OBJECTIVE To optimize the preparation technology of Jineijin danggui ruchuang ointment and to establish its quality standard. METHODS Using oil phase dosage， emulsifier dosage and emulsification temperature as the indicators， the preparation technology of Jineijin danggui ruchuang ointment was optimized by response surface method. Gallus gallus domesticus and Angelica sinensis in the ointment were identified by TLC. The property of the ointment was observed， and its particle size and deliverable volume were inspected according to Chinese Pharmacopoeia. The contents of uridine， ferulic acid and ligustilide in the ointment were determined by high-performance liquid chromatography. RESULTS The optimal preparation technology of Jineijin danggui ruchuang ointment was as follows： 4.0 g of white vaseline， 7.0 g of liquid paraffin， 5.0 g of lanolin （oil phase）， 0.44 g of triethanolamine as the emulsifier， and emulsification temperature of 78 ℃ . Jineijin danggui ruchuang ointment prepared according to the optimal preparation method was a beige paste， and its particle size and deliverable volume inspection all met the requirements of the Chinese Pharmacopoeia. The identification of TLC for G. gallus domesticus and A. sinensis obtained satisfactory results. The linear ranges of uridine， ferulic acid and ligustilide were 1.6-25.6 μg/mL， 0.003 15-0.100 8 mg/mL， 0.006- 0.192 mg/mL （all r＞0.999）. RSD for the inspection， stability， reproducibility and recovery tests were all less than 2%（ n＝6）. The average contents of uridine， ferulic acid and ligustilide were 0.081 2， 0.100 0 and 0.396 9 mg/g， respectively. CONCLUSIONS The optimal preparation technology can be used for the production of the in-hospital preparation of Jineijin danggui ruchuang ointment； the content determination method can be used for the quality control of the ointment.

HDAC7, a member of class IIa HDACs, plays a pivotal regulatory role in tumor, immune, fibrosis, and angiogenesis, rendering it a potential therapeutic target. Nevertheless, due to the high similarity in the enzyme active sites of class IIa HDACs, inhibitors encounter challenges in discerning differences among them. Furthermore, the substitution of key residue in the active pocket of class IIa HDACs renders them pseudo-enzymes, leading to a limited impact of enzymatic inhibitors on their function. In this study, proteolysis targeting chimera (PROTAC) technology was employed to develop HDAC7 drugs. We developed an exceedingly selective HDAC7 PROTAC degrader B14 which showcased superior inhibitory effects on cell proliferation compared to TMP269 in various diffuse large B cell lymphoma (DLBCL) and acute myeloid leukemia (AML) cells. Subsequent investigations unveiled that B14 disrupts BCL6 forming a transcriptional inhibition complex by degrading HDAC7, thereby exerting proliferative inhibition in DLBCL. Our study broadened the understanding of the non-enzymatic functions of HDAC7 and underscored the importance of HDAC7 in the treatment of hematologic malignancies, particularly in DLBCL and AML.

OBJECTIVE To investigate the improvement effects of total flavonoids from Bidens pilosa （TFB）against Alzheimer’s disease （AD） and elucidate its potential mechanism. METHODS The network pharmacology was adopted to explore active constituents and core targets of TFB for AD， followed by gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analyses. Based on the results of network pharmacology， an AD model was induced in male BALB/c mice by D-galactose subcutaneous injection and aluminum chloride gavage. The effects of TFB on behavioral indicators （including escape latency， the number of platform crossings， and the proportion of dwell time spent in the original platform quadrant）， as well as on acetylcholinesterase （AChE）， acetylcholine （ACh）， choline acetyltransferase （ChAT）， amyloid β-protein （Aβ）， phosphorylated Tau protein （p-Tau）， and inflammatory factors [interleukin-1β （IL-1β）， IL-6， and tumor necrosis factor-α （TNF-α）] were investigated. Additionally， its effects on the pathological changes in hippocampal neurons， as well as the expressions of related proteins and mRNAs were evaluated. RESULTS Network pharmacology revealed 6 active components in TFB （e.g. luteolin， quercetin， kaempferol） and 165 overlapping targets with AD， including 29 core targets （Akt1， TP53， etc.）. The common targets were primarily enriched in biological processes such as positive regulation of gene expression and negative regulation of apoptotic processes， molecular functions including enzyme binding and identical protein binding， cellular components like extracellular space， plasma membrane and receptor complex， as well as signaling pathways such as cancer pathways and phosphoinositide 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway. The results of animal experiments showed that， compared with model group， the pathological changes such as disordered arrangement， degeneration， and necrosis of neurons in the hippocampal CA3 region of mice in administration groups were alleviated. The escape latency （except for the low-dose TFB group）， the contents of AChE （except for the low-dose TFB group）， Aβ40， Aβ42 （except for the low-dose TFB group）， p-Tau （except for the low- and medium-dose TFB groups）， IL-1β， IL-6 （except for the low-dose TFB group）， and TNF- α in brain tissue， as well as the expressions of Bax and caspase-3 mRNA， were all significantly shortened/reduced/down-regulated. Conversely， the number of platform crossings， the proportion of dwell time spent in the original platform quadrant， the contents of ChAT and ACh， the phosphorylation levels of PI3K and Akt， and the mRNA expressions of PI3K， Akt and Bcl-2 （except for PI3K mRNA and Akt mRNA in the low- and medium-dose TFB groups， and Bcl-2 mRNA in the low-dose TFB group） were all significantly increased （P＜0.05 or P＜0.01）. CONCLUSIONS TFB can exert anti-AD effect through multiple components， multiple targets， and multiple pathways. Its underlying mechanisms may be related to the activation of the PI3K/Akt signaling pathway， improvement of the cholinergic system， reduction of Aβ deposition and Tau protein hyperphosphorylation， as well as inhibition of neuroinflammatory responses and neuronal apoptosis.

OBJECTIVE To investigate the effect and mechanism of total flavonoids of Bidens pilosa L. （TFB） on lipopolysaccharide （LPS）-induced neuroinflammation in mice. METHODS Fifty C57BL/6 mice were randomly divided into normal control group， LPS group and TFB low-dose， medium-dose and high-dose groups， with 10 mice in each group. TFB low-dose， medium-dose and high-dose groups were given TFB solution intragastrically at 60， 120 and 240 mg/kg， and the normal control group and LPS group were given corresponding volume of normal saline， once a day， for consecutive 21 d. From the 15th day of administration， except for the normal control group， other groups were given LPS （400 μg/kg） intraperitoneally for 7 consecutive days to establish neuroinflammatory model. Brain tissues were taken under anesthesia 4 h after the final administration. The morphological changes of neuronal cells in mice were observed； the contents of nitric oxide （NO）， tumor necrosis factor α （TNF- α）， interleukin-1β （IL-1β）， IL-6 and IL-10 were measured， and the expressions of inflammatory pathway-related proteins [inducible NO synthase （iNOS）， cyclooxygenase-2 （COX-2）， myeloid differentiation factor 88 （Myd88） and protein kinase C （PKC）] were measured in the brain tissues of mice. RESULTS Compared with the normal control group， the neuronal arrangement in the hippocampal region of the brain tissue of mice in the LPS group was sparsely disorganized， with a large number of neuronal fixations and shrunken nuclei； the contents of TNF-α， IL-1β， IL-6 and NO in the brain tissue were significantly increased， the contents of IL-10 were significantly decreased， and the relative expressions of iNOS， COX-2， Myd88 and PKC proteins were significantly increased （P＜0.05）. Compared with the LPS group， the neuronal pathological changes in the brain tissue of mice in the TFB low-dose， medium-dose and high-dose groups were 202014810） significantly improved， and the changes of the above indices in the brain tissue were significantly reversed （P＜0.05） CONCLUSIONS TFB has an inhibitory effect on E-mail：pangxjun@163.com neuroinflammation， and its mechanism of action may be related to down-regulation of the expressions of inflammatory pathway-related proteins iNOS， COX-2， Myd88 and PKC， and reduction of inflammatory factors release.

OBJECTI VE To explore the effects of total flavonoids of Bidens polisa L.（TFB）on insulin resistance （IR）of HepG2 cells. METHODS B. polisa L. was refluxed and extracted with 80％ ethanol to obtain TFB. Palmitic acid was used to induce IR mode of HepG 2 cells in vitro . The effects of low-concentration ，medium-concentration and high-concentration （20，40， 80 mg/L） of TFB on the consumption of glucose were investigated. Using metformin as positive control ，the effects of low-concentration，medium-concentration and high-concentration （20，40，80 mg/L）of TFB on the protein expression of insulin receptor substrate- 1（IRS-1），c-Jun N-terminal kinase （JNK）and protein kinase C （PKC）were investigated. Molecular docking technology was used to explore the interaction between eight main active components of TFB such as quercetin ，quercitrin and IRS-1，JNK and PKC proteins. RESULTS The glucose consumption of TFB low-concentration ，medium-concentration and high-concentration groups were increased significantly （P＜0.05 or P＜0.01）. Compared with normal group ，the expression of IRS-1 and JNK protein in the model group decreased significantly ，and the expression of PKC protein increased significantly （P＜ 0.01）. Compared with model group ，the protein expression of IRS- 1 and JNK could up-regulated while the protein expression of PKC down-regulated in TFB low-concentration ，medium-concentration and high-concentration groups and metformin positive control group （P＜0.05 or P＜0.01）. The score of molecular docking energy between maritimetin in TFB and IRS- 1 protein was －7.9 kcal/mol（1 kcal＝4.816 kJ）. The scores of molecular docking energy of maritimetin ，rutin and JNK protein were －9.3 kcal/mol. The score of molecular docking energy between quercitrin and PKC protein was －4.9 kcal/mol. Interactions between components and proteins included forming hydrogen bonds ，hydrophobic bonds and so on. CONCLUSIONS TFB can significantly improve IR of HepG 2 cells，the mechanism of which may be related to the regulation of protein expression of IRS ，JNK and PKC. Maritimetin，rutin and quercitrin may be potential active ingredients for improving IR.

Objective To investigate the global research status and trends ofrehabilitation after arthroplasty.Methods The Wed of Science database was used to search the publications on rehabilitation after arthroplasty from 1994 to 2018.The included publish items were statistically analyzed by bibliometrics.VOSviewer software was used to analyze the visual transformation of literature coupling (including author coupling,mechanism coupling and country coupling) and co-occurrence analysis.The research status and trends of rehabilitation after arthrop]asty in recent years were analyzed and predicted.Results A total of 1 702 studies were included in the present study.The number of literatures increased year by year globally,including 612 in the United States as the top number of studies in the world.The total citation frequency (15 433 times) and H index (61) of the research publications were also the highest in the world.China (79 literatures) ranked 6th in the number of global research publications,with total citation frequency (451 times) and H index (12) ranked 14th.The number of publications published by JOURNAL OF ARTHROPLASTY and ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION on rehabilitation after arthroplasty was the highest.The University of Pittsburgh and the University of Toronto were the biggest contributors to publications on rehabilitation after arthroplasty.The theme of rehabilitation after arthroplasty can be divided into five categories:pain management,functional exercise,hospital management,complications and clinical trials.Hospital management wasthe main research field recently and the orthopedic specialty hospital would become a hot research topic in the fulure.Conclusion According to the current global trends,rehabilitation study is deepening and the number of publications will increase continuously.The United States is the largest contributor in this area.The current researches focus on the "hospital management" after arthroplasty.The new type of orthopedic specialty hospital may be the next research hotspot for arthroplasty.

Objective We aimed to explor the correlation between the serum resistin levels and the collapse process of femoral head necrosis. Methods Eighty-eight patients with osteonecrosis of the femoral head were included in this study (26, 34 and 28 cases at ARCO stage Ⅱ, Ⅲ and Ⅳ, respectively). Fifty healthy controls were enrolled. The serum resistin levels were detected with ELISA method. We compared the serum resistin levels between the patient group and control group. The differences of serum resistin levels between different ARCO stagesand various disease causes were analyzed in the patient group. Results The resistin levels were significantly higher in patients with osteonecrosis of the femoral than healthy control group (P = 0.026). Compared with control group, the resistin levels significantly increased in patients at ARCO stage Ⅲ and ARCO stage Ⅳ respectively (P = 0.001).The resistin levels of procollapse group (ARCO stage Ⅲ and Ⅳ) were significantly higher than that of precollapse group (ARCO stage Ⅱ) (P = 0.000). There was no statistic difference between ARCO stage Ⅲ andⅣ in resistin levels (P> 0.05). No statistical significance was found between different disease causes. ROC curve analysis of resisrin level indicated theertain accuracy (AUC = 0.749) , sensitivity and significant specificity (77.4％, 61.5％, respectively) in the diagnosis of femoral head necrosis. Conclusions Resistin is closely related to the collapse process of femoral head necrosis. The level of resistin was significantly increased after the collapse of femoral head, which could be useful for the clinical diagnosis of the collapse of femoral head necrosis.

Objective To investigate the effect of hypertonic saline on the expressions of aquaporin 4 (AQP4) and caspase-3 in the brain edema area after traumatic brain injury (TBI) in rats Methods Seventy-two male SD rats weighing 220-250 g were selected and randomly divided into three groups (24 rats per group):sham operation group (Group A),traumatic brain injury + normal saline group (Group B) and traumatic brain injury + hypertonic saline group (Group C).Moderate TBI model was induced by Feeney's free falling method.Normal saline and hypertonic saline were delivered respectively.The neurological score was measured at 6,24,and 48 hours after operation.The brain water content was measured,and the blood brain barrier stability was detected by Evans blue staining.AQP4 positive cells was detected by immunohistochemistry.The expressions of AQP4 and caspase-3 protein in brain tissue were detected by Western blot,and the apoptosis of neurons in brain tissue by TUNEL method.Results Compared with Group A,the neurological score of Group B were obviously decreased,while the water content in the brain tissue,Evans blue staining,AQP4 positive cells,AQP4 (6 hours:1.73 ±0.31 vs.0.33 ±0.13;24 hours:2.47 ±0.27 vs.0.33 ±0.14;48 hours:2.18 ± 0.19 vs.0.33 ±0.12),caspase-3 protein expression(6 hours:0.53 ±0.18 vs.0.34 ±0.07;24 hours:0.58 ±0.16 vs.0.33 ± 0.08;48 hours:0.59 ± 0.11 vs.0.33 ± 0.07) and apoptosis index in brain tissue in Group B were significantly increased (all P ＜ 0.05).Compared with Group B,the neurological score of Group C were obviously increased,while the water content in the brain tissue,Evans blue staining,AQP4 positive cells,AQP4 (6 hours:1.51 ±0.27 vs.1.73 ±0.31;24 hours:2.13 ±0.13 vs.2.47±0.27;48 hours:1.84 ±0.22 vs.2.18 ±0.19) and Caspase-3 protein expression (6 hours:0.44±0.09vs.0.53±0.18;24 hours:0.46±0.10vs.0.58±0.16;48 hours:0.48±0.12 vs.0.59 ± 0.11) and apoptosis index in brain tissue of Group C were significantly decreased (all P ＜ 0.05).Conclusion Hypertonic saline can attenuate TBI-induced brain edema and have a significant neuroprotective effect,possibly by down-regulating the expressions of AQP4 and caspase-3.

Objective To explore the feasibility and efficacy of an MRI-visible,targeted,nano-vector which is synthesized by attaching a targeting ligand,the GD2 single chain antibody (scAb GD2),to the distal ends of PEG-g-PEI-SPION as a carrier for gene delivery into human bone marrow mesenchymal stem cells (hBMSCs) and in vitro cellular MR imaging.Methods scAbGD2-PEG-g-PEI-SPION was synthesized as previously reported.Gel electrophoresis was performed to assess the pDNA condensation ability of scAbGD2-PEG-g-PEI-SPION.The particle size and Zeta potential of scAbGD2-PEG-g-PEI-SPION/pDNA nanocomplexes were observed by dynamic light scattering.Cytotoxicity of scAbGD2-PEG-g-PEI-SPI-ON was evaluated by CCK-8 assay using hBMSCs.Gene transfection efficiency of scAbGD2-PEG-g-PEI-SPION in hBMSCs was quantified by flow cytometry,PEG-g-PEI-SPION,scAbGD2-PEG-g-PEI-SPION,scAbGD2-PEG-g-PEI-SPION+ free AbGD2 and scAbIgG2a-PEG-g-PEI-SPION group was established.The cellular internalization of scAbGD2-PEG-g-PEI-SPION/pDNA nanocomplexes was observed by confocal laser scanning microscopy and Prussian blue staining.MRI of scAbGD2-PEG-g-PEI-SPION was performed by cellular MRI scanning in vitro.Results scAbGD2-PEG-g-PEI-SPION condensed pDNA to form stable nanocomplexes of 80-100 nm in diameter and showed low cytotoxicity to hBMSCs.At the same N/P ratio,the transfection efficiency of scAbGD2-PEG-g-PEI-SPION group was significantly higher than those of other groups (P＜0.001).At the optimal N/P ratio of 20,scAbGD2-PEG-g-PEI-SPION/pDNA obtained the highest transfection efficiency of (59.60 ± 4.50) ％ in hBMSCs.Furthermore,hBMSCs labeled with scAbGD2-PEG-g-PEI-SPION showed sensitive low signal intensity on MRI T2/T2 *-weighted images in vitro.Conclusion scAbGD2-PEG-g-PEI-SPION is an efficient MRL visible targeted nano vector for gene delivery into hBMSCs.

Objective To investigate the protective effect of Jiejiu oral liquid on acute alcohol-induced gastric mucosal lesions in mice.Methods Sixty Knming''s mice were randomly divided into normal control group,model control group,sucralfate group(600 mg·kg-1),the dose of 25.0 g·kg-1 group,the dose of 12.5 g·kg-1 group and the dose of 6.25 g·kg-1 group of the Jiejiu oral liquid (n=10 each).Except for the normal control group,other groups were intragastrically administered with 95% ethanol to create the alcohol-induced acute gastritis model.The effect of pathological histology,injury of gastric mucosa,the mucosal NO,ET-1,TNF-α,IL-6 and PGE2 content of acute alcohol-induced gastric mucosal lesions in mouse were observed.Results The gastric mucosa in model control group appeared obvious bleeding,erosion,and flake ulcer.Compared with the model control group,the acute damage index of the Jiejiu oral liquid therapy groups were obviously reduced (P<0.05 or P<0.01).The content of ET-1,TNF-α and IL-6 in the 25.0 g·kg-1 and the 12.5 g·kg-1 dose group of the Jiejiu oral liquid significantly decreased compared with the model control group (P<0.05 or P<0.01).The content of NO in the 25.0 g·kg-1 group of the Jiejiu oral liquid increased (P<0.05).Jiejiu oral liquid had no significant effect on the content of PGE2 (P>0.05).Histopathologic examination revealed Jiejiu oral liquid can reduce the shedding of gastric mucosa and inflammatory cells infiltration.Conclusion The Chinese herbal mixture Jiejiu oral liquid has a protective effect on acute alcohol-induced gastric mucosal lesions in mice.