Osteonecrosis of femoral head （ONFH） is a disease that causes osteocyte death due to interruption of blood supply of the femoral head， which may cause symptoms such as joint movement disorders， pain， and even femoral head collapse. Currently， the commonly used methods for treating ONFH in clinical practice are accompanied by problems such as long-term side effects， inaccurate efficacy， technical limitations， and complication risks. Traditional Chinese medicine （TCM） has shown unique advantages of holistic regulation， mild side effects， and symptom alleviation. A review of the related literature shows that Salviae Miltiorrhizae Radix et Rhizoma， as a representative Chinese herbal medicine for activating blood and resolving stasis， has the effects of activating blood， resolving stasis， dredging meridians， and relieving pain. Its active ingredients （such as salvianolic acid B， tanshinone Ⅱ_A， and tanshinone Ⅰ） interfere with bone metabolism balance， osteogenesis and differentiation， and improve bone microcirculation and bone microstructure. Salviae Miltiorrhizae Radix et Rhizoma is often combined with the herbal medicines with the effects of tonifying the liver and spleen or activing blood to form herb pairs （such as Salviae Miltiorrhizae Radix et Rhizoma-Angelicae Sinensis Radix， Salviae Miltiorrhizae Radix et Rhizoma-Chuanxiong Rhizoma， and Salviae Miltiorrhizae Radix et Rhizoma-Drynariae Rhizoma）， which enhances the efficacy through synergistic effects. In the application of TCM compound formulas， Bushen Huoxue prescription， Bushen Huoxue capsules， Gubi Tongxiao granules， and Shenggu Zaizao pills can regulate signaling pathways such as Wnt/β-catenin， Hedgehog， Notch， transforming growth factor（TGF）-β₁/Smads， and mitogen-activated protein kinase （MAPK） through multiple targets to significantly improve bone metabolism and hip joint function， playing an important role in preventing and treating ONFH. Through a review of available studies， this paper systematically explains the outstanding advantages of the active ingredients， herb pairs， and compound formulas of Salviae miltiorrhizae Radix et Rhizoma in the prevention and treatment of ONFH. The mechanisms may be related to factors such as promoting osteoblast generation and inhibiting osteoclast formation， increasing osteogenic differentiation， promoting angiogenesis， increasing bone density， inhibiting inflammatory response， and regulating signaling pathways. In the future， modern technology can be employed to optimize dosage forms， and high-quality clinical research should be conducted to further clarify its mechanism of action and promote the precise application of TCM. This review aims to provide more thinking directions for the application of Salviae miltiorrhizae Radix et Rhizoma in preventing and treating ONFH.

This article discusses the key pathogenesis of atherosclerosis （AS） based on the physiological characteristics and pathological changes of lipids and introduces the therapeutic effect of Zhuyuwan on AS， aiming to provide a theoretical basis for the treatment of cardiovascular diseases from the spleen. As essential substances， lipids have the same essence but different forms. They circulate throughout the body with body fluids under the action of Yang Qi to nourish the nutrient Qi and support the defensive Qi. Lipid metabolism disorder often leads to the obstruction of Qi movement， the accumulation of dampness and turbidity， and the generation of phlegm and blood stasis. It has been proven that the formation of vulnerable plaques in AS is attributed to the interaction of three pathogenic factors： deficiency of healthy Qi， phlegm-turbidity， and collateral stasis. Their pathological essence is closely related to abnormal lipid metabolism. As lipids constitute the thick and dense components of body fluids， their impaired dispersion may lead to phlegm-turbidity and blood stasis， the pathological process of which is predominantly ascribed to the dysfunction of the spleen in distributing essence. Therefore， AS is rooted in spleen-stomach disorder， manifests as plaques formed by pathological product accumulation in vessels， with lipid transport disorder as its core pathogenesis. Specifically speaking， the dysfunction of spleen in transportation with accumulation of dampness-turbidity marks the initial stage， and blood turbidity and coagulation and phlegm-nodules accumulating in vessels represent the intermediate phase. Cold accumulation and stagnated heat transforming into toxins represent the terminal stage. Zhuyuwan， first recorded in Taiping Holy Prescriptions for Universal Relief， contains equal proportions of Coptidis Rhizoma and Evodiae Fructus. Coptidis Rhizoma， bitter and cold， exerts descending and purging actions to assist stomach Qi in lowering turbidity. Evodiae Fructus， pungent-bitter and hot， disperses obstruction and promotes free flow to support spleen Qi in ascending the clear. The compatibility of Coptidis Rhizoma and Evodiae Fructus ascends the clear and descends the turbid to harmonize Yin and Yang， assisting the spleen in distributing essence and resolving lipid accumulation to reduce lipid levels. In terms of the therapeutic mechanism， Zhuyuwan modulates lipid metabolism by correcting immune-inflammation network imbalance， improving gut microbiota composition and metabolism， and enhancing reverse cholesterol transport. By analyzing the pathological characteristics of lipid transport disorder in AS， this study delves into the intrinsic connections between cardiovascular disease and lipid transport disorder， giving novel insights into the prevention and treatment of AS.

This article discusses the key pathogenesis of atherosclerosis （AS） based on the physiological characteristics and pathological changes of lipids and introduces the therapeutic effect of Zhuyuwan on AS， aiming to provide a theoretical basis for the treatment of cardiovascular diseases from the spleen. As essential substances， lipids have the same essence but different forms. They circulate throughout the body with body fluids under the action of Yang Qi to nourish the nutrient Qi and support the defensive Qi. Lipid metabolism disorder often leads to the obstruction of Qi movement， the accumulation of dampness and turbidity， and the generation of phlegm and blood stasis. It has been proven that the formation of vulnerable plaques in AS is attributed to the interaction of three pathogenic factors： deficiency of healthy Qi， phlegm-turbidity， and collateral stasis. Their pathological essence is closely related to abnormal lipid metabolism. As lipids constitute the thick and dense components of body fluids， their impaired dispersion may lead to phlegm-turbidity and blood stasis， the pathological process of which is predominantly ascribed to the dysfunction of the spleen in distributing essence. Therefore， AS is rooted in spleen-stomach disorder， manifests as plaques formed by pathological product accumulation in vessels， with lipid transport disorder as its core pathogenesis. Specifically speaking， the dysfunction of spleen in transportation with accumulation of dampness-turbidity marks the initial stage， and blood turbidity and coagulation and phlegm-nodules accumulating in vessels represent the intermediate phase. Cold accumulation and stagnated heat transforming into toxins represent the terminal stage. Zhuyuwan， first recorded in Taiping Holy Prescriptions for Universal Relief， contains equal proportions of Coptidis Rhizoma and Evodiae Fructus. Coptidis Rhizoma， bitter and cold， exerts descending and purging actions to assist stomach Qi in lowering turbidity. Evodiae Fructus， pungent-bitter and hot， disperses obstruction and promotes free flow to support spleen Qi in ascending the clear. The compatibility of Coptidis Rhizoma and Evodiae Fructus ascends the clear and descends the turbid to harmonize Yin and Yang， assisting the spleen in distributing essence and resolving lipid accumulation to reduce lipid levels. In terms of the therapeutic mechanism， Zhuyuwan modulates lipid metabolism by correcting immune-inflammation network imbalance， improving gut microbiota composition and metabolism， and enhancing reverse cholesterol transport. By analyzing the pathological characteristics of lipid transport disorder in AS， this study delves into the intrinsic connections between cardiovascular disease and lipid transport disorder， giving novel insights into the prevention and treatment of AS.

Objective: To explore the application effect of a specialized team consisting of specialist nurses and some emergency care′s or intensive care′s head nurses of critically ill patients in the hospital. Methods: From 2016 to 2018, the Critical Care Professional Group of implemented a provincial and above specialist nurses and the backbone of the specialist care departments of the acute and critical departments. A total of 23 members were composed of core members. A total of 56 liaison officers from each ward were selected to participate. The training and assessment activities presided over by the core staff of the professional group; at the same time, the professional group liaison officer is also the leader of the critical care quality control team in this ward, and implements the quality control of critical care patients; the core members are responsible for the guidance of the nursing care of critical patients in the hospital. The liaison staff carries out the training and assessment of the intensive care knowledge, skills and related nursing standards, norms, as well as the sharing of new technologies and new projects or research topics for acute and critical care, and the training of intensive care posts in the hospital. Before and after the operation of the specialized nursing team, the quality control scores of critically ill patients in 2015-2018, the satisfaction survey of nursing, the number of patents published by nurses in 2-25 years, the mortality rate of patients, and the results of unplanned extubation in 2016-2018 Compare. Results: The quality control scores of critical care patients in 2015-2018 were 93.91±1.23, 94.07±1.38,94.33±1.24, 95.42±1.56. The difference was statistically significant (F=49.597, P < 0.01). Satisfaction survey scores were 94.92±2.28, 97.08±1.37, 97.82±1.52, 97.94±1.68, the difference was statistically significant (F=30.882, P < 0.01); work 2-20 years The number of nurses was 678, 809, 853, and 925 respectively. The number of patents published was 76, 119, 147, and 237, respectively. The difference was statistically significant (χ²=36.77, P < 0.01). 2016-2018 unplanned extubation rate was 4.98‰(127/25 517), 4.01‰(115/28 713), 3.25‰(112/34 493), the difference was statistically significant (χ²=10.958, P <0.01). Conclusions The professional nursing team operation mode can improve the core ability and comprehensive quality of nursing staff's intensive care, improve the quality of care management of critically ill patients, ensure patient safety, and achieve continuous improvement of nursing quality.

BACKGROUND:Mechanical, inflammatory, and biochemical factors, particularly matrix metaloproteinases and reactive oxygen lead to chondrocyte degeneration in osteoarthritis. Curcumin has been shown to be a potent antioxidant; however, its protective effects against chondrocyte degeneration in osteoarthritis remain unclear.
OBJECTIVE:To investigate the potential molecular mechanisms underlying the protective effects of curcumin on articular cartilage of osteoarthritis in rats.
METHODS:A total of 30 Sprague-Dawley rats were used and randomly divided into model group (positive control,n=15) and normal group (negative control,n=15). Rat models of traumatic osteoarthritis were established, and then cartilage cels were isolated from articular cartilage and culturedin vitro. Chondrocytes were treated with curcumin (curcumin group) or PDTC (an inhibitor of nuclear factor-kappa B) for 24 hours. The expression level of nuclear factor-kappa B P65 in nucleus and cytoplasm in chondrocytes were determined by western blot assay and immunofluorescence. Moreover, mRNA expressions of type II colagen, matrix metaloproteinase-1 and -13 were analyzed using RT-qPCR.
RESULTS AND CONCLUSION: Nuclear factor-kappa B P65 protein was mainly expressed in nucleus, but few in cytoplasm in positive control group; the reversed results were found in the curcumin group. Nuclear translocation of nuclear factor-kappa B P65 was observed mainly in nucleus in the positive control group; however, that was observed mainly in cytoplasm in the negative control, curcumin, and PDTC groups. Matrix metaloproteinase-1 and -13 mRNA expressions were significantly decreased, while type II colagen mRNA expression was significantly increased in the curcumin group compared with the positive control group. These findings indicated that curcumin protect chondrocytes against degeneration through inhibiting the activation of nuclear factor-kappa B signaling pathway, suppressing nuclear translocation of nuclear factor-kappa B P65 and inhibiting the expressions of matrix metaloproteinase-1 and -13, which are responsible for upregulation of type II colagen expression.

AIM: To study the effect of calcium sensing receptor (CaSR) on icariin (ICA) induced mouse embryonic stem cells ( mESCs) to differentiate into cardiomyocytes in vitro.METHODS:mESCs were cultured to embry-oid bodies ( EBs) by direct suspension method and the differentiation of EBs into cardiomyocytes was induced by ICA.The expression of cardiac specific proteinsα-actinin and cardiac troponin-I ( cTnI) was analyzed by Western blot and immuno-fluorescence.The differentiation rate was determined by flow cytometry.The ultrastructure of the derived cardiomyocytes was further characterized by transmission electron microscopy.The expression of cardiac-specific transcription factors Nkx2.5 and GATA-4,as well as CaSR was detected by Western blot.RESULTS: After induction with ICA, the positive characteristics of myocardial cells appeared in the EBs cultured for 2 d.The expression of cardiac-specific sarcomeric pro-tein actinin (α-actinin) and cTnI showed an overall upward trend by Western blot in different phases of ICA induced differ-entiation.The expression of CaSR, Nkx2.5 and GATA-4 was the highest at an early stage of ICA-induced differentiation. Neomycin (an activator of CaSR) up-regulated CaSR, NKx2.5 and GATA-4 expression in the EBs at early stage of ICA-in-duced differentiation, all of which were reversed by NPS2390 ( an inhibitor of CaSR) .CONCLUSION:CaSR is function-ally expressed in mESC-derived cardiomyocytes, and activation of CaSR is involved in the differentiation of mESCs into car-diomyocytes by facilitating the expression of NKx2.5 and GATA-4.

BACKGROUND:Intra-articular injection of sodium hyaluronate or dexamethasone can relieve pain and increase range of motion after traumatic arthritis. OBJECTIVE:To observe the effect of dexamethasone combined with sodium hyaluronate on traumatic arthritis of rat knees. METHODS:Forty-eight Sprague-Dawley rats were randomly divided into four groups. The anterior ligament of the left knee was resected and the medial meniscus was removed to establish models of traumatic arthritis in al the rats. After 3 weeks, the four groups were respectively injected dexamethasone+sodium hyaluronate (combined group), dexamethasone, sodium hyaluronate, and nothing (control group). After 4, 8, 12 weeks of injection, the samples were obtained for gross observation, anteroposterior and lateral X-ray films and hematoxylin-eosin staining. RESULTS AND CONCLUSION:At 12 weeks after injection, X-ray films showed that there was no stenosis in the combined group, mild stenosis in the dexamethasone and sodium hyaluronate groups, and obvious stenosis in the control group (indicating severe osteoarthritis);hematoxylin-eosin staining exhibited the fibrous cartilage-like tissue grew wel in the combined group, varying degrees of proliferation of fibrous cartilage-like cells were visible in the dexamethasone and sodium hyaluronate groups, and there was a smal amount of fibrosis in the control group. These findings suggest that the combination of dexamethasone and sodium hyaluronate can improve the cartilage repair and restore the joint function.

Objective To explore the mechanism underlying the rapid shortening of outflow tract and the formation of the right ventricle of the embryonic mouse heart .Methods Serial sections of embryonic mouse hearts from embryonic day 9 (E9) to E12(3 to 5 embryos for each stage)were stained with antibodies against α-sarcomeric actin (SCA), α-smooth muscle actin (SMA), GATA-4, myosin heavy chain (MHC), proliferating cell nuclear antigen (PCNA) or active caspase-3 (CAS-3).Results At E11, the aortic sac and the distal border of cardiac outflow tract had regressed towards the ventricle into the pericardial cavity , while GATA-4、SCA and SMA staining showed that precursors from the second heart field were differentiating into cardiomyocytes adding to the arterial pole of the heart to lengthen the outflow tract .The length of outflow tract rapidly shortened at E12.Before and during its shortening , no CAS-3 positive cell was detected in the entire outflow tract.During E10-12, the cardiomyocytes in the right ventricle and proximal outflow tract wall proliferated inward to form trabeculae, with some trabeculae extending into the ridges .Proximal extremities of the outflow tract ridges were gradually myocardialized remodeling into the trabeullar right ventricle wall .At E12, scattered SCA and SMA staining cells and SCA and SMA weak positive mesenchymal cell clusters , which were continuous with the outflow tract myocardium were detected in the mesenchymal proximal outflow tract ridges .These results suggested that the proximal outflow tract was remodeled into the right ventricle by trabecularization , during which mesenchymal ridges were trabecularlly myocardialized . Conclusion Ventricularization of the proximal outflow tract contributes to the trabecular right ventricle and resultes in the vapid shortening of outflow tract in the mouse embryonic heart .Cardiomyocyte appoptosis and transdifferentiation are found to play a more limited contribution during this process .

AIM:To observe the functional expression of calcium-sensing receptor (CaSR) in the mouse em-bryonic stem cells (mESCs).METHODS:The expression and distribution of CaSR were detected by Western blotting and immunofluorescence observation in 129 mouse ES-D3 cells.The intracellular concentration of free calcium ([Ca2+]i) was determined by confocal laser scanning microscopy .The cell viability was analyzed by MTT assay and flow cytometry .RE-SULTS:CaSR protein was expressed in mESCs .Extracellular calcium or neomycin significantly increased the expression of CaSR and [Ca2+]i.Neomycin increased the cell viability , up-regulated the protein expression of p-ERK2.These effects of neomycin were inhibited by NPS2390.CONCLUSION:CaSR is expressed in mESCs .The activation of CaSR is involved in the proliferation of mESCs .

BACKGROUND:The bone metabolism of osteoarthritis is regulated by estrogen with osteoblasts, osteoclasts and cytokines, as wel as a number of regulatory pathways.
OBJECTIVE:To describe the role of estrogen and estrogen-related compounds for joint protection, repair of bone and cartilage cells, and inhibition of synovitis in osteoarthritis.
METHODS:Author researched PubMed, Embase, Elseveir database from 1992 to 2014, with the key words of“osteoarthritis, estrogens, matrix metal oproteinases, interleukins, tumor necrosis factor-alpha”. After the quality of the included studies was evaluation, valid data were extracted and analyzed.
RESULTS AND CONCLUSION:Estrogen can increase the expression of osteoprotegerin and nuclear factor-κB factor ligands in osteoblasts, inhibit bone resorption, prevent the onset and progression of osteoarthritis. Estrogen upregulates anti-osteoclast cytokines, downregulates pro-osteoclast factors, and contribute to regulate bone metabolism of osteoarthritis patients through bone morphogenetic protein and Wnt signaling. Estrogen promotes the adrenal cortex secretion of glucocorticoids and indirectly inhibits the production of matrix metal oproteinases by the hypothalamus-hypophysis-adrenal gland axis. Exogenous estrogen inhibits bone resorption, which may help to delay the development of osteoarthritis. Estrogen and estrogen-related compounds may inhibit the cartilage loss caused by synovitis and inflammatory factors in the late stage of osteoarthritis.