BACKGROUND:Bone relies on the close connection between blood vessels and bone cells to maintain its integrity.Bones are in a physiologically hypoxic environment.Therefore,the study of angiogenesis and osteogenesis in hypoxic environment is closer to the microenvironment in vivo. OBJECTIVE:To explore the influence of Wenshen Tongluo Zhitong(WSTLZT)formula on H-type bone microvascular endothelial cell/bone marrow mesenchymal stem cell co-culture system in hypoxia environment and its related mechanism. METHODS:Enzyme digestion method and flow sorting technique were used to isolate and identify H-type bone microvascular endothelial cells.Mouse bone marrow mesenchymal stem cells were isolated and obtained by bone marrow adhesion method.H-type bone microvascular endothelial cell/bone marrow mesenchymal stem cell hypoxic co-culture system was established using Transwell chamber and anoxic culture workstation.WSTLZT formula powder was used to intervene in each group at a mass concentration of 50 and 100 μg/mL.The angiogenic function of H-type bone microvascular endothelial cells in the co-culture system was evaluated by scratch migration test and tube formation test.The osteogenic differentiation ability of bone marrow mesenchymal stem cells in the co-cultured system was evaluated by alkaline phosphatase staining and alizarin red staining.The protein and mRNA expression changes of PDGF/PI3K/AKT signal axis related molecules in H-type bone microvascular endothelial cells in the co-cultured system were detected by Western Blotting and q-PCR,respectively. RESULTS AND CONCLUSION:(1)Compared with the normal oxygen group,the scratch mobility and new blood vessel length of H-type bone microvascular endothelial cells were significantly higher(P<0.05);the osteogenic differentiation capacity of bone marrow mesenchymal stem cells was higher(P<0.05);the expression of PDGF/PI3K/AKT axis-related molecular protein and mRNA increased(P<0.05)in the hypoxia group.(2)Compared with the hypoxia group,scratch mobility and new blood vessel length were significantly increased in the H-type bone microvascular endothelial cells(P<0.05);bone marrow mesenchymal stem cells had stronger osteogenic function(P<0.05);the expression of PDGF/PI3K/AKT axis-related molecular proteins and mRNA further increased(P<0.05)after treatment with different dose concentrations of WSTLZT formula.These findings conclude that H-type angiogenesis and osteogenesis under hypoxia may be related to the PDGF/PI3K/AKT signaling axis,and WSTLZT formula may promote H-type vasculo-dependent bone formation by activating the PDGF/PI3K/AKT signaling axis,thereby preventing and treating osteoporosis.

OBJECTIVE To study the intervention effects of Wenshen Tongluo Zhitong Recipe(WTZR)on macrophage senes-cence and senile osteoporosis.METHODS The senescent macrophage model was established using hydrogen peroxide(H2 O2)and subsequently divided into four groups:control,model,low-dose drug-treated serum,and high-dose drug-treated serum.β-galactosidase staining,Western blot and qPCR were employed to evaluate the mRNA expression of senescence markers p21 and p53.ROS staining and JC-1 staining were applied to assess mitochondrial function in macrophages.The mRNA levels of Interleukin(IL)-6,IL-10,CD206,and inducible nitric oxide synthase(iNOS)were determined by qPCR analysis.Immunofluorescence was used to evaluate argi-nase(ARG1)and iNOS protein expressions for assessing the impact of drug-containing serum on macrophage polarization.qPCR analy-sis was conducted to measure osteocalcin(OCN),collagen type Ⅰ alpha 1(Col1a1),runt-related transcription factor 2(Runx2)mRNA levels as osteoblast-related markers;ALP staining along with alizarin red staining were performed to evaluate the effect of macrophage conditioned medium treated with drug-containing serum on bone marrow mesenchymal stromal cell(BMSC)osteogenic differentiation.C57BL/6J mice were randomly allocated into four groups:control group,model group,WTZR low-dose group,and WTZR high-dose group.The senile osteoporosis(SOP)mouse model was established by D-galactose.Micro-CT scanning analyzed fe-mur microstructure while HE staining detected pathological changes in femur bone tissue samples collected from each experimental con-dition.Furthermore,Western blot was used to detect the senescence-related molecules p21 and p53 and the osteogenesis-related mark-ers OCN and Runx2,qPCR analysis measured tibial expression levels of senescence-related molecules(p21,p53)as well as macro-phage polarisation-related molecules(IL-6,iNOS,CD206,and IL-10)to assess the effect of this compound on a mouse model simula-ting SOP.RESULTS Following intervention with serum containing WTZR,there was a significant decrease in the number of senes-cent positive cells compared to the model group.Additionally,there was a notable decrease in p21 and p53 mRNA and proteins expres-sion(P＜0.05,P＜0.01,P＜0.001).Furthermore,drug-containing WTZR effectively inhibited ROS production induced by H2 O2 and mitigated mitochondrial membrane potential reduction in macrophages(P＜0.05,P＜0.001).Treatment with drug-containing WTZR re-sulted in down-regulated mRNA expression of M1-related gene iNOS(P＜0.05)while up-regulating mRNA expression of M2-related genes CD163 and CD206(P＜0.05).The drug-containing WTZR significantly reduced fluorescence intensity for iNOS(P＜0.01)while increasing ARG1(P＜0.05)fluorescence intensity.Moreover,conditioned medium from macrophages treated with drug-containing ser-um increased ALP positive cell count(P＜0.01,P＜0.001),alizarin red positive area(P＜0.05),as well as Col1a1,Runx2 and OCN mRNA expression levels(P＜0.05,P＜0.01).The Tb.N,BMD,and BV/TV were significantly higher in the WTZR group compared to the model group(P＜0.05,P＜0.01,P＜0.001);meanwhile,Tb.Sp was notably lower than that observed in the model group(P＜0.05,P＜0.01);bone trabeculae were significantly improved,increased in number and widened.Additionally,the compound could significantly inhibit the D-galactose induced up-regulation of tibial senescence-related genes and proteins p21 and p53(P＜0.05,P＜0.001,P＜0.0001),promote the expression of osteogenesis-related markers OCN and Runx2 protein(P＜0.01,P＜0.0001),promote the down-regulation of M1 related genes IL-6 and iNOS(P＜0.05),and promote the expression of M2 related genes IL-10 and CD206(P＜0.05,P＜0.01).CONCLUSION Wenshen Tongluo Zhitong Recipe may play an anti-osteoporosis effect by inhibiting macrophage senescence and promoting the osteogenic differentiation of BMSC.

Bile reflux gastritis is a common and frequently occurring disease of the digestive system,and the pathology is diverse.Professor Zhou Xinyou emphasized that the disease primarily affects the gallbladder,liver and stomach,advocating for a comprehensive differentiation of its etiology and pathogenesis across three distinct stages.In the early stage,the gallbladder is dysfunctional,which then affects the stomach;In the intermediate stage,there is congestion in the liver and gallbladder,leading to excessive wood element suppressing the earth element;in the late stage,gastric collaterals damage,with qi deficiency and blood stasis.Professor Zhou Xinyou follows the diagnosis and treatment ideas of"multiple compound methods,comprehensive application,and overall adjustment".For typical clinical symptoms,he has formulated the treatment principles and treatment methods of pain separation,general use,oral bitterness and upset,purging heat and stomach,treating gallbladder and stomach,regulating qi and resolving depression,so as to achieve both symptoms and root causes of treatment,gallbladder and stomach regulation.

Patients with type 2 diabetes mellitus (T2DM) typically have a higher risk of cardiovascular diseases, including coronary artery disease (CAD). Currently, the gold standard for diagnosing the severity of coronary artery lesions in T2DM patients is coronary angiography (CAG). This retrospective analysis reviewed data from T2DM patients who underwent CAG at Hengshui People′s Hospital between May 2020 and July 2022. Utilizing multivariate logistic regression analysis, factors associated with the severity of coronary artery stenosis in T2DM patients were identified. Based on these findings, a predictive model was developed to evaluate CAD severity in T2DM patients, incorporating smoking history, elevated triglyceride-glucose (TyG) index, and elevated monocyte to high-density lipoprotein cholesterol ratio (MHR). The combination of the TyG index and MHR model provides insights into coronary artery stenosis severity in T2DM patients, potentially reducing unnecessary invasive CAG procedures.

Objective:To summarize evidence for physical activity management in cancer patients based on the Joanna Briggs Institute (JBI) approach for evidence synthesis in health care, providing a scientific basis for the clinical standardization of physical activity management in cancer patients.Methods:Literature was searched according to the "6S" pyramid model of evidence, using BMJ Best Practice, UpToDate, JBI Evidence-Based Practice Database, Cochrane Library, global guideline websites, professional cancer association websites, and relevant Chinese and English databases for all evidence regarding physical activity in cancer patients. The search covered the period from February 13, 2018, to February 13, 2023. Guided by the JBI approach for evidence synthesis, two researchers independently evaluated the quality of the literature and extracted relevant evidence in accordance with clinical scenarios.Results:Thirty articles were included, comprising two guidelines, three expert consensuses, one evidence summary, 21 systematic reviews, and three randomized controlled trials. A total of 29 best evidence points were summarized in six aspects: benefits of physical activity, physically active people, pre-activity assessment, implementation of physical activity programs, safety monitoring of physical activity, and ongoing support strategies.Conclusions:This study supplements and updates 15 pieces of evidence based on existing evidence, ultimately forming a best evidence summary for the management of physical activity in cancer patients, providing evidence-based support for clinical management. Most evidence comes from international studies. It is recommended that Chinese researchers consider the activity ability and willingness of cancer patients when applying these findings in future research, and consider the specific clinical context, or conduct foundational research to further validate the evidence, to comprehensively improve the quality of life of cancer patients.

Objective:To study the expression level of peripheral blood microRNA(miRNA)-21 and miRNA-192 in patients with papillary thyroid carcinoma (PTC) and their relationship with pathological features and prognosis.Methods:A total 107 PTC patients admitted to Huaian Cancer Hospital in Jiangsu Province from June 2018 to June 2021 were selected as the PTC group, another 76 healthy individuals who underwent physical examination during the same period were selected as the control group. Real-time fluorescence quantitative PCR (qRT-PCR) was used to measure the expression levels of miRNA-21 and miRNA-192 in the peripheral blood of two populations, and the expression of miRNA-21 and miRNA-192 in the peripheral blood of the two populations and patients with different characteristics was compared and analyzed. Kaplan-Meier (K-M) method was used to analyze the relationship between the expression levels of miRNA-21, miRNA-192 in peripheral blood of PTC patients and prognosis.Results:The expression level of miRNA-21 in the peripheral blood of patients in the PTC group (2.21 ± 0.64) was higher than that in the control group (1.01 ± 0.02), while miRNA-192 (0.42 ± 0.14) was lower than that in the control group (0.99 ± 0.03, t = 16.33, 34.90, P < 0.001). In different clinical stages, the expression level of miRNA-21 in peripheral blood of patients in stages Ⅲ - Ⅳ was higher than that in stages Ⅰ - Ⅱ, and the level of miRNA-192 was lower than that in stages Ⅰ - Ⅱ ( t = 9.98, 11.75, P < 0.001). In the case of lymph node metastasis, the expression level of miRNA-21 in peripheral blood of patients with lymph node metastasis was higher than that of the group without lymph node metastasis, and the level of miRNA-192 was lower than that of the group without lymph node metastasis ( t = 12.81, 18.75, P < 0.001). There was no statistically significant difference in the expression levels of miRNA-21 and miRNA-192 in peripheral blood of patients with different genders, ages, body mass index, and tumor sizes ( t = 0.57, 0.42, 0.54, 0.62, 1.15, 1.47, 0.74, 1.13, P > 0.05). The K-M survival curve results showed that the progression free survival time (39.02 months) with high miRNA-21 expression was lower than that with low miRNA-21 expression (55.97 months, P = 0.026); the progression free survival time (34.97 months) with low miRNA-192 expression was lower than that with high miRNA-192 expression (57.04 months, P = 0.008). Conclusion:The high expression of miRNA-21 and low expression of miRNA-192 in peripheral blood of PTC patients, and they are closely related to the clinical stage, lymph node metastasis, and prognosis of patients.

Macrophages have strong plasticity and heterogeneity,and can undergo functional transformation in response to different signal stimuli,such as classical activation of M1 type(M1 type polarization)and selective activation of M2 type(M2 type polarization).The pathways of macrophage M1/M2 polarization are quite extensive,involving nuclear factor-κB(NF-κB)/mitogen-activated protein kinase(MAPK)signaling pathway,interleukin-4(IL-4)/signal transduction and activator of transcription 6(STAT6)signaling pathway,Notch signaling pathway,Wnt/β-catenin signaling pathway,etc.At the same time,M1/M2 polarization of macrophages is also regulated by exosomes,metabolites,non-coding RNA,electrical stimulation,probiotics,etc.,and its imbalance is closely related to the occurrence and development of different types of liver disease.In this paper,the mechanism of its polarization was reviewed,and it was found that M1 polarization of macrophages played a promoting role in the process of liver tissue injury,inflammation and fibrosis,while M2 polarization of macrophages played the opposite role.Among them,hepatocellular carcinoma,as the advanced stage of chronic liver disease,was characterized by increased M2 polarization and impaired M1 polarization of macrophages.Therefore,this paper pays attention to the role of M1/M2 polarization of macrophages in different types of liver diseases,in order to better establish the targeted therapy of macrophage subsets.

ObjectiveTo explore the possible mechanism of Pingwei Capsules （平胃胶囊） for chronic atrophic gastritis from rapidly accelerated fibrosarcoma / mitogen-activated protein kinase /extracellular-signal-regulated kinase （Raf/MEK/ERK） pathway that influences the activation of fibrosarcoma protein/mitogen. MethodsFifteen SD rats were randomly divided into 5 rats in the blank group and 10 rats in Pingwei Capsules group. The rats in the blank group were given 1 ml/100 g of saline by gavage， and the rats in Pingwei Capsules group were given 0.63 g/（kg·d） of Pingwei Capsule suspension by gavage， and serum was collected for 3 consecutive days. N-methyl-N'-nitro-N-nitrosoguanidine （MNNG） was used to induce human gastric mucosal epithelial cells GES-1 to establish a precancerous lesion cell model. The successful cells were divided into control group （10% fetal bovine serum）， blank serum group （10% fetal bovine serum plus 10% blank serum）， and medication-containing serum group （serum with medication of Pingwei Capsule）， and the volume fraction and time of intervention of Pingwei Capsule-containing serum were screened by CCK-8 assay. Human gastric mucosal epithelial cells GES-1 were divided into normal group， model group， blank serum group， medication-containing serum group， U0126 group， and combined group， with 6 replicate wells in each group. After successful modelling of the cells in all groups except the blank group， an equal volume of fetal bovine serum was added to the normal and model groups， an equal volume of blank serum was added to the blank serum group， a screening volume fraction of Pingwei Capsule-containing serum was added to Pingwei Capsule group， a 10 μmol/L mitogen-activated extracellular signal regulated kinase 1 （MEK1） inhibitor U0126 was administered in the U0126 group， an equal dose of Pingwei Capsule-containing serum plus 10 μmol/L of U0126 was administered to the combined group. After the selected incubation time， the level of interleukin 6 （IL-6） was detected in the cells by ELISA， the expression of IL-6 and MEK1 was detected by immunofluorescence， and the expression of IL-6， Raf， MEK1， and ERK mRNA was detected by RT-qPCR， and the expression of IL-6， Raf， MEK1， and ERK mRNA in the cells was detected by Western blot. ResultsThe 5.35% volume fraction， 48 h intervention of Pingwei Capsule-containing serum was selected for subsequent experiments. Compared with the normal group， the IL-6 content in cell supernatants and the expression of IL-6， Raf， MEK1， ERK mRNA and ERK1/2 proteins in cells increased in the model group and blank serum group （P＜0.01）. Compared with the model group， all of the above indexes were improved in medication-containing serum group， U0126 group， and combined group （P＜0.05 or P＜0.01）. Compared with medication-containing serum group， the expression of IL-6， MEK1 expression， the expression of IL-6， Raf， MEK1 and ERK mRNA， and the expression of IL-6， Raf， MEK1 and ERK1/2 proteins reduced in the cells of combined group （P＜0.05 or P＜0.01）. Compared with the U0126 group， IL-6 expression reduced and IL-6， MEK1 and ERK1/2 protein expression reduced in cells of combined group （P＜0.05 or P＜0.01）. ConclusionThe Pingwei Capsule-containing serum may play a role in the treatment of chronic atrophic gastritis by improving the inflammation-cancer transformation of GES-1 cells through inhibiting the Raf/MEK/ERK pathway.

Objective To investigate the correlations of serum zinc finger E-box-binding protein 1 (ZEB1) and DNA methyltransferase 1 (DNMTl) with neurological deficit and prognosis in patients with acute cerebral hemorrhage (ACH). Methods A total of 105 ACH patients in the authors′hospital from July 2019 to July 2022 were selected as ACH group, and they were divided into mild group (n=34), moderate group (n=41) and severe group (n=30) according to the National Institutes of Health Stroke Scale (NIHSS) score at admission. ACH patients were divided into good prognosis group (n=65) and poor prognosis group (n=40) according to the score of modified Rankin Scale (mRS). Another 105 healthy individuals with physical examination in the same period were included as control group. A total of 45 diagnosed ACH patients treated in authors′ hospital from July 2021 to July 2022 were selected to verify the constructed receiver operating characteristic (ROC) curve for predicting the prognosis of ACH. Serum ZEB1 and DNMT1 levels were detected by enzyme-linked immunosorbent assay; the Spearman method was used to analyze the relationship of ZEB1 and DNMT1 levels with the NIHSS score in ACH patients; the multivariate Logistic regression model was used to analyze the influencing factors for prognosis of ACH patients, and the ROC curve was used to evaluate the predictive value of serum ZEB1 and DNMT1 levels for the prognosis of ACH patients. Results Compared with the control group, serum levels of ZEB1 and DNMT1 were significantly higher in the ACH group (P < 0.05). Compared with the mild group, the ACH patients in moderate group and severe group had significant higher serum levels of ZEB1 and DNMT1 as well as NIHSS score (P < 0.05); compared with the moderate group, ACH patients in severe group had significant higher serum levels of ZEB1 and DNMT1 as well as NIHSS score (P < 0.05). Spearman analysis result showed that serum levels of ZEB1 and DNMT1 were positively correlated with NIHSS scores in ACH patients (r=0.569, 0.763, P < 0.001). Univariate analysis revealed that compared to the good prognosis group, patients in the poor prognosis group had significant higher or larger NIHSS score, hematoma volume, and serum levels of ZEB1 and DNMT1 (P < 0.05). Logistic regression analysis demonstrated that increases in ZEB1 and DNMT1, NIHSS score, and hematoma volume were the risk factors for poor prognosis in ACH patients (P < 0.05). Values of area under the curve (AUC) of serum ZEB1 and DNMT1 iin predicting prognosis of ACH patients were 0.834 and 0.854 respectively, and the AUC of ZEB1 combined with DNMT1 for prediction of prognosis of ACH patients was 0.944, with sensitivity of 95.0% and specificity of 86.2%. The ROC curve for predicting prognosis was validated by the validation group, and the results showed the AUC was 0.903 (95%CI, 0.854 to 0.951), indicating that the prognosis prediction curve has good discrimination. Conclusion The levels of serum ZEB1 and DNMT1 are high in patients with ACH, both of which are significantly related to neurological defect and prognosis in patients with ACH. The combination of serum ZEB1 and DNMT1 may be more helpful for clinical evaluation of prognosis in patients with ACH.

Objective To investigate radiation doses to examinees undergoing computed tomography (CT) scanning of different body parts (the head, chest, and abdomen) in medical institutions of Shijiazhuang, China, and to provide a reference for optimizing radiation protection for examinees in medical institutions. Methods March 2021 to March 2022, eleven medical institutions of radiation monitoring in Shijiazhuang were surveyed for the basic information, scanning parameters, and dosimetric data of a total of 930 adults and children who received CT examinations. The dosimetric data of the subjects were analyzed and compared with the domestic and international diagnostic reference levels and the results of other cities in China. Results In the above hospitals, the CTDI_vol(P₅₀) of CT subjects in children's group were 17.42-50.45 mGy, 2.13-14.01 mGy and 3.58-28.20 mGy, respectively. DLP(P₅₀) ranges from 228.87 to 966.97 mGy·cm, 33.20 to 296.03 mGy·cm, and 74.90 to 926.53 mGy·cm, respectively. In the adult group, the CTDI_vol(P₅₀) in the head, chest and abdomen of CT subjects were 37.28-54.05 mGy, 6.43-14.99 mGy and 8.28-18.75 mGy, respectively. DLP(P₅₀) ranges from 372.81 to 630.56 mGy·cm, from 219.77 to 467.93 mGy·cm, and from 313.86 to 689.87 mGy·cm, respectively. The distribution of radiation doses in different-grade hospitals varied greatly. The abdomen dose of the children's hospital was higher than other hospitals. Especially the primary hospitals were significantly higher than the recommended diagnostic reference level (DRL). Conclusion In some secondary and primary hospitals, the setting of CT scanning parameters was simplified, not specific to the subjects’ age and body types. They should strictly comply with the principal of optimizing radiation protection to strengthen radiation dose optimization and supervision, reducing the radiation dose of examinees in future examinations .