Objective To investigate the role and potential mechanism of secreted phosphoprotein 1 (SPP1)⁺ macrophages in the formation of chronic renal allograft fibrosis. Methods The expression features of SPP1⁺ macrophages in renal allografts of chronic allograft dysfunction (CAD) patients were analyzed based on single-cell transcriptome data of renal tissues from patients with CAD. Transcription factor VIPER analysis and DoRothEA transcription factor activity analysis were performed on the single-cell transcriptome data. Renal tissue samples were collected from kidney transplant recipients, including the CAD group (n=5) and the non-renal allograft fibrosis group (CTL group, n=5). A mouse model of chronic allograft rejection was established and divided into the allogeneic kidney transplantation group (CAD group, n=3) and the syngeneic kidney transplantation group (SYN group, n=3). Hematoxylin-eosin staining was used to detect renal tissue injury in mice, and Masson staining was used to detect renal tissue fibrosis. Immunofluorescence staining was performed to detect SPP1 expression in renal tissues of transplant recipients and mouse renal allografts. Bone marrow-derived macrophages (BMDMs) were extracted from mice and subjected to hypoxia stimulation. The expression of hypoxia-inducible factor (HIF)-1α and SPP1 was detected by Western blot, and SPP1 expression was detected by flow cytometry. BMDMs were transfected with HIF-1α overexpression plasmid and HIF-1α small interfering RNA (siRNA) followed by hypoxia intervention, and the expression of HIF-1α and SPP1 was detected by Western blot. Mouse aortic endothelial cells (MAECs) were co-cultured with the supernatant of BMDMs, and the expression of endothelial-mesenchymal transition (EndMT)-related markers was detected by Western blot and immunofluorescence. Results Single-cell transcriptome analysis showed that the proportion of SPP1⁺ macrophages in renal allograft tissues was significantly higher in the CAD group than in the CTL group (P<0.05). The renal injury score and the percentage of interstitial fibrotic area in the CAD group were significantly higher than those in the SYN group (both P<0.05). Immunofluorescence staining showed that the proportion of SPP1⁺ macrophages was increased in the CAD group compared with the CTL group, and also increased in the CAD group compared with the SYN group (both P<0.05). VIPER analysis and DoRothEA transcription factor activity analysis revealed activation of the hypoxia pathway and upregulated expression of transcription factors such as HIF-1α in SPP1⁺ macrophages. SPP1 expression was elevated in BMDMs under hypoxic conditions. Knockdown of HIF-1α inhibited hypoxia-induced SPP1 protein expression, whereas overexpression of HIF-1α upregulated SPP1 protein levels. After co-culture of hypoxia-induced BMDMs with MAECs, the expression levels of EndMT-related markers were increased. Conclusions SPP1⁺ macrophages differentiated under hypoxia are significantly infiltrated in the formation of chronic renal allograft fibrosis, and may promote renal allograft fibrosis by inducing EndMT in renal vascular endothelial cells.

ObjectiveThis study aimed to investigate the action mechanism by which Banxia Xiexintang （BXT） inhibits epithelial-mesenchymal transition （EMT） in chronic atrophic gastritis （CAG） rats by regulating the interleukin-17（IL-17）/extracellular regulated protein kinases（ERK）/CCAAT enhancer binding protein β（C/EBPβ）signaling pathway， thereby providing new theoretical evidence for the treatment of CAG with classic traditional Chinese medicine formulas. MethodsA CAG rat model was established by using the combined factor method. After successful modeling， the rats were randomly divided into the model group， low-， medium-， and high-dose groups （0.549， 1.098， 2.196 g·kg^-1， respectively） of BXT， and the positive drug group （vitacoenzyme， 0.3 g·kg^-1）. A normal control group was also set up. After 8 weeks of intervention， the pathological changes of gastric tissue were evaluated. The enzyme-linked immunosorbent assay （ELISA） was used to detect the contents of IL-17， tumor necrosis factor-α （TNF-α）， cyclooxygenase-2 （COX-2）， and C/EBPβ in serum， as well as the contents of EMT markers in gastric mucosal tissue including E-cadherin， N-cadherin， and vimentin. The immunohistochemistry method was employed to determine the localization and protein expression levels of IL-17， p-ERK， and C/EBPβ in gastric mucosal tissue. Western blot was used to detect the protein expressions of C/EBPβ， ERK， and its phosphorylated form （p）-ERK in gastric mucosa. Real-time polymerase chain reaction （Real-time PCR） was applied to measure the mRNA expression levels of ERK， COX-2， and C/EBPβ in gastric mucosa. ResultsCompared with those in the normal control group， the rats in the model group showed gastric mucosal glandular atrophy and inflammatory cell infiltration. The protein and their related mRNA expressions of C/EBPβ， ERK， and p-ERK in gastric mucosa were significantly increased （P<0.05，P<0.01）. The levels of IL-17， TNF-α， COX-2， and C/EBPβ in serum were significantly increased （P<0.01）. The contents of N-cadherin and vimentin in gastric mucosal tissue were significantly increased， while the content of E-cadherin was significantly decreased （P<0.01）. Compared with the model group， after intervention with different doses of BXT， the pathological damage of the gastric mucosa was improved to varying degrees. The protein and mRNA expressions of C/EBPβ， ERK， and p-ERK in gastric mucosa were significantly reduced （P<0.05，P<0.01）. The levels of IL-17， TNF-α， COX-2， and C/EBP β in serum were significantly decreased （P<0.01）. The contents of N-cadherin and vimentin in gastric mucosa tissue were decreased， while the content of E-cadherin was increased （P<0.05，P<0.01）. ConclusionBXT can effectively improve the pathological damage of gastric mucosal tissue in CAG rats. Its action mechanism may be related to reducing the levels of IL-17 and TNF-α in serum， regulating the IL-17/ERK/C/EBPβ signaling pathway and inhibiting the EMT process.

Liver cancer is one of the most common malignant tumors in the digestive system and ranks sixth among newly diagnosed malignant tumors worldwide. Transforming growth factor-β （TGF-β） regulates cell differentiation， proliferation， apoptosis， and other physiological and pathological mechanisms and exerts cancer-suppressive and pro-cancerous dual effects in the process of tumor development. In recent years， with the continuous exploration of the mechanism of liver cancer， it has been found that the conversion of the cancer-suppressive effect into a pro-cancerous effect of this pathway plays a key role in the development of liver cancer. Traditional Chinese medicine （TCM） provides a unique perspective for the classification， diagnosis， and treatment of liver cancer with its comprehensive regulatory effects of multi-components， multi-targets， and multi-pathways. This paper summarized that the cancer-suppressive mechanisms of the TGF-β signaling pathway included promoting cancer cell cycle arrest， apoptosis， autophagy， et al， while the pro-cancerous mechanisms included promoting cancer cell proliferation， invasion and metastasis， immunosuppression， angiogenesis， et al. The TCM compounds intervening this pathway were sorted out， including Jianpi Huayu compound， Fuyang Baoyuan compound， Yipi Yanggan compound， Fuzheng Jiedu compound， compound Astragalus and Salvia， Biejia Jianwan， Dahuang Zhechong pill， and Qingxiang powder. The single TCMs mainly included Schizocapsa plantaginea， Dendrobii Caulis， Gleditsia sinensis， and Dracaena cochinchinensis. The active ingredients of TCM are mainly concentrated on flavonoids， alkaloids， glycosides， phenolics， terpenoids， polysaccharides， and other kinds of compounds. At the same time， it summarized that the liver cancer inhibition mechanism of TCM by regulating this pathway mainly included promoting apoptosis of liver cancer cells， blocking the cell cycle， and inhibiting liver cancer cell proliferation， migration， invasion， angiogenesis， immune escape， etc. The mechanism aims to give full play to the advantages of TCM and precisely regulate the TGF-β signal， thereby exerting positive anti-tumor effects， opening up a new direction for the precise targeted treatment of liver cancer， and providing a scientific basis and a new strategy for the application of TCM in the treatment of liver cancer.

Liver cancer is one of the most common malignant tumors in the digestive system and ranks sixth among newly diagnosed malignant tumors worldwide. Transforming growth factor-β （TGF-β） regulates cell differentiation， proliferation， apoptosis， and other physiological and pathological mechanisms and exerts cancer-suppressive and pro-cancerous dual effects in the process of tumor development. In recent years， with the continuous exploration of the mechanism of liver cancer， it has been found that the conversion of the cancer-suppressive effect into a pro-cancerous effect of this pathway plays a key role in the development of liver cancer. Traditional Chinese medicine （TCM） provides a unique perspective for the classification， diagnosis， and treatment of liver cancer with its comprehensive regulatory effects of multi-components， multi-targets， and multi-pathways. This paper summarized that the cancer-suppressive mechanisms of the TGF-β signaling pathway included promoting cancer cell cycle arrest， apoptosis， autophagy， et al， while the pro-cancerous mechanisms included promoting cancer cell proliferation， invasion and metastasis， immunosuppression， angiogenesis， et al. The TCM compounds intervening this pathway were sorted out， including Jianpi Huayu compound， Fuyang Baoyuan compound， Yipi Yanggan compound， Fuzheng Jiedu compound， compound Astragalus and Salvia， Biejia Jianwan， Dahuang Zhechong pill， and Qingxiang powder. The single TCMs mainly included Schizocapsa plantaginea， Dendrobii Caulis， Gleditsia sinensis， and Dracaena cochinchinensis. The active ingredients of TCM are mainly concentrated on flavonoids， alkaloids， glycosides， phenolics， terpenoids， polysaccharides， and other kinds of compounds. At the same time， it summarized that the liver cancer inhibition mechanism of TCM by regulating this pathway mainly included promoting apoptosis of liver cancer cells， blocking the cell cycle， and inhibiting liver cancer cell proliferation， migration， invasion， angiogenesis， immune escape， etc. The mechanism aims to give full play to the advantages of TCM and precisely regulate the TGF-β signal， thereby exerting positive anti-tumor effects， opening up a new direction for the precise targeted treatment of liver cancer， and providing a scientific basis and a new strategy for the application of TCM in the treatment of liver cancer.

ObjectiveTo explore the effects of Jingui Shenqiwan （JSW） and Liuwei Dihuangwan （LDW） on the reproductive ability and brain function of normal mice and compare the actions of the two medications. MethodsSeven groups of female and male mice were divided at a ratio of 2∶1. Except for the control group， the other six groups were as follows： a group of both males and females receiving JSW （3.0 g·kg^-1）， a group of both males and females receiving LDW （4.5 g·kg^-1）， a group of males receiving water and females receiving JSW， a group of males receiving water while females receiving LDW， a group of females receiving water while males receiving JSW， and a group of females receiving water while males receiving LDW. Each group was administered the drug for 14 days and then caged together at a 2∶1 （female∶male） ratio to detect the number of pregnant mice and calculate the pregnancy rate. Pregnant mice continued receiving the drug until they naturally gave birth， which was followed by the observation of newborn mice， calculation of their average number， and the measurement of the offspring's preference for sugar water and neonatal recognition index. At the end of the experiment， the weights of the thymus and spleen were measured to calculate the organ coefficients， and mRNA or protein expression was analyzed in the brain and testes or ovaries. A 1% sucrose solution was used to examine the euphoria of their brain reward systems， while novel object recognition test （NOR） was applied to assess their memory capabilities. mRNA expression was detected using real-time quantitative polymerase chain reaction （Real-time PCR） assay， and protein expression was analyzed with Western blot. ResultsCompared with the control group， oral administration of JSW to both male and female mice for 14 days significantly increased the pregnancy rate of female mice on day 2 after being caged together （P<0.05）， while LDW showed a trend but no statistical significance. Additionally， compared with the control group， JSW could upregulate the gene expression of gonadotropin-releasing hormone （GnRH） in the thalamus， as well as reproductive stem cell factor （SCF） and tyrosine kinase receptor （c-Kit） in the testes and reproductive stem cell marker mouse vasa homologue （MVH） in the ovaries， upregulate the expression of proteins influencing neuronal functional activity， such as brain-derived neurotrophic factor （BDNF）， in hippocampal neurons （P<0.05）， and enhance sucrose preference in male mice （P<0.05）. Compared with the control group， JSW significantly increased sucrose preference and novel object recognition index in offspring mice （P<0.05）， which was related to the upregulation of hippocampal dopamine D1 receptor （D1R） and N-methyl-D-aspartate receptor （Nmdar） gene expression. Compared with the control group， both JSW and LDW could upregulate the protein expression of glucocorticoid receptor （GR）， BDNF， and tyrosine kinase receptor B （TrkB） in the hippocampus of offspring mice （P<0.05）. ConclusionJSW significantly enhances the reproductive ability of normal mice， which is not only related to the release of gonadotropin but also associated with its regulation of brain function. Additionally， JSW has a certain regulatory effect on the brain function of the offspring mice.

ObjectiveRetinal vein occlusion （RVO） is the second most common vascular disease leading to vision loss. Since its pathogenesis remains unclear， current Western medical treatments primarily target complications such as macular edema and neovascularization. The main therapeutic approaches include intravitreal injections of anti-vascular endothelial growth factor （VEGF） agents or corticosteroids， laser photocoagulation， and pars plana vitrectomy. However， these treatments cannot fully reverse disease progression or structural damage. Traditional Chinese medicine （TCM） has unique advantages in the clinical diagnosis and treatment of RVO， and integrated Chinese and Western medicine approaches may offer better clinical outcomes. This study， based on the clinical manifestations of RVO， systematically reviews the existing literature and evaluates the alignment of current RVO animal models with clinical manifestations. The aim is to identify the characteristics and limitations of existing models and provide recommendations and prospects for developing RVO animal models featuring the combination of disease and syndrome. MethodsDatabases including CNKI， Wanfang Data， PubMed， and Web of Science were searched with the keywords of "retinal vein occlusion" and "animal model". Model characteristics were assessed based on the diagnostic criteria for diseases and syndromes in both TCM and Western medicine. The alignment of each model with clinical manifestations was analyzed and evaluated. ResultsThe available RVO models were primarily established via methods such as laser photocoagulation， photodynamic therapy， diathermy， intravitreal drug injection， and mechanical modeling. These models demonstrated moderate overall alignment with clinical manifestations， mainly reflecting disease characteristics. However， they generally lack representation of TCM syndrome features. ConclusionExisting RVO models are predominantly based on Western medicine and lack TCM syndrome features. Western medical treatments for RVO have certain limitations， while syndrome differentiation and treatment in TCM offer potential advantages. Future research should focus on developing disease-syndrome integrated animal models that incorporate both pathological features and TCM syndrome characteristics. This approach will enhance the design of RVO models and facilitate both basic and clinical research， which make it a scientifically valuable and necessary endeavor.

ObjectiveRetinal vein occlusion （RVO） is the second most common vascular disease leading to vision loss. Since its pathogenesis remains unclear， current Western medical treatments primarily target complications such as macular edema and neovascularization. The main therapeutic approaches include intravitreal injections of anti-vascular endothelial growth factor （VEGF） agents or corticosteroids， laser photocoagulation， and pars plana vitrectomy. However， these treatments cannot fully reverse disease progression or structural damage. Traditional Chinese medicine （TCM） has unique advantages in the clinical diagnosis and treatment of RVO， and integrated Chinese and Western medicine approaches may offer better clinical outcomes. This study， based on the clinical manifestations of RVO， systematically reviews the existing literature and evaluates the alignment of current RVO animal models with clinical manifestations. The aim is to identify the characteristics and limitations of existing models and provide recommendations and prospects for developing RVO animal models featuring the combination of disease and syndrome. MethodsDatabases including CNKI， Wanfang Data， PubMed， and Web of Science were searched with the keywords of "retinal vein occlusion" and "animal model". Model characteristics were assessed based on the diagnostic criteria for diseases and syndromes in both TCM and Western medicine. The alignment of each model with clinical manifestations was analyzed and evaluated. ResultsThe available RVO models were primarily established via methods such as laser photocoagulation， photodynamic therapy， diathermy， intravitreal drug injection， and mechanical modeling. These models demonstrated moderate overall alignment with clinical manifestations， mainly reflecting disease characteristics. However， they generally lack representation of TCM syndrome features. ConclusionExisting RVO models are predominantly based on Western medicine and lack TCM syndrome features. Western medical treatments for RVO have certain limitations， while syndrome differentiation and treatment in TCM offer potential advantages. Future research should focus on developing disease-syndrome integrated animal models that incorporate both pathological features and TCM syndrome characteristics. This approach will enhance the design of RVO models and facilitate both basic and clinical research， which make it a scientifically valuable and necessary endeavor.

OBJECTIVE To explore a model for constructing a platform for medical institution formulation and provide insights for promoting their development. METHODS By systematically reviewing the development status and challenges of medical institution preparations in China， and based on the theory of industry-university-research collaborative innovation， the organizational structure， collaborative processes， and safeguard mechanisms of the platform were designed. RESULTS & CONCLUSIONS Medical institution formulations in China mainly faced challenges such as weak research and development （R&D） capacity， uneven quality standards， and blocked transformation pathways. This study established a full-chain， whole- industry collaborative innovation network covering the government， medical institutions， universities/research institutes， pharmaceutical enterprises， and the market， forming a new “government-industry-university-research-application” five-in-one platform model for medical institution formulations. By establishing mechanisms such as multi-entity collaborative cooperation， full- chain intellectual property management， contribution-based benefit distribution， staged risk-sharing， and third-party evaluation， the model clarified the responsibilities and collaborative pathways of all parties. The new model highlights the whole-process transformation of clinical experience-based prescriptions， enabling precise alignment between clinical needs and technological R&D， as well as between preparation achievements and industrial transformation. While breaking down the barriers of traditional platform construction， it effectively achieves optimal resource allocation and complementary advantages， addresses problems emerging in the development of medical institution preparations， and provides reference value for the formulation of relevant systems.

Objective: To analyze adverse event following immunization(AEFI) with the domestic bivalent human papilloma virus (HPV) vaccine among female students in primary, junior, and senior high schools in Hebei Province from 2022 to 2024, aiming to provide evidence for the vaccination program. Methods: On May 14, 2025, AEFI case data and vaccination data for the domestic bivalent HPV vaccine among female students in primary, junior, and senior high schools in Hebei Province from 2022 to 2024 were collected from the China Disease Control and Prevention Information System and the Hebei Provincial Immunization Program Information Management System, respectively. Statistical analysis was performed by using descriptive and analytical epidemiological methods, with intergroup comparisons conducted by using the Chi square test or Fisher s exact probability test. Results: From 2022 to 2024, a total of 817 900 doses of the domestic bivalent HPV vaccine were administered to female students in primary, junior, and senior high schools in Hebei Province. A total of 68 AEFI cases were reported, comprising 57 common vaccine reactions, 7 rare vaccine reactions, 3 coincidental events, and 1 psychogenic reaction. The overall AEFI reporting rate was 8.31 per 100 000 doses, 4 cases (2.30/100 000 doses), 31 cases (8.73/100 000 doses), and 33 cases (11.41/100 000 doses) were reported in 2022, 2023, and 2024, respectively, with a statistically significant difference across years ( χ 2=10.97, P <0.01). The reporting rates for common and rare vaccine reactions were 6.97 per 100 000 doses and 0.86 per 100 000 doses, respectively. The AEFI reporting rates were 15.14 per 100 000 doses among primary school girls and 8.20 per 100 000 doses among secondary school girls, though the difference was not statistically significant (Fisher s exact test, P =0.30). The reporting rate was higher after the first dose (10.91/100 000 doses) than after the second dose (5.96/100 000 doses; χ 2=5.85, P =0.02).The second quarter recorded the highest AEFI reporting rate at 11.21 per 100 000 doses. The majority of AEFI cases (56 cases, 82.35%) occurred within 24 hours post vaccination. Conclusion The domestic bivalent HPV vaccine demonstrates a favorable safety profile among female students in Hebei Province, with a low overall AEFI reporting rate that consisted predominantly of general reactions and occasional cardiac related reactions.

Hepatocellular carcinoma（HCC）， as one of the common malignant tumours， has seen a continuous rise in incidence and mortality worldwide， posing a serious threat to human health. However， traditional treatments have certain limitations， therefore， the exploration of new therapeutic strategies is particularly urgent. In recent years， with in-depth research on the regulatory mechanisms of microRNA（miRNA） in tumour occurrence and development， it has become new targets for HCC diagnosis and treatment. As a traditional treatment method， Chinese medicine， due to its multi-component， multi-pathway， and multi-target overall regulatory characteristics， shows broad prospects in treating HCC by regulating miRNAs. Accordingly， this paper reviews recent studies on the role of miRNAs in HCC and research advances in traditional Chinese medicine interventions， finding that various miRNAs play key roles in HCC cell cycle regulation， proliferation and apoptosis， invasion and metastasis， immune microenvironment， and drug resistance. It summarises how active ingredients， extracts， medicinal pairs， and formulas of Chinese medicine act on specific miRNAs to regulate their downstream target gene expression， affecting the malignant behaviour of HCC cells and exerting anti-cancer effects. This study aims to provide a theoretical basis for miRNAs as potential biomarkers and therapeutic targets for HCC， as well as to offer new ideas for developing miRNA-based targeted Chinese medicine therapies.