Rosuvastatin(RVS)is an excellent drug with anti-inflammatory and lipid-lowering properties in the aca-demic and medical fields.However,this drug faces a series of challenges when used to treat atherosclerosis caused by hyperhomocysteinemia(HHcy),including high oral dosage,poor targeting,and long-term toxic side effects.In this study,we applied nanotechnology to construct a biomimetic nano-delivery system,macrophage membrane(M?m)-coated RVS-loaded Prussian blue(PB)nanoparticles(MPR NPs),for improving the bioavailability and targeting capacity of RVS,specifically to the plaque lesions associated with HHcy-induced atherosclerosis.In vitro assays demonstrated that MPR NPs effectively inhibited the Toll-like receptor 4(TLR4)/hypoxia-inducible factor-1α(HIF-1α)/nucleotide-binding and oligomerization domain(NOD)-like receptor thermal protein domain associated protein 3(NLRP3)signaling pathways,reducing pyroptosis and inflammatory response in macrophages.Additionally,MPR NPs reversed the abnormal distribution of adenosine triphosphate(ATP)-binding cassette transporter A1(ABCA1)/ATP binding cassette transporter G1(ABCA1)/ATP binding cassette transporter G1(ABCG1)caused by HIF-1α,promoting cholesterol efflux and reducing lipid deposition.In vivo studies using apolipoprotein E knockout(ApoE-/-)mice confirmed the strong efficacy of MPR NPs in treating atherosclerosis with favorable bio-security,and the mechanism behind this efficacy is believed to involve the regulation of serum metabolism and the remodeling of gut microbes.These findings suggest that the synthesis of MPR NPs provides a promising nanosystem for the targeted therapy of HHcy-induced atherosclerosis.

Objective To investigate the expression of long non-coding RNA(lncRNA)CCAT2 and o-varian cancer domain-containing protease 1(OTUD1)in multiple myeloma(MM)tissue and their correlation with clinicopathological characteristics and prognosis of MM.Methods A total of 132 patients with MM(MM group)diagnosed and treated in this hospital from April 2018 to April 2020 were selected.Seventy patients with non-hematological disease who underwent bone marrow puncture without abnormal bone marrow func-tion during the same period served as the control group.The real-time fluorescence quantitative PCR was used to detect the expression levels of lncRNA CCAT2 and OTUD1 mRNA in bone marrow tissue.The Pearson correlation was performed to analyze the correlation between lncRNA CCAT2 and OTUD1 mRNA expression in bone marrow tissues.The expression differences of lncRNA CCAT2 and OTUD1 mRNA were compared a-mong the MM patients with different clinical and pathological characteristics.The Kaplan-Meier curve was used to analyze the difference of prognosis among the MM patients with different lncRNA CCAT2 and OTUD1 mRNA expressions.The Cox regression was performed to analyze the factors affecting the prognosis in MM patients.Results The expression level of lncRNA CCAT2 in the bone marrow tissue of the MM group was significantly higher than that of the control group(2.31±0.67 vs.0.85±0.24),while the expression level of OTUD1 mRNA in the MM group was lower than that of the control group(1.22±0.37 vs.2.54±0.75),and the differences were statistically significant(t=17.624,16.760,all P＜0.001).The lncRNA CCAT2 expression level in the bone marrow tissue of the MM group had significantly negative correlation with the OTUD1 mRNA expression level(r=-0.731,P＜0.001).The lncRNA CCAT2 and OTUD1 mRNA expression levels had statistical differences among the MM patients with different ISS stages and β2-micro-globulin levels(P＜0.001).The 3-year overall survival rates of the high and low expression groups of ln-cRNA CCAT2 were 42.19％(27/64)and 66.18％(45/68),respectively.The 3-year overall survival rates of the high and low expression groups of OTUD1 mRNA were 72.31％(47/65)and 37.31％(25/67)respective-ly.The 3-year cumulative survival rate of MM patients in the lncRNA CCAT2 low expression group was sig-nificantly higher than that in the lncRNA CCAT2 high expression group,and the difference was statistically significant(Log Rank X2=7.151,P=0.007).The 3-year cumulative survival rate of MM patients in the OTUD1 mRNA low expression group was significantly lower than that in the OTUD1 mRNAhigh expression group(Log Rank x2=13.667,P＜0.001).The ISS stage Ⅲ and lncRNA CCAT2 high expression were the risk factors affecting the prognosis of MM patients(P＜0.01),while the OTUD1 mRNA high expression was the protective factor.Conclusion The lncRNA CCAT2 expression level in bone marrow tissue of the MM pa-tients is increased and OTUD1 expression level is decreased,the both are associated with adverse clinical and pathological characteristics of MM and independent factors affecting the prognosis of MM patients.

In the era of evidence-based medicine, it is necessary to explore the unique advantages of traditional Chinese medicine (TCM) based on standardized technical methods and operating procedures in order to achieve the modernization and internationalization of TCM and benefit all humanity. The proposal of a three-pronged evidence system combining TCM theory, human experience and experimental evidence marks an important progress in the thinking method of the TCM evaluation system. The multi-evidence body integrated through appropriate methods provides a strong support for the clinical guideline recommendations and evidence-based health decision-making in TCM. Based on the current methodological progress of international evidence synthesis and grading, this paper proposes a novel approach for integrating multi-evidence in TCM: the MERGE framework. The aim is to establish a solid foundation for the development of this methodology and provide guidance for the advancement of evidence-based medicine framework in TCM.

Objective:To investigate the initial effectiveness of manual techniques versus navigation positioning system-assisted reconstruction for anterior cruciate ligament (ACL) injuries in children and adolescent populations.Methods:A retrospective analysis was conducted on 28 patients with ACL rupture who underwent primary total epiphyseal ACL reconstruction in the Sports Medicine Treatment Center of Honghui Hospital Affiliated to Xi'an Jiaotong University from January 2019 to October 2022. Patients were categorized into two groups based on the method of guide needle insertion: the manual group (guide needle insertion relying on the operator's expertise) and the robot-assisted group (guide needle insertion assisted by the Tianji robot navigation and positioning system). The manual group comprised 14 cases (9 males, 5 females) with an average age of 13.59±1.59 years, while the robot-assisted group included 14 patients (10 males, 4 females) with an average age of 13.27±1.66 years. The operation time, intraoperative fluoroscopy times, guide needle placement times, the distance between the central point of the internal articular opening of the tibial and femoral bone tunnel and the ideal point, the rate of epiphyseal inflammation, and the International Knee Documentation Committee (IKDC) subjective score, Lysholm score, KT-2000 ligament relaxation, lower limb force line were compared between the two groups.Results:The follow-up duration was 19.9±6.3 months for the manual group and 18.8±4.9 months for the robot group ( t=0.546, P=0.589). The manual group's operation duration was 123.0±12.6 min, significantly longer than the robot group's 96.4±12.9 min ( t=5.502, P<0.001). Intraoperative fluoroscopy was performed 11.8±3.1 times in the manual group, markedly more than the robot group's 3.7±0.8 times ( t=9.434, P<0.001). The robot group required only one guide needle placement for both femur and tibia, while the manual group had 5.7±1.2 placements on the femur side and 4.6±1.8 on the tibia side. The distance between the femoral joint's central point and the ideal point was 0.87±0.20 mm in the robot group, superior to the manual group's 1.92±0.64 mm ( t=5.816, P<0.001). Similarly, the distance between the central point and the ideal point was 1.15±0.34 mm for the robot group, better than the manual group's 1.94±0.55 mm ( t=4.582, P<0.001). No cases of epiphyseal irritation were observed in the robot group, while 21% (3/14) of the manual group experienced tibial or femoral epiphyseal plate involvement. At 3 months post-surgery, the robot group exhibited higher IKDC subjective scores (90.57±8.46) and Lysholm scores (86.29±5.09) compared to the manual group (83.50±6.19 and 80.93±5.93), respectively ( P<0.05). However, at the final follow-up, there were no significant differences in IKDC subjective scores, Lysholm scores, or KT-2000 ligament relaxation between the two groups ( P>0.05). Both groups showed normal lower limb force alignment and no abnormal growth or development. Conclusion:Tianji robot navigation and positioning system-assisted ACL reconstruction in children and adolescents offer advantages such as precise positioning, shorter operation times, reduced intraoperative fluoroscopy, faster recovery, and enhanced epiphyseal protection compared to manual methods.

Botulinum toxin is a potent protein toxin produced by Clostridium botulinum. It acts directly on the brain nerve nucleus and peripheral neuromuscular junction, blocking the release of acetylcholine and thereby affecting nerve impulse transmission, ultimately leading to muscle paralysis. Mild cases may present with ocular muscle involvement, whereas severe cases may involve dysphagia, general paralysis, respiratory depression, and even death. This article reports on a patient who experienced severe poisoning symptoms after using type A botulinum toxin obtained through informal channels. The patient was treated with antitoxin on the 13th day after symptoms onset and achieved a significant improvement in their condition.

Botulinum toxin is a potent protein toxin produced by Clostridium botulinum. It acts directly on the brain nerve nucleus and peripheral neuromuscular junction, blocking the release of acetylcholine and thereby affecting nerve impulse transmission, ultimately leading to muscle paralysis. Mild cases may present with ocular muscle involvement, whereas severe cases may involve dysphagia, general paralysis, respiratory depression, and even death. This article reports on a patient who experienced severe poisoning symptoms after using type A botulinum toxin obtained through informal channels. The patient was treated with antitoxin on the 13th day after symptoms onset and achieved a significant improvement in their condition.

Objective:To observe the effect of hypoxia on the dedifferentiation process of chondrocytes in vitro and explore the role of collagen prolyl 4-hydroxylase (C-P4Hs).Methods:Chondrocytes were treated with COCl 2 for different concentrations, and selecting the optimal COCl 2 concentration for hypoxia inductionwas100 μmol/L, the mouse costal chondrocytes were divided into the normal oxygen group and the hypoxia group, and the indexes of the 3rd generation 0.5-72 h and the 1st, 3rd, 5th and 7th generation at 72 h were detected respectively. The proliferation rate was determined by CCK8 method and cell count, and the dynamic changes of HIF-1α, P4Hα1, P4Hα2 and Col II in each group were detected by RT-qPCR, IF and Western blot. Results:Costal chondrocytes were cultured under different concentration of COCl 2 for 48 h. When COCl 2>150 μmol/L, the proliferation rate ( P<0.05) was significantly decreased. Normal oxygen and hypoxia induced rib chondrocytes for 0-72 h, and RT-qPCR showed significant increases in P4Hα2 and Col II mRNA in hypoxia group ( P<0.05). IF showed that HIF-1α and P4Hα2 accumulated in the nucleus under hypoxia, and P4Hα2 gradually entered the cytoplasm from the nucleus. Westernblot analysis showed that HIF-1α and P4Hα2 protein expressions were significantly increased in hypoxia group ( P<0.05). The expression of Col II protein in hypoxia group ( P<0.05) increased at the induction stage. CCK8 and cell count results showed that the proliferation rate and cell number of each generation in the hypoxic group were significantly increased ( P<0.05), and there was still potential for proliferation when the cells were transferred to the 6-7 generation. RT-qPCR showed that hypoxia group each generation cells P4Hα2, Col II mRNΑ were significantly increased ( P<0.05). Westernblot results showed that HIF-1α, P4Hα2 and Col II protein expressions were increased in each generation of hypoxia group ( P<0.05). ConcIusion:Increased expression of P4Hα2 through hypoxia induced HIF-1α can accelerate post-translational modification of Col II in chondrocytes and increase synthesis and accumulation of Col II. P4Hα2 may be responsible for increased proliferation rate and delayed dedifferentiation of chondrocytes cultured in vitro under hypoxia condition.

BACKGROUND: Fat infiltration is a key factor in the failure of rotator cuff repair. However, the pathological mechanism of fatty infiltration after rotator cuff injury is unclear. OBJECTIVE: To explore the differences in the expression of key genes after rotator cuff injury, to determine their functions and mechanism pathways, and to provide a theoretical basis for the pathological mechanism of fatty infiltration after rotator cuff injury. METHODS: GSE93661 was obtained through GEO database to screen differentially expressed genes. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were used to analyze the underlying mechanism of fatty infiltration. The protein-protein interaction network was constructed to obtain the pivot genes and analyze the potential pathogenic targets. RESULTS AND CONCLUSION: A total of 471 differentially expressed genes were identified. GO and KEGG analysis showed that neuroactive ligand-receptor interactions and cell adhesion molecular pathways were potential mechanisms of fat infiltration in rotator cuff tears. Leukotriene B4 receptor, as a pivot gene in the protein-protein interaction network, may be a key target for fat infiltration in rotator cuff tears. We have discovered potential key genes and pathways in the pathological development of fatty infiltration, providing a reference direction for future treatment.

Objective To investigate the effect of acidic tumor microenvironment on invasion and migration and its mechanism in glioma cells. Methods (1) The pH value of the medium was adjusted by acid-base titration. Human glioma cells U87 and U251 were cultured in the acid group and the normal group with pH values of 6.4 and 7.4, respectively; and 3 d after cultivation, the expressions of hypoxia-inducible factor-2α (HIF-2α) and CD44 were detected by Western blotting; Transwell assay was used to examine the invasion and migration of U87 and U251 cells; immunofluorescence was employed to examine the CD44 expression. (2) The U87 and U251 cells were divided into small interfering RNA (siRNA) -nonsense sequence group and siRNA-CD44-1 group, and the siRNA nonsense sequences and siRNA-CD44-1 interfering fragments were transfected by lipofectin-3000, respectively; three d after transfection, the migration and invasion abilities of cells from the two groups were detected by Transwell assay. (3) U87 and U251 cells were divided into acid group (cultured with a pH value of 6.4), blank control group, siRNA nonsense sequence group, siRNA-CD44-1 group, and siRNA-CD44-2 group; and cells from the later four groups were cultured with a pH value of 7.4; after culture for 4 d, the siRNA-nonsense sequence group, siRNA-CD44-1 group and siRNA-CD44-2 group were transfected with siRNA-nonsense sequences, siRNA-cd44-1 interfering fragments and siRNA-CD44-2 interfering fragments, respectively; three d after transfection, the expressions of CD44, N-Ca, Vimentin, and matrix metalloproteinase (MMP)-2 proteins in these 5 groups were detected by Western blotting. Results (1) As compared with the normal group, the expression levels of HIF-2α and CD44 in U87 and U251 cells of the acid group were significantly increased; both Transwell and invasion experiments showed that the number of transmembrane cells in the acid group was significantly larger than that in the normal group (P<0.05); immunofluorescence staining showed that the CD44 expression in acid group was significantly higher than that in normal group (P<0.05). (2) Both Transwell and invasion experiments showed that the number of transmembrane cells in the siRNA-CD44-1 group was significantly smaller than that in the siRNA nonsense sequence group (P<0.05). (3) Western blotting showed that the expression levels of CD44, N-Ca, Vimentin and MMP-2 in U87 and U251 cells of the blank control group, siRNA nonsense sequence group, siRNA-CD44-1 group, and siRNA-CD44-2 group were obviously decreased as compared with those in the acid group; the expression levels of CD44, N-Ca, Vimentin and MMP-2 in U87 and U251 cells of the siRNA-CD44-1 group and siRNA-CD44-2 group were obviously lower than those in the siRNA nonsense sequence group. Conclusion Acidic tumor microenvironment enhances the capabilities of invasion and migration of glioma cells through increasing CD44 expression.

Objective To study the influence of micro (miR)-325 in progression of glioma and its molecular mechanism by regulating transferrin receptor (TFRC) gene expression in glioma cells. Methods (1) Thirty-five glioma tissues and paired adjacent normal tissues were collected during surgical excision performed in our hospital from January 2015 to January 2018. The miR-325 and TFRC mRNA expression levels in the glioma tissues and paired adjacent normal tissues were detected by inverse transcription-quantitative PCR (RT-qPCR); the expression of miR-325 in glioma tissues of patients with different clinical characteristics and the survival curves of patients with low or high miR-325 expressions were compared. (2) RT-qPCR was used to examine the miR-325 expression in HA, U251, and U87 cell lines in vitro; the regulatory relations between miR-325 and its potential target gene TFRC in U251, and U87 cell lines were measured by luciferase report assay; miR-325 mimic and its negative control were transfected into U251 and U87 cell lines for 48 h, and then, the mRNA and protein expressions of TFRC were detected by RT-qPCR and Western blotting, respectively; control small interfering RNA (siRNA)+nonsense inhibitor, TFRC siRNA+nonsense inhibitor, and siTFRC+miR-325 inhibitor were transfected into U251 and U87 cell lines for 48 h, respectively, Western blotting was employed to detect the TFRC protein expression, cell proliferation was detected by CCK-8 assay, and cell invasion was detected by Transwell assay; pcDNA3.1 empty vector+nonsense sequence, TFRC pcDNA3. 1+nonsense sequence, TFRC pcDNA3.1+miR-325 mimic were transfected into U251 and U87 cell lines for 48 h, respectively, TFRC protein expression was detected by Western blotting, cell proliferation was detected by CCK-8 assay, and cell invasion was detected by Transwell assay. Results (1) As compared with those in the adjacent tissues, the miR-325 expression was significantly decreased and the TFRC mRNA expression was statistically increased in glioma tissues (P<0.05); the TFRC mRNA expression and miR-325 expression were negatively correlated in glioma tissues (P<0.05); as compared with patients with Karnofsky functional status scores≥80, patients with scores<80 had significantly decreased miR-325 expression; as compared with glioma tissues of WHO grading I-II, glioma tissues of grading III-IV had significantly decreased miR-325 expression (P<0.05); the survival rate of patients with low miR-325 expression was statistically lower than that of patients with high miR-325 expression (P< 0.05). (2) As compared with that in HA cells, the miR-325 expression was statistically down-regulated in U87 and U251 cells (P<0.05); in TFRC wild-type (TFRC WT) transfected cells, the miR-325 mimic group had significantly lower luciferase activity than the nonsense sequence group, while the miR-325 inhibitor group had significantly higher luciferase activity than the nonsense inhibitor group (P<0.05); as compared with those in the nonsense sequence group, the TFRC mRNA and protein expressions were statistically decreased in U87 and U251 cells of miR-325 mimic group; as compared with those in the control siRNA+nonsense inhibitor group, the TFRC protein expression and absorbance value were significantly decreased, and number of invasive cells was significantly smaller in the siTFRC+nonsense inhibitor group; and as compared with those in the siTFRC+nonsense inhibitor group, the TFRC protein expression and absorbance value were significantly increased, and number of invasive cells was significantly larger in the siTFRC+miR-325 inhibitor group (P<0.05); as compared with the pcDNA3.1 empty vector+nonsense sequence group, the TFRC protein expression and absorbance value were significantly increased, and number of invasive cells was significantly larger in the TFRC pcDNA3.1 +nonsense sequence group, and as compared with the TFRC pcDNA3.1+nonsense sequence group, the TFRC protein expression and absorbance value were significantly decreased, and number of invasive cells was significantly smaller in the TFRC pcDNA3.1+miR-325 mimic group (P<0.05). Conclusion The miR-325 expression is decreased in glioma cells and has a tumor suppressor effect; patients with low miR-325 expression have poor prognosis; miR-325 inhibits cancer cell progression by inhibiting the expression of the target gene TFRC.