ObjectiveTo explore the regulation of Shaoyaotang on glucose metabolism reprogramming of macrophages and the mechanism of this decoction in inhibiting macrophage polarization toward the M1 phenotype. MethodsHuman monocytic leukemia-1 （THP-1） cells were treated with 100 ng·L^-1 phorbol myristate acetate for induction of macrophages as the normal control group. The cells treated with 100 ng·L^-1 lipopolysaccharide combined with 20 ng·L^-1 interferon （IFN）-γ for induction of M1-type macrophages were taken as the M1 model group. M1-type macrophages were treated with the blank serum， Shaoyaotang-containing serum， 0.5 mol·L^-1 2-deoxy-D-glucose （2-DG）， and Shaoyaotang-containing serum + 2-DG， respectively. After intervention， the expression of CD86 and CD206 was examined by flow cytometry. The levels of interleukin （IL）-6， tumor necrosis factor （TNF）-α， IL-10， and transforming growth factor （TGF）-β were assessed by ELISA. Real-time PCR and Western blot were employed to determine the mRNA and protein levels， respectively， of hypoxia-inducible factor-1 alpha （HIF-1α）， glucose transporter 1 （GLUT1）， hexokinase 2 （HK2）， glyceraldehyde-3-phosphate dehydrogenase （GAPDH）， and 6-phosphofructo-2-kinase/fructose-2，6-bisphosphatase 3 （PFKFB3）. ResultsCompared with that in the normal control group， the expression of CD86， the marker of M1-type macrophages， increased in the M1 model group and blank serum group （P<0.01）， which indicated that the M1 inflammatory model was established successfully. In addition， the M1 model group was observed with up-regulated mRNA and protein levels of proinflammatory cytokines IL-6 and TNF-α and glycolysis-related factors HIF-1α， GLUT1， HK2， GAPDH， and PFKFB3 （P<0.01）. Compared with the M1 model group， the Shaoyaotang-containing serum， 2-DG， and combined intervention groups showed decreased expression of CD86 （P<0.01）， down-regulated mRNA and protein levels of proinflammatory factors IL-6 and TNF-α and glycolysis-related factors HIF-1α， GLUT1， HK2， GAPDH， and PFKFB3 produced by M1-type macrophages （P<0.01）， increased expression of CD206 （marker of M2-type macrophages） （P<0.01）， and elevated levels of IL-10 and TGF-β produced by M2-type macrophages （P<0.01）. ConclusionShaoyaotang inhibits macrophage differentiation toward pro-inflammatory M1-type macrophages and promotes the differentiation toward anti-inflammatory M2-type macrophages by regulating glucose metabolism reprogramming. The evidence gives insights into new molecular mechanisms and targets for the treatment of ulcerative colitis with Shaoyaotang.

ObjectiveTo explore the regulation of Shaoyaotang on glucose metabolism reprogramming of macrophages and the mechanism of this decoction in inhibiting macrophage polarization toward the M1 phenotype. MethodsHuman monocytic leukemia-1 （THP-1） cells were treated with 100 ng·L^-1 phorbol myristate acetate for induction of macrophages as the normal control group. The cells treated with 100 ng·L^-1 lipopolysaccharide combined with 20 ng·L^-1 interferon （IFN）-γ for induction of M1-type macrophages were taken as the M1 model group. M1-type macrophages were treated with the blank serum， Shaoyaotang-containing serum， 0.5 mol·L^-1 2-deoxy-D-glucose （2-DG）， and Shaoyaotang-containing serum + 2-DG， respectively. After intervention， the expression of CD86 and CD206 was examined by flow cytometry. The levels of interleukin （IL）-6， tumor necrosis factor （TNF）-α， IL-10， and transforming growth factor （TGF）-β were assessed by ELISA. Real-time PCR and Western blot were employed to determine the mRNA and protein levels， respectively， of hypoxia-inducible factor-1 alpha （HIF-1α）， glucose transporter 1 （GLUT1）， hexokinase 2 （HK2）， glyceraldehyde-3-phosphate dehydrogenase （GAPDH）， and 6-phosphofructo-2-kinase/fructose-2，6-bisphosphatase 3 （PFKFB3）. ResultsCompared with that in the normal control group， the expression of CD86， the marker of M1-type macrophages， increased in the M1 model group and blank serum group （P<0.01）， which indicated that the M1 inflammatory model was established successfully. In addition， the M1 model group was observed with up-regulated mRNA and protein levels of proinflammatory cytokines IL-6 and TNF-α and glycolysis-related factors HIF-1α， GLUT1， HK2， GAPDH， and PFKFB3 （P<0.01）. Compared with the M1 model group， the Shaoyaotang-containing serum， 2-DG， and combined intervention groups showed decreased expression of CD86 （P<0.01）， down-regulated mRNA and protein levels of proinflammatory factors IL-6 and TNF-α and glycolysis-related factors HIF-1α， GLUT1， HK2， GAPDH， and PFKFB3 produced by M1-type macrophages （P<0.01）， increased expression of CD206 （marker of M2-type macrophages） （P<0.01）， and elevated levels of IL-10 and TGF-β produced by M2-type macrophages （P<0.01）. ConclusionShaoyaotang inhibits macrophage differentiation toward pro-inflammatory M1-type macrophages and promotes the differentiation toward anti-inflammatory M2-type macrophages by regulating glucose metabolism reprogramming. The evidence gives insights into new molecular mechanisms and targets for the treatment of ulcerative colitis with Shaoyaotang.

ObjectiveTo investigate the effect and underlying mechanism of the Wulao Qisun prescription on pathological new bone formation in ankylosing spondylitis （AS）. MethodsSynovial fibroblasts were isolated from the hip joints of AS patients and observed under a microscope to assess cell morphology. The cells were identified using immunofluorescence staining. The isolated AS fibroblasts were divided into blank group， low drug-containing serum group， medium drug-containing serum group， high drug-containing serum group， and positive drug group. After drug intervention， cell proliferation was measured using the cell counting kit-8 （CCK-8） assay to observe fibroblast growth and determine the optimal intervention time. Alkaline phosphatase （ALP） activity was measured using the alkaline phosphatase assay. Protein expression of osteocalcin （OCN）， osteopontin （OPN）， and runt-related transcription factor 2 （Runx2） was detected by Western blot. The mRNA expression levels of Wnt5a， β-catenin， and Dickkopf-1 （DKK-1） were measured by real-time quantitative polymerase chain reaction （Real-time PCR）. ResultsCompared with the blank group， each drug-containing serum group of Wulao Qisun prescription and the positive drug group inhibited the proliferation of AS fibroblasts and reduced ALP expression （P<0.01）. Compared with the blank group， the low drug-containing serum group of Wulao Qisun prescription downregulated β-catenin mRNA expression （P<0.05）. The medium and high drug-containing serum groups and the positive drug group significantly downregulated Wnt5a and β-catenin mRNA expression （P<0.05， P<0.01）， with the positive drug group showing the most pronounced effect （P<0.01）. The high drug-containing serum group and the positive drug group significantly upregulated DKK-1 mRNA expression （P<0.01）. Compared with the blank group， the low drug-containing serum group of Wulao Qisun prescription inhibited the expression of OPN and Runx2 proteins （P<0.05， P<0.01）， while the medium and high drug-containing serum groups and the positive drug group inhibited the expression of OCN， OPN， and Runx2 proteins （P<0.05， P<0.01）. ConclusionThe Wulao Qisun prescription can inhibit the proliferation and osteogenic differentiation of AS fibroblasts， thereby delaying the formation of pathological new bone in AS. The possible mechanism involves the regulation of Wnt/β-catenin-related gene expression， further inhibiting the transcription of downstream target genes.

In recent years， as the incidence of ulcerative colitis （UC） is growing， intestinal mucosal injury has garnered increasing attention， and it is characterized by high recurrence， risk of inflammation-cancer transformation， and difficulty in repair. Intestinal mucosal injury in UC is centered on persistent inflammation and barrier dysfunction， with its pathological mechanisms involving endoplasmic reticulum stress （ERS）-mediated changes such as abnormal apoptosis， abnormal autophagy， and inflammatory responses. ERS induces apoptosis of intestinal epithelial cells， disrupts tight junction proteins， and exacerbates inflammatory responses through pathways such as protein kinase R-like endoplasmic reticulum kinase （PERK）， inositol-requiring enzyme 1 alpha （IRE1α）， and activating transcription factor 6 （ATF6）， ultimately causing intestinal mucosal injury. Traditional Chinese medicine （TCM） has a long history of research on UC. The theory of sores depending on spleen-earth holds that spleen deficiency is the fundamental cause of UC， while pathological products such as dampness-turbidity and blood stasis are the secondary manifestations. Dysfunction of the spleen-earth leads to insufficient production and transformation of Qi and blood， malnutrition of the intestinal mucosa， and invasion of external pathogens. In the active phase of UC， spleen deficiency is often accompanied by excessive pathogenic factors such as dampness-heat and heat-toxin， leading to acute intestinal mucosal damage. In the remission phase， however， it is mainly characterized by spleen deficiency and healthy Qi deficiency， accompanied by residual pathogens， resulting in weak intestinal mucosal repair. Studies have shown that the endoplasmic reticulum， as a key site for protein synthesis and folding， has functions highly similar to the TCM concept of the spleen governing transportation and transformation. From a TCM perspective， the endoplasmic reticulum can be regarded as the carrier of spleen transportation， and ERS is a microcosmic manifestation of spleen dysfunction， leading to intestinal mucosal injury. ERS impairs the structure and function of the endoplasmic reticulum， induces the generation of abnormal Qi， and triggers pathological changes， making inflammation difficult to be reduced and causing the aggravation of ERS， forming a vicious cycle of spleen deficiency-pathological products-intestinal injury. TCM has unique advantages in regulating ERS to prevent and treat intestinal mucosal injury. According to the theory of sores depending on spleen-earth and the modern medical understanding of ERS， this paper delves into the TCM and Western medicine pathogenesis of intestinal mucosal injury in UC. Furthermore， this paper discusses the roles of TCM active components and compound formulas in reducing intestinal mucosal injury in UC by regulating ERS under the guidance of the treatment principles of invigorating the spleen and replenishing Qi as the key and dispelling dampness and removing blood stasis as the supplementation， aiming to provide new ideas and methods for the prevention and treatment of UC.

This paper reviews the origin, content and framework, evaluation tools, and application status of Snyder hope theory in clinical nursing practice both domestically and internationally, and explores the application prospects of Snyder hope theory, aiming to provide a basis for promoting its development in nursing.

Background The benchmark dose (BMD) method calculates the dose associated with a specific change in response based on a specific dose-response relationship. Compared with the traditional no observed adverse effect level (NOAEL) method, the BMD method has many advantages, and the 95% lower confidence limit of benchmark dose lower limit (BMDL) is recommended to replace NOAEL in deriving biological exposure limits. No authority has yet published any health-based guideline for rare earth elements. Objective To evaluate genotoxicity threshold induced by acute exposure to neodymium nitrate in mice using BMD modeling through micronucleus test and comet assay. Methods SPF grade mice (n=90) were randomly divided into nine groups, including seven neodymium nitrate exposure groups, one control group (distilled water), and one positive control group (200 mg·kg⁻¹ ethyl methanesulfonate), 10 mice in each group, half male and half female. The seven dose groups were fed by gavage with different concentrations of neodymium nitrate solution (male: 14, 27, 39, 55, 77, 109, and 219 mg·kg⁻¹; female: 24, 49, 69, 97, 138, 195, and 389 mg·kg⁻¹) twice at an interval of 21 h. Three hours after the last exposure, the animals were neutralized by cervical dislocation. The bone marrow of mice femur was taken to calculate the micronucleus rate of bone marrow cells, and the liver and stomach were taken for comet test. Results The best fitting models for the increase of polychromatophil micronucleus rate in bone marrow of female and male mice induced by neodymium nitrate were the exponential 4 model and the hill model, respectively. The BMD and the BMDL of female mice were calculated to be 31.37 mg·kg⁻¹ and 21.90 mg·kg⁻¹, and those of male mice were calculated to be 58.62 mg·kg⁻¹ and 54.31 mg·kg⁻¹, respectively. The best fitting models for DNA damage induced by neodymium nitrate in female and male mouse hepatocytes were the exponential 5 model and the exponential 4 model, respectively, and the calculated BMD and BMDL were 27.15 mg·kg⁻¹ and 11.99 mg·kg⁻¹ for female mice, and 16.28 mg·kg⁻¹ and 10.47 mg·kg⁻¹ for male mice, respectively. The hill model was the best fitting model for DNA damage of gastric adenocytes in both female and male mice, and the calculated BMD and BMDL were 36.73 mg·kg⁻¹ and 19.92 mg·kg⁻¹ for female mice, and 24.74 mg·kg⁻¹ and 14.08 mg·kg⁻¹ for male mice, respectively. Conclusion Taken the micronucleus rate of bone marrow cells, DNA damage of liver cells and gastric gland cells as the end points of genotoxicity, the BMDL of neodymium nitrate is 10.47 mg·kg⁻¹, which can be used as the threshold of genotoxic effects induced by acute exposure to neodymium nitrate in mice.

Ankylosing spondylitis （AS） is an inflammatory autoimmune disease with chronic low back pain as the main clinical manifestation， which mainly affects the axial joints， peripheral joints and various organs. In severe cases， the spine is stiff or deformed， which affects the quality of life and health of patients. The pathogenic factors of AS are complex， which are related to heredity， immunity and intestinal flora. The pathogenesis of AS is not clear yet. Among them， inflammatory reaction， bone destruction and heterotopic ossification are the main pathological features of AS， which play an important role in the disease process of AS. Traditional Chinese medicine has multi-target， multi-channel and multi-component pharmacological effects， which can prevent and treat AS by anti-inflammation， inhibiting bone destruction and preventing heterotopic ossification， and the clinical effect is remarkable， but there is no relevant literature report. Therefore， this review expounds the relationship between inflammatory reaction， bone destruction and heterotopic ossification and the occurrence and development of AS， and summarizes the latest research reports of traditional Chinese medicine in treating AS from anti-inflammatory， inhibiting bone destruction and preventing heterotopic ossification， aiming at providing reference and new ideas and directions for further research on the prevention and treatment of AS by traditional Chinese medicine.

Objective:To compare the consistency between bioelectrical impedance analysis(BIA)and dual-energy X-ray absorptiometry(DXA)in skeletal muscle mass assessment in elderly patients with advanced chronic kidney disease(CKD), and to provide a basis for accurate clinical diagnosis of sarcopenia.Methods:Elderly patients with advanced CKD at the Department of Nephrology of Shanghai Sixth People's Hospital were included.Parameters for physical performance included handgrip strength and gait speed, and body muscle mass was measured by DXA and multifrequency BIA.The consistency between the two methods was assessed by the intraclass correlation coefficient, Bland-Altman analysis and kappa coefficient test.Results:This study included 67 elderly patients with advanced CKD with a mean age of(70.7±6.1)years and an average BMI of(24.6±3.5)kg/m 2.The proportion of enrolled male patients was 61.2% and the mean estimated glomerular filtration rate was(27.7±12.7)ml·min -1·1.73m -2.The intraclass correlation coefficients of muscle mass and appendicular skeletal-muscle mass index(ASMI)measured by BIA and DXA ranged from 0.81 to 0.90.Bland-Altman analysis showed that BIA overestimated muscle mass against DXA, and the mean difference in ASMI was(0.44±0.13)kg/m 2.In addition, there was a moderate agreement between the two measurement methods for determining muscle loss(Kappa=0.47). Conclusions:BIA and DXA offer a fair level of consistency in the assessment of muscle mass in elderly patients with advanced CKD.However, compared with DXA, BIA overestimates muscle mass in elderly patients with CKD.

Objective:To investigate the risk factors for axial deviation in the treatment of tibial defect susing Orthofix unilateral external fixator and proximal tibial osteotomy for bone transport.Methods:A retrospective study was performed to analyze the clinical data of 90 patients who had been treated for tibial bone defects by the Orthofix unilateral external fixator at Department of Microrepair and Reconstruction, The First Hospital Affiliated to Xinjiang Medical University from May 2012 to June 2019. There were 77 males and 13 females with a mean age of 41.2 years (from 17 to 63 years).The bone defects ranged from 4 to 13 cm in length. According to the Paley criteria for axial deviation, the 90 patients were divided into 2 groups: a deviation-free group with no axial deviation or an axial deviation ≤5° and a deviation group with an axial deviation>5°. The 2 groups were compared in terms of age, number of prior surgery, defect length, placement angle of Schanz screws, external fixation time, external fixation index and bending degree of Schanz screws at the last follow-up.The factors with P<0.05 were analyzed by multivariate logistic regression to find the risk factors for coronal axial deviation. Results:The 90 patients were followed up for an average of 23 months (from 12 to 40 months). The incidence of axial deviation in this cohort was 36.7% (33/90).The deviation group had a significantly larger number of prior surgery [5 (3, 6) times], a significantly longer defect length [8 (8, 9) cm], a significantly longer external fixation time [400.0 (341.8, 426.3) d], and a significantly greater bending degree of Schanz screws at the last follow-up [1.2° (0.4°, 3.5°)] than the deviation-free group [3 (2, 3) times, 6 (5, 8) cm, 340.8 (226.5, 422.8) d, and 0.8° (0.2°, 3.7°)] (all P<0.05). Multivariate logistic regression analysis showed that the number of prior surgery ( OR=2.581, 95% CI: 1.496-4.450, P=0.001) and the defect length ( OR=5.310, 95% CI: 1.952-14.442, P=0.001) were the risk factors for the axial deviation. Conclusion:In the treatment of tibial defect susing Orthofix unilateral external fixator and proximal tibial osteotomy for bone transport, the more prior surgeries and the longer a bone defect, the higher the risk for axial deviation.

Objective To study the effect of nicotinamide mononucleotide (NMN) on the mortality of the lipopoly-saccharide (LPS)-induced endotoxic shock mouse model. Methods 10-week-old C57BL/6J male mice were randomly divided into groups, and were injected intraperitoneally (i.p.) with LPS (10 mg/kg) to induce endotoxic shock models. NMN was i.p. injected in three ways: (1) 0.5 h after modeling, doses of 10, 30, 100 and 300 mg/kg; (2) 0.5 h before modeling, doses of 30, 100, 300 and 600 mg/kg; or (3) 0.5 and 12 h after modeling, dose of 300 mg/kg each time. The death times of each group were recorded, and the survival curves were drawn. Results Compared with the solvent control group, NMN at different doses given 0.5 h after or before modeling didn’t improve the survival rate or delay the death time of endotoxic shock mice; But when given at 0.5 and 12 h 300 mg/kg after modeling, NMN accelerated the death of mice and increased the mortality of mice. NMN products by two manufacturers showed similar effects. Conclusion NMN has no therapeutic effect on LPS-induced endotoxic shock, and repeated administration of NMN after endotoxic shock will increase the mortality.