BACKGROUND:How to repair bone defect has been a clinical problem for a long time.The effective ingredients of traditional Chinese medicine have good biological activity and therapeutic effect,and the combination of effective ingredients of traditional Chinese medicine and tissue engineering materials has a broad prospect in the field of bone repair.The combination of different effective ingredients of traditional Chinese medicine and scaffolds has similarities in their functional relationships. OBJECTIVE:To collect the cases of the combinations of effective ingredients of traditional Chinese medicine and scaffolds,then analogize tissue engineering scaffolds and effective ingredients of traditional Chinese medicine into two types of traditional Chinese medicine that generate compatibility relationships based on the inspiration of the compatibility of seven emotions and summarize the relationship between the two based on their functional relationships. METHODS:Relevant articles from January 1998 to January 2024 were searched in PubMed and China National Knowledge Infrastructure(CNKI),using English search terms"traditional Chinese medicine,Chinese medicine,traditional Chinese medicine monomers,bone defect,bone repair,bone tissue engineering,tissue engineering,scaffold"and Chinese search terms"traditional Chinese medicine,effective ingredients of traditional Chinese medicine,traditional Chinese medicine monomers,bone tissue engineering,bone tissue engineering scaffold,scaffold,tissue engineering,bone defect,bone repair."A total of 88 articles were included for review and analysis. RESULTS AND CONCLUSION:(1)Both tissue engineering scaffold materials and active ingredients of traditional Chinese medicine have been widely used in the field of bone repair.Although they have obvious advantages in osteogenesis,there are still many shortcomings.Many studies are dedicated to preparing composite materials from the two,hoping to exert a detoxification and synergism through the interaction between the two.(2)Some drugs and materials can promote each other in osteogenesis,antibacterial,and promoting angiogenesis,enhancing their original effects.Inspired by the traditional concept of prescription compatibility,this article summarized it as a"Mutual promotion"relationship and provided examples to support it.(3)Some drugs can enhance the strength of materials,while some materials can achieve sustained release and controlled release effects,increase drug loading and stability,or achieve targeted delivery of drugs loaded on them.The article summarized this unilateral enhancement effect as a"Mutual assistance"relationship.(4)The combination of some traditional Chinese medicine and materials can reduce the toxic side effects of the other party.The article summarizes this detoxification relationship as"Mutual restraint and detoxification."(5)The article provided a new perspective on traditional Chinese medicine composite scaffolds,inspired by the seven emotions compatibility relationship and based on the classification of action relationships.It introduced traditional Chinese medicine concepts into the field of tissue engineering,providing new research ideas for subsequent researchers of composite scaffolds,and providing certain convenience in material selection and matching.

Objective To investigate the effects of LBL-007, a novel fully human lymphocyte activation gene 3 (LAG-3) monoclonal antibody, in combination with programmed cell death protein 1 (PD-1) antibody, on the invasion, migration and proliferation of tumor cells, and to elucidate the underlying mechanisms. Methods Human lymphocyte cells Jurkat were co-cultured with A549 and MGC803 tumor cell lines and treated with the isotype control antibody human IgG, LBL-007, anti-PD-1 antibody BE0188, or tumor necrosis factor-alpha (TNF-α, the NF-κB signaling pathway agonist). Tumor cell proliferation was assessed using a colony formation assay; invasion was measured by Transwell^TM assay; migration was evaluated using a wound healing assay. Western blotting was employed to determine the expression levels of NF-κB pathway-related proteins: IκB inhibitor kinase alpha (Ikkα), phosphorylated Ikkα (p-IKKα), NF-κB subunit p65, phosphorylated p65 (p-p65), NF-κB Inhibitor Alpha (IκBα), phosphorylated IκBα (p-IκBα), matrix metalloproteinase 9 (MMP9), and MMP2. Results Compared with the control and IgG isotype groups, LBL-007 and BE0188 significantly reduced tumor cell proliferation, invasion, and migration. They also decreased the phosphorylation of p-IKKα, p-p65 and p-IκBα, and the expression of MMP9 and MMP2 of tumor cells in the co-culture system. The combined treatment of LBL-007 and BE0188 enhanced inhibitory effects. Treatment with the NF-κB signaling pathway agonist TNF-α reversed the suppressive effects of LBL-007 and BE0188 on tumor cell proliferation, invasion, migration, and NF-κB signaling. Conclusion LBL-007 and anti-PD-1 antibody synergistically inhibit the invasion, migration, and proliferation of A549 and MGC803 tumor cells by blocking the NF-κB signaling pathway.
Humans ; Cell Proliferation/drug effects* ; Cell Movement/drug effects* ; Signal Transduction/drug effects* ; NF-kappa B/metabolism* ; Neoplasm Invasiveness ; Antibodies, Monoclonal/pharmacology* ; Programmed Cell Death 1 Receptor/antagonists & inhibitors* ; Cell Line, Tumor ; Antigens, CD/immunology* ; Lymphocyte Activation Gene 3 Protein ; A549 Cells ; I-kappa B Kinase/metabolism* ; Jurkat Cells ; Matrix Metalloproteinase 9/metabolism*

Objective:To investigate the efficacy of cytoreductive radical prostatectomy (CRP) in patients with oligometastatic prostate cancer, and to assess its impact on progression-free survival (PFS), overall survival (OS), as well as the incidence and severity of complications.Methods:A prospective, monocentric non-randomized controlled trial including 80 cases of oligometastatic prostate cancer admitted to the Second Affiliated Hospital of Air Force Military Medical University from January 2020 to June 2024 was conducted. There were 40 patients each assigned to CRP group and no local treatment (NLT) group. The study used multivariate analysis to account for potential biases, analyzed the effects of CRP on PFS, OS as well as circulating tumor cell (CTC) and DNA methylation status. Meanwhile, the incidence and severity of complications were recorded. Measurement data were expressed as mean ± standard deviation ( ± s), and t-test was used for inter-group comparison. Count data and rank data were expressed as number of cases and percentage, and Chi-test was used for comparison between groups. Kaplan-Meier method was used to calculate PFS and OS, and Log-rank test was used to compare differences between groups. Multivariate analysis was performed using Cox proportional hazard regression model. A time-dependent Cox regression model was used to consider the effect of follow-up time on the results. Results:The PFS and OS in the CRP group were significantly better than those in the NLT group. The PFS rates in CRP group and NLT group at 12 months were 60% and 35% ( P=0.030). The OS rates at 12 months in the CRP group reached 80%, compared to 50% in the NLT group ( P=0.040). The level of CTC in the CRP group decreased from 50 cells/mL at first month to 5 cells/mL at 12th month, and the DNA methylation status decreased from 0.75 at first month to 0.30 at 12th month, which were significantly better than those in the NLT group ( P<0.05). The incidence of complications decreased gradually from first month to 12th month, with the CRP group from 30% to 10%, and the NLT group from 25% to 12% ( P=0.080). Although the severity of complications was slightly higher in the CRP group than in the NLT group at the early stage, the difference in severity gradually narrowed and eventually became similar between the two groups by the 12th month of follow-up. Conclusion:CRP significantly prolonged PFS and OS in patients with oligometastatic prostate cancer, reduced tumor burden, and despite a higher incidence of early complications, overall safety was good.

Anaplastic thyroid carcinoma(ATC)is the most aggressive malignancy with poor prognosis.The pathogenesis of ATC is complex,and there is no effective treatment at present.In recent years,with the deep understanding of the genetic(such as BRAF V600E,TP53,TERT,PIK3CA mutations,etc.)and epigenetic(such as histone methylation,histone deacetylation,microRNA regulatory pathways,etc.)changes driving ATC,molecular targeted therapy has brought new hope to ATC patients.This article reviews the molecular mechanisms of ATC and the latest achievements in targeted therapy and other therapies.

Objective:To investigate the expression of HBB in anaplastic thyroid cancer(ATC)cells and its regulatory effect on proliferation,invasion,migration and apoptosis of ATC cells and its potential mechanism.Methods:The expression of HBB in thyroid cancer and paracancerous tissues was analyzed through TIMER database.The correlation between the expression of HBB and the overall survival time of thyroid cancer patients was analyzed through KM-plotter database.The expression of HBB mRNA in ATC cells was detected by RT-qPCR.The HBB knockout or overexpression plasmid was transfected into ATC cells.The expression of HBB protein was detected by Western blot.The proliferation activity was detected by CCK-8 assay.The migration and invasion ability was detected by Transwell assay.The apoptosis was detected by flow cytometry.The expression of β-catenin was detected by Western blot.Results:The expression of HBB was low in thyroid cancer,and the overall survival time of patients with high expression of HBB was high.The expression of HBB protein was down-regulated in ATC cells.Knockout of HBB increased the ability of proliferation,migration and invasion of ATC cells and the expression of β-catenin protein,and inhibited apoptosis.However,overexpression of HBB decreased the ability of proliferation,migration and invasion of ATC cells and the expression of β-catenin protein,and promoted apoptosis.Conclusions:High HBB expression is associated with higher overall survival in patients with thyroid cancer.It may inhibit the proliferation,migration and invasion of ATC cells and promote apoptosis through Wnt/β-catenin signal pathway.

Objective:To analyze the causal relationship between gut microbiota and gestational diabetes,and to clarify its mechanism.Methods:Two-sample Mendelian randomization(MR)analysis was conducted by using summary data from genome-wide association study(GWAS)for gut microbiota and gestational diabetes.The GWAS data of gut microbiota were obtained from a GWAS study from the MiBioGen consortium;the GWAS data on gestational diabetes were sourced from the FinnGen consortium's publicly available R8 dataset;inverse variance weighted(IVW)method was used as the primary method to detect the causal association between the gut microbiota and the gestational diabetes.Sensitivity analysis was performed by Weighted Median and MR Egger methods;heterogeneity and pleiotropy were detected by Cochran's Q,MR-PRESSO,Egger intercept tests and Leave-One-Out analysis;multivariable MR was used to adjust for the effect of body mass index(BMI);reverse MR was used to explore the presence of reverse causal associations;Gene Ontology(GO)fuctional and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling enrichment analyses were used to explore the potential pathways through which gut microbiota may have impact on gestational diabetes.Results:Four gut microbes were found to be causally associated with gestational diabetes:the genus Methanobrevibacter and the phylum Euryarchaeota displayed negative causal relationships with the risk of gestational diabetes,while the genus Olsenella and genus Lachnoclostridium exhibited positive causal associations.No significant heterogeneity or horizontal pleiotropy was detected in the analysis.The reverse MR analysis did not reveal any causal relationship.After adjusting for BMI,the multivariable MR analysis results showed there were the causal associations between the genus Olsenella and the phylum Euryarchaeota with the risk of gestational diabetes.The GO fuctional and KEGG signaling pathway enrichment analyses results showed that axon development,axon production,insulin secretion and other pathways were significantly enriched.Conclusion:There are causal associations between four gut microbes and gestational diabetes.Among them,the significant correlations with gestational diabetes are still observed in phylum Euryarchaeota and genus Olsenella after adjusting for BMI.

Objective To explore the role of sulodexide(SDX)in neointimal hyperplasia of arteriovenous fistulas(AVFs)in chronic kidney disease(CKD)rats and its possible mechanism.Methods A total of 18 male rats(weighing 300±50 g)were randomly and equally divided into AVF group,CKD+AVF group(CKD induction followed by AVF surgery and then gavaged with normal saline for 2 months),and CKD+AVF+SDX group[treated as in the CKD+AVF group but with 8 mg/(kg·d)SDX gavage].HE staining was used to observe the degree of neointimal hyperplasia.The expression of Hippo pathway related molecules,Yes-associated protein(YAP),pYAP and connective tissue growth factor(CTGF,YAP downstream target protein,one of mesenchymal marker)was detected by immunofluorescence assay.After human umbilical vein cell fusion EAHy926 cells were treated with 0,2.5,5,10,20 or 40 μg/mL SDX for 24 h,and with 2.5 μg/mL SDXfor24,48 or 72 h,respectively,CCK-8 assay was used to measure cell survival rate.Moreover,the serum sample from CKD rat was used to treat EAHy926 cells,and then the cells were treated with SDX or YAP inhibitor verteporfin.The expression levels of YAP,pYAP,CTGF and endothelial cell marker CD31 were detected by Western blotting.Results HE staining and immunofluorescence assay showed that CKD rats had serious neointimal hyperplasia in AVFs(P＜0.05),and slightly lower expression of pYAP and enhanced expression of CTGF(P＜0.05)when compared with the rats of the AVF group.While,SDX treatment alleviated the neointimal hyperplasia of AVFs,enhanced the expression of pYAP and reduced the expression of CTGF(P＜0.05).CCK-8 assay showed that cell survival rate was decreased significantly in a dose-and time-dependent manner after SDX treatment(P＜0.05).Western blotting revealed that SDX increased the expression of pYAP and CD31 while inhibited the expression of CTGF in EAHy926 cells(P＜0.05),which was consistent with the effect of verteporfin treatment.Conclusion SDX can block YAP activation caused by CKD and attenuate neointimal hyperplasia in AVFs.

[Objective] To explore the efficacy and safety of retrograde intrarenal surgery (RIRS) using a flexible negative pressure suction sheath in the treatment of upper urinary tract stones >2 cm in diameter, to provide reference for the diagnosis and treatment of such disease. [Methods] Clinical data of 155 patients who underwent surgery for upper urinary tract stones during Nov.2022 and Nov.2023 at the Second Affiliated Hospital of Shaanxi University of Chinese Medicine were retrospectively analyzed.The patients were divided into 3 groups: percutaneous nephrolithotripsy (PCNL) group (n=54), conventional sheath RIRS group (n=41), and flexible sheath RIRS group (n=60). The general and clinical data of the 3 groups were compared. [Results] The PCNL group had more patients with severe hydronephrosis (22.22% vs. 4.88%, 5.00%, P=0.027) and smaller IPA involving the lower calyx [(36.17±17.6)° vs. (48.57±17.56)°, (47.41±10.82)°, P=0.014] than the conventional sheath RIRS group and flexible sheath RIRS group.Three days after operation, the stone-free rate (SFR) was 90.74%, 53.66% and 78.33% in the PCNL, conventional sheath RIRS, and flexible sheath RIRS groups, respectively (P<0.05). At 1 month postoperatively, the SFR was 92.59%, 73.17%, and 81.67%, with no statistically significant difference between the PCNL and flexible sheath RIRS groups (P>0.05), but was higher than that in the conventional sheath RIRS group (P<0.05). The PCNL group had shorter operation time than the two RIRS groups [(65.22±17.67) min vs. (91.73±20.57) min, (94.38±24.75) min, P<0.001], longer postoperative hospital stay [(5.0(4.0, 7.0) d vs.3.0(2.0, 4.0) d, 3.0(2.0, 4.0) d, P<0.001], greater decrease in hemoglobin level [(18.00±5.78) g/L vs. (5.57±5.16) g/L, (7.42±5.09) g/L, P<0.001], and higher visual analogue scale (VAS) score [(4.83±1.48) min vs. (2.95±1.07) min, (3.05±1.21) min, P<0.001], while there was no difference between the two RIRS groups (P>0.05). The costs were lower in the flexible sheath RIRS group than in the conventional sheath RIRS group but higher than in the PCNL group [(23 311.19±1 341.20)yuan vs.(24 550.49±1 172.51)yuan, (15 351.97±1 101.4)yuan, P<0.001]. The overall incidence of complications was similar among the three groups, but stone street occurred only in the conventional sheath RIRS group. [Conclusion] For the treatment of patients with upper urinary tract stones >2 cm, RIRS has shorter postoperative hospital stay, lower hemoglobin decrease, and lower VAS score compared to PCNL; the early postoperative SFR of flexible sheath RIRS is superior to that of conventional sheath RIRS, and the 1-month SFR is comparable to that of PCNL, with a low incidence of stone street.

Objective To investigate the serum levels of peroxisome proliferator-activated receptor-γ coactivator-1α(PGC-1α)and fibronectin type Ⅲ domain-containing protein 5(FNDC5)in patients with hypertensive cerebral hemor-rhage and their association with disease severity and prognosis.Methods A total of 80 patients with hypertensive cere-bral hemorrhage who were diagnosed and treated in our hospital from July 2019 to February 2022 were enrolled as case group,and 80 individuals undergoing physical examination were enrolled as control group.ELISA was used to measure the serum levels of PGC-1α and FNDC5,and the receiver operating characteristic(ROC)curve was used to investigate their value in predicting the prognosis of patients with hypertensive cerebral hemorrhage.The logistic regression analysis was used to investigate the influencing factors for poor prognosis in patients with hypertensive cerebral hemorrhage.Results The case group had significantly lower serum levels of PGC-1α and FNDC5 than the control group(P<0.05),and the good prognosis group also had significantly higher serum levels of PGC-1α and FNDC5 than the poor prognosis group.Disease severity,PGC-1α,and FNDC5 were influencing factors for poor prognosis in patients(P<0.05).Serum PGC-1α and FNDC5 alone or in combination had an area under the ROC curve of 0.957,0.937,and 0.985,respec-tively,in predicting poor prognosis in patients with hypertensive cerebral hemorrhage.Conclusion There are low expres-sion levels of PGC-1α and FNDC5 in patients with hypertensive cerebral hemorrhage,which are associated with the sever-ity and prognosis of patients.Both of them are independent protective factors for prognosis and have a certain application value in evaluating prognosis in clinical practice.

To analyze the epidemiological characteristics of acute respiratory infections (ARIs) during the autumn-winter season in Beijing, providing evidence for the prevention, control, diagnosis, and treatment of ARIs.