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 investigate the role of evidence-based clinical guidelines combined with "rain classroom" smart teaching in standardized residency training in endocrinology department.Methods:The 100 trainees who underwent standardized residency training in the Department of Endocrinology at Xiamen Hospital from September 2022 to September 2023 were selected as the research subjects. They were divided into groups based on the parity of their admission batches, with even-numbered batches assigned to the control group and odd-numbered batches to the experimental group, with 50 trainees in each group. The control group received traditional teaching, while the experimental group was taught using evidence-based clinical guidelines combined with "rain classroom" smart teaching. Statistical comparisons were made between the two groups in terms of exit examination scores, teaching effectiveness, teaching satisfaction, and evaluation of trainees by teachers. SPSS 22.0 was used for t test and Chi-square test. Results:The experimental group demonstrated significantly higher scores in theoretical knowledge [(25.62±3.12) vs. (22.71±3.27)], case analysis [(25.18±3.24) vs. (22.24±3.35)], clinical operation [(25.01±3.19) vs. (22.12±3.29)], and daily performance [(8.12±1.01) vs. (7.21±1.13)] compared to the control group in exit examination ( P<0.001). Additionally, the experimental group showed superior performance in self-learning [(8.57±1.12) vs. (7.64±1.24)], clinical thinking [(8.61±1.16) vs. (7.78±1.28)], evidence-based thinking [(8.52±1.13) vs. (7.69±1.26)], clinical skills [(8.49±1.17) vs. (7.61±1.23)], communication skills [(8.53±1.18) vs. (7.67±1.29)], and literature review [(8.59±1.15) vs. (7.71±1.27)], with statistically significant differences ( P<0.05). Teaching satisfaction in the experimental group (96.00%) was significantly higher than that in the control group (82.00%) ( P=0.025). The pass rates rated by teachers were higher in the experimental group in medical history collection (94.00% vs. 80.00%), physical examination (96.00% vs. 82.00%), clinical thinking (92.00% vs. 76.00%), communication skills (94.00% vs. 80.00%), literature review (96.00% vs. 84.00%), specialized skills (94.00% vs. 78.00%), and diagnosis and treatment plan formulation (92.00% vs. 74.00%), with statistically significant differences ( P<0.05). Conclusions:The implementation of evidence-based clinical guidelines combined with "rain classroom" smart teaching in the standardized residency training in endocrinology department can significantly improve the exit examination scores and teaching satisfaction of trainees, teaching effectiveness, and evaluation of trainees by teachers. This teaching method has a positive role in improving the clinical comprehensive ability of trainees such as evidence-based medical thinking and standardized clinical diagnosis and treatment.

Objective The development status,hot spots and trends of traditional Chinese medicine in the treatment of multiple sclerosis(MS)were analyzed by bibliometric and visual analysis.Methods Literatures related to the treatment of MS by traditional Chinese medicine were searched from CNKI,Wanfang Data and VIP from January 2000 to July 2024.CiteSpace software was used to visually analyze the number of publications,authors,institutions and key words in relevant literatures.Results A total of 438 literatures were included,and the number of published literatures showed an overall increasing trend.Fan Yongping pubilshed the most papers.The research institutions were mainly Dongzhimen Hospital of Beijing University of Chinese Medicine and Beijing Tiantan Hospital Affiliated to Capital Medical University.The current high-frequency key words in this field included acupuncture,treatment based on syndrome differentiation,traditional Chinese medicine,etc.A total of 9 clusters were formed."Acupuncture"was the most prominent.Conclusion Scholars have carried out active exploration and research in the field of traditional Chinese medicine in the treatment of MS,and the overall development trend is good.The research hot spots include acupuncture,treatment based on syndrome differentiation,traditional Chinese medicine,etc.,and the etiology and pathogenesis may be the future research trend.

Objective:To investigate the role of evidence-based clinical guidelines combined with "rain classroom" smart teaching in standardized residency training in endocrinology department.Methods:The 100 trainees who underwent standardized residency training in the Department of Endocrinology at Xiamen Hospital from September 2022 to September 2023 were selected as the research subjects. They were divided into groups based on the parity of their admission batches, with even-numbered batches assigned to the control group and odd-numbered batches to the experimental group, with 50 trainees in each group. The control group received traditional teaching, while the experimental group was taught using evidence-based clinical guidelines combined with "rain classroom" smart teaching. Statistical comparisons were made between the two groups in terms of exit examination scores, teaching effectiveness, teaching satisfaction, and evaluation of trainees by teachers. SPSS 22.0 was used for t test and Chi-square test. Results:The experimental group demonstrated significantly higher scores in theoretical knowledge [(25.62±3.12) vs. (22.71±3.27)], case analysis [(25.18±3.24) vs. (22.24±3.35)], clinical operation [(25.01±3.19) vs. (22.12±3.29)], and daily performance [(8.12±1.01) vs. (7.21±1.13)] compared to the control group in exit examination ( P<0.001). Additionally, the experimental group showed superior performance in self-learning [(8.57±1.12) vs. (7.64±1.24)], clinical thinking [(8.61±1.16) vs. (7.78±1.28)], evidence-based thinking [(8.52±1.13) vs. (7.69±1.26)], clinical skills [(8.49±1.17) vs. (7.61±1.23)], communication skills [(8.53±1.18) vs. (7.67±1.29)], and literature review [(8.59±1.15) vs. (7.71±1.27)], with statistically significant differences ( P<0.05). Teaching satisfaction in the experimental group (96.00%) was significantly higher than that in the control group (82.00%) ( P=0.025). The pass rates rated by teachers were higher in the experimental group in medical history collection (94.00% vs. 80.00%), physical examination (96.00% vs. 82.00%), clinical thinking (92.00% vs. 76.00%), communication skills (94.00% vs. 80.00%), literature review (96.00% vs. 84.00%), specialized skills (94.00% vs. 78.00%), and diagnosis and treatment plan formulation (92.00% vs. 74.00%), with statistically significant differences ( P<0.05). Conclusions:The implementation of evidence-based clinical guidelines combined with "rain classroom" smart teaching in the standardized residency training in endocrinology department can significantly improve the exit examination scores and teaching satisfaction of trainees, teaching effectiveness, and evaluation of trainees by teachers. This teaching method has a positive role in improving the clinical comprehensive ability of trainees such as evidence-based medical thinking and standardized clinical diagnosis and treatment.

Objective The development status,hot spots and trends of traditional Chinese medicine in the treatment of multiple sclerosis(MS)were analyzed by bibliometric and visual analysis.Methods Literatures related to the treatment of MS by traditional Chinese medicine were searched from CNKI,Wanfang Data and VIP from January 2000 to July 2024.CiteSpace software was used to visually analyze the number of publications,authors,institutions and key words in relevant literatures.Results A total of 438 literatures were included,and the number of published literatures showed an overall increasing trend.Fan Yongping pubilshed the most papers.The research institutions were mainly Dongzhimen Hospital of Beijing University of Chinese Medicine and Beijing Tiantan Hospital Affiliated to Capital Medical University.The current high-frequency key words in this field included acupuncture,treatment based on syndrome differentiation,traditional Chinese medicine,etc.A total of 9 clusters were formed."Acupuncture"was the most prominent.Conclusion Scholars have carried out active exploration and research in the field of traditional Chinese medicine in the treatment of MS,and the overall development trend is good.The research hot spots include acupuncture,treatment based on syndrome differentiation,traditional Chinese medicine,etc.,and the etiology and pathogenesis may be the future research trend.

Prolyl hydroxylase domain 2 (PHD2) is the primary oxygen sensing enzyme involved in hydroxylation of hypoxia-inducible factor (HIF). Under normoxic conditions, PHD2 hydroxylates specific proline residues in HIF-1α and HIF-2α, promoting their ubiquitination and subsequent proteasomal degradation. Although PHD2 activity decreases in hypoxia, notable residual activity persists, but its function in these conditions remains unclear. Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) targets proteins with phosphorylated serine/threonine-proline (pSer/Thr-Pro) motifs. As PHD2 contains several pSer/Thr-Pro motifs, it may be a potential substrate of Pin1. In the present study, we found Pin1 and PHD2 interactions in human breast cancer MDA-MB-231 cells. The breast cancer tissue array revealed higher levels of PHD2 and Pin1 in tumors compared to adjacent normal tissues. Through liquid chromatography-tandem mass spectrometry spectrometry, three phosphorylation sites (S125, T168, and S174) on PHD2 were identified, with serine 125 as the main site for Pin1 binding. As a new Pin1 binding partner, oncogenic PHD2 could be a potential therapeutic target for breast cancer treatment.

Prolyl hydroxylase domain 2 (PHD2) is the primary oxygen sensing enzyme involved in hydroxylation of hypoxia-inducible factor (HIF). Under normoxic conditions, PHD2 hydroxylates specific proline residues in HIF-1α and HIF-2α, promoting their ubiquitination and subsequent proteasomal degradation. Although PHD2 activity decreases in hypoxia, notable residual activity persists, but its function in these conditions remains unclear. Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) targets proteins with phosphorylated serine/threonine-proline (pSer/Thr-Pro) motifs. As PHD2 contains several pSer/Thr-Pro motifs, it may be a potential substrate of Pin1. In the present study, we found Pin1 and PHD2 interactions in human breast cancer MDA-MB-231 cells. The breast cancer tissue array revealed higher levels of PHD2 and Pin1 in tumors compared to adjacent normal tissues. Through liquid chromatography-tandem mass spectrometry spectrometry, three phosphorylation sites (S125, T168, and S174) on PHD2 were identified, with serine 125 as the main site for Pin1 binding. As a new Pin1 binding partner, oncogenic PHD2 could be a potential therapeutic target for breast cancer treatment.