Bone repair remains an important target in tissue engineering, making the development of bioactive scaffolds for effective bone defect repair a critical objective. In this study, β-tricalcium phosphate (β-TCP) scaffolds incorporated with processed pyritum decoction (PPD) were fabricated using three-dimensional (3D) printing-assisted freeze-casting. The produced composite scaffolds were evaluated for their mechanical strength, physicochemical properties, biocompatibility, in vitro pro-angiogenic activity, and in vivo efficacy in repairing rabbit femoral defects. They not only demonstrated excellent physicochemical properties, enhanced mechanical strength, and good biosafety but also significantly promoted the proliferation, migration, and aggregation of pro-angiogenic human umbilical vein endothelial cells (HUVECs). In vivo studies revealed that all scaffold groups facilitated osteogenesis at the bone defect site, with the β-TCP scaffolds loaded with PPD markedly enhancing the expression of neurogenic locus Notch homolog protein 1 (Notch1), vascular endothelial growth factor (VEGF), bone morphogenetic protein-2 (BMP-2), and osteopontin (OPN). Overall, the scaffolds developed in this study exhibited strong angiogenic and osteogenic capabilities both in vitro and in vivo. The incorporation of PPD notably promoted the angiogenic-osteogenic coupling, thereby accelerating bone repair, which suggests that PPD is a promising material for bone repair and that the PPD/β-TCP scaffolds hold great potential as a bone graft alternative.
Calcium Phosphates/chemistry* ; Animals ; Bone Regeneration ; Rabbits ; Tissue Scaffolds ; Printing, Three-Dimensional ; Humans ; Human Umbilical Vein Endothelial Cells ; Neovascularization, Physiologic ; Osteogenesis ; Tissue Engineering/methods* ; Biomimetic Materials ; Cell Proliferation ; Angiogenesis

The disease risk prediction model is the basis of precision prevention and an essential reference for clinical treatment decisions. The development of risk prediction models requires the support of a large amount of high-quality data. A large population cohort study is an important basis for this study. The United Kingdom Biobank (UKB), as a mega-population cohort and biobank, has played an essential role in the exploration of disease etiology and research related to disease prevention and control, with its rich baseline and follow-up data and concepts and mechanisms shared globally. This study followed PRISMA guidelines and included 210 articles with corresponding authors from 18 countries, of which 58 (27.62%) were from the UKB. A total of 491 disease risk prediction models were extracted for cancer, cardiovascular and cerebrovascular diseases, endocrine and metabolic diseases, respiratory diseases, and other diseases and their subgroups, of which 132 were developed by UKB without validation, 183 were developed by UKB with internal validation, 17 were developed by UKB with external validation, and 159 were developed by external development with UKB validation. A total of 188 models used only macro variables (38.29%), and 303 models combined macro and micro variables (61.71%). Model construction methods included survival outcome models, logistic regression, and machine learning. Survival outcome models were dominated by Cox proportional risk regression models and a few models considering competitive risk, accelerated failure models, or different baseline risk functions. Machine learning models included random forest, XGBoost, CatBoost, support vector machine, convolutional neural network, and other methods. The UKB is an essential resource for multiple disease risk prediction modeling studies.

ObjectiveTo investigate the regulatory effect of Danggui Shaoyaosan on adenosine monophosphate-activated protein kinase （AMPK）/mammalian target of rapamycin （mTOR）/Unc-51-like kinase-1 （ULK1） signaling pathway in the rat model of metabolism-associated fatty liver disease （MAFLD）. MethodSixty SD rats were randomized into control， model， western medicine （polyene phosphatidylcholine capsules，0.144 g·kg^-1）， and low-， medium-， and high-dose （2.44， 4.88， 9.76 g·kg^-1， respectively） Danggui Shaoyaosan groups. After being fed with a high-fat diet for 8 weeks， the rats in each group were administrated with corresponding drugs for 4 weeks. At the end of drug treatment， serum and liver tissue were collected for subsequent determination of related indicators. ResultCompared with the control group， the model group showed increased contents of total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C） and activities of alanine aminotransferase （ALT） and aspartate aminotransferase （AST） in the serum， increased contents of TC， TG， and free fatty acids （FFAs） in the liver （P<0.01）， and decreased content of high-density lipoprotein cholesterol （HDL-C） in the serum （P<0.01）. Furthermore， the model group showed down-regulated protein levels of p-AMPK， microtubule-associated protein 1 light chain 3B （LC3B） Ⅱ， Beclin1， and ULK1 （P<0.01） and up-regulated protein levels of p-mTOR and ubiquitin-binding protein p62 in the liver （P<0.01）. The hepatic steatosis was obvious and the NAFLD activity score （NAS） and oil red O staining area increased in the model group， （P<0.05， P<0.01）. Compared with the model group， Danggui Shaoyaosan reduced the contents of TC and TG and the activities of ALT and AST in the serum， lowered the levels of TC， TG， and FFA in the liver， down-regulated the protein levels of p-mTOR and p62 （P<0.01）， elevated the serum HDL-C level， and up-regulated the protein levels of p-AMPK， LCBⅡ， Beclin1， and ULK1 in the liver （P<0.05， P<0.01）. Moreover， it alleviated hepatic steatosis and decreased the NAS and oil red O staining area （P<0.05， P<0.01）. ConclusionDanggui Shaoyaosan has therapeutic effect on MAFLD rats by regulating AMPK/mTOR/ULK1 signaling pathway to enhance autophagy.

Objective:To investigate the clinical value of applying pain tolerance index(PTi) to guide multimodal analgesic regimen during the perioperative period in elderly hip fractures.Methods:A total of 100 elderly patients with hip fracture admitted to Fuyang People′s Hospital from April 2022 to April 2023 were selected as the study objects. The patients were underwent hip replacement and were divided into two groups according to the different analgesic methods used during the operation. The control group (50 cases) was given routine analgesia during the operation, and the experimental group (50 cases) was given multimode analgesia under the guidance of PTi during the operation. The anesthetic analgesic effect, hemodynamic indexes, inflammatory factors, visual analogue scale (VAS) score, hip function and analgesic drug application were compared between the two groups.Results:The excellent rate of anesthesia and analgesia in the experimental group was higher than that in the control group: 96.00%(48/50) vs. 82.00%(41/50), there was statistical difference ( χ2 = 5.00, P<0.05). The fluctuation ranges of mean arterial pressure (MAP) and heart rate (HR) at the beginning of operation, 30 min after operation and the end of operation in the experimental group were lower than those in the control group ( P<0.05). The serum levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in the experimental groups were lower than those in the control group at 1 and 3 d after operation ( P<0.05). The scores of VAS at 24, 48 and 72 h after operation in the experimental group were lower than those in the control group ( P<0.05). The total scores of Harris questionnaire in the experimental group was higher than that in the control group at 6 weeks after operation: (85.93 ± 3.22) scores vs. (75.19 ± 4.18) scores, there was statistical difference ( P<0.05). The intraoperative dosage of propofol and sufentanil and the number of postoperative analgesic drugs in the experimental groups were lower than those in the control group: (430.61 ± 20.09) mg vs. (475.58 ± 23.17) mg, (33.24 ± 8.11) μg vs. (42.90 ± 9.64) μg, (1.54 ± 0.31) times vs. (2.07 ± 0.44) times, there were statistical differences ( P<0.05). The incidence of nausea and vomiting in the experimental group was lower than that in the control group: 2.00% (1/50) vs. 14.00% (7/50), there was statistical difference ( χ2 = 4.89, P<0.05). Conclusions:The application of PTi guided multimodal analgesia in elderly hip fracture surgery has a definite clinical effect, can maintain hemodynamic stability, reduce postoperative inflammatory stress and pain, promote hip joint function recovery, and has certain safety.

Nowadays potential preclinical drugs for the treatment of nonalcoholic steatohepatitis (NASH) have failed to achieve expected therapeutic efficacy because the pathogenic mechanisms are underestimated. Inactive rhomboid protein 2 (IRHOM2), a promising target for treatment of inflammation-related diseases, contributes to deregulated hepatocyte metabolism-associated nonalcoholic steatohepatitis (NASH) progression. However, the molecular mechanism underlying Irhom2 regulation is still not completely understood. In this work, we identify the ubiquitin-specific protease 13 (USP13) as a critical and novel endogenous blocker of IRHOM2, and we also indicate that USP13 is an IRHOM2-interacting protein that catalyzes deubiquitination of Irhom2 in hepatocytes. Hepatocyte-specific loss of the Usp13 disrupts liver metabolic homeostasis, followed by glycometabolic disorder, lipid deposition, increased inflammation, and markedly promotes NASH development. Conversely, transgenic mice with Usp13 overexpression, lentivirus (LV)- or adeno-associated virus (AAV)-driven Usp13 gene therapeutics mitigates NASH in 3 models of rodent. Mechanistically, in response to metabolic stresses, USP13 directly interacts with IRHOM2 and removes its K63-linked ubiquitination induced by ubiquitin-conjugating enzyme E2N (UBC13), a ubiquitin E2 conjugating enzyme, and thus prevents its activation of downstream cascade pathway. USP13 is a potential treatment target for NASH therapy by targeting the Irhom2 signaling pathway.

BACKGROUND: With the improvement in medical level, the clinical demand for bone repair materials is gradually Increasing, and the requirements are also getting more and more. OBJECTIVE: To review the related research progress In the field of bone repair materials In recent years, to analyze the advantages and disadvantages of different materials, and to guide future development In this research field. METHODS: A computer-based online search of CNKI, Wanfang, PubMed, Web of Science databases was performed to retrieve papers published during 1950-2019 with the search terms “tissue engineering, bone repair material, bone defect, natural bone material, bone graft replacement material, traditional Chinese medicine” in Chinese and English. A total of over 900 papers were retrieved, and 68 of them were included In the final analysis. RESULTS AND CONCLUSION: In recent year, with the flourish development of bone tissue engineering, the research of bone tissue repair materials is in the ascendant. In addition to optimizing natural bone, a variety of bone graft substitute materials have been developed, for example, natural macromolecule materials, synthetic macromolecule materials, biomedical ceramics materials, biomedical metal materials, etc., but these materials have different properties. Although there are many bone repair materials at present, the Ideal bone repair materials are few. Therefore, bone tissue repair and bone remodeling is still one of the urgent orthopedic problems to be solved In the clinic. In addition, the traditional Chinese medicine for bone repair, such as pyritum combined with modern bone repair materials, can effectively avoid some of the drawbacks of the current bone repair materials, thereby effectively treating bone defect diseases. This deserves In-depth investigation In the field of bone repair.

Objective To evaluate the relationship between concurrent myocardial bridge at anterior descending branch and the formation of coronary atherosclerosis plaques by using transluminal attenuation gradient (TAG). Methods A total of 198 patients underwent coronary CTA in Renji Hospital of Shanghai Jiaotong University School of Medcine from June 2017 to March 2018 and the results showed the anterior descending myocardial bridge. The data were retrospectively analyzed. All patients completed the coronary CTA with 320?row detector CT. According to the manifestations of myocardial bridge on CTA,the patients were divided into deep and superficial myocardial bridge groups. According to whether the patients were complicated with coronary atherosclerotic plaques, they were divided into isolated myocardial bridge group and myocardial bridge with coronary atherosclerotic plaque group. The thickness and length of myocardial bridge, the volume of coronary atherosclerotic plaques at the site of myocardial bridge, the pre?bridge and post?bridge TAG values, and the K ratio were recorded. Independent sample t test (normal distribution) or Mann?Whitney U test (skewed distribution) was used to compare the difference of measurement data among different groups. χ2 test was used to compare the difference of enumeration data among different groups. Pearson correlation test was used to analyze the correlation among pre?bridge and post?bridge TAG values,K ratio,thickness and length of myocardial bridge and plaque volume. The influence of above indexes on plaque occurrence was analyzed by binary logistic regression analysis. The relationship between main influence indexes and plaque formation was analyzed by receiver operating characteristic curve (ROC). Results Ninety nine patients had isolated myocardial bridge,99 with myocardial bridge and coronary atherosclerotic plaques,27 with superficial myocardial bridge and 171 with deep myocardial bridge. All atherosclerotic plaques occurred in pre?bridge and the mean volume of plaques was (91.6±83.0)mm3. The differences in sex, age, height, body weight and body mass index werenot statistically significant between isolated myocardial bridge group and myocardial bridge with coronary atherosclerotic plaque group (all P>0.05). The difference in pre?bridge TAG value was statistically significant between the isolated myocardial bridge group and myocardial bridge with coronary atherosclerotic plaque group (all P<0.05), but not statistically significant in post?bridge TAG value and K ratio (all P>0.05). The difference in pre?bridge and post?bridge TAG values and K value was not statistically significant between the superficial group and the deep group (all P>0.05). There was a weak negative correlation (r=-0.205,-0.316,-0.339,respectively,P<0.05) between the plaque volume and pre?bridge&post?bridge TAG values and K ratio. The pre?bridge TAG value significantly affected the plaque formation (P=0.014) and the odds ratio was 0.884 (95% CI 0.801 to 0.976). While other factors had no significant effects on plaque formation (all P>0.05). The area under curveof plaque formation promoted by pre?bridge TAG value was 0.582. When the diagnostic critical value was －37.26 HU/mm, the sensitivity and specificity of pre?bridge TAG value in plaque formation were 31.31% and 81.82%, respectively. Conclusion The TAG value of anterior descending bridge is an independent risk factor for plaque occurrence. The abnormal TAG value of anterior descending myocardial bridge can be detected early by CTA.

Objective: To analyze the basic characteristics of patients with hepatocellular carcinoma (HCC), and further explore the major factors affecting the prognosis of HCC patients. Methods: A total of 800 HCC patients were randomly selected from the Cancer Hospital, Chinese Academy of Medical Sciences. Their clinical and follow-up information was obtained from medical record. Univariate analysis of variance, Kaplan-Meier method and Cox regression analysis were used to analyze the patients′ age at diagnosis and survival time, etc. Results: The average age of diagnosis was 55.04 years among all the 800 HCC patients, and the sex ratio of male to female was 4.48. The infection rates of HBV and HCV were 78.6% (629/800) and 5.8% (46/800), respectively. The smoking rate was 41.0% (328/800) and the alcohol consumption rate was 38.5% (328/800). 259 (32.4%) patients underwent radical treatments with liver resection as major therapy, and 541 (67.6%) patients adopted non-radical treatments with transcatheter arterial chemoembolization (TACE) as major therapy. The 1-, 3- and 5-year survival rates of the HCC patients were 73.2%, 53.7% and 42.4%, respectively. The risk factors for prognosis included alcohol abuse and treatment methods. The HR of alcohol abuse was 1.326 (95%CI: 1.058 to 1.661) and HR of treatment methods was 3.301 (95% CI: 2.483 to 4.387). Conclusions Men account for the majority of HCC patients, and most patients have a lower age at diagnosis and adopt non-radical treatments. The exposure rates of HBV infection and alcohol abuse of HCC patients are significantly higher than those of general population. The major risk factors affecting prognosis and survival are treatments and alcohol abuse. Alcohol abuse and HBV may have synergistic effects on the survival of HCC patients.

ThevolatilecompositionsofDuchesneaindicawerestudiedbyheadspacesolid-phase microextraction ( HS-SPME ) , soxhlet extraction ( SE ) , ultrasonic assistant extraction ( UAE ) and steam distillation ( SD) coupled with gas chromatography-mass spectrometry ( GC-MS) . The experimental parameters of HS-SPME, including fiber type, extraction temperature, extraction time and desorption time were investigated. 47, 32, 16 and 16 compounds were identified by HS-SPME, SD, SE and UAE extracting methods, respectively. 66 compounds were obtained in total, among which 47 compounds were first reported in Duchesnea indica. The experimental results showed that terpenoids were the most abundant compositions in HS-SPME and SD, but acids accounted for 61. 44% and 69. 54% of the total content obtained by SE and UAE.

Objective To evaluate the role of Akt-glycogen synthase kinase-3 beta (GSK3β) signaling pathway in the long-term neuroprotection induced by propofol postconditioning in a rat model of focal cerebral ischemia/reperfusion (I/R) injury.Methods Two hundred and sixteen male Sprague-Dawley rats,weighing 250-280 g,were randomly divided into 4 groups (n =54 each):sham operation group (group S),I/R group,intralipid control group (group I) and propofol postconditioning group (group P).The model of focal cerebral I/R injury was established by middle cerebral artery occlusion.Propofol 20 mg·kg-1 · h-1 was infused over 2 h starting from the onset of reperfusion in group P,the equal volume of normal saline was given in groups S and I/R and the equal volume of 10％ intralipid was given in group I.Six rats were chosen at 3,7,14 and 28 days after occlusion and sacrificed,and brains were removed for determination of the cerebral infarct size by TTC staining.Another 6 rats were chosen at 3,7,14 and 28 days after occlusion to detect the expression of Akt,GSK3β and phosphorylation of Akt and GSK3β by Western blot.The left 6 rats were chosen at 28 day after occlusion to measure the number of newly generated neurons in hippocampal dentate gyms on the ischemic side.Results Compared with group S,the cerebral infarct volume was significantly enlarged,the newly generated neurons number was increased in the other 3 groups,and the phosphorylation of Akt and GSK3β was decreased in groups I/R and I,while increased in group P (P ＜ 0.05).The cerebral infarct volume was significantly smaller,and the newly generated neurons number and phosphorylation of Akt and GSK3β were higher in group P than in group I/R (P ＜ 0.05).Conclusion The mechanism by which propofol postconditioning provides the long-term neuroprotection is related to Akt-GSK3β signaling pathway in a rat model of focal cerebral I/R injury.