1.Clinical Research and Basic Study on Effect of Huangqin Qingre Chubi Capsule (黄芩清热除痹胶囊) on Self-Perception of Patients and Immune Inflammation in Rheumatoid Arthritis
Fanfan WANG ; Jian LIU ; Qin ZHOU ; Jianting WEN ; Yue SUN ; Mingyu HE
Journal of Traditional Chinese Medicine 2026;67(5):544-556
ObjectiveTo evaluate the comprehensive intervention effects of Huangqin Qingre Chubi Capsule (黄芩清热除痹胶囊, HQC) on self-perception of patients (SPP) and immune inflammation in patients with rheumatoid arthritis (RA), and to explore its potential mechanisms. MethodsClinical data of 452 RA patients were retrospectively collected. Patients were divided into a control group (274 cases), treated with conventional western medicine, and an observation group (178 cases), treated with HQC for at least 2 weeks in addition to conventional western medicine. The treatment duration was 2 weeks for both groups. Propensity score matching (PSM) was performed at a ratio of 1∶1 to match patients between groups. SPP including the Chinese version of the short form-36 health survey (SF-36), self-rating anxiety scale (SAS), self-rating depression scale (SDS), visual analog scale (VAS), and Chinese patient-reported index for rheumatoid arthritis (CPRI-RA), as well as immune inflammatory indicators, including erythrocyte sedimentation rate (ESR), high-sensitivity C-reactive protein (hs-CRP), rheumatoid factor (RF), anti-cyclic citrullinated peptide antibody (anti-CCP), interleukin-6 (IL-6), immunoglobulin A (IgA), immunoglobulin G (IgG), immunoglobulin M (IgM), complement C3, and complement C4, were collected before and after treatment. Spearman correlation analysis was used to assess the relationships between SPP and immune inflammatory indicators. Logistic regression, association rule analysis, and mediation analysis were performed to evaluate the effects and potential pathways of HQC on SPP and immune inflammatory indicators. Network pharmacology was applied to identify the active components and core targets of HQC in the treatment of RA, followed by molecular docking verification. In cell experiments, cells were divided into normal group, model group, 20% medicated serum group, and 80 nmol/L control group. Human synovial fibroblasts (FLS) were cultured with complete medium in the normal group, while human rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) were cultured in the model group. In the 20% medicated serum group, RA-FLS were cultured with medium containing 20% HQC-medicated serum, and in the 80 nmol/L control group, RA-FLS were cultured with complete medium containing 80 nmol/L methotrexate suspension. After 48 h of culture, cell viability was detected by cell counting kit-8 (CCK-8) assay. Levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), and interleukin-10 (IL-10) in the cell supernatant were measured by enzyme-linked immunosorbent assay (ELISA). Protein levels of matrix metalloproteinase 9 (MMP9), transcription factor AP-1 subunit (JUN), vascular endothelial growth factor A (VEGFA), and C-X-C motif chemokine ligand 8 (CXCL8) were detected by Western Blot, and cell migration ability was evaluated using Transwell assay. ResultsAfter PSM, 178 cases were included in each group. After treatment, SF-36 scores increased, while scores of SAS, SDS, VAS and CPRI-RA, levels of ESR, hs-CRP, IL-6, complement C3, and complement C4 levels decreased in both groups; IgG and IgM levels were also reduced in the observation group (P<0.05). Physical functioning (correlation coefficient -0.19, P<0.05) and social functioning (correlation coefficient -0.18, P<0.05) of SF-36 were negatively correlated with hs-CRP, while VAS score was positively correlated with hs-CRP (correlation coefficient 0.19, P<0.05). HQC showed high associations with improvements in multiple indicators of SPP and immune inflammatory, and acted as a protective factor for the improvement of several SPP; hs-CRP and ESR played partial mediating roles in the improvement of SPP induced by HQC (P<0.05). Network pharmacology analysis identified baicalein, quercetin, α1-sitosterol, β-sitosterol, stigmasterol, baicalin, and crocetin as the core active components, and JUN, IL-6, VEGFA, MMP9, IL-1β, and CXCL8 as the core targets. Molecular docking results showed strong binding affinities of quercetin with VEGFA, JUN, MMP9, IL-6, and IL-1β, of baicalin with VEGFA and MMP9, and of wogonin with CXCL8. Cell experiments demonstrated that HQC and methotrexate inhibited RA-FLS viability and migration, reduced levels of IL-1β, IL-6, and IL-8, decreased protein levels of MMP9, JUN, VEGFA, and CXCL8, and increased IL-10 levels (P<0.05). ConclusionHQC can improve SPP in RA by regulating immune inflammatory responses. Its mechanism may be related to multi-pathway and multi-target inhibition of synovial cell inflammation and migration.
2.Intervention mechanism of Yiqi Fumai Formula in mice with experimental heart failure based on "heart-gut axis".
Zi-Xuan ZHANG ; Yu-Zhuo WU ; Ke-Dian CHEN ; Jian-Qin WANG ; Yang SUN ; Yin JIANG ; Yi-Xuan LIN ; He-Rong CUI ; Hong-Cai SHANG
China Journal of Chinese Materia Medica 2025;50(12):3399-3412
This paper aimed to investigate the therapeutic effect and mechanism of action of the Yiqi Fumai Formula(YQFM), a kind of traditional Chinese medicine(TCM), on mice with experimental heart failure based on the "heart-gut axis" theory. Based on the network pharmacology integrated with the group collaboration algorithm, the active ingredients were screened, a "component-target-disease" network was constructed, and the potential pathways regulated by the formula were predicted and analyzed. Next, the model of experimental heart failure was established by intraperitoneal injection of adriamycin at a single high dose(15 mg·kg~(-1)) in BALB/c mice. After intraperitoneal injection of YQFM(lyophilized) at 7.90, 15.80, and 31.55 mg·d~(-1) for 7 d, the protective effects of the formula on cardiac function were evaluated using indicators such as ultrasonic electrocardiography and myocardial injury markers. Combined with inflammatory factors in the cardiac and colorectal tissue, as well as targeted assays, the relevant indicators of potential pathways were verified. Meanwhile, 16S rDNA sequencing was performed on mouse fecal samples using the Illumina platform to detect changes in gut flora and analyze differential metabolic pathways. The results show that the administration of injectable YQFM(lyophilized) for 7 d significantly increased the left ventricular end-systolic internal diameter, fractional shortening, and ejection fraction of cardiac tissue of mice with experimental heart failure(P<0.05). Moreover, markers of myocardial injury were significantly decreased(P<0.05), indicating improved cardiac function, along with significantly suppressed inflammatory responses in cardiac and intestinal tissue(P<0.05). Additionally, the species of causative organisms was decreased, and the homeostasis of gut flora was improved, involving a modulatory effect on PI3K-Akt signaling pathway-related inflammation in cardiac and colorectal tissue. In conclusion, YQFM can affect the "heart-gut axis" immunity through the homeostasis of the gut flora, thereby exerting a therapeutic effect on heart failure. This finding provides a reference for the combination of TCM and western medicine to prevent and treat heart failure based on the "heart-gut axis" theory.
Animals
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Drugs, Chinese Herbal/administration & dosage*
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Heart Failure/microbiology*
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Mice
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Mice, Inbred BALB C
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Male
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Disease Models, Animal
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Gastrointestinal Microbiome/drug effects*
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Heart/physiopathology*
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Humans
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Signal Transduction/drug effects*
3.Anti-SARS-CoV-2 prodrug ATV006 has broad-spectrum antiviral activity against human and animal coronaviruses.
Tiefeng XU ; Kun LI ; Siyao HUANG ; Konstantin I IVANOV ; Sidi YANG ; Yanxi JI ; Hanwei ZHANG ; Wenbin WU ; Ye HE ; Qiang ZENG ; Feng CONG ; Qifan ZHOU ; Yingjun LI ; Jian PAN ; Jincun ZHAO ; Chunmei LI ; Xumu ZHANG ; Liu CAO ; Deyin GUO
Acta Pharmaceutica Sinica B 2025;15(5):2498-2510
Coronavirus-related diseases pose a significant challenge to the global health system. Given the diversity of coronaviruses and the unpredictable nature of disease outbreaks, the traditional "one bug, one drug" paradigm struggles to address the growing number of emerging crises. Therefore, there is an urgent need for therapeutic agents with broad-spectrum anti-coronavirus activity. Here, we provide evidence that ATV006, an anti-SARS-CoV-2 nucleoside analog targeting RNA-dependent RNA polymerase (RdRp), has broad antiviral activity against human and animal coronaviruses. Using mouse hepatitis virus (MHV) and human coronavirus NL63 (HCoV-NL63) as a model, we show that ATV006 has potent prophylactic and therapeutic activity against murine coronavirus infection in vivo. Remarkably, ATV006 successfully inhibits viral replication in mice even when administered 96 h after infection. Due to its oral bioavailability and potency against multiple coronaviruses, ATV006 has the potential to become a useful antiviral agent against SARS-CoV-2 and other circulating and emerging coronaviruses in humans and animals.
4.SRSF7 promotes pulmonary fibrosis through regulating PKM alternative splicing in lung fibroblasts.
Tongzhu JIN ; Huiying GAO ; Yuquan WANG ; Zhiwei NING ; Danyang BING ; Yan WANG ; Yi CHEN ; Xiaomu TIAN ; Qiudi LIU ; Zhihui NIU ; Jiayu GUO ; Jian SUN ; Ruoxuan YANG ; Qianqian WANG ; Shifen LI ; Tianyu LI ; Yuhong ZHOU ; Wenxin HE ; Yanjie LU ; Yunyan GU ; Haihai LIANG
Acta Pharmaceutica Sinica B 2025;15(6):3041-3058
Idiopathic pulmonary fibrosis (IPF), a chronic interstitial lung disease, is characterized by aberrant wound healing, excessive scarring and the formation of myofibroblastic foci. Although the role of alternative splicing (AS) in the pathogenesis of organ fibrosis has garnered increasing attention, its specific contribution to pulmonary fibrosis remains incompletely understood. In this study, we identified an up-regulation of serine/arginine-rich splicing factor 7 (SRSF7) in lung fibroblasts derived from IPF patients and a bleomycin (BLM)-induced mouse model, and further characterized its functional role in both human fetal lung fibroblasts and mice. We demonstrated that enhanced expression of Srsf7 in mice spontaneously induced alveolar collagen accumulation. Mechanistically, we investigated alternative splicing events and revealed that SRSF7 modulates the alternative splicing of pyruvate kinase (PKM), leading to metabolic dysregulation and fibroblast activation. In vivo studies showed that fibroblast-specific knockout of Srsf7 in conditional knockout mice conferred resistance to bleomycin-induced pulmonary fibrosis. Importantly, through drug screening, we identified lomitapide as a novel modulator of SRSF7, which effectively mitigated experimental pulmonary fibrosis. Collectively, our findings elucidate a molecular pathway by which SRSF7 drives fibroblast metabolic dysregulation and propose a potential therapeutic strategy for pulmonary fibrosis.
5.Engineered platelet-derived exosomal spheres for enhanced tumor penetration and extended circulation in melanoma immunotherapy.
Jian ZHAO ; Xinyan LV ; Qi LU ; Kaiyuan WANG ; Lili DU ; Xiaoyuan FAN ; Fei SUN ; Fengxiang LIU ; Zhonggui HE ; Hao YE ; Jin SUN
Acta Pharmaceutica Sinica B 2025;15(7):3756-3766
Cells and exosomes derived from them are extensively used as biological carrier systems. Cells demonstrate superior targeting specificity and prolonged circulation facilitated by their rich array of surface proteins, while exosomes, due to their small size, cross barriers and penetrate tumors efficiently. However, challenges remain, cells' large size restricts tissue penetration, and exosomes have limited targeting accuracy and short circulation times. To address these challenges, we developed a novel concept termed exosomal spheres. This approach involved incorporating platelet-derived exosomes shielded with phosphatidylserine (PS) and linked via pH-sensitive bonds for drug delivery applications. The study demonstrated that, compared with exosomes, the exosomal spheres improved blood circulation through the upregulation of CD47 expression and shielding of phosphatidylserine, thereby minimizing immune clearance. Moreover, the increased expression of P-selectin promoted adhesion to circulating tumor cells, thereby enhancing targeting efficiency. Upon reaching the tumor site, the hydrazone bonds of exosome spheres were protonated in the acidic tumor microenvironment, leading to disintegration into uniform-sized exosomes capable of deeper tumor penetration compared to platelets. These findings suggested that exosome spheres addressed the challenges and offered significant potential for efficient and precise drug delivery.
6.Cytoplasmic and nuclear NFATc3 cooperatively contributes to vascular smooth muscle cell dysfunction and drives aortic aneurysm and dissection.
Xiu LIU ; Li ZHAO ; Deshen LIU ; Lingna ZHAO ; Yonghua TUO ; Qinbao PENG ; Fangze HUANG ; Zhengkun SONG ; Chuanjie NIU ; Xiaoxia HE ; Yu XU ; Jun WAN ; Peng ZHU ; Zhengyang JIAN ; Jiawei GUO ; Yingying LIU ; Jun LU ; Sijia LIANG ; Shaoyi ZHENG
Acta Pharmaceutica Sinica B 2025;15(7):3663-3684
This study investigated the role of the nuclear factor of activated T cells c3 (NFATc3) in vascular smooth muscle cells (VSMCs) during aortic aneurysm and dissection (AAD) progression and the underlying molecular mechanisms. Cytoplasmic and nuclear NFATc3 levels were elevated in human and mouse AAD. VSMC-NFATc3 deletion reduced thoracic AAD (TAAD) and abdominal aortic aneurysm (AAA) progression in mice, contrary to VSMC-NFATc3 overexpression. VSMC-NFATc3 deletion reduced extracellular matrix (ECM) degradation and maintained the VSMC contractile phenotype. Nuclear NFATc3 targeted and transcriptionally upregulated matrix metalloproteinase 9 (MMP9) and MMP2, promoting ECM degradation and AAD development. NFATc3 promoted VSMC phenotypic switching by binding to eukaryotic elongation factor 2 (eEF2) and inhibiting its phosphorylation in the VSMC cytoplasm. Restoring eEF2 reversed the beneficial effects in VSMC-specific NFATc3-knockout mice. Cabamiquine-targets eEF2 and inhibits protein synthesis-inhibited AAD development and progression in VSMC-NFATc3-overexpressing mice. VSMC-NFATc3 promoted VSMC switch and ECM degradation while exacerbating AAD development, making it a novel potential therapeutic target for preventing and treating AAD.
7.Expert consensus on pulpotomy in the management of mature permanent teeth with pulpitis.
Lu ZHANG ; Chen LIN ; Zhuo CHEN ; Lin YUE ; Qing YU ; Benxiang HOU ; Junqi LING ; Jingping LIANG ; Xi WEI ; Wenxia CHEN ; Lihong QIU ; Jiyao LI ; Yumei NIU ; Zhengmei LIN ; Lei CHENG ; Wenxi HE ; Xiaoyan WANG ; Dingming HUANG ; Zhengwei HUANG ; Weidong NIU ; Qi ZHANG ; Chen ZHANG ; Deqin YANG ; Jinhua YU ; Jin ZHAO ; Yihuai PAN ; Jingzhi MA ; Shuli DENG ; Xiaoli XIE ; Xiuping MENG ; Jian YANG ; Xuedong ZHOU ; Zhi CHEN
International Journal of Oral Science 2025;17(1):4-4
Pulpotomy, which belongs to vital pulp therapy, has become a strategy for managing pulpitis in recent decades. This minimally invasive treatment reflects the recognition of preserving healthy dental pulp and optimizing long-term patient-centered outcomes. Pulpotomy is categorized into partial pulpotomy (PP), the removal of a partial segment of the coronal pulp tissue, and full pulpotomy (FP), the removal of whole coronal pulp, which is followed by applying the biomaterials onto the remaining pulp tissue and ultimately restoring the tooth. Procedural decisions for the amount of pulp tissue removal or retention depend on the diagnostic of pulp vitality, the overall treatment plan, the patient's general health status, and pulp inflammation reassessment during operation. This statement represents the consensus of an expert committee convened by the Society of Cariology and Endodontics, Chinese Stomatological Association. It addresses the current evidence to support the application of pulpotomy as a potential alternative to root canal treatment (RCT) on mature permanent teeth with pulpitis from a biological basis, the development of capping biomaterial, and the diagnostic considerations to evidence-based medicine. This expert statement intends to provide a clinical protocol of pulpotomy, which facilitates practitioners in choosing the optimal procedure and increasing their confidence in this rapidly evolving field.
Humans
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Calcium Compounds/therapeutic use*
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Consensus
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Dental Pulp
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Dentition, Permanent
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Oxides/therapeutic use*
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Pulpitis/therapy*
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Pulpotomy/standards*
8.Expert consensus on peri-implant keratinized mucosa augmentation at second-stage surgery.
Shiwen ZHANG ; Rui SHENG ; Zhen FAN ; Fang WANG ; Ping DI ; Junyu SHI ; Duohong ZOU ; Dehua LI ; Yufeng ZHANG ; Zhuofan CHEN ; Guoli YANG ; Wei GENG ; Lin WANG ; Jian ZHANG ; Yuanding HUANG ; Baohong ZHAO ; Chunbo TANG ; Dong WU ; Shulan XU ; Cheng YANG ; Yongbin MOU ; Jiacai HE ; Xingmei YANG ; Zhen TAN ; Xiaoxiao CAI ; Jiang CHEN ; Hongchang LAI ; Zuolin WANG ; Quan YUAN
International Journal of Oral Science 2025;17(1):51-51
Peri-implant keratinized mucosa (PIKM) augmentation refers to surgical procedures aimed at increasing the width of PIKM. Consensus reports emphasize the necessity of maintaining a minimum width of PIKM to ensure long-term peri-implant health. Currently, several surgical techniques have been validated for their effectiveness in increasing PIKM. However, the selection and application of PIKM augmentation methods may present challenges for dental practitioners due to heterogeneity in surgical techniques, variations in clinical scenarios, and anatomical differences. Therefore, clear guidelines and considerations for PIKM augmentation are needed. This expert consensus focuses on the commonly employed surgical techniques for PIKM augmentation and the factors influencing their selection at second-stage surgery. It aims to establish a standardized framework for assessing, planning, and executing PIKM augmentation procedures, with the goal of offering evidence-based guidance to enhance the predictability and success of PIKM augmentation.
Humans
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Consensus
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Dental Implants
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Mouth Mucosa/surgery*
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Keratins
9.The 512th case: fever, cough, acute kidney injury
Xiaochen YU ; Hanxue LI ; Minting CHEN ; Ning MA ; Kun HE ; Jian SUN ; Jianing NIU ; Qiang WANG ; Peng XIA
Chinese Journal of Internal Medicine 2025;64(10):1017-1022
A 70-year-old female patient presented with fatigue and edema for 3 months and was found to have elevated serum creatinine for 3 weeks. During the course of the disease, she had fever and cough. Examinations revealed multiple ground-glass opacities in both lungs and positivity for myeloperoxidase-anti-neutrophil cytoplasmic antibodies (ANCA), leading to a diagnosis of ANCA-associated vasculitis. The patient′s condition initially improved after pulse glucocorticoid therapy combined with cyclophosphamide. During treatment, however, the patient developed hematochezia, and colonoscopy revealed multiple colonic ulcers. Immunohistochemistry of colonic mucosal biopsy confirmed cytomegalovirus (CMV) positivity, establishing a diagnosis of CMV colitis. The patient was found to have concurrent Clostridioidesdifficile and pulmonary infections. During the disease course, the patient also developed deep vein thrombosis and roxadustat-associated central hypothyroidism. Given the presence of multiple comorbidities, rituximab was subsequently used for vasculitis treatment, resulting in sustained remission. This case highlights the importance of highly individualized treatment strategies for older patients with vasculitis, requiring adjustment of immunosuppressive therapy intensity based on disease progression.
10.Evidence-based guideline for diagnosis and early fixation of severe open tibiofibular fractures (version 2025)
Yongjun RUI ; Yongqing XU ; Qingtang ZHU ; Xin WANG ; Zhao XIE ; Shanlin CHEN ; Jingyi MI ; Xianyou ZHENG ; Juyu TANG ; Xiaoheng DING ; Aixi YU ; Tao SONG ; Jianxi HOU ; Jian QI ; Xinyu FAN ; Jun FEI ; Lin GUO ; Xingwen HAN ; Weixu LI ; Aiguo WANG ; Yun XIE ; Tao XING ; Meng LI ; Baoqing YU ; Yan ZHUANG ; Xiaoqing HE ; Tao SUN ; Pengcheng LI ; Jihui JU ; Hongxiang ZHOU ; Haidong REN ; Guangyue ZHAO ; Gang ZHAO ; Yongwei WU ; Jun LIU ; Yunhong MA ; Yapeng WANG
Chinese Journal of Trauma 2025;41(11):1021-1034
Severe open tibiofibular fractures account for approximately 28.1% of all open fractures. Among them, Gustilo-Anderson type IIIB/C fractures present significant clinical challenges due to associated bone and soft tissue defects, high infection rates, and risk of amputation. Inadequate preoperative assessment may lead to suboptimal emergency surgical planning or intraoperative complications. Historically, external fixation was often preferred, but this approach has been associated with limitations such as restricted joint mobility, delayed bone union, joint stiffness, and disuse osteoporosis, resulting in poor functional recovery. With advancements of debridement techniques, standardization of antibiotic use, and popularization of early soft tissue coverage, early internal fixation has gained broader acceptance. Nevertheless, controversies persist regarding the choice of fixation method, timing of definitive fixation, use of reamed versus unreamed intramedullary nailing, and necessity of fibular fixation. To standardize the diagnosis and early management of severe open tibiofibular fractures, reduce complication rates, and improve functional recovery, the Society of Microsurgery of the Chinese Medical Association organized a panel of domestic experts to develop the Evidence-based guideline for the diagnosis and early fixation of severe open tibiofibular fractures ( version 2025), using evidence-based methodology. The guidelines provided 12 recommendations covering diagnostic and early fixation strategies of severe open tibiofibular fractures, aiming to provide clinicians with scientifically grounded and standardized guidance.

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