°, respectively in the control group. There were no significant differences in the range of joint motion and elbow hyperextension angle range between the two groups (both P > 0.05). The excellent and good rate of joint function in the control and observation groups was 92.5% (37/40) and 92.1% (35/38), respectively. There was no significant difference in excellent and good rate of joint function between the two groups ( P > 0.05). There were three cases of postoperative nerve damage in the control group and no vascular or nerve damage was observed in the observation group. There were significant differences in the number of cases of vascular or nerve injury between the two groups ( χ2 = 3.97, both P < 0.05). Conclusion:Ultrasound-guided closed reduction and percutaneous Kirschner wire fixation for the treatment of supracondylar fractures of the humerus can shorten the operative time, decrease the incidence of intraoperative nerve injury, and reduce the X-ray exposure time of doctors and patients.
10.Validity and reliability of the Chinese version of children’s trust in general nurses scale
Qingqing CHONG ; Dan CHEN ; Zhiheng ZHAN ; Jing CHEN ; Enfang SHAN ; Xianwen LI
Chinese Journal of Behavioral Medicine and Brain Science 2023;32(11):1032-1037
Objective:To translate the Children's trust in general nurses scale (CTGNS) into Chinese, and conduct item response theory (IRT) analysis and reliability and validity evaluation.Methods:Following Brislin's translation model, the CTGNS was translated, back-translated, and cross-culturally adapted to form the Chinese version of the CTGNS.A total of 502 pediatric inpatients from a pediatric hospital in Nanjing city were surveyed from July to August 2022.The Samejima graded response model in IRT was used to calculate the difficulty and discrimination parameters of each item, while item characteristic curves were plotted.The reliability and validity of the Chinese version CTGNS were evaluated.SPSS 26.0, Mplus 8.0 and MULTILOG 7.03 softwares were used for data analysis.Results:The item discrimination of the Chinese version CTGNS ranged from 0.088 to 2.730.The difficulty parameters ranged from -4.667 to 26.094 and increased with increasing difficulty levels without any reverse thresholds.The item characteristic curves exhibited sound shapes for all items except for item 9.Based on the selection criteria of the corresponding parameters, 8 items were retained.The revised Chinese version CTGNS (8 items) consisted of 3 dimensions.The content validity index (CVI) of each item ranged from 0.833 to 1.000, and the total scale CVI was 0.960.The Cronbach's α coefficient for the overall scale was 0.822, and the Cronbach's α coefficients for each dimension ranged from 0.752 to 0.852.The test-retest reliability of the scale was 0.87.Exploratory factor analysis yielded 3 common factors with a cumulative variance contribution rate of 73.468%.Confirmatory factor analysis indicated a good model fit( χ2/ df=2.674, RMSEA=0.082, SRMR=0.046, CFI=0.964). Conclusion:The revised Chinese version CTGNS demonstrates sound reliability and validity and can be used as an assessment tool for measuring children's trust in nurses.

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