ObjectiveThis study aimed to investigate whether Bushen Tongluo prescription inhibits macrophage polarization by regulating the Wnt3a/β-catenin signaling pathway， thereby reducing epithelial-mesenchymal transition and excessive extracellular matrix deposition， in order to elucidate the anti-pulmonary fibrosis mechanisms of Bushen Tongluo prescription and provide a new theoretical basis for the clinical treatment of pulmonary fibrosis. MethodsFifty male Sprague-Dawley （SD） rats were randomly divided into a blank group， model group， pirfenidone group， and high- and low-dose Bushen Tongluo prescription groups. Except for the blank group， the pulmonary fibrosis model was established by intratracheal instillation of bleomycin. Intervention was initiated on day 28 after modeling. The high- and low-dose Bushen Tongluo prescription groups were administered Bushen Tongluo prescription at doses of 30.88， 15.44 g·kg^-1， respectively， by intragastric gavage. The pirfenidone group was administered pirfenidone capsules at 110 mg·kg^-1 by intragastric gavage. The blank and model groups were given an equal volume of normal saline by gavage， once daily for 90 days. After treatment， the level of transforming growth factor-β₁ （TGF-β₁） in bronchoalveolar lavage fluid （BALF） was detected by enzyme-linked immunosorbent assay （ELISA）. Morphological changes in lung tissue and the collagen volume fraction were compared. The protein distribution and expression of E-cadherin， cytokeratin 19， α-smooth muscle actin （α-SMA）， vimentin， collagen type Ⅰ （Col Ⅰ）， and collagen type Ⅲ （Col Ⅲ） in lung tissue were detected by immunohistochemistry. The protein distribution and expression of CD68， arginase-1 （Arg-1）， inducible nitric oxide synthase （iNOS）， Wnt3a， and β-catenin in lung tissue were detected by immunofluorescence. The protein expression of Wnt3a and β-catenin in lung tissue was detected by Western blot， and the mRNA expression of Wnt3a and β-catenin was detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. ResultsCompared with the blank group， a large number of inflammatory cells infiltrated the airway walls， alveolar spaces， and interstitial tissue in the model group， with obvious fibrous tissue hyperplasia. The level of TGF-β₁ in BALF was significantly increased. The protein expression of E-cadherin and cytokeratin 19 in lung tissue was decreased， whereas the protein expression of α-SMA， Vimentin， Wnt3a， β-catenin， Col Ⅰ， and Col Ⅲ was increased. The fluorescence-positive area ratios of CD68， Arg-1， iNOS， Wnt3a， and β-catenin in lung tissue were increased. The protein and mRNA expression levels of Wnt3a and β-catenin in lung tissue were significantly increased （P<0.01）. Compared with the model group， all treatment groups showed varying degrees of improvement in inflammatory cell infiltration and fibrous tissue hyperplasia in the airway walls， alveolar spaces， and interstitial tissue， decreased TGF-β₁ levels in BALF， increased protein expression of E-cadherin and cytokeratin 19 in lung tissue， decreased protein expression of α-SMA， Vimentin， Col Ⅰ， and Col Ⅲ， decreased fluorescence-positive area ratios of CD68， Arg-1， iNOS， Wnt3a， and β-catenin in lung tissue， and decreased protein and mRNA expression levels of Wnt3a and β-catenin in lung tissue （P<0.05， P<0.01）. ConclusionBushen Tongluo prescription can improve bleomycin-induced pulmonary fibrosis in rats by inhibiting epithelial-mesenchymal transition and reducing excessive extracellular matrix deposition. The mechanism may be related to inhibition of the Wnt3a/β-catenin signaling pathway and the macrophage polarization mediated by this pathway.

Non-alcoholic fatty liver disease （NAFLD） is one of the most prevalent forms of liver diseases globally. Its progression can lead to cirrhosis and end-stage liver disease， and there is currently a lack of effective pharmacological treatments. Adenosine monophosphate-activated protein kinase （AMPK）， as a regulatory hub for maintaining cellular energy homeostasis， can coordinate key cellular processes such as adipogenesis， glucose metabolism， and mitochondrial functions. Its activation exerts metabolic regulatory effects through pathways including inhibiting lipogenesis， enhancing mitochondrial β-oxidation， regulating inflammation and oxidative stress， and promoting autophagy. Accordingly， AMPK emerges as a potential target for the prevention and treatment of NAFLD. Traditional Chinese Medicine （TCM）， with low toxicity， high accessibility， and multi-component， multi-target synergistic effects， has demonstrated unique value in NAFLD treatment， particularly showing notable advantages in regulating the AMPK signaling pathway. Sichuan is known as the treasure house of TCM， and the active components of its authentic medicinal materials such as Coptidis Rhizoma not only reflect regional characteristics in AMPK signaling regulation but also form a multi-level metabolic regulatory network through crosstalk with pathways such as sirtuin 1 （SIRT1） and peroxisome proliferator-activated receptor α （PPARα）. They can achieve specific regulation by directly activating AMPK and modulating upstream and downstream targets， exerting prominent effects in ameliorating hepatic steatosis and inflammation. This study systematically reviews the research findings on TCM for the prevention and treatment of NAFLD over the past five years， elaborating the mechanisms by which TCM treats NAFLD through regulating the AMPK signaling pathway. It aims to provide new perspectives and references for clinical diagnosis and treatment， basic research， and drug development.

ObjectiveTo observe the effects of the Fuyuan Tongluo prescription （composed of Astragali Radix， Carthami Flos， Spatholobi Caulis， Liquidambaris Fructus， Lycopodii Herba， Centellae Herba， etc.） in the treatment of restenosis with collateral obstruction syndrome after interventional operation of lower limb arteriosclerosis obliterans， and its impact on the primary patency rate. MethodsA total of 88 patients with collateral obstruction syndrome after interventional surgery for lower limb arteriosclerosis obliterans were randomly divided into two groups. The control group （n₁=44） received dual antiplatelet therapy with aspirin and clopidogrel. The observation group （n₂=44） was treated with Fuyuan Tongluo prescription non-decocted granules in addition to aspirin and clopidogrel. Both groups received treatment for 24 weeks and were followed up for 36 weeks. The changes in primary patency rate， symptom scores， ankle-brachial index （ABI）， coagulation function， and inflammatory markers before and after treatment were compared between the two groups. ResultsFor primary patency rate， after 36 weeks of treatment， the observation group had a significantly better primary patency rate than the control group （χ²=4.14，P<0.05）. After 24 weeks of treatment， there was no significant difference in primary patency rate between the two groups. Clinical efficacy comparison： Based on symptom quantification scores， and using the Nimodipine method as a reference， the overall efficacy of the observation group was superior to that of the control group after 24 weeks of treatment （χ²=2.24，P<0.05）. ABI levels： The observation group had a higher ABI than the control group after 24 and 36 weeks of treatment （P<0.05）. Coagulation function indicators： After 24 and 36 weeks of treatment， D-dimer and fibrinogen levels in both groups were lower than before treatment （P<0.05）. Inflammatory markers： After 24 and 36 weeks of treatment， CRP levels in the observation group were lower than those in the control group （P<0.05）. There were no significant differences in white blood cell （WBC） and erythrocyte sedimentation rate （ESR） levels before and after treatment between the two groups. ConclusionAdding Fuyuan Tongluo prescription non-decocted granules to dual antiplatelet therapy can improve the primary patency rate of the affected vessels in patients with lower limb arteriosclerosis obliterans after interventional surgery. Longer use of Fuyuan Tongluo prescription can significantly improve clinical symptoms， demonstrating clinical application value.

ObjectiveTo observe the effects of the Fuyuan Tongluo prescription （composed of Astragali Radix， Carthami Flos， Spatholobi Caulis， Liquidambaris Fructus， Lycopodii Herba， Centellae Herba， etc.） in the treatment of restenosis with collateral obstruction syndrome after interventional operation of lower limb arteriosclerosis obliterans， and its impact on the primary patency rate. MethodsA total of 88 patients with collateral obstruction syndrome after interventional surgery for lower limb arteriosclerosis obliterans were randomly divided into two groups. The control group （n₁=44） received dual antiplatelet therapy with aspirin and clopidogrel. The observation group （n₂=44） was treated with Fuyuan Tongluo prescription non-decocted granules in addition to aspirin and clopidogrel. Both groups received treatment for 24 weeks and were followed up for 36 weeks. The changes in primary patency rate， symptom scores， ankle-brachial index （ABI）， coagulation function， and inflammatory markers before and after treatment were compared between the two groups. ResultsFor primary patency rate， after 36 weeks of treatment， the observation group had a significantly better primary patency rate than the control group （χ²=4.14，P<0.05）. After 24 weeks of treatment， there was no significant difference in primary patency rate between the two groups. Clinical efficacy comparison： Based on symptom quantification scores， and using the Nimodipine method as a reference， the overall efficacy of the observation group was superior to that of the control group after 24 weeks of treatment （χ²=2.24，P<0.05）. ABI levels： The observation group had a higher ABI than the control group after 24 and 36 weeks of treatment （P<0.05）. Coagulation function indicators： After 24 and 36 weeks of treatment， D-dimer and fibrinogen levels in both groups were lower than before treatment （P<0.05）. Inflammatory markers： After 24 and 36 weeks of treatment， CRP levels in the observation group were lower than those in the control group （P<0.05）. There were no significant differences in white blood cell （WBC） and erythrocyte sedimentation rate （ESR） levels before and after treatment between the two groups. ConclusionAdding Fuyuan Tongluo prescription non-decocted granules to dual antiplatelet therapy can improve the primary patency rate of the affected vessels in patients with lower limb arteriosclerosis obliterans after interventional surgery. Longer use of Fuyuan Tongluo prescription can significantly improve clinical symptoms， demonstrating clinical application value.

BACKGROUND:Pinoresinol diglucoside promotes bone formation and bone matrix synthesis and accelerates bone tissue repair.However,the mechanism of action and effects of this compound in osteoblasts need to be further explored. OBJECTIVE:To investigate the effect and mechanism of action of pinoresinol diglucoside on dexamethasone-treated osteoblasts based on the Wnt/β-catenin signaling pathway. METHODS:Different concentrations of dexamethasone groups and pinoresinol diglucoside groups were set to treat osteoblasts for 24 hours,and the optimal intervention concentrations were screened.Osteoblasts were treated with dexamethasone,pinoresinol diglucoside and inhibitor XAV-939.Then,control group,dexamethasone group,XVA-939 group,pinoresinol diglucoside group,pinoresinol diglucoside+XVA-939 group were set up.Cell counting kit-8 assay was used to detect cell activity.Alkaline phosphatase activity and caspase3/7 enzyme activity in cells were detected.Annexin V/PI staining and EdU assay were used to detect cell apoptosis and proliferation.Real-time qPCR and western blot were used to detect the mRNA and protein expression levels of Wnt3a,β-catenin,c-myc,osteocalcin,and type I collagen,respectively. RESULTS AND CONCLUSION:After dexamethasone and pinoresinol diglucoside intervened in osteoblasts for 24 hours,10 μmol/L dexamethasone was found to be the optimal intervention concentration for cell inhibition,and cell proliferation was most pronounced at a concentration of pinoresinol diglucoside of 100 μmol/L.Compared with the dexamethasone group,alkaline phosphatase activity was significantly enhanced(P<0.05)and caspase3/7 enzyme activity was significantly reduced(P<0.05)in the pinoresinol diglucoside group.Annexin V/PI staining and cell proliferation assay by EdU method showed that pinoresinol diglucoside inhibited apoptosis and promoted proliferation of osteoblasts after dexamethasone intervention.The mRNA and protein expression levels of Wnt3a,β-catenin,c-myc,osteocalcin,and type I collagen were significantly higher in the pinoresinol diglucoside group and pinoresinol diglucoside+XVA-939 group compared with the dexamethasone and XVA-939 groups(P<0.05).To conclude,pinoresinol diglucoside can inhibit osteoblast apoptosis after dexamethasone intervention,protect osteoblast activity and promote osteoblast proliferation by activating the Wnt/β-catenin signaling pathway,which may play a role in delaying steroid-induced osteonecrosis of the femoral head.

In recent years, studies have demonstrated that exosomes can replace mesenchymal stem cell for chronic wound repair. However, exosomes have some problems such as poor targeting, low availability and low yield, which collectively limit their therapeutic efficacy in chronic wound treatment. Maximizing the therapeutic benefits of exosomes is the primary challenge that needs to be overcome when used for chronic wound repair. Studies have shown that the treatment potential of exosomes can be further developed by pretreatment and engineering modification of exosomes. This article reviewed the research progress of exosome pretreatment and engineering modification in chronic wound repair, and provided reference for subsequent research and clinical application.

Objective To analyze the medication law and compatibility characteristics of TCM compounds for the treatment of myocardial infarction in the national patent database.Methods TCM compounds for treating myocardial infarction were retrieved from CNIPA patent publication website.A prescription database was built using Excel 2019 software to statistically analyze the frequency of medicinal use and their properties,taste and meridian tropism;SPSS Modeler 18.0 software was used to analyze the association rules of drugs;a network of Chinese materia medica co-occurrence was constructed using Cytoscape 3.10.0,and systematic clustering analysis was performed on the Chinese materia medica in the core network.Results A total of 146 patents of TCM compounds were included,involved 440 kinds of Chinese materia medica.High frequency drugs included Salviea Miltiorrhizae Radix et Rhizoma,Chuanxiong Rhizoma,Angelicae Sinensis Radix,Glycyrrhizae Radix et Rhizoma,etc.The main property was warm,the main tastes were bitter,sweet and pungent,and the medicines mostly belongs to the liver meridian,heart meridian and spleen meridians.Commonly used medicinal pairs included Angelicae Sinensis Radix-Chuanxiong Rhizoma,Astragali Radix-Salviea Miltiorrhizae Radix et Rhizoma,Paeoniae Radix Rubra-Angelicae Sinensis Radix,etc.Commonly used tripartite combinations included Paeoniae Radix Rubra-Chuanxiong Rhizoma-Angelicae Sinensis Radix,Carthami Flos-Angelicae Sinensis Radix-Chuanxiong Rhizoma,Carthami Flos-Chuanxiong Rhizoma-Angelicae Sinensis Radix,etc.Clustering analysis showed four types of combinations.Conclusion TCM compound patents for the treatment of myocardial infarction is based on promoting blood circulation,removing blood stasis,and relieving pain,while also using methods such as eliminating phlegm,tonifying qi,warming yang,and nourishing yin.It can provide references for clinical medication.

This study identified CLDN14 gene variants in two Chinese Han pedigrees with autosomal recessive deafness 29 through whole-exome sequencing. The proband in pedigree 1 carried the known pathogenic variant c.301G>A (p.Gly101Arg) and a novel variant c.370delC (p.Leu124Serfs*33), classified as pathogenic according to the American College of Medical Genetics and Genomics standards (PVS1+PS2+PM2). The proband in pedigree 2 carried two novel variants, c.51dupC (p.Met18Hisfs*142) and c.74_76delCCA (p.Thr25del), both classified as likely pathogenic. Short tandem repeat analysis confirmed the familial relationship in pedigree 1. Prenatal diagnosis revealed that the fetuses in both pedigrees had inherited only a single heterozygous variant. Postnatal hearing screening in pedigree 1 and a 3-year follow-up in pedigree 2 revealed no abnormalities.

Objective:To investigate whether there is an association between the total dose of breast cancer radiotherapy, the mean dose of radiation field involving the heart and its substructures, and the long-term incidence of coronary heart disease (CHD) in patients.Methods:A retrospective analysis was conducted on 1125 patients with breast cancer who received radiotherapy with radiation fields involving the hear at Beijing Hospital from January 2009 to June 2022. The heart and its substructures of 54 patients were manually delineated, trained an automatic delineation model, and applied this model to the original radiotherapy planning images to automatically extract dosimetric parameters for the heart and substructures in the original plan. Based on the follow-up results, 1125 breast cancer patients were categorized into the CHD event group ( n=19) and non-event group ( n=1106). Wilcoxon rank-sum test, Chi-square test and adjustment for confounding factors using inverse probability weighting were used to compare the mean radiation dose received by the heart and its substructures, age at presentation, history of smoking, history of alcohol consumption, history of hypertension, and history of diabetes between two groups. The influencing factors of CHD were analyzed by univariate and multivariate logistic regression models. Results:The mean heart dose ( P=0.035), mean dose of right atrium ( P=0.049), right coronary artery ( P=0.013), septum ( P=0.045), and right ventricle ( P=0.039) of the event group were higher than that of the non-event group, and the differences were statistically significant. History of alcohol consumption was an independent risk factor for long-term CHD events in the breast cancer patients ( OR=7.35,95% CI: 1.56-25.58, P=0.004). After adjusting for confounding factors using inverse probability weighting, age at presentation was an independent risk factor for long-term CHD events ( OR=1.03, 95% CI: 1.01-1.05, P=0.004). Conclusions:In the breast cancer population with traditional high-risk factors of CHD receiving radiotherapy, the possibility of CHD probably remains high even if the dose of radiation field involving the heart and its substructures is low. Compared to traditional risk factors of CHD, the mean dose to the heart and its substructures in the radiation field of breast cancer patients exerts less impact on the occurrence of CHD after radiotherapy.

Objective:To investigate analgesic effect of fire needle on postherpetic neuralgia(PHN)rats and its effect on IL-10/β-endorphin(β-EP)signaling pathway.Methods:Forty rats were randomly divided into 4 groups:control group,model group,fire needle group and drug group,with 10 rats in each group.PHN model was constructed by intraperitoneal injection of resin toxin.Af-ter successful modeling,fire needle group was intervened by fire needle at L4～6 Jiaji points,and drug group was intervened by intra-peritoneal injection of gabapentin.Von Frey electronic pain meter was used to measure paw withdrawal mechanical threshold(PW-MT)of rats in each group.Thermal latency of paw withdrawal(PWTL)of rats was measured by thermal radiation stimulator.Prosta-glandin E2(PGE2)and substance P(SP)in dorsal root ganglion tissues,serum IL-6,TNF-α and IL-1β levels were detected by ELI-SA.IL-10 and β-EP protein expressions in spinal cord of rats were detected by Western blot.Results:Compared with control group,PWMT of model group was decreased significantly(P<0.05),PWTL,levels of PGE2 and SP in spinal cord tissue and levels of IL-6,TNF-α and IL-1β in serum were increased significantly(P<0.05),IL-10 and β-EP protein expressions in spinal dorsal horn were decreased significantly(P<0.05).Compared with model group,PWMT of fire needle group and drug group was significantly increased(P<0.05),PWTL,PGE2 and SP in spinal cord tissue and serum IL-6,TNF-α and IL-1β levels were significantly decreased(P<0.05),IL-10 and β-EP protein expressions in spinal dorsal horn were significantly increased(P<0.05).Conclusion:Fire needle can improve pain response of PHN rats and reduce peripheral blood inflammation level,which may be related to activation of IL-10/β-EP signaling pathway.