1.Junctophilin-2 MORN-Helix Domain: Structural Basis for Membrane Binding and Hypertrophic Cardiomyopathy-associated Mutations
Jing-Xin WANG ; Zhi-Wei LI ; Wei LIU ; Wen-Qing ZHANG ; Jian-Chao LI
Progress in Biochemistry and Biophysics 2025;52(8):2103-2116
ObjectiveJunctophilin-2 (JPH2) is an essential structural protein that maintains junctional membrane complexes (JMCs) in cardiomyocytes by tethering the plasma membrane to the sarcoplasmic reticulum, thereby facilitating excitation-contraction (E-C) coupling. Mutations in JPH2 have been associated with hypertrophic cardiomyopathy (HCM), but the molecular mechanisms governing its membrane-binding properties and the functional relevance of its membrane occupation and recognition nexus (MORN) repeat motifs remain incompletely understood. This study aimed to elucidate the structural basis of JPH2 membrane association and its implications for HCM pathogenesis. MethodsA recombinant N-terminal fragment of mouse JPH2 (residues1-440), encompassing the MORN repeats and an adjacent helical region, was purified under near-physiological buffer conditions.X-ray crystallography was employed to determine the structure of the JPH2 MORN-Helix domain. Sequence conservation analysis across species and junctophilin isoforms was performed to assess the evolutionary conservation of key structural features. Functional membrane-binding assays were conducted using liposome co-sedimentation and cell-based localization studies in COS7 and HeLa cells. In addition, site-directed mutagenesis targeting positively charged residues and known HCM-associated mutations, including R347C, was used to evaluate their effects on membrane interaction and subcellular localization. ResultsThe crystal structure of the mouse JPH2 MORN-Helix domain was resolved at 2.6 Å, revealing a compact, elongated architecture consisting of multiple tandem MORN motifs arranged in a curved configuration, forming a continuous hydrophobic core stabilized by alternating aromatic residues. A C-terminal α-helix further reinforced structural integrity. Conservation analysis identified the inner groove of the MORN array as a highly conserved surface, suggesting its role as a protein-binding interface. A flexible linker segment enriched in positively charged residues, located adjacent to the MORN motifs, was found to mediate direct electrostatic interactions with negatively charged phospholipid membranes. Functional assays demonstrated that mutation of these basic residues impaired membrane association, while the HCM-linked R347C mutation completely abolished membrane localization in cellular assays, despite preserving the overall MORN-Helix fold in structural modeling. ConclusionThis study provides structural insight into the membrane-binding mechanism of the cardiomyocyte-specific protein JPH2, highlighting the dual roles of its MORN-Helix domain in membrane anchoring and protein interactions. The findings clarify the structural basis for membrane targeting via a positively charged linker and demonstrate that disruption of this interaction—such as that caused by the R347C mutation—likely contributes to HCM pathogenesis. These results not only enhance current understanding of JPH2 function in cardiac E-C coupling but also offer a structural framework for future investigations into the assembly and regulation of JMCs in both physiological and disease contexts.
2.Programmed death-ligand 1 tumor proportion score in predicting the safety and efficacy of PD-1/PD-L1 antibody-based therapy in patients with advanced non-small cell lung cancer: A retrospective, multicenter, observational study.
Yuequan SHI ; Xiaoyan LIU ; Anwen LIU ; Jian FANG ; Qingwei MENG ; Cuimin DING ; Bin AI ; Yangchun GU ; Cuiying ZHANG ; Chengzhi ZHOU ; Yan WANG ; Yongjie SHUI ; Siyuan YU ; Dongming ZHANG ; Jia LIU ; Haoran ZHANG ; Qing ZHOU ; Xiaoxing GAO ; Minjiang CHEN ; Jing ZHAO ; Wei ZHONG ; Yan XU ; Mengzhao WANG
Chinese Medical Journal 2025;138(14):1730-1740
BACKGROUND:
This study aimed to investigate programmed death-ligand 1 tumor proportion score in predicting the safety and efficacy of PD-1/PD-L1 antibody-based therapy in treating patients with advanced non-small cell lung cancer (NSCLC) in a real-world setting.
METHODS:
This retrospective, multicenter, observational study enrolled adult patients who received PD-1/PD-L1 antibody-based therapy in China and met the following criteria: (1) had pathologically confirmed, unresectable stage III-IV NSCLC; (2) had a baseline PD-L1 tumor proportion score (TPS); and (3) had confirmed efficacy evaluation results after PD-1/PD-L1 treatment. Logistic regression, Kaplan-Meier analysis, and Cox regression were used to assess the progression-free survival (PFS), overall survival (OS), and immune-related adverse events (irAEs) as appropriate.
RESULTS:
A total of 409 patients, 65.0% ( n = 266) with a positive PD-L1 TPS (≥1%) and 32.8% ( n = 134) with PD-L1 TPS ≥50%, were included in this study. Cox regression confirmed that patients with a PD-L1 TPS ≥1% had significantly improved PFS (hazard ratio [HR] 0.747, 95% confidence interval [CI] 0.573-0.975, P = 0.032). A total of 160 (39.1%) patients experienced 206 irAEs, and 27 (6.6%) patients experienced 31 grade 3-5 irAEs. The organs most frequently associated with irAEs were the skin (52/409, 12.7%), thyroid (40/409, 9.8%), and lung (34/409, 8.3%). Multivariate logistic regression revealed that a PD-L1 TPS ≥1% (odds ratio [OR] 1.713, 95% CI 1.054-2.784, P = 0.030) was an independent risk factor for irAEs. Other risk factors for irAEs included pretreatment absolute lymphocyte count >2.5 × 10 9 /L (OR 3.772, 95% CI 1.377-10.329, P = 0.010) and pretreatment absolute eosinophil count >0.2 × 10 9 /L (OR 2.006, 95% CI 1.219-3.302, P = 0.006). Moreover, patients who developed irAEs demonstrated improved PFS (13.7 months vs. 8.4 months, P <0.001) and OS (28.0 months vs. 18.0 months, P = 0.007) compared with patients without irAEs.
CONCLUSIONS
A positive PD-L1 TPS (≥1%) was associated with improved PFS and an increased risk of irAEs in a real-world setting. The onset of irAEs was associated with improved PFS and OS in patients with advanced NSCLC receiving PD-1/PD-L1-based therapy.
Humans
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Carcinoma, Non-Small-Cell Lung/metabolism*
;
Male
;
Female
;
Retrospective Studies
;
Middle Aged
;
Lung Neoplasms/metabolism*
;
Aged
;
B7-H1 Antigen/metabolism*
;
Programmed Cell Death 1 Receptor/metabolism*
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Adult
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Aged, 80 and over
;
Immune Checkpoint Inhibitors/therapeutic use*
3.Expert Consensus on Clinical Application of Qinbaohong Zhike Oral Liquid in Treatment of Acute Bronchitis and Acute Attack of Chronic Bronchitis
Jian LIU ; Hongchun ZHANG ; Chengxiang WANG ; Hongsheng CUI ; Xia CUI ; Shunan ZHANG ; Daowen YANG ; Cuiling FENG ; Yubo GUO ; Zengtao SUN ; Huiyong ZHANG ; Guangxi LI ; Qing MIAO ; Sumei WANG ; Liqing SHI ; Hongjun YANG ; Ting LIU ; Fangbo ZHANG ; Sheng CHEN ; Wei CHEN ; Hai WANG ; Lin LIN ; Nini QU ; Lei WU ; Dengshan WU ; Yafeng LIU ; Wenyan ZHANG ; Yueying ZHANG ; Yongfen FAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(4):182-188
The Expert Consensus on Clinical Application of Qinbaohong Zhike Oral Liquid in Treatment of Acute Bronchitis and Acute Attack of Chronic Bronchitis (GS/CACM 337-2023) was released by the China Association of Chinese Medicine on December 13th, 2023. This expert consensus was developed by experts in methodology, pharmacy, and Chinese medicine in strict accordance with the development requirements of the China Association of Chinese Medicine (CACM) and based on the latest medical evidence and the clinical medication experience of well-known experts in the fields of respiratory medicine (pulmonary diseases) and pediatrics. This expert consensus defines the application of Qinbaohong Zhike oral liquid in the treatment of cough and excessive sputum caused by phlegm-heat obstructing lung, acute bronchitis, and acute attack of chronic bronchitis from the aspects of applicable populations, efficacy evaluation, usage, dosage, drug combination, and safety. It is expected to guide the rational drug use in medical and health institutions, give full play to the unique value of Qinbaohong Zhike oral liquid, and vigorously promote the inheritance and innovation of Chinese patent medicines.
4.Characteristic Expression of Multiple Neurotransmitters Oscillation Imbabance in Brains of 1 028 Patients with Depression
Anqi WANG ; Xuemei QING ; Yanshu PAN ; Pingfa ZHANG ; Ying ZHANG ; Jian LI ; Cheng ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):278-286
ObjectiveTo analyze the characteristic expression patterns of six neurotransmitters including 5-hydroxytryptamine (5-HT), dopamine (DA), acetylcholine (ACh), norepinephrine (NE), inhibitory neurotransmitter (INH), and excitatory neurotransmitter (EXC) in the whole brain and different brain regions of depression patients by Search of Encephalo Telex (SET), providing new ideas for the study of heterogeneous etiology of depression. Methods(1) A retrospective study was conducted on supra-slow signals of EEG fluctuations in 1 028 patients with depression. The SET system was used to obtain the expression information of six neurotransmitters in the whole brain and 12 brain regions: left frontal region (F3), right frontal region (F4), left central region (C3), right central region (C4), left parietal region (P3), right parietal region (P4), left occipital region (O1), right occipital region (O2), left anterior temporal region (F7), right anterior temporal region (F8), left posterior temporal region (T5), and right posterior temporal region (T6). The expression information of each neurotransmitter was compared with the normal model, and it was found that single neurotransmitter was in one of three states: increased, decreased, or normal expression. The simultaneous expression states of six neurotransmitters in the brain space were referred to as the expression pattern of multiple neurotransmitters. (2) A MySQL database was established to analyze the actual expression patterns of different neurotransmitters in the whole brain of patients with depression. (3) Factor analysis was conducted to further analyze the characteristic rules of 78 variables of neurotransmitters in the whole brain and 12 brain regions in depression patients. Results(1) The expression of single neurotransmitters in the whole brain and different brain regions of the total depression population showed one of three expression states (increased/decreased/normal), being normal in the majority. The decreased and increased expression of 5-HT, ACh, DA, INH, EXC, and NE in the whole brain occurred in 6% and 25%, 31% and 17%, 36% and 9%, 15% and 31%, 32% and 14%, and 22% and 22%, respectively. (2) The antagonizing pairs of neurotransmitters (EXC/INH, DA/5-HT, and ACh/NE) showed significant antagonistic relationships in the whole brain and different brain regions, with a strong negative correlation between EXC and INH (P<0.01, |r| values ranging from 0.69 to 0.76), a strong negative correlation between DA and 5-HT (P<0.01, |r| values ranging from 0.83 to 0.90), and a moderate negative correlation between ACh and NE (P<0.01, with |r| values ranging from 0.56 to 0.66). Meanwhile, non-antagonizing pairs of neurotransmitters in the whole brain and different brain regions also showed correlations, with DA/NE (P<0.01, |r| values ranging from 0.38 to 0.46) and NE/EXC (P<0.01, |r| values ranging from 0.56 to 0.61) showing weak and moderate negative correlations, respectively, and DA/EXC showing a weak positive correlation (P<0.01, |r| values ranging from 0.38 to 0.47). (3) The six neurotransmitters in the 1 028 patients with depression presented a total of 170 expression patterns in the whole brain. The top 30 expression patterns were reported in this paper, with a cumulative rate of 60.60%, including patterns ① INH+/5-HT-/ACh+/DA+/NE-/EXC- (9.05%), ② INH+/5-HT-/ACh↓/DA+/NE-/EXC- (4.57%), and ③ INH+/5-HT-/ACh+/DA+/NE↓/EXC- (3.31%). That is, the proportion of depression patients with normal levels of all the six neurotransmitters was 9.05%, and the patients with at least one neurotransmitter abnormality accounted for 91.95%. (4) The factor analysis extracted 22 common factors from 78 variables in the whole brain and different brain regions. These common factors showed the absolute values of loadings ranging from 0.32 to 0.86 and the eigenvalues (F) ranging from 1.03 to 13.43, with a cumulative contribution rate of 76.82%. The characteristic expression patterns included ① AChP3↓/AChW↓/AChC3↓/AChF3↓/AChO1↓/AChT5↓/AChF7↓/NEP3↑/NEW↑/NEC3↑/NEF3↑/NEO1↑/NET5↑/NEF7↑ (F=13.43, whole brain), ② 5-HTO2↑/DAO2↓/5-HTP4↑/DAP4↓/5-HTW↑/DAW↓/5-HTC4↑/DAC4↓ (F=5.94), and ③ EXCF4↓/DAF4↓/NEF4↑/INHF4↑/5-HTF4↑/AChF4↓ (F=5.33). ConclusionThe actual 170 expression patterns of 6 neurotransmitters in the whole brain of 1 028 depression patients indicate that depression is a heterogeneous disease with individualized characteristics. The 22 characteristic expression patterns in the whole brain and 12 brain regions verify the pathogenesis hypothesis of multi-neurotransmitters oscillation imbalance in brains of depression patients. In summary, this study provides new guidance for the etiology, diagnosis, and treatment of depression and establishes a methodological foundation for the effectiveness evaluation of individualized treatment of depression by traditional Chinese medicine based on the objective biological markers.
5.Characteristic Expression of Multiple Neurotransmitters Oscillation Imbabance in Brains of 1 028 Patients with Depression
Anqi WANG ; Xuemei QING ; Yanshu PAN ; Pingfa ZHANG ; Ying ZHANG ; Jian LI ; Cheng ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):278-286
ObjectiveTo analyze the characteristic expression patterns of six neurotransmitters including 5-hydroxytryptamine (5-HT), dopamine (DA), acetylcholine (ACh), norepinephrine (NE), inhibitory neurotransmitter (INH), and excitatory neurotransmitter (EXC) in the whole brain and different brain regions of depression patients by Search of Encephalo Telex (SET), providing new ideas for the study of heterogeneous etiology of depression. Methods(1) A retrospective study was conducted on supra-slow signals of EEG fluctuations in 1 028 patients with depression. The SET system was used to obtain the expression information of six neurotransmitters in the whole brain and 12 brain regions: left frontal region (F3), right frontal region (F4), left central region (C3), right central region (C4), left parietal region (P3), right parietal region (P4), left occipital region (O1), right occipital region (O2), left anterior temporal region (F7), right anterior temporal region (F8), left posterior temporal region (T5), and right posterior temporal region (T6). The expression information of each neurotransmitter was compared with the normal model, and it was found that single neurotransmitter was in one of three states: increased, decreased, or normal expression. The simultaneous expression states of six neurotransmitters in the brain space were referred to as the expression pattern of multiple neurotransmitters. (2) A MySQL database was established to analyze the actual expression patterns of different neurotransmitters in the whole brain of patients with depression. (3) Factor analysis was conducted to further analyze the characteristic rules of 78 variables of neurotransmitters in the whole brain and 12 brain regions in depression patients. Results(1) The expression of single neurotransmitters in the whole brain and different brain regions of the total depression population showed one of three expression states (increased/decreased/normal), being normal in the majority. The decreased and increased expression of 5-HT, ACh, DA, INH, EXC, and NE in the whole brain occurred in 6% and 25%, 31% and 17%, 36% and 9%, 15% and 31%, 32% and 14%, and 22% and 22%, respectively. (2) The antagonizing pairs of neurotransmitters (EXC/INH, DA/5-HT, and ACh/NE) showed significant antagonistic relationships in the whole brain and different brain regions, with a strong negative correlation between EXC and INH (P<0.01, |r| values ranging from 0.69 to 0.76), a strong negative correlation between DA and 5-HT (P<0.01, |r| values ranging from 0.83 to 0.90), and a moderate negative correlation between ACh and NE (P<0.01, with |r| values ranging from 0.56 to 0.66). Meanwhile, non-antagonizing pairs of neurotransmitters in the whole brain and different brain regions also showed correlations, with DA/NE (P<0.01, |r| values ranging from 0.38 to 0.46) and NE/EXC (P<0.01, |r| values ranging from 0.56 to 0.61) showing weak and moderate negative correlations, respectively, and DA/EXC showing a weak positive correlation (P<0.01, |r| values ranging from 0.38 to 0.47). (3) The six neurotransmitters in the 1 028 patients with depression presented a total of 170 expression patterns in the whole brain. The top 30 expression patterns were reported in this paper, with a cumulative rate of 60.60%, including patterns ① INH+/5-HT-/ACh+/DA+/NE-/EXC- (9.05%), ② INH+/5-HT-/ACh↓/DA+/NE-/EXC- (4.57%), and ③ INH+/5-HT-/ACh+/DA+/NE↓/EXC- (3.31%). That is, the proportion of depression patients with normal levels of all the six neurotransmitters was 9.05%, and the patients with at least one neurotransmitter abnormality accounted for 91.95%. (4) The factor analysis extracted 22 common factors from 78 variables in the whole brain and different brain regions. These common factors showed the absolute values of loadings ranging from 0.32 to 0.86 and the eigenvalues (F) ranging from 1.03 to 13.43, with a cumulative contribution rate of 76.82%. The characteristic expression patterns included ① AChP3↓/AChW↓/AChC3↓/AChF3↓/AChO1↓/AChT5↓/AChF7↓/NEP3↑/NEW↑/NEC3↑/NEF3↑/NEO1↑/NET5↑/NEF7↑ (F=13.43, whole brain), ② 5-HTO2↑/DAO2↓/5-HTP4↑/DAP4↓/5-HTW↑/DAW↓/5-HTC4↑/DAC4↓ (F=5.94), and ③ EXCF4↓/DAF4↓/NEF4↑/INHF4↑/5-HTF4↑/AChF4↓ (F=5.33). ConclusionThe actual 170 expression patterns of 6 neurotransmitters in the whole brain of 1 028 depression patients indicate that depression is a heterogeneous disease with individualized characteristics. The 22 characteristic expression patterns in the whole brain and 12 brain regions verify the pathogenesis hypothesis of multi-neurotransmitters oscillation imbalance in brains of depression patients. In summary, this study provides new guidance for the etiology, diagnosis, and treatment of depression and establishes a methodological foundation for the effectiveness evaluation of individualized treatment of depression by traditional Chinese medicine based on the objective biological markers.
6.Comparison of posterior C2-3 fixation combined with bucking bar technique and posterior C2-3 fixation alone in treatment of unstable Hangman fractures
Hao ZHANG ; Qing WANG ; Jian ZHANG ; Guangzhou LI ; Gaoju WANG
Chinese Journal of Tissue Engineering Research 2025;29(9):1848-1854
BACKGROUND:Types II,IIA,and III of Hangman fractures often require surgical treatment,and the selection of surgical methods is controversial.Current surgeries have shortcomings such as incomplete reduction and malunion after surgery.In the early stage,our team used C2-3 lag screws combined with a bucking bar.Intermittent pushing of the C2 vertebral body in the oropharynx has achieved satisfactory clinical results.However,the preliminary studies included few samples and lacked a control group for comparison. OBJECTIVE:To compare the clinical efficacy of posterior C2-3 fixation combined with the bucking bar technique and posterior C2-3 fixation alone in the treatment of unstable Hangman fractures. METHODS:The clinical and imaging data of 55 patients with unstable Hangman fractures who underwent posterior C2-3 internal fixation in Affiliated Hospital of Southwest Medical University were retrospectively analyzed.According to the surgical plan,the patients were divided into two groups.Among them,23 patients received posterior cervical C2-3 internal fixation combined with the bucking bar technique(group A),and 32 patients received simple posterior C2-3 internal fixation(group B).Operation time,intraoperative blood loss,complications,pain visual analog scale score,neck disability index,American Spinal Injury Association classification,and patient satisfaction(Odom's classification)preoperation and during follow-up were compared between the two groups.The changes in C2-3 displacement and angulation and other imaging indicators were compared at each observation time point. RESULTS AND CONCLUSION:(1)There was no statistically significant difference in operation time,intraoperative blood loss,and postoperative complications between the two groups(P>0.05).(2)The neck pain visual analog scale and neck disability index scores of the two groups of patients at the final follow-up were significantly improved compared with those before surgery(P<0.05).The Odom standard classification showed that 21 cases(91%)in group A were excellent and 29 cases(91%)were excellent and good in group B.There was no statistically significant difference in the clinical efficacy indicators between the two groups(all P>0.05).(3)There was no significant difference in C2-3 angulation and displacement between the two groups before operation(P>0.05).Postoperation and at the last follow-up,the angle and displacement of C2-3 in both groups were significantly smaller than before surgery,and the difference was statistically significant(P<0.01).There was no statistically significant difference in the above indicators after surgery and at the last follow-up(P>0.05).After surgery and at the last follow-up,the displacement and angle of C2-3 in group A were significantly smaller than those in group B(P<0.05).(4)At the last follow-up,no patients in group A had residual deformity,and 4 cases(13%,4/32)in group B had residual deformity.(5)Therefore,posterior C2-3 fixation combined with transoral bucking bar technology may be beneficial to the reduction and stabilization of the vertebral body,reduces malunion,and can achieve better reduction.
7.Identification of tissue distribution components and mechanism of antipyretic effect of famous classical formula Dayuanyin.
Yu-Jie HOU ; Kang-Ning XIAO ; Jian-Yun BI ; Xin-Rui LI ; Ming SU ; Li-Jie WANG ; Yu-Qing WANG ; Dan-Dan SUN ; Hui ZHANG ; Xin-Jun ZHANG ; Shan-Xin LIU
China Journal of Chinese Materia Medica 2025;50(10):2810-2824
Based on the ultra performance liquid chromatography-quadrupole Exactive Orbitrap mass spectrometry(UPLC-Q-Exactive Orbitrap-MS) technology, combined with related literature, databases, and reference material information, this study qualitatively analyzed the components of Dayuanyin in the tissue of rats after gavage and employed molecular docking technology to predict the rationality of the mechanism behind the antipyretic effect of the in vivo components in Dayuanyin. A total of 21, 26, 20, 21, 14, and 31 prototype components and 3, 16, 3, 7, 5, and 24 metabolites were identified from the heart, liver, spleen, lung, kidney, and hypothalamus of the rats, respectively, and the binding ability of key components and targets was further verified by molecular docking. The results showed that all components had good binding ability with targets. The established UPLC-Q-Exactive Orbitrap-MS could effectively and quickly identify the Dayuanyin components distributed in tissue and preliminarily identify their metabolites. Many components were identified in the hypothalamus, which suggested that the components delivered to the brain should be focused on in the study on Dayuanyin in the treatment of febrile diseases. The molecular docking technology was used to predict the rationality of the mechanism behind its antipyretic effect, which lays the foundation for the clarification of the material basis and action mechanism of Dayuanyin, the development of new preparations, and the prediction of quality markers.
Animals
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Drugs, Chinese Herbal/administration & dosage*
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Rats
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Molecular Docking Simulation
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Male
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Antipyretics/metabolism*
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Rats, Sprague-Dawley
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Tissue Distribution
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Mass Spectrometry
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Chromatography, High Pressure Liquid
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Hypothalamus/metabolism*
8.Characterization of hippocampal components of Danzhi Xiaoyao Formula based on HPLC-Q-TOF-MS/MS and network pharmacology and assessment of its therapeutic potential for nervous system diseases.
Wen-Qing HU ; Hui-Yuan GAO ; Li YANG ; Yu-Xin WANG ; Hao-Jie CHENG ; Si-Yu YANG ; Mei-Yu ZHANG ; Jian SUN
China Journal of Chinese Materia Medica 2025;50(14):4053-4062
In this study, the pharmacodynamic components and potential pharmacological functions of Danzhi Xiaoyao Formula in treating nervous system diseases were investigated by hippocampal component characterization and network pharmacology. After rats were administrated with Danzhi Xiaoyao Formula by gavage, high performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry(HPLC-Q-TOF-MS/MS) was employed to explore the components in the hippocampus of rats. Fifty-seven components were identified in the hippocampus of rats by comparing the extract of Danzhi Xiaoyao Formula, herbal components in the hippocampus after administration, and blank samples. KEGG and GO analyses predicted 74 core targets including GSK3B, MAPK1, AKT, IL6. These targets were involved in PI3K/Akt, NF-κB, MAPK, JAK/STAT, Wnt, and other signaling pathways. The results indicated that Danzhi Xiaoyao Formula may ameliorate other nervous system diseases enriched in DO, such as neurodegenerative diseases, cerebrovascular diseases, and mental and emotional disorders by mediating target pathways, inhibiting inflammation, reducing neuronal damage, and alleviating hippocampal atrophy. The relevant activities exhibited by this formula in nervous system diseases such as Alzheimer's disease, Parkinson's disease, and diabetic neuropathy have extremely high development value and are worthy of further in-depth research. This study provides a theoretical basis and practical guidance for expanding the application of Danzhi Xiaoyao Formula in the treatment of nervous system diseases.
Drugs, Chinese Herbal/administration & dosage*
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Animals
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Rats
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Hippocampus/metabolism*
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Network Pharmacology
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Chromatography, High Pressure Liquid
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Tandem Mass Spectrometry
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Rats, Sprague-Dawley
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Male
;
Nervous System Diseases/genetics*
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Humans
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Signal Transduction/drug effects*
9.Differences in intestinal absorption characteristics of Rubus multibracteatus extract in normal and inflammatory pain model rats by in-vitro everted intestine sac method.
Ming-Li BAO ; Qing ZHANG ; Yang JIN ; Yi CHEN ; Jian-Qing PENG ; Si-Ying CHEN ; Zhi-Jie MA ; Jian LIAO ; Jing HUANG ; Zi-Peng GONG
China Journal of Chinese Materia Medica 2025;50(16):4690-4704
This study compared the differences in intestinal absorption characteristics of eleven active components in Rubus multibracteatus(RM) extract(protocatechuic acid, tiliroside, scutellarin, luteoloside, astragalin, epicatechin, catechin, xanthotoxin, p-coumaric acid, caffeic acid, and apigenin-7-O-glucuronide) between normal rats and inflammatory pain model rats using the in-vitro everted intestinal sac model. The RM extract was administered at absorption concentrations of 25.0, 50.0, and 100.0 mg·mL~(-1). The contents of the eleven components in intestinal absorption solution samples were quantified by ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS), and their cumulative absorption(Q) and absorption rate constant(K_a) were calculated to evaluate the absorption characteristics of these components in normal rats and inflammatory pain model rats. The results show that except for catechin, epicatechin, and caffeic acid, the cumulative absorption-time curves of the other eight components(protocatechuic acid, tiliroside, scutellarin, luteoloside, astragalin, xanthotoxin, p-coumaric acid, and apigenin-7-O-glucuronide) exhibit an upward trend without saturation, with correlation coefficients(R~2) all > 0.9, indicating linear absorption. However, the overall absorption of all components is not dose-dependent with increasing concentration, suggesting that their absorption mechanisms are not solely passive diffusion. In both normal and model rats, the jejunum shows the highest absorption for all components except xanthotoxin. The overall absorption of seven components(excluding protocatechuic acid, caffeic acid, apigenin-7-O-glucuronide, and luteoloside) in normal rats is better than that in model rats across all intestinal segments. These findings indicate that the pathological state of inflammatory pain alters the intestinal absorption of RM extract, and its mechanism needs further investigation.
Animals
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Rats
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Intestinal Absorption/drug effects*
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Male
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Rats, Sprague-Dawley
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Drugs, Chinese Herbal/metabolism*
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Disease Models, Animal
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Pain/metabolism*
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Intestines/drug effects*
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Intestinal Mucosa/metabolism*
10.Imaging observation of possible mechanism and stability of type B Hangman's fracture.
Hanming LI ; Qing WANG ; Guangzhou LI ; Gaoju WANG ; Jin YANG ; Hao ZHANG ; Jian ZHANG ; Zhike CHEN
Chinese Journal of Reparative and Reconstructive Surgery 2025;39(10):1318-1324
OBJECTIVE:
To investigate the possible mechanism and fracture stability of subtypes of type B Hangman's fracture by using imaging observation.
METHODS:
Patients with type B Hangman's fractures admitted to multiple centers between January 2008 and October 2023 were selected as the research objects. The clinical data and imaging data of patients who met the selection criteria were extracted. The patients' age, gender, cause of fracture, disease duration, visual analogue scale (VAS) score of neck pain, neck disability index (NDI), and American Spinal Injury Association (ASIA) classification of spinal cord function were collected. Based on the imaging data, the anatomical structure of the contralateral superior articular process fracture, the relationship between the superior articular process fracture line and the position of the odontoid process, the associated posterior vertebral wall fracture and its classification, the incidence of vertebral arch floating and C 2, 3 instability were observed. The superior articular fracture angle (SAFA), superior articular fracture displacement distance (SAFD), and C 2 vertebral body rotation (VBRA) were measured. According to the anatomical structure of the contralateral superior articular process fracture, the patients were divided into a pedicle fracture group (POA group), a inferior articular process fracture group (IAP group), and a laminar fracture group (CSL group). The baseline data and imaging indexes were analyzed between groups, and the imaging anatomical characteristics of each subtype of fracture were observed to explore its possible mechanism and fracture stability.
RESULTS:
A total of 86 cases of type B Hangman's fractures were collected. There were 67 males and 19 females. The mean age was 51.0 years (range, 21-78 years). There were 48 cases of pedicle fracture (POA group), 25 cases of inferior articular process fracture (IAP group), and 13 cases of laminar fracture (CSL group). There was no significant difference in age, gender, cause of fracture, disease duration, VAS score of neck pain, and NDI between groups ( P>0.05). However, the incidence of spinal cord injury in POA group was the highest ( P<0.05). The incidences of superior articular process fracture line posterior to the odontoid process and posterior vertebral wall fracture in POA group were the highest ( P<0.05). The incidences of vertebral arch floating and C 2, 3 instability in IAP group were the highest ( P<0.05). There were significant differences in SAFA and VBRA between groups ( P<0.05). There was no significant difference in SAFD between groups ( P>0.05). The differences in the incidences of fracture displacement>3 mm and VBRA>5° between groups were significant ( P<0.05). There were 78 cases of unstable Hangman's fracture, including 2 cases of simple C 2、3 instability, 22 cases of simple axis rotation and displacement instability, 8 cases of simple vertebral arch floating instability, and the rest of the patients had two or more types of instability.
CONCLUSION
The mechanism of different subtypes of type B Hangman's fracture may be that the lateral mass of the rotation of the atlas applied the overextension compression force to the unilateral superior articular process of the axis vertebra, and the contralateral pedicle, inferior articular process and lamina fractures were caused by direct violence or/and rotational violence to different degrees. The decomposition of this type of fracture into C 2, 3 intervertebral, axis vertebra body displacement and rotation and vertebral arch floating instability is beneficial to the treatment and surgical approach selection.
Humans
;
Spinal Fractures/surgery*
;
Male
;
Female
;
Cervical Vertebrae/diagnostic imaging*
;
Middle Aged
;
Adult
;
Tomography, X-Ray Computed
;
Aged
;
Odontoid Process/injuries*
;
Fracture Fixation, Internal/methods*
;
Young Adult

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