Osteoporosis is a common senile bone metabolism disease， clinically characterized by decreased bone mass， destruction of bone microstructure， increased bone fragility， and easy fracture. It tends to occur in the elderly and postmenopausal women， seriously threatening the quality of life and physical and mental health of the elderly. At present， the treatment of osteoporosis is mainly based on oral western medicines， such as calcium， Vitamin D， and bisphosphonates. Still， there are drawbacks such as a long medication cycle and many adverse reactions. In recent years， due to the advantages of multi-component， multi-pathway， and multi-target， some traditional Chinese medicines and effective ingredients can regulate the osteogenic and osteoclastic differentiation process in both directions and are widely used in the prevention and treatment of osteoporosis. Hippophae rhamnoides is a commonly used herbal medicine， and its fruits are rich in flavonoids， polyphenols， fatty acids， vitamins， and trace elements， which have been proven to have a good anti-osteoporosis effect. Isorhamnetin is the main effective ingredient of Hippophae rhamnoides fruits， which has many pharmacological effects such as anti-inflammation， anti-oxidative stress， anti-aging， and anti-tumor. Studies have shown that isorhamnetin can participate in the regulation of bone metabolism and has a good anti-osteoporosis effect. However， the pharmacological effects and related mechanisms of isorhamnetin against osteoporosis have not been systematically summarized. Therefore， this paper reviewed the pharmacological effects and related mechanisms of isorhamnetin against osteoporosis by referring to relevant literature to provide more basis for the development and application of isorhamnetin.

OBJECTIVE To construct the simulated traditional Chinese medicine pharmacy based on virtual simulation technology， and assist in the development of the new mode of traditional Chinese medicine dispensing education training. METHODS The field research and questionnaire surveys were conducted to identify the needs of Chinese medicine students and practitioners for the content and presentation of knowledge on the construction of simulated traditional Chinese medicine pharmacy. Taking the laws and regulations on the construction of traditional Chinese medicine pharmacy and the related teaching materials and literature on traditional Chinese medicine preparation as the knowledge source， the virtual simulation technology was applied to build a simulated traditional Chinese medicine pharmacy so as to achieve the functions of browsing the traditional Chinese medicine pharmacy， learning the knowledge of traditional Chinese medicine preparation and practical skills training. A multi-site simulated traditional Chinese medicine pharmacy evaluation scale study was conducted based on platform operational testing. RESULTS A simulated traditional Chinese medicine pharmacy was constructed， consisting of four core modules： video teaching， animation video， simulated pharmacy， and simulated experience. The overall score of evaluation scale was 93.31， with all entries scoring above 80； the ones with evaluation scales above 90 accounted for 92.31% （60/65）. CONCLUSIONS Simulated traditional Chinese medicine pharmacy based on virtual simulation technology meets the learning needs of users and enhances the teaching effect of traditional Chinese medicine dispensing technology training.

Objective To construct an accurate clinical model of lower limb varicose veins in rats through surgery that provides theoretical support for evaluating drug therapy.Methods 30 SD rats,15 males and 15 females,were randomly divided into a control group and surgical group.In the surgical group,the rats lower limb veins(including the small saphenous vein and femoral vein)were ligated via improved lower limb vein ligation,i.e.,the small saphenous vein was completely ligated with the femoral vein,and the thrombosis result ed in a lasting increase in the internal pressure of the deep veins of the lower limb,causing varicose symptoms.On the 6th week after surgery,the varicose veins of the rats in the surgical group were scored to select those that were successfully modeled.Then,the successfully modeled rats were randomly divided into a model group and Maizhiling group.Maizhiling 62.5 mg/kg was orally administered to the treatment group once a day,while the control and model group received an equal volume of physiological saline orally every day for 20 consecutive days.On the day before administration and 7 d,14 d and 20 d after administration,macro photography and scoring were performed on the lower limbs of the rats.After completion,an approximately 1 cm long saphenous vein above the ankle joint of the lower limb on the surgical side was removed from the model group and Maizhiling group rats,while from the control group,the corresponding saphenous vein of the lower limb on the same side was removed.Pathological tissue observation was performed using HE staining,Masson staining,and immunohistochemical examination for interleukin-2(IL-2)and tissue inhibitor of metalloproteinases(TIMP-1).Results Of the 22 rats in the surgical group,20 were successfully modeled,with a success rate of 91％.According to the manifestations of venous dilation,varicose veins,and redness in the lower limbs of rats,the varicose vein score of the model group increased significantly compared with that of the control group(P＜0.01).After the therapeutic dose of Maizhiling was administered,the varicose vein score in the Maizhiling group decreased significantly compared with that of the model group(P＜0.01).Pathological examination showed significant varicose-vein-like changes and mild inflammation in the model group.The Maizhiling group showed reduced varicose veins and inflammation.Conclusions A rat model of lower limb varicose veins was successfully established,providing a new research method for the study of drugs and treatment method related to lower limb varicose diseases.

Objective To construct an accurate clinical model of lower limb varicose veins in rats through surgery that provides theoretical support for evaluating drug therapy.Methods 30 SD rats,15 males and 15 females,were randomly divided into a control group and surgical group.In the surgical group,the rats lower limb veins(including the small saphenous vein and femoral vein)were ligated via improved lower limb vein ligation,i.e.,the small saphenous vein was completely ligated with the femoral vein,and the thrombosis result ed in a lasting increase in the internal pressure of the deep veins of the lower limb,causing varicose symptoms.On the 6th week after surgery,the varicose veins of the rats in the surgical group were scored to select those that were successfully modeled.Then,the successfully modeled rats were randomly divided into a model group and Maizhiling group.Maizhiling 62.5 mg/kg was orally administered to the treatment group once a day,while the control and model group received an equal volume of physiological saline orally every day for 20 consecutive days.On the day before administration and 7 d,14 d and 20 d after administration,macro photography and scoring were performed on the lower limbs of the rats.After completion,an approximately 1 cm long saphenous vein above the ankle joint of the lower limb on the surgical side was removed from the model group and Maizhiling group rats,while from the control group,the corresponding saphenous vein of the lower limb on the same side was removed.Pathological tissue observation was performed using HE staining,Masson staining,and immunohistochemical examination for interleukin-2(IL-2)and tissue inhibitor of metalloproteinases(TIMP-1).Results Of the 22 rats in the surgical group,20 were successfully modeled,with a success rate of 91％.According to the manifestations of venous dilation,varicose veins,and redness in the lower limbs of rats,the varicose vein score of the model group increased significantly compared with that of the control group(P＜0.01).After the therapeutic dose of Maizhiling was administered,the varicose vein score in the Maizhiling group decreased significantly compared with that of the model group(P＜0.01).Pathological examination showed significant varicose-vein-like changes and mild inflammation in the model group.The Maizhiling group showed reduced varicose veins and inflammation.Conclusions A rat model of lower limb varicose veins was successfully established,providing a new research method for the study of drugs and treatment method related to lower limb varicose diseases.

External apical root resorption is among the most common risks of orthodontic treatment, and it cannot be completely avoided and predicted. Risk factors causing orthodontic root resorption can generally be divided into patient- and treatment-related factors. Root resorption that occurs during orthodontic treatment is usually detected by radiographical examination. Mild or moderate root absorption usually does no obvious harm, but close attention is required. When severe root resorption occurs, it is generally recommended to suspend the treatment for 3 months for the cementum to be restored. To unify the risk factors of orthodontic root resorption and its clinical suggestions, we summarized the theoretical knowledge and clinical experience of more than 20 authoritative experts in orthodontics and related fields in China. After discussion and summarization, this consensus was made to provide reference for orthodontic clinical practice.
Humans ; Tooth Movement Techniques/adverse effects* ; Root Resorption/etiology* ; Consensus ; Dental Cementum ; Risk Factors

LIN28 is an RNA binding protein with important roles in early embryo development, stem cell differentiation/reprogramming, tumorigenesis and metabolism. Previous studies have focused mainly on its role in the cytosol where it interacts with Let-7 microRNA precursors or mRNAs, and few have addressed LIN28's role within the nucleus. Here, we show that LIN28 displays dynamic temporal and spatial expression during murine embryo development. Maternal LIN28 expression drops upon exit from the 2-cell stage, and zygotic LIN28 protein is induced at the forming nucleolus during 4-cell to blastocyst stage development, to become dominantly expressed in the cytosol after implantation. In cultured pluripotent stem cells (PSCs), loss of LIN28 led to nucleolar stress and activation of a 2-cell/4-cell-like transcriptional program characterized by the expression of endogenous retrovirus genes. Mechanistically, LIN28 binds to small nucleolar RNAs and rRNA to maintain nucleolar integrity, and its loss leads to nucleolar phase separation defects, ribosomal stress and activation of P53 which in turn binds to and activates 2C transcription factor Dux. LIN28 also resides in a complex containing the nucleolar factor Nucleolin (NCL) and the transcriptional repressor TRIM28, and LIN28 loss leads to reduced occupancy of the NCL/TRIM28 complex on the Dux and rDNA loci, and thus de-repressed Dux and reduced rRNA expression. Lin28 knockout cells with nucleolar stress are more likely to assume a slowly cycling, translationally inert and anabolically inactive state, which is a part of previously unappreciated 2C-like transcriptional program. These findings elucidate novel roles for nucleolar LIN28 in PSCs, and a new mechanism linking 2C program and nucleolar functions in PSCs and early embryo development.
Animals ; Cell Differentiation ; Embryo, Mammalian/metabolism* ; Embryonic Development ; Mice ; Pluripotent Stem Cells/metabolism* ; RNA, Messenger/genetics* ; RNA, Ribosomal ; RNA-Binding Proteins/metabolism* ; Transcription Factors/metabolism* ; Zygote/metabolism*

Objective:To examine the survival status and explore factors related to death among human immunodeficiency virus （HIV） infected patients receiving antiretroviral therapy （ART） in Taizhou City during 2006‒2019. Methods:A retrospective cohort study was conducted to analyze the data on HIV-infected patients receiving ART in Taizhou during 2006‒2019. Kaplan-Meier （K-M） method was used to calculate the cumulative survival rate and cumulative treatment success rate. Cox regression model was used to determine survival status and factors associated with ART. Results:A total of 2 904 HIV-infected patients was included. The cumulative survival rate after 1， 3， 5， and 8 years of ART were 96.9%， 94.9%， 93.1% and 92.1%， respectively， and the cumulative treatment response rate were 91.3%， 85.3%， 81.8% and 73.8%， respectively. Compared with aged 18-30 years old， baseline CD4⁺T cell >350 count/μL， normal hemoglobin level， effective ART， no clinical symptom at baseline， and homosexual transmission， we found that aged 51-60 years old（HR=4.94，95%CI：1.66-14.69）， aged over 60 years old（HR=9.14，95%CI：3.14-26.63）， anemia at baseline（HR=2.24，95%CI：1.55-3.23）， baseline CD4⁺T cell <200 count/μL（HR=4.35，95%CI：2.14-8.86）， ART failure （HR=3.90，95%CI：2.73-5.58）， heterosexual transmission（HR=1.92，95%CI：1.15-3.20）， and signs of symptom at baseline（HR=1.68，95%CI：1.16-2.41） were risk factors of HIV-related death. Conclusion:The effect of ART in Taizhou City is confirmed with a high cumulative survival rate and treatment success. We should pay additional attention to senior HIV-infected patients with anemia at baseline and intensively monitor the effect of ART. Interventions such as “treat after discover” are supposed to be implemented more widely to further reduce HIV-related mortality.