BACKGROUND:Autologous bone,allogeneic bone or artificial bone has been used to promote bone defect repair in the clinic,but the rate of non-healing is still high.The key is to ignore the importance of periosteum in the bone healing process.In the early stage of the project,the project team constructed an electrospinning membrane loaded with vascular endothelial growth factor to highly simulate the intramembranous osteogenesis of natural periosteum at the bone defect site,which promoted bone regeneration to a certain extent.However,the injured area often faces the dilemma of severe inflammatory response mediated by macrophages and lack of seed cells,resulting in the risk of inactivation or diffusion of delivered biological factors.Therefore,it is necessary to further optimize and coordinate the immune regulation and angiogenesis functions of biomimetic periosteum to promote bone repair.OBJECTIVE:To investigate the physicochemical properties of stem cell-engineered bionic periosteum and its role in regulating the inflammatory microenvironment to promote bone repair.METHODS:By combining L-polylactic acid-based microsol electrospinning,type Ⅰ collagen self-assembly and gel stem cell transplantation technology,a bionic periosteum(M@C-B)was constructed,in which the core layer loaded with vascular endothelial growth factor and the shell layer delivered bone marrow mesenchymal stem cells to regulate the immune microenvironment of bone defects.The physicochemical properties of the periosteum were characterized by scanning electron microscopy,transmission electron microscopy,and Fourier transform infrared spectroscopy.A co-culture system was established between the bionic periosteum and macrophages,bone marrow mesenchymal stem cells and human umbilical vein endothelial cells to explore immune regulation and in vitro osteogenic and angiogenic abilities.Finally,the osteogenic properties of the stem cell engineered bionic periosteum were further verified in a rat femoral condyle defect model.RESULTS AND CONCLUSION:(1)Transmission electron microscopy results showed that the micro-sol electrospinning(MS)formed a distinct core-shell structure.Scanning electron microscopy indicated that after the assembly of the collagen-l artificial periosteum(M@C)on the surface of the vascular endothelial growth factor-loaded micro-sol,a distinct"spider web-like"fibrous structure was deposited.Infrared spectroscopy further confirmed the successful self-assembly of collagen-l.Release experiments demonstrated that the M@C group mitigated the burst release phenomenon compared to the MS group,maintaining internal vascular endothelial growth factor activity and sustained release.(2)Live/dead cell staining and CCK-8 assay showed that bone marrow mesenchymal stem cells proliferated well and survived on three types of artificial periosteum:MS,purely aligned poly(L-lactic acid)(PLLA)surface self-assembled collagen-l artificial periosteum(PLLA@C),and vascular endothelial growth factor-loaded micro-sol fiber surface self-assembled collagen-l-bone marrow mesenchymal stem cells artificial periosteum(M@C-B).Among them,the M@C-B group had the highest number of live cells and the fastest proliferation rate.(3)Alkaline phosphatase staining,alizarin red staining,and osteopontin immunofluorescence staining showed that the PLLA@C and M@C-B groups significantly promoted osteogenic differentiation of bone marrow mesenchymal stem cells.Angiogenesis experiments demonstrated that the vascular endothelial growth factor-loaded groups(MS and M@C-B)had longer blood vessel lengths and more reticular vascular-like structures with more cross-linked nodes,with the M@C-B group being the most prominent.(4)Immunofluorescence and flow cytometry showed that artificial periosteum in the M@C-B group significantly inhibited the pro-inflammatory macrophage phenotype and promoted the polarization of macrophages towards the anti-inflammatory M2 phenotype.(5)In vivo studies further confirmed that the M@C-B group showed superior bone mineral density,trabecular thickness,relative bone volume,and trabecular spacing compared to other groups.(6)These results indicate that bone marrow mesenchymal stem cell-engineered artificial periosteum,through the rapid regulation of the bone defect immune microenvironment by the collagen-l-bone marrow mesenchymal stem cells outer phase and the sustained release of vascular endothelial growth factor by the micro-sol electrospinning core-shell structure of the inner phase,synergistically promotes bone healing.

BACKGROUND:Autologous bone,allogeneic bone or artificial bone has been used to promote bone defect repair in the clinic,but the rate of non-healing is still high.The key is to ignore the importance of periosteum in the bone healing process.In the early stage of the project,the project team constructed an electrospinning membrane loaded with vascular endothelial growth factor to highly simulate the intramembranous osteogenesis of natural periosteum at the bone defect site,which promoted bone regeneration to a certain extent.However,the injured area often faces the dilemma of severe inflammatory response mediated by macrophages and lack of seed cells,resulting in the risk of inactivation or diffusion of delivered biological factors.Therefore,it is necessary to further optimize and coordinate the immune regulation and angiogenesis functions of biomimetic periosteum to promote bone repair.OBJECTIVE:To investigate the physicochemical properties of stem cell-engineered bionic periosteum and its role in regulating the inflammatory microenvironment to promote bone repair.METHODS:By combining L-polylactic acid-based microsol electrospinning,type Ⅰ collagen self-assembly and gel stem cell transplantation technology,a bionic periosteum(M@C-B)was constructed,in which the core layer loaded with vascular endothelial growth factor and the shell layer delivered bone marrow mesenchymal stem cells to regulate the immune microenvironment of bone defects.The physicochemical properties of the periosteum were characterized by scanning electron microscopy,transmission electron microscopy,and Fourier transform infrared spectroscopy.A co-culture system was established between the bionic periosteum and macrophages,bone marrow mesenchymal stem cells and human umbilical vein endothelial cells to explore immune regulation and in vitro osteogenic and angiogenic abilities.Finally,the osteogenic properties of the stem cell engineered bionic periosteum were further verified in a rat femoral condyle defect model.RESULTS AND CONCLUSION:(1)Transmission electron microscopy results showed that the micro-sol electrospinning(MS)formed a distinct core-shell structure.Scanning electron microscopy indicated that after the assembly of the collagen-l artificial periosteum(M@C)on the surface of the vascular endothelial growth factor-loaded micro-sol,a distinct"spider web-like"fibrous structure was deposited.Infrared spectroscopy further confirmed the successful self-assembly of collagen-l.Release experiments demonstrated that the M@C group mitigated the burst release phenomenon compared to the MS group,maintaining internal vascular endothelial growth factor activity and sustained release.(2)Live/dead cell staining and CCK-8 assay showed that bone marrow mesenchymal stem cells proliferated well and survived on three types of artificial periosteum:MS,purely aligned poly(L-lactic acid)(PLLA)surface self-assembled collagen-l artificial periosteum(PLLA@C),and vascular endothelial growth factor-loaded micro-sol fiber surface self-assembled collagen-l-bone marrow mesenchymal stem cells artificial periosteum(M@C-B).Among them,the M@C-B group had the highest number of live cells and the fastest proliferation rate.(3)Alkaline phosphatase staining,alizarin red staining,and osteopontin immunofluorescence staining showed that the PLLA@C and M@C-B groups significantly promoted osteogenic differentiation of bone marrow mesenchymal stem cells.Angiogenesis experiments demonstrated that the vascular endothelial growth factor-loaded groups(MS and M@C-B)had longer blood vessel lengths and more reticular vascular-like structures with more cross-linked nodes,with the M@C-B group being the most prominent.(4)Immunofluorescence and flow cytometry showed that artificial periosteum in the M@C-B group significantly inhibited the pro-inflammatory macrophage phenotype and promoted the polarization of macrophages towards the anti-inflammatory M2 phenotype.(5)In vivo studies further confirmed that the M@C-B group showed superior bone mineral density,trabecular thickness,relative bone volume,and trabecular spacing compared to other groups.(6)These results indicate that bone marrow mesenchymal stem cell-engineered artificial periosteum,through the rapid regulation of the bone defect immune microenvironment by the collagen-l-bone marrow mesenchymal stem cells outer phase and the sustained release of vascular endothelial growth factor by the micro-sol electrospinning core-shell structure of the inner phase,synergistically promotes bone healing.

Lung cancer constitutes the most prevalent and lethal malignant tumor in China. Approximately 85% of lung cancer diagnoses correspond to the non-small cell histological subtype [non-small cell lung cancer (NSCLC)]. Despite surgery being the mainstay for early-stage disease, postoperative recurrence remains high and adjuvant chemotherapy offers limited benefit. In recent years, targeted therapy has demonstrated substantial advantages in driver mutation-positive NSCLC. To this end, the Lung Cancer Medical Education Committee of the Chinese Medical Education Association developed guidelines based on a systematic review of evidence through November 2025, using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach and a modified Delphi method. Focusing on epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK), and addressing ROS proto-oncogene 1 (ROS1), B-Raf proto-oncogene serine/threonine kinase (BRAF) V600E mutation, and mesenchymal-epithelial transition factor (MET) exon 14 (METex14) skipping, the guideline covers molecular testing, neoadjuvant/adjuvant therapy, perioperative strategies, minimal residual disease monitoring, and postoperative surveillance. It defines testing requirements, specifies stage-directed and subtype-specific treatments, and standardizes minimal residual disease monitoring. These recommendations emphasize precision and feasibility to improve survival and quality of life.

OBJECTIVE To explore the effect and potential mechanism of 717 Jiedu decoction in ameliorating local tissue injury induced by Gloydius brevicaudus venom via regulating macrophage phenotype transformation.METHODS Rat blank-serum and drug-containing serum were prepared by intragastric administration of normal saline， tail-vein injection of anti- G. brevicaudus venom serum （0.6 mL per rat）， and intragastric administration of 717 Jiedu decoction at doses of 0.495， 0.99 and 1.98 g/kg （calculated as crude drug）. M0-type macrophages derived from human leukemia monocytic THP-1 cells induced and differentiated by PMA were divided into normal control group， model group， positive control group， and low-， medium- and high-concentration 717 Jiedu decoction drug-containing serum groups. Except for the normal control group， all other groups were treated with 10 μg/mL G. brevicaudus venom working solution and 10% blank or drug-containing serum. After the cultivation period， the cellular ultrastructural changes in each group were observed； the proportions of M1- and M2-type macrophages， as well as the mRNA and protein expression of macrophage phenotype transformation and hypoxia-inducible factor-1α （HIF-1α） were detected.RESULTS Compared with the normal control group， cells in the model group presented ultrastructural injuries including mitochondrial swelling， cristae rupture and cytoplasmic vacuolization. The proportion of M1-type macrophages and the mRNA and protein expression levels of related phenotype transformation markers [inducible nitric oxide synthase， tumor necrosis factor-α， interleukin-6 （IL-6）， IL-1β] and HIF-1α were significantly increased （ P ＜0.05），whereas the proportion of M2-type macrophages and the mRNA and protein expression levels of related phenotype transformation markers （arginase-1， IL-10， mannose receptor C type 1 and chitinase-3-like protein 1） were significantly decreased （ P ＜0.05）. Compared with the model group， cellular ultrastructural injuries were obviously alleviated， and the above-mentioned indexes were significantly reversed in the high-concentration 717 Jiedu decoction drug-containing serum group （ P ＜0.05）.CONCLUSIONS717 Jiedu decoction can exert anti-inflammatory and tissue-repairing effects by regulating the balance of M1-， M2-type macrophages phenotype transformation and repairing cellular ultrastructural damage. Its mechanism may be related to inhibiting the excessive activation of the HIF-1α pathway.

Objective To study the relationship between serum visfatin, neutrophil-to-lymphocyte ratio (NLR) and disease severity of coronary heart disease (CHD) in elderly patients (≥90 years old). Methods One hundred and two elderly patients (≥90 years old) with CHD who received coronary CT angiography (CTA) were selected from January 2020 to June 2024. In addition, thirty-five elderly patients (≥90 years old) without CHD who underwent coronary CTA during the same period were included in the control group. The CHD patients were divided into mild group, moderate group and severe group by CT-SYNTAX score. The clinical data and levels of serum visfatin and NLR were compared, and the correlation and diagnostic value of the above levels with disease severity of CHD in elderly patients were analyzed. Results Serum visfatin and NLR were manifested as severe group>moderate group>mild group>control group (P<0.05). Pearson correlation analysis found that serum visfatin and NLR were moderately positively correlated with CT-SYNTAX score (r=0.574, 0.482, P<0.001). Receiver operating characteristics (ROC) curve indicated that the area under the curve (AUC) of combination of serum visfatin and NLR in diagnosing severe lesion in elderly patients (≥90 years old) with CHD was 0.882, which was higher than that of visfatin or NLR alone, and its 95%CI was 0.803-0.938. Conclusion There is a certain correlation between serum visfatin, NLR and disease severity of CHD in elderly patients. The combination of the above indicators has a higher predictive value on severe lesion.

OBJECTIVE: Prunella vulgaris L. has long been used for liver protection according to traditional Chinese medicine theory and has been proven by modern pharmacological research to have multiple potential liver-protective effects. However, its effects on non-alcoholic steatohepatitis (NASH) are currently uncertain. Our study explores the effects of P. vulgaris polysaccharides on NASH and intestinal homeostasis. METHODS: An aqueous extract of the dried fruit spikes of P. vulgaris was precipitated in an 85% ethanol solution (PVE85) to extract crude polysaccharides from the herb. A choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) was administrated to male C57BL/6 mice to establish a NASH animal model. After 4 weeks, the PVE85 group was orally administered PVE85 (200 mg/[kg·d]), while the control group and CDAHFD group were orally administered vehicle for 6 weeks. Quantitative real-time polymerase chain reaction analysis, Western blotting, immunohistochemistry and other methods were used to assess the impact of PVE85 on the liver in mice with NASH. 16S rRNA gene amplicon analysis was employed to evaluate the gut microbiota abundance and diversity in each group to examine alterations at various taxonomic levels. RESULTS: PVE85 significantly reversed the course of NASH in mice. mRNA levels of inflammatory mediators associated with NASH and protein expression of hepatic nucleotide-binding leucine-rich repeat and pyrin domain-containing protein 3 (NLRP3) were significantly reduced after PVE85 treatment. Moreover, PVE85 attenuated the thickening and cross-linking of collagen fibres and inhibited the expression of fibrosis-related mRNAs in the livers of NASH mice. Intriguingly, PVE85 restored changes in the gut microbiota and improved intestinal barrier dysfunction induced by NASH by increasing the abundance of Actinobacteria and reducing the abundance of Proteobacteria at the phylum level. PVE85 had significant activity in reducing the relative abundance of Clostridiaceae at the family levels. PVE85 markedly enhanced the abundance of some beneficial micro-organisms at various taxonomic levels as well. Additionally, the physicochemical environment of the intestine was effectively improved, involving an increase in the density of intestinal villi, normalization of the intestinal pH, and improvement of intestinal permeability. CONCLUSION PVE85 can reduce hepatic lipid overaccumulation, inflammation, and fibrosis in an animal model of CDAHFD-induced NASH and improve the intestinal microbial composition and intestinal structure. Please cite this article as: Zhu MJ, Song YJ, Rao PL, Gu WY, Xu Y, Xu HX. Therapeutic role of Prunella vulgaris L. polysaccharides in non-alcoholic steatohepatitis and gut dysbiosis. J Integr Med. 2025; 2025; 23(3): 297-308.
Animals ; Non-alcoholic Fatty Liver Disease/drug therapy* ; Male ; Dysbiosis/drug therapy* ; Mice, Inbred C57BL ; Gastrointestinal Microbiome/drug effects* ; Polysaccharides/therapeutic use* ; Prunella/chemistry* ; Mice ; Liver/metabolism* ; Plant Extracts/therapeutic use* ; Disease Models, Animal ; Diet, High-Fat

OBJECTIVE: The relationship between fish consumption and stroke is inconsistent, and it is uncertain whether this association varies across predicted stroke risks. METHODS: A cohort study comprising 95,800 participants from the Prediction for Atherosclerotic Cardiovascular Disease Risk in China project was conducted. A standardized questionnaire was used to collect data on fish consumption. Participants were stratified into low- and moderate-to-high-risk categories based on their 10-year stroke risk prediction scores. Hazard ratios ( HRs) and 95% confidence intervals ( CIs) were estimated using Cox proportional hazard models and additive interaction by relative excess risk due to interaction (RERI), attributable proportion (AP), and synergy index (SI). RESULTS: During 703,869 person-years of follow-up, 2,773 incident stroke events were identified. Higher fish consumption was associated with a lower risk of stroke, particularly among moderate-to-high-risk individuals ( HR = 0.53, 95% CI: 0.47-0.60) than among low-risk individuals ( HR = 0.64, 95% CI: 0.49-0.85). A significant additive interaction between fish consumption and predicted stroke risk was observed (RERI = 4.08, 95% CI: 2.80-5.36; SI = 1.64, 95% CI: 1.42-1.89; AP = 0.36, 95% CI: 0.28-0.43). CONCLUSION Higher fish consumption was associated with a lower risk of stroke, and this beneficial association was more pronounced in individuals with moderate-to-high stroke risk.
Humans ; China/epidemiology* ; Male ; Female ; Stroke/etiology* ; Middle Aged ; Prospective Studies ; Incidence ; Aged ; Animals ; Fishes ; Risk Factors ; Diet ; Seafood ; Adult ; Cohort Studies

Objective To explore the changes in trace elements and amino acid profiles in serum of patients with hepatocellular carcinoma(HCC) providing a reference for clinical diagnosis and treatment.Methods A total of 104 patients with HCC who underwent surgical treatment in the Department of Hepatobiliary Surgery of our hospital from January 2024 to April 2024 were selected as the study group, and 139 patients with benign biliary diseases during the same period were selected as the control group. Atomic absorption spectrometry was used to detect the levels of six trace elements (copper, zinc, calcium, magnesium, iron, and lead) in the serum of both groups, and liquid chromatography-tandem mass spectrometry was used to measure the concentrations of 21 amino acids.Results Compared with the control group, the serum copper level in the HCC group was significantly increased (P<0.05), while the levels of zinc and iron were significantly decreased (P<0.05). Amino acid profile analysis revealed that, compared with the control group, the concentrations of tyrosine, methionine, and phenylalanine in the HCC group were increased (P<0.05), while the concentrations of valine, leucine, isoleucine, glutamine, and arginine were decreased (P<0.05). Further analysis of the correlation between trace elements and amino acids with statistical differences between the groups showed that copper was negatively correlated with valine and leucine (P<0.05), while zinc and iron were positively correlated with valine, leucine, and isoleucine (P<0.01).Conclusions Imbalances in trace elements and amino acid metabolism changes are common in patients with HCC, and there may be an intrinsic connection between the two.

Ocular trauma is a leading cause of permanent visual impairment and loss of working a-bility.Among them,orbital foreign body injuries are often accompanied by multiple injuries to the eye-ball and surrounding tissues,adversely affecting the quality of life.This paper reported a 33-year-old male patient with right orbital foreign body resulting in eyeball contusion,extraocular muscle injury,and restricted ocular movement.After surgical removal of the foreign body combined with integrated traditional Chinese and western medicine treatment,the patient's visual acuity improved from 0.4 to 0.8,and ocular motility function significantly improved.This suggests that comprehensive treatment contributes to promoting functional recovery and enhancing clinical efficacy.

Huaihuasan， first recorded in Experiential Prescriptions for Universal Relief （Pu Ji Ben Shi Fang）， is a classic prescription for the treatment of ''hematochezia due to intestinal wind''. In 2018， it was included by the National Administration of Traditional Chinese Medicine as one of the first 100 classic prescriptions. This formula consists of four ingredients， i.e.， Sophorae Flos， Platycladi Cacumen， Schizonepetae Spica， and Aurantii Fructus. It is known for its ability to clear the intestines， dispel wind， cool the blood， and stop bleeding. In modern clinical practice， Huaihuasan， often with modifications， is widely used to treat various digestive tract diseases， including ulcerative colitis （UC）， with significant long-term effects. UC is a chronic， non-specific inflammatory bowel disease. Currently， Western medicine primarily treats UC with glucocorticoids， aminosalicylates， and immunosuppressants， which have good short-term efficacy but numerous adverse reactions， high recurrence rates， and the need for lifelong medication. Modern clinical studies have shown that Huaihuasan can significantly improve symptoms of UC， such as abdominal pain and diarrhea， reduce disease activity scores （Sutherland）， promote intestinal mucosal healing， alleviate anxiety and depression， and significantly improve the quality of life of patients. Pharmacological studies have shown that the main active components of Huaihuasan include quercetin， rutin， kaempferol， naringenin， and volatile oils. These compounds exert their effects by inhibiting inflammatory responses and protecting the intestinal mucosal barrier. They also exhibit antioxidant properties and regulate various signaling pathways， including tumor necrosis factor-α （TNF-α）， interleukin-2 （IL-2）， interleukin-4 （IL-4）， interleukin-1β （IL-1β）， monocyte chemoattractant protein-1 （MCP-1）， nuclear factor-κB （NF-κB）， Janus kinase （JAK）/signal transducer and activator of transcription （STAT）， and the KRAS-regulated mitogen-activated protein kinase （MEK）-extracellular signal-regulated kinase （ERK） pathway. These multi-target pathways improve UC symptoms， inhibit inflammation-cancer transition， and help maintain intestinal homeostasis. However， the precise mechanism of action has not yet been systematically elucidated. This paper reviews the research progress on Huaihuasan and main ingredients from its component drugs， focusing on their effects against UC. It also discusses current research limitations and suggests strategies for improvement， aiming to provide a reference for further studies on Huaihuasan in the treatment of UC and the development of new drugs.