BACKGROUND:Gradient artificial bone repair scaffolds can mimic unique anatomical features in musculoskeletal tissues,showing great potential for repairing injured musculoskeletal tissues. OBJECTIVE:To review the latest research advances in gradient artificial bone repair scaffolds for tissue engineering in the musculoskeletal system and describe their advantages and fabrication strategies. METHODS:The first author of the article searched the Web of Science and PubMed databases for articles published from 2000 to 2023 with search terms"gradient,bone regeneration,scaffold".Finally,76 papers were analyzed and summarized after the screening. RESULTS AND CONCLUSION:(1)As an important means of efficient and high-quality repair of skeletal system tissues,gradient artificial bone repair scaffolds are currently designed bionically for the natural gradient characteristics of bone tissue,bone-cartilage,and tendon-bone tissue.These scaffolds can mimic the extracellular matrix of native tissues to a certain extent in terms of structure and composition,thus promoting cell adhesion,migration,proliferation,differentiation,and regenerative recovery of damaged tissues to their native state.(2)Advanced manufacturing technology provides more possibilities for gradient artificial bone repair scaffold preparation:Gradient electrospun fiber scaffolds constructed by spatially differentiated fiber arrangement and loading of biologically active substances have been developed;gradient 3D printed scaffolds fabricated by layered stacking,graded porosity,and bio-3D printing technology;gradient hydrogel scaffolds fabricated by in-situ layered injections,simple layer-by-layer stacking,and freeze-drying method;and in addition,there are also scaffolds made by other modalities or multi-method coupling.These scaffolds have demonstrated good biocompatibility in vitro experiments,were able to accelerate tissue regeneration in small animal tests,and were observed to have significantly improved histological structure.(3)The currently developed gradient artificial bone repair scaffolds have problems such as mismatch of gradient scales,unclear material-tissue interactions,and side effects caused by degradation products,which need to be further optimized by combining the strengths of related disciplines and clinical needs in the future.

Tumors exhibit abnormal glucose metabolism, consuming excessive glucose and excreting lactate, which constructs a tumor microenvironment that facilitates cancer progression and disrupts immunotherapeutic efficacy. Currently, tumor glucose metabolic dysregulation to reshape the immunosuppressive microenvironment and enhance immunotherapy efficacy is emerging as an innovative therapeutic strategy. However, glucose metabolism modulators lack specificity and still face significant challenges in overcoming tumor delivery barriers, microenvironmental complexity, and metabolic heterogeneity, resulting in poor clinical benefit. Nanomedicines, with their ability to selectively target tumors or immune cells, respond to the tumor microenvironment, co-deliver multiple drugs, and facilitate combinatorial therapies, hold significant promise for enhancing immunotherapy through tumor glucose metabolic reprogramming. This review explores the complex interactions between tumor glucose metabolism-specifically metabolite transport, glycolysis processes, and lactate-and the immune microenvironment. We summarize how nanomedicine-mediated reprogramming of tumor glucose metabolism can enhance immunotherapy efficacy and outline the prospects and challenges in this field.

Objective To investigate the effects of long non-coding RNA FEZ family zinc finger 1 antisense RNA 1(lncRNA FEZF1-AS1)on enhancer of zeste homolog 2(EZH2)in regulation of proliferation,migration,invasion and epithelial-mesenchymal transition(EMT)of pulmonary interstitial cells and its mechanism.Methods The A549 cells human lung adenocarcinoma cell line were divided into control group and model group[model cells were induced into lung interstitial cells after being treated with transforming growth factor β1(TGF-β1)20 ng/mL for 48 h].The protein expression of E-cadherin,N-cadherin and vimentin in each group was detected by Western blot.The expression of lncRNA FEZF1-AS1 and EZH2 in the two groups was detected by RT-qPCR.Cells in the trans-fection group were divided into si NC group,lncRNA FEZF1-AS1+OE vector group and si lncRNA FEZF1-AS1+OE EZH2 group.Cell proliferation was examined by CCK-8 method,cell migration was detected by cell scratch,and cell invasion was detected by Transwell assays.The protein expression of E-cadherin,N-cadherin,vimentin and EZH2 in each group was detected by Western blot.The direct binding effect of FEZF1-AS1 and EZH2 was deter-mined by RNA immuno-precipitation(RIP).Results Compared with the control group,the protein expression level of E-cadherin in the model group was significantly decreased(P＜0.05),and the protein expression of N-cadherin and vimentin was significantly increased(P＜0.05).Compared with the control group,the expression level of lncRNA FEZF1-AS1 and EZH2 genes was significantly increased in the model group(P＜0.05).Compared with si NC group,the proliferation,migration and invasion ability of si lncRNA FEZF1-AS1+OE vector group were decreased,the ex-pression of E-cadherin protein was increased while the expression of N-cadherin,vimentin and EZH2 was decreased(P＜0.05).Compared with si lncRNA FEZF1-AS1+OE vector group,the proliferation,invasion and migration of si lncRNA FEZF1-AS1+OE EZH2 group were increased(P＜0.05).E-cadherin expression was decreased,while N-cad-herin,vimentin and EZH2 expressions were increased(P＜0.05).RIP experiment further confirmed that lncRNA FEZF1-AS1 had direct binding effect with EZH2.Conclusions LncRNA FEZF1-AS1 can promote the proliferation,invasion,metastasis and EMT process of pulmonary fibrosis cells by regulating EZH2.

Delirium is an acute brain dysfunction syndrome characterized by confusion and difficulty concentrating,which mainly affects intensive care unit patients and elderly inpatients.Treatment is expensive and may also lead to increased risks of serious complications and death.The complex etiology and unknown pathological mechanisms of delirium mean that clinical drug treatment is largely ineffective.Animal models therefore provide a powerful tool to help understand the mechanism of delirium,screen new drugs,and study potential intervention measures.We review experimental research related to delirium animal models worldwide,and summarize the latest progress in the construction and evaluation of these models from the aspects of animal selection,model construction method,and model evaluation,to provide a reference for further experimental research based on delirium animal models.

Objective:To comprehensively search the relevant literature on prone position-cardiopulmonary resuscitation (PP-CPR) in adults at home and abroad, analyze the content, summarize the evidence, and provide reference for clinical health care professionals.Methods:Systematic search of CNKI, China Biomedical Literature Service System (SinoMed), Wanfang Data, VIP database, PubMed, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochran Library, Web of Science, Scopus literature database and other Chinese and English databases was conducted. The search period was from inception to June 15 in 2024. The contents of PP-CPR from randomized controlled trial (RCT), non-RCT (prospective or retrospective), cohort studies and case reports were extracted and systematically analyzed. The search results were standardized by the method of scoping review.Results:A total of 523 articles were obtained through preliminary search, and 14 references and gray literature were retrieved, totaling 537 articles. After strict screening by two researchers, a total of 26 literatures were included, 3 were non-RCT and 23 were case reports, involving 12 countries, including 3 in Chinese, 19 in English, 2 in French, 1 in German, and 1 in Korean. Three non-RCT demonstrated that compared with standard cardiopulmonary resuscitation (CPR), PP-CPR could produce higher pressure, and provide good respiratory and circulatory support. A total of 25 adult patients were included in the 23 case reports, of which 17 reported total recovery time and 13 reported PP-CPR time ≤ 5 minutes, all of which recovered spontaneous circulation, indicating the effectiveness of PP-CPR technology. In terms of final outcome, 4 patients (16.0%) died and 21 patients (84.0%) survived, indicating that PP-CPR technology could provide timely blood circulation and improve clinical outcomes for prone cardiac arrest patients. Among the 11 patients who reported complications after resuscitation, no neurological damage was found in the short-term outcomes, indicating that PP-CPR technology had a certain level of safety.Conclusions:PP-CPR can provide timely blood circulation for patients with cardiac arrest who are unable to lie supine quickly, and win "golden time" for defibrillation and further treatment. In clinical practice, medical staff need to evaluate the emergency environment, the number of rescuers and the specific condition of the patient, and implement first aid as soon as possible, so as to reduce the time of no blood flow in the vital organs of patients with cardiac arrest in prone position, and improve the clinical prognosis.

OBJECTIVE: To analyze the accuracy of prosthesis size selection in Naton robot-assisted medial unicondyle knee arthroplasty by comparing the actual prosthesis size used during operation and the preoperative planning. METHODS: The clinical data of 100 patients (110 knees) who underwent Naton robot-assisted medial unicondylar knee arthroplasty between June 2023 and July 2024 was retrospectively analyzed, including 47 knees on left side and 63 knees on right side. There were 37 males (40 knees) and 63 females (70 knees) with a mean age of 65.4 years (range, 59-71 years). Body mass index was 22.2-28.6 kg/m ² (mean, 25.4 kg/m ²). The disease duration ranged from 1 to 8 years (mean, 3.4 years). Preoperative planning was performed by Naton robotic surgical system based on lower limb CT data. The final prosthesis size after osteotomy was recorded and compared with the preoperative plan to analyse whether it was consistent with the preoperative plan, as well as the situation of knee flexion and extension gaps (<0.5 mm, >2.0 mm) corresponding to the different models of prostheses. RESULTS: During operation, 5 patients (5 knees) were treated with traditional UKA due to mechanical arm failure, software obstacles, significant bone amputation bias, or loose reference frame, and were excluded from the final analysis. The remaining 95 patients (105 knees) successfully received Naton robot-assisted surgery, and no related complications occurred. The prosthesis size was consistent with the preoperative plan in 101 knees (96.2%) on the femur side, 100 knees (95.2%) on the tibia side, and 97 knees (92.4%) on both femur and tibia sides. The prosthesis size was inconsistent in 3 cases (2.86%) on the femur side alone, 4 cases (3.81%) on the tibial side alone, and 1 case (0.95%) on both femur and tibial sides. Among the prostheses with different models, the flexion and extension gaps were less than 0.5 mm in 3 knees, the flexion gap was less than 0.5 mm and the extension gap was more than 2.0 mm in 3 knees, and the flexion gap was more than 2.0 mm and the extension gap was less than 0.5 mm in 2 knees. CONCLUSION The accuracy of prosthesis size selection for Naton robot-assisted medial unicondylar knee arthroplasty is relatively high.
Humans ; Arthroplasty, Replacement, Knee/instrumentation* ; Female ; Male ; Middle Aged ; Aged ; Knee Prosthesis ; Retrospective Studies ; Robotic Surgical Procedures/methods* ; Prosthesis Design ; Knee Joint/surgery* ; Osteoarthritis, Knee/surgery* ; Range of Motion, Articular

ObjectiveTo explore the differences between the ancient decocting methods and modern decocting method of Yihuangtang by taking the dry extract rate， the content of active ingredients and the fingerprint information as indicators， so as to provide reference for the preparation of benchmark samples and the development of compound preparations of this famous classical formula. MethodAccording to the three decocting methods recorded in Paozhi Dafa and Jianming Yigou and Management Specifications of Traditional Chinese Medicine Decoction Chambers in Medical Institutions， the Yihuangtang was decocted respectively. The polysaccharide content in the samples was determined by ultraviolet spectrophotometer （UV） at 488 nm， and the contents of alkaloids （berberine hydrochloride， phellodendrine chloride and magnoflorine） in the samples and their fingerprint profiles were determined by high performance liquid chromatography （HPLC）， and the dry extract rate was combined to compare the differences of the three decocting methods of Yihuangtang. Among them， the fingerprint was gradient eluted with acetonitrile （A） -0.1% phosphoric acid aqueous solution （B） as mobile phase （0-10 min， 5%-8%A； 10-35 min， 8%A； 35-45 min， 8%-12% A； 45-75 min， 12%-17%A； 75-105 min， 17%-35%A； 105-110 min， 35%-100%A； 110-112 min， 100%-5%A； 112-122 min， 5%A）， and the detection wavelength was 230 nm. ResultWhen the decoction was carried out according to the method described in Paozhi Dafa， the content of polysaccharides was higher than that of the modern decocting method and the method described in Jianming Yigou. However， the contents of berberine hydrochloride， phellodendrine chloride and magnoflorine were the highest in the modern decocting method. Meanwhile， the number of peaks in fingerprint of the samples prepared by the three decocting methods was basically the same， and 13 common peaks were matched， and the three common peaks of berberine hydrochloride， phellodendrine chloride and magnoflorine were identified. However， the relative peak areas of the common peaks in the fingerprint of the samples prepared by the three decocting methods varied greatly， suggesting that there were differences in the extracting effects of different decocting methods. In addition， there were also differences in the dry extract rate among the three decocting methods of Yihuangtang， and the highest value was obtained by decocting the samples according to the method recorded in Paozhi Dafa. ConclusionDecocting method can affect the dry extract rate， fingerprint information and active ingredient content of Yihuangtang， among which the modern decocting method is conducive to the extraction of alkaloids and the preparation transformation of this famous classical formula， and it is recommended to determine its preparation process by optimizing the modern decocting method.

Drug adulteration and contamination are serious threats to human health therefore,their accurate monitoring is very important.Allopurinol(Alp)and theophylline(Thp)are commonly used drugs for the treatment of gout and bronchitis,while their isomers hypoxanthine(Hyt)and theobromine(Thm)have no effect and affect the efficacy of the drug.In this work,the drug isomers of Alp/Hyt and Thp/Thm are simply mixed with α-,β-,y-cyclodextrin(CD)and metal ions and separated using trapped ion mobility spectrometry-mass spectrometry(TIMS-MS).TIMS-MS results showed that Alp/Hyt and Thp/Thm iso-mers could interact with CD and metal ions and form corresponding binary or ternary complexes to achieve their TIMS separation.Different metal ions and CDs showed different separation effect for the isomers,among which Alp and Hyt could be successfully distinguished from the complexes of[Alp/Hyt+y-CD+Cu-H]+with separation resolution(Rp-p)of 1.51;whereas Thp and Thm could be baseline separated by[Thp/Thm+y-CD+Ca-H]+with Rp-p of 1.96.Besides,chemical calculations revealed that the complexes were in the inclusion forms,and microscopic interactions were somewhat different,making their mobility separation.Moreover,relative and absolute quantification was investigated with an internal standard to determine the precise isomers content,and good linearity(R2＞0.99)was ob-tained.Finally,the method was applied for the adulteration detection where different drugs and urine were analyzed.In addition,due to the advantages of fast speed,simple operation,high sensitivity,and no chromatographic separation required,the proposed method provides an effective strategy for the drug adulteration detection of isomers.

OBJECTIVE: To explore the effect of leucine-rich α-2-glycoprotein (LRG1) derived from hepatocytes on activation of hepatic M1 Kupffer cells. METHODS: A metabolic dysfunction-associated fatty liver disease (MAFLD) model was established in BALB/c mice by high-fat diet (HFD) feeding for 16 weeks. Oleic acid was used to induce steatosis in primary cultures of mouse hepatocytes. The mRNA and protein expressions of LRG1 in mouse liver tissues and hepatocytes were detected by real-time PCR and Western blotting. Primary hepatic macrophages were stimulated with the conditioned medium (CM) from steatotic hepatocyte along with LRG1 or transforming growth factor-β1 (TGF-β1), or both for 24 h, and the expression levels of inducible nitric oxide synthase (iNOS) was detected with Western botting, and the mRNA expressions of iNOS, chemokine ligand 1 (CXCL-1) and interleukin-1β (IL-1β) were measured by RT-PCR. The MAFLD mice were injected with LRG1 (n=6), TGF-β1 (n=6), or both (n=6) through the caudal vein, and the live tissues were collected for HE staining and immumohistochemical detection of F4/80 expression; the mRNA expressions of iNOS, CXCL-1 and IL-1β in liver tissues were detected using RT-PCR. RESULTS: The mRNA and protein expression levels of LRG1 were significantly downregulated in the liver tissues of MAFLD mice and steatotic hepatocytes (P < 0.05). Treatment of the hepatic macrophages with CM from steatosis hepatocytes significantly enhanced the mRNA expression levels of iNOS, CXCL-1 and IL-1β, and these changes were significantly inhibited by the combined treatment with TGF-β1 and LRG1 (P < 0.05). In MAFLD mice, injections with either LRG1 or TGF-β1 alone reduced hepatic lipid deposition and intrahepatic macrophage infiltration, and these effects were significantly enhanced by their combined treatment, which also more strongly inhibited the mRNA expression levels of iNOS, CXCL-1 and IL-1β (P < 0.05). CONCLUSION LRG1 inhibits hepatic macrophage infiltration by enhancing TGF-β1 signaling to alleviate fatty liver inflammation in MAFLD mice.
Animals ; Mice ; Transforming Growth Factor beta1 ; Macrophage Activation ; Signal Transduction ; Non-alcoholic Fatty Liver Disease ; Culture Media, Conditioned ; Glycoproteins

Objective:To investigate the clinical efficacy differences of stereotactic electroencephalogram (SEEG) electrode implantation in medically-refractory temporal lobe epilepsy (TLE) patients with different neuroimaging manifestations before surgery.Methods:A total of 59 patients with medically-refractory TLE who accepted SEEG electrode implantation in Department of Neurosurgery, First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital) from January 2018 to December 2021 were enrolled. These were divided into groups according to neuroimaging manifestations before surgery, including MRI-positive group and MRI-negative group, PET-positive group and PET-negative group, or PET&MRI concordant group (concordant group) and PET&MRI discordant group (discordant group). Modified Engel classification was used to evaluate the clinical efficacy of these patients at 12-month follow-up after surgery, and efficacy differences among different patient groups were compared.Results:Significant differences were noted in distributions of modified Engel classification between the MRI positive and negative groups, as well as the concordant and discordant groups at 12-month follow-up after surgery ( P<0.05); patients in the MRI positive group had better outcomes than those in the MRI negative group (mean rank judgment: 27.00 and 34.08), while patients in concordant group had better outcomes than those in discordant group (mean rank judgment: 23.32 and 31.19). Significant differences were noted in distributions of modified Engel classification at 12-month follow-up after surgery between different signal abnormal regions in the MRI positive group ( P<0.05); patients with hippocampal sclerosis or amygdala abnormalities had better outcomes than those with simultaneous abnormalities in the temporal lobe internal and external regions (mean rank judgment: 14.50 and 16.50). Conclusion:When the preoperative MRI of patients with medically-refractory TLE is negative, especially when results of structural imaging and functional imaging are inconsistent, SEEG electrode implantation and path planning as well as later surgical plan should be considered more carefully.