1.Staged Efficacy of Qijia Rougan Prescription Combined with Entecavir for Chronic Hepatitis B-related Hepatic Fibrosis with Qi Deficiency and Collateral Stasis Syndrome Based on "Zhu Ke Jiao" Theory
Baixue LI ; Xin WANG ; Jibin LIU ; Li WEN ; Cen JIANG ; Wenjun WU ; Dong WANG ; Shuwan LIU ; Huabao LIU ; Yongli ZHENG ; Liang HUANG ; Yue SU ; Song ZHANG ; Yanan SHANG ; Hang ZHOU ; Quansheng FENG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(9):180-188
ObjectiveThis paper aims to investigate and evaluate the staged efficacy and safety of the representative empirical prescription of the “Zhu Ke Jiao” theory, Qijia Rougan prescription, combined with entecavir in the treatment of hepatic fibrosis in chronic hepatitis B. MethodsA multicenter randomized controlled clinical study was conducted, and 101 patients diagnosed with chronic hepatitis B-related hepatic fibrosis (CHB-HF) who met the diagnosis and inclusion criteria were randomly assigned to an observation group (Qijia Rougan prescription + entecavir) and a control group (entecavir). The treatment duration was 24 weeks. Liver stiffness measurement (LSM), fibrosis-4 index (FIB-4), portal vein diameter, hepatitis B serology, biochemical indicators, hepatic fibrosis markers in serum [hyaluronic acid (HA), laminin (LN), procollagen Ⅲ peptide (PⅢP), and type Ⅳ collagen (Ⅳ-C)], and traditional Chinese medicine syndrome scores were used as efficacy evaluation indicators. Efficacy assessments and explorations of different staged subgroups of Qijia Rougan prescription were conducted according to LSM values based on the Metavir pathological staging standard. ResultsA total of 98 cases were included for statistical analysis, with 49 cases in the observation group and 49 in the control group. The general data of the patients in both groups were comparable. Compared with the same group before treatment, the observation group showed a significant reduction in LSM and FIB-4 (P<0.01), as well as notable improvements in LN, Ⅳ-C, and various TCM syndrome scores (P<0.05, P<0.01). When compared to the control group after treatment, the observation group demonstrated significant improvements in LSM, FIB-4, and various TCM syndrome score indicators (P<0.05, P<0.01), indicating that the observation group performed better than the control group. Subgroup analysis of the regression of hepatic fibrosis stages showed that compared to the same group before treatment, the observation group had better improvement in regression of stages F2 and F3 (P<0.05). When compared to the control group after treatment, the observation group exhibited superior improvement in regression of stage F3 (P<0.05). No adverse events occurred in either group during the treatment period. ConclusionCompared with entecavir alone, the combination of Qijia Rougan prescription and entecavir significantly improves the degree of hepatic fibrosis and clinical TCM symptoms in patients. The optimal intervention period is primarily during stage F3, which is a potential “interception” point of the “Zhu Ke Jiao” theory.
2.A Systematic Strategy for Discovering First-in-class Anti-fibrotic Drugs from Traditional Chinese Medicine
Wen HUANG ; Guang XIN ; Sanyin ZHANG ; Tao WANG ; Wei CHEN ; Zeliang WEI ; Qilong ZHOU ; Ke LI ; Dan SUN ; Kui YU ; Shilin CHEN
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(10):296-307
Pulmonary fibrosis(PF) is a progressive and life-threatening disease with limited therapeutic options, highlighting the urgent need for innovative drug discovery strategies. To address this challenge, the authors propose the formula-originated rational intelligent screening&translation(FIRST), a systematic framework for developing anti-fibrotic monomers derived from classical traditional Chinese medicine(TCM). The strategy integrates three key dimensions, including tissue-oriented intelligent screening of active compounds, structural optimization based on drug-target spatial interactions and plant biosynthetic pathways, and cross-scale validation of drug. We further highlight its applications in discovering tissue-oriented novel drugs from clinically validated TCM, the development and mechanistic elucidation of anti-fibrotic therapeutics, as well as the clinical translation and secondary development of candidate drugs. This strategy paves the way for first-in-class, formula-derived monomeric drugs with defined structures, clarified mechanisms, and proven safety, offering a transformative avenue to meet the urgent therapeutic needs of PF and setting a new paradigm for TCM-based drug innovation.
3.A Systematic Strategy for Discovering First-in-class Anti-fibrotic Drugs from Traditional Chinese Medicine
Wen HUANG ; Guang XIN ; Sanyin ZHANG ; Tao WANG ; Wei CHEN ; Zeliang WEI ; Qilong ZHOU ; Ke LI ; Dan SUN ; Kui YU ; Shilin CHEN
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(10):296-307
Pulmonary fibrosis(PF) is a progressive and life-threatening disease with limited therapeutic options, highlighting the urgent need for innovative drug discovery strategies. To address this challenge, the authors propose the formula-originated rational intelligent screening&translation(FIRST), a systematic framework for developing anti-fibrotic monomers derived from classical traditional Chinese medicine(TCM). The strategy integrates three key dimensions, including tissue-oriented intelligent screening of active compounds, structural optimization based on drug-target spatial interactions and plant biosynthetic pathways, and cross-scale validation of drug. We further highlight its applications in discovering tissue-oriented novel drugs from clinically validated TCM, the development and mechanistic elucidation of anti-fibrotic therapeutics, as well as the clinical translation and secondary development of candidate drugs. This strategy paves the way for first-in-class, formula-derived monomeric drugs with defined structures, clarified mechanisms, and proven safety, offering a transformative avenue to meet the urgent therapeutic needs of PF and setting a new paradigm for TCM-based drug innovation.
4.Application of Recombinant Collagen in Biomedicine
Huan HU ; Hong ZHANG ; Jian WANG ; Li-Wen WANG ; Qian LIU ; Ning-Wen CHENG ; Xin-Yue ZHANG ; Yun-Lan LI
Progress in Biochemistry and Biophysics 2025;52(2):395-416
Collagen is a major structural protein in the matrix of animal cells and the most widely distributed and abundant functional protein in mammals. Collagen’s good biocompatibility, biodegradability and biological activity make it a very valuable biomaterial. According to the source of collagen, it can be broadly categorized into two types: one is animal collagen; the other is recombinant collagen. Animal collagen is mainly extracted and purified from animal connective tissues by chemical methods, such as acid, alkali and enzyme methods, etc. Recombinant collagen refers to collagen produced by gene splicing technology, where the amino acid sequence is first designed and improved according to one’s own needs, and the gene sequence of improved recombinant collagen is highly consistent with that of human beings, and then the designed gene sequence is cloned into the appropriate vector, and then transferred to the appropriate expression vector. The designed gene sequence is cloned into a suitable vector, and then transferred to a suitable expression system for full expression, and finally the target protein is obtained by extraction and purification technology. Recombinant collagen has excellent histocompatibility and water solubility, can be directly absorbed by the human body and participate in the construction of collagen, remodeling of the extracellular matrix, cell growth, wound healing and site filling, etc., which has demonstrated significant effects, and has become the focus of the development of modern biomedical materials. This paper firstly elaborates the structure, type, and tissue distribution of human collagen, as well as the associated genetic diseases of different types of collagen, then introduces the specific process of producing animal source collagen and recombinant collagen, explains the advantages of recombinant collagen production method, and then introduces the various systems of expressing recombinant collagen, as well as their advantages and disadvantages, and finally briefly introduces the application of animal collagen, focusing on the use of animal collagen in the development of biopharmaceutical materials. In terms of application, it focuses on the use of animal disease models exploring the application effects of recombinant collagen in wound hemostasis, wound repair, corneal therapy, female pelvic floor dysfunction (FPFD), vaginal atrophy (VA) and vaginal dryness, thin endometritis (TE), chronic endometritis (CE), bone tissue regeneration in vivo, cardiovascular diseases, breast cancer (BC) and anti-aging. The mechanism of action of recombinant collagen in the treatment of FPFD and CE was introduced, and the clinical application and curative effect of recombinant collagen in skin burn, skin wound, dermatitis, acne and menopausal urogenital syndrome (GSM) were summarized. From the exploratory studies and clinical applications, it is evident that recombinant collagen has demonstrated surprising effects in the treatment of all types of diseases, such as reducing inflammation, promoting cell proliferation, migration and adhesion, increasing collagen deposition, and remodeling the extracellular matrix. At the end of the review, the challenges faced by recombinant collagen are summarized: to develop new recombinant collagen types and dosage forms, to explore the mechanism of action of recombinant collagen, and to provide an outlook for the future development and application of recombinant collagen.
5.Analyzing Differences in Volatile Components of Citri Reticulatae Pericarpium Before and After Being Stir-fried with Halloysitum Rubrum Based on HS-GC-MS and Intelligent Sensory Technology
Li XIN ; Jiawen WEN ; Wenhui GONG ; Beibei ZHAO ; Shihao YAN ; Huashi CHEN ; Haiping LE ; Jinlian ZHANG ; Yanhua XUE
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):157-162
ObjectiveTo analyze the differences in color, odor and volatile components of Citri Reticulatae Pericarpium(CRP) before and after being stir-fried with Halloysitum Rubrum, and to explore the material basis of enhancing the effect of strengthening spleen after processing and the scientific connotation of decoction pieces processed with Halloysitum Rubrum as the auxiliary material. MethodsThe volatile components of the samples before and after processing were identified and relatively quantified by headspace gas chromatography-mass spectrometry(HS-GC-MS), and the volatile components were analyzed by principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA). According to the principle of variable importance in the projection(VIP) value>1.5, volatile differential components before and after processing were screened. And combined with intelligent sensory technologies such as colorimeter and electronic nose, the chroma and odor information of CRP before and after being stir-fried with Halloysitum Rubrum were identified. Pearson correlation analysis was used to explore the correlation between volatile differential components and chroma values. ResultsA total of 112 volatile components were identified from CRP and CRP stir-fried with Halloysitum Rubrum, of which 84 were from CRP and 97 were from CRP stir-fried with Halloysitum Rubrum. And 7 differential components were selected, including α-pinene, β-myrcene, linalool, sabinene, ocimene isomer mixture, A-ocimene, and δ-elemene. After being processed with Halloysitum Rubrum, the brightness value(L*), yellow-blue value(b*) and total chromatic value(E*ab) of CRP were decreased(P<0.01), and red-green value(a*) was increased(P<0.01), the response values of S4, S5, S10 and S13 sensors were significantly increased(P<0.05), and the response values of S3 and S8 sensors were significantly decreased(P<0.05). Correlation analysis showed that α-pinene and β-myrcene were negatively correlated with L* and E*ab, but positively correlated with a*. Sabinene was positively correlated with L* and E*ab. Linalool was positively correlated with L* and E*ab, and negatively correlated with a*. The ocimene isomer mixture was positively correlated with the L*. ConclusionAfter being processed with Halloysitum Rubrum, the appearance color, odor and volatile components of CRP change significantly, and α-pinene, β-myrcene, sabinene, linalool and A-ocimene are the characteristic volatile components before and after processing, which can provide references for the quality evaluation and clinical application of CRP and its processed products.
6.Analyzing Differences in Volatile Components of Citri Reticulatae Pericarpium Before and After Being Stir-fried with Halloysitum Rubrum Based on HS-GC-MS and Intelligent Sensory Technology
Li XIN ; Jiawen WEN ; Wenhui GONG ; Beibei ZHAO ; Shihao YAN ; Huashi CHEN ; Haiping LE ; Jinlian ZHANG ; Yanhua XUE
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):157-162
ObjectiveTo analyze the differences in color, odor and volatile components of Citri Reticulatae Pericarpium(CRP) before and after being stir-fried with Halloysitum Rubrum, and to explore the material basis of enhancing the effect of strengthening spleen after processing and the scientific connotation of decoction pieces processed with Halloysitum Rubrum as the auxiliary material. MethodsThe volatile components of the samples before and after processing were identified and relatively quantified by headspace gas chromatography-mass spectrometry(HS-GC-MS), and the volatile components were analyzed by principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA). According to the principle of variable importance in the projection(VIP) value>1.5, volatile differential components before and after processing were screened. And combined with intelligent sensory technologies such as colorimeter and electronic nose, the chroma and odor information of CRP before and after being stir-fried with Halloysitum Rubrum were identified. Pearson correlation analysis was used to explore the correlation between volatile differential components and chroma values. ResultsA total of 112 volatile components were identified from CRP and CRP stir-fried with Halloysitum Rubrum, of which 84 were from CRP and 97 were from CRP stir-fried with Halloysitum Rubrum. And 7 differential components were selected, including α-pinene, β-myrcene, linalool, sabinene, ocimene isomer mixture, A-ocimene, and δ-elemene. After being processed with Halloysitum Rubrum, the brightness value(L*), yellow-blue value(b*) and total chromatic value(E*ab) of CRP were decreased(P<0.01), and red-green value(a*) was increased(P<0.01), the response values of S4, S5, S10 and S13 sensors were significantly increased(P<0.05), and the response values of S3 and S8 sensors were significantly decreased(P<0.05). Correlation analysis showed that α-pinene and β-myrcene were negatively correlated with L* and E*ab, but positively correlated with a*. Sabinene was positively correlated with L* and E*ab. Linalool was positively correlated with L* and E*ab, and negatively correlated with a*. The ocimene isomer mixture was positively correlated with the L*. ConclusionAfter being processed with Halloysitum Rubrum, the appearance color, odor and volatile components of CRP change significantly, and α-pinene, β-myrcene, sabinene, linalool and A-ocimene are the characteristic volatile components before and after processing, which can provide references for the quality evaluation and clinical application of CRP and its processed products.
7.Clinical practice guidelines for intraoperative cell salvage in patients with malignant tumors
Changtai ZHU ; Ling LI ; Zhiqiang LI ; Xinjian WAN ; Shiyao CHEN ; Jian PAN ; Yi ZHANG ; Xiang REN ; Kun HAN ; Feng ZOU ; Aiqing WEN ; Ruiming RONG ; Rong XIA ; Baohua QIAN ; Xin MA
Chinese Journal of Blood Transfusion 2025;38(2):149-167
Intraoperative cell salvage (IOCS) has been widely applied as an important blood conservation measure in surgical operations. However, there is currently a lack of clinical practice guidelines for the implementation of IOCS in patients with malignant tumors. This report aims to provide clinicians with recommendations on the use of IOCS in patients with malignant tumors based on the review and assessment of the existed evidence. Data were derived from databases such as PubMed, Embase, the Cochrane Library and Wanfang. The guideline development team formulated recommendations based on the quality of evidence, balance of benefits and harms, patient preferences, and health economic assessments. This study constructed seven major clinical questions. The main conclusions of this guideline are as follows: 1) Compared with no perioperative allogeneic blood transfusion (NPABT), perioperative allogeneic blood transfusion (PABT) leads to a more unfavorable prognosis in cancer patients (Recommended); 2) Compared with the transfusion of allogeneic blood or no transfusion, IOCS does not lead to a more unfavorable prognosis in cancer patients (Recommended); 3) The implementation of IOCS in cancer patients is economically feasible (Recommended); 4) Leukocyte depletion filters (LDF) should be used when implementing IOCS in cancer patients (Strongly Recommended); 5) Irradiation treatment of autologous blood to be reinfused can be used when implementing IOCS in cancer patients (Recommended); 6) A careful assessment of the condition of cancer patients (meeting indications and excluding contraindications) should be conducted before implementing IOCS (Strongly Recommended); 7) Informed consent from cancer patients should be obtained when implementing IOCS, with a thorough pre-assessment of the patient's condition and the likelihood of blood loss, adherence to standardized internally audited management procedures, meeting corresponding conditions, and obtaining corresponding qualifications (Recommended). In brief, current evidence indicates that IOCS can be implemented for some malignant tumor patients who need allogeneic blood transfusion after physician full evaluation, and LDF or irradiation should be used during the implementation process.
8.Analysis of Changes on Volatile Components of Ligusticum sinense cv. Chaxiong Rhizome Before and After Wine Processing Based on Electronic Nose and HS-GC-MS
Wen ZHANG ; Peng ZHENG ; Jiangshan ZHANG ; Xiaolin XIAO ; Zaodan WU ; Li XIN ; Wenhui GONG ; Jinlian ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(2):173-181
ObjectiveBy comparing the composition and content of volatile components in raw products, wine-washed products and wine-fried products of Ligusticum sinense cv. Chaxiong rhizome(LSCR), to investigate the influence of wine processing on the volatile components of LSCR, in order to provide a basis for the development of quality standards for LSCR and its processed products. MethodsElectronic nose was used to identify the odors of LSCR, wine-washed and wine-fried LSCR, and their volatile components were detected by headspace gas chromatography-mass spectrometry(HS-GC-MS), and the relative mass fractions of these components were determined by peak area normalization method. Principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA) were performed on the obtained sample data by SIMCA 14.1 software, and the differential components of LSCR, wine-washed and wine-fried LSCR were screened according to the variable importance in the projection(VIP) value>1. Pearson correlation analysis was used to explore the relationship between volatile differential flavor components and electronic nose sensors. ResultsElectronic nose detection results showed that there were significant differences in the odors of LSCR, wine-washed and wine-fried LSCR, mainly reflected in the sensors S2, S4, S5, S6, S11, S12, S13. And a total of 62 compounds were identified from LSCR and its wine-processed products, among which 46, 50 and 51 compounds were identified from LSCR, wine-fried and wine-washed LSCR, respectively. There were 21 differential components between the raw products and wine-fried products, of which 10 components were increased and 11 were decreased after processing. There were 20 differential components between the raw products and wine-washed products, of which 11 constituents increased and 9 decreased after processing. There were 17 differential components between the wine-wash products and wine-fried products. Compared with the wine-washed products, the contents of 13 components in the wine-fried products increased, and the contents of 4 components decreased. The increasing trend of the content of phthalides in the wine-washed products was more obvious than that in the wine-fried products, but the content of total volatile components was higher in the wine-fried products than the wine-washed products. Correlation analysis showed that there were different degrees of correlation between the 7 differential sensors of electronic nose and 24 differential volatile components, mainly phthalides and olefins. ConclusionThe odor and the content of volatile components in LSCR changed obviously after wine processing, and n-butylphthalide, Z-butylidenephthalide and E-ligustilide can be used as the candidate differential markers of volatile components in LSCR before and after wine processing.
9.Effects of fractionated low-dose ionizing radiation on differentially expressed genes in ferroptosis of human bronchial epithelial cells
Min ZHANG ; Lingyu ZHANG ; Yashi CAI ; Huixian LI ; Yanting CHEN ; Guanyou CHEN ; Xin LAN ; Changyong WEN ; Weixu HUANG ; Jianming ZOU ; Huifeng CHEN
Chinese Journal of Radiological Health 2025;34(3):310-317
Objective To investigate the effects of fractionated low-dose ionizing radiation (LDIR) on the ferroptosis in human bronchial epithelial (HBE) cells as well as the associated differentially expressed genes (DEGs), biological processes, and signaling pathways. Methods HBE cells were exposed to different single doses of X-ray irradiation (0, 25, 50, 75, and 100 mGy) for 24, 48, and 72 h, respectively. The change in cell viability was detected by MTT assay. Cells were irradiated with 0, 25, 50, and 100 mGy X-rays 5 times, with 48 h between each irradiation and a dose rate of 50 mGy/min. Cells were harvested 24 h after irradiation for the measurement of the expression of ferroptosis-related genes SLC7A11 and GPX4 at the mRNA and protein levels, cellular iron content, and the expression of FTH1 and FTL mRNAs. High-throughput sequencing was used to screen for the DEGs in each dose group, followed by Gene Ontology-Biological Process (GO-BP) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and Gene Set Enrichment Analysis (GSEA). Results Compared with the control group, single-dose LDIR significantly increased cell proliferation at 75 mGy after 24 h (P < 0.05), at 50, 75, and 100 mGy after 48 h (P < 0.05), and at 75 and 100 mGy after 72 h (P < 0.05). Compared with the control group, at the end of the fifth fractionated LDIR, SLC7A11 and GPX4 mRNAs decreased at all doses (P < 0.05), SLC7A11 protein decreased at all doses, GPX4 protein decreased at 25 and 100 mGy, iron content increased at all doses, and FTH1 and FTL mRNAs decreased at all doses (P< 0.05). Sequencing analysis identified 248, 30, and 291 DEGs and 10, 2, and 9 ferroptosis-associated genes at the three doses compared to the control. Gene Ontology-Biological Process analysis showed that DEGs were mainly enriched in biological processes such as response to lipids, cell death, and response to unfolded proteins. Kyoto Encyclopedia of Genes and Genomes analysis showed that DEGs were mainly enriched in the JAK-STAT signaling pathway, lipids and atherosclerosis, ferroptosis, protein processing in the endoplasmic reticulum, and FoxO signaling pathway. Gene set enrichment analysis showed that DEGs were mainly enriched in ferroptosis, fatty acid degradation, and glutathione metabolism. Conclusion Fractionated low-dose radiation induced ferroptosis in HBE cells, and DEGs were predominantly enriched in biological processes and signaling pathways related to inflammation, ferroptosis, and endoplasmic reticulum stress.
10.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.

Result Analysis
Print
Save
E-mail