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.

BACKGROUND:Wogonin is a flavonoid extracted from the root of Scutellaria baicalensis.Previous studies have shown that baicalein has protective effects against cerebral ischemia-reperfusion injury,and can also reduce blood sugar and complications in diabetic mice,but its role and mechanism in diabetic cerebral infarction remain unclear. OBJECTIVE:To explore the effect of wogonin on nerve injury in rats with diabetic cerebral infarction and its mechanism. METHODS:Sprague-Dawley rats were randomly divided into six groups:control group,model group,low-dose wogonin group,medium-dose wogonin group,high-dose wogonin group,and high-dose wogonin+Ras homolog gene family member A(RhoA)activator group.Except for the control group,the other rats were established with diabetes and cerebral ischemia models using intraperitoneal injection of streptozotocin and middle cerebral artery occlusion.Low,medium-and high-dose wogonin groups were intragastrically given 10,20,40 mg/kg wogonin,respectively;high-dose wogonin+RhoA activator group was intragastrically given 40 mg/kg wogonin and intraperitoneally injected 10 mg/kg lysophosphatidic acid;control group and model group were given the same amount of normal saline once a day for 7 consecutive days.Rats in each group were evaluated for neurological deficits and their blood glucose levels were measured after the last dose.TTC staining was applied to detect the volume of cerebral infarction.Hematoxylin-eosin staining was applied to observe pathological changes in brain tissue.ELISA kit was applied to detect tumor necrosis factor-α,interleukin-6,malondialdehyde,and superoxide dismutase levels in brain tissue.Western blot was applied to detect the protein expression of RhoA and Rho-associated protein kinase(ROCK)2 in brain tissue. RESULTS AND CONCLUSION:Compared with the control group,the neuronal structure of rats in the model group was severely damaged,with cell necrosis and degeneration,the neurological deficit score,blood glucose level,and infarct volume were significantly elevated(P<0.05),the levels of tumor necrosis factor-α,interleukin-6,and malondialdehyde,and the protein expression of RhoA and ROCK2 in brain tissue were significantly increased(P<0.05),and the superoxide dismutase level was decreased(P<0.05).Compared with the model group,the low-,medium-,and high-dose wogonin groups showed improved neuronal damage,reduced cell degeneration and necrosis,a significant reduction in neurological deficit score,blood glucose level,infarct volume,and the levels of tumor necrosis factor-α,interleukin-6,and malondialdehyde,and the protein expression of RhoA and ROCK2 in brain tissue,and an increase in the superoxide dismutase level(P<0.05).Compared with the high-dose wogonin group,the high-dose wogonin+RhoA activator group significantly weakened the improvement in the above indexes of rats with diabetic cerebral infarction(P<0.05).To conclude,wogonin can improve the blood glucose level in rats with diabetic cerebral infarction,reduce cerebral infarction and nerve injury,and its mechanism may be related to the inhibition of RhoA/ROCK signaling pathway.

Objective:To analyze the clinical and radiographic effectiveness of a calcium silicate-based bioactive ceramic iRoot BP Plus? pulpotomy of immature permanent teeth with complicated crown fracture and to evaluate the factors influencing its long-term success rate.Methods:The digital medical records of patients under 13 years old who had undergone iRoot BP Plus? pulpotomy in the Department of Oral Emergency or the First Clinical Division,Peking University School and Hospital of Stomatology from March 2017 to September 2022 due to complicated crown fracture of anterior teeth,and had taken at least one post-operation apical radiograph were reviewed.The clinical and radiographic information at the initial examination and follow-up period were obtained,including crown color,mobility,percussion,cold test(partial pulpotomy teeth),dental restoration,fistula,swelling or inflammation of the gingival tissue,the formation of apical foramen,pathologic radiolucency and calcification of pulp chamber or root canal obliteration.Data were tested by Fisher exact test and a multiple comparison.Results:In the study,64 patients including 37 males(57.8％)and 27 females(42.2％)with a mean age of 9.1 years were finally enrolled.The total number of permanent teeth that received pulpotomy was 75,and the average follow-up time was 19.3 months.The success rate was 93.1％with the time interval between dental injury and treatment in 24 h,while the success rate dropped to 88.2％with the time intervals beyond 24 h.The time intervals did not significantly affect the pulp survival rate(P=0.61)after pulpotomy(partial or co-ronal).The success rate 6 months after pulpotomy was 96.0％,and one-year success rate was 94.7％.A total of 23 cases were reviewed for more than 2 years after pulpotomy,and 6 cases failed.The mobility had no significant effect on the success rate(P=0.28).Pulp chamber calcification and pulp canal obli-teration were not observed in all the post-operative radiographs.Conclusion:The one year clinical and radiographic success rates obtained in this study indicate that iRoot BP Plus? is an appropriate pulp cap-ping material option for pulpotomy treatment of complicated crown fracture in immature permanent teeth without displacement injuries.This technique has broad promotional value.

Objective:To explore the early coagulation function changes of penetrating intestinal firearm injury of pig in high-altitude environments.Methods:Twenty healthy long white piglets were selected and divided into the plain group and the high-altitude group using the random number table method, with 10 pigs in each group. Pigs in the plain group were placed in a plain environment at an altitude of 800 meters, while pigs in the high-altitude group were placed in an experimental chamber simulating an altitude of 6 000 meters for 48 hours. Both groups received pistol gunshot to have firearm penetrating wounds to the abdominal intestinal tract and then returned to the plain observation room. At 0, 2, 4, 8, 12 and 24 hours after injury, coagulation in the peripheral blood and fibrinolytic indexes [prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen (Fbg), D-dimer (D-D), and fibrinogen degradation product (FDP)], thromboelastogram (TEG) [reaction time (R), clotting time (K), clot formation rate (α), maximum amplitude (MA) and coagulation composite index (CI) ], platelet parameters [platelet count (PLT), mean platelet volume (MPV), platelet distribution width (PDW), and platelet-large cell ratio (P-LCR)] in the two groups were detected separately.Results:The PT values at 0 and 2 hours after injury in the high-altitude group were significantly lower than those in the plain group, while they were significantly higher at 8, 12 and 24 hours than those in the plain group ( P<0.01); there was no significant difference at 4 hours between the two groups ( P>0.05). The APTT values at 0, 2 and 4 hours after injury in the high-altitude group were significantly lower than those in the plain group, while they were significantly higher at 8, 12 and 24 hours after injury than those in the plain group ( P<0.01). The TT values at 0, 2 and 4 hours after the injury in the high-altitude group were significantly lower than those in the plain group, while they were significantly higher at 12 and 24 hours after injury than those in the plain group ( P<0.01); there was no significant difference at 8 hours after injury between the two groups ( P>0.05). The Fbg, D-D and FDP values at 0, 2, 4, 8, 12 and 24 hours after injury were higher in the high-altitude group than those in the plain group ( P<0.01). The R values at 0, 2 and 4 hours after injury in the high-altitude group were significantly lower than those in the plain group, while they were significantly higher at 8, 12 and 24 hours after injury than those in the plain group ( P<0.01). The K values at 0, 2, 4 and 8 hours after injury in the high-altitude group were significantly lower than those in the plain group, while they were significantly higher at 12 and 24 hours after injury than those in the plain group ( P<0.05 or 0.01). The α angles at 0, 2 and 4 hours after injury in the high-altitude group were significantly higher than those in the plain group, while they were significantly lower at 8, 12 and 24 hours after injury than those in the plain group ( P<0.01). The MA values at 0, 2 and 4 hours after the injury in the high-altitude group were significantly higher than those in the plain group, while they were significantly lower at 8, 12 and 24 hours after injury than those in the plain group ( P<0.01). The CI values at 0, 2 and 4 hours after injury in the high-altitude group were significantly higher than those in the plain group, while they were significantly lower at 8, 12 and 24 hours after injury than those in the plain group ( P<0.01). The PLT values at 0, 2, 4 and 8 hours after injury in the high-altitude group were significantly higher than those in the plain group, while they were significantly lower at 12 and 24 hours after injury than those in the plain group ( P<0.05 or 0.01). The MPV values at 0, 2, 4, 8, 12 and 24 hours after injury in the high-altitude group were significantly higher than those in the plain group ( P<0.01). The PDW values at 2, 4, 8, 12 and 24 hours after injury in the high-altitude group were significantly higher than those in the plain group ( P<0.05 or 0.01), while there was no significant difference in PDW at 0 hour after injury between the two groups ( P>0.05). The P-LCR values at 0, 2, 4, 8, 12 and 24 hours after injury in the high-altitude group were all significantly higher than those in the plain group ( P<0.01). Conclusion:Compared with the plain environments, pig intestinal firearm penetrating injury in the high-altitude environments is more prone to early hypercoagulable state accompanied by mild hyperfibrinolysis, and faster to reach a hypocoagulable state accompanied by obvious hyperfibrinolysis.

Background::Although overnight fasting is recommended prior to endoscopic retrograde cholangiopancreatography (ERCP), the benefits and safety of high-carbohydrate fluid diet (CFD) intake 2 h before ERCP remain unclear. This study aimed to analyze whether high-CFD intake 2 h before ERCP can be safe and accelerate patients’ recovery.Methods::This prospective, multicenter, randomized controlled trial involved 15 tertiary ERCP centers. A total of 1330 patients were randomized into CFD group ( n = 665) and fasting group ( n = 665). The CFD group received 400 mL of maltodextrin orally 2 h before ERCP, while the control group abstained from food/water overnight (>6 h) before ERCP. All ERCP procedures were performed using deep sedation with intravenous propofol. The investigators were blinded but not the patients. The primary outcomes included postoperative fatigue and abdominal pain score, and the secondary outcomes included complications and changes in metabolic indicators. The outcomes were analyzed according to a modified intention-to-treat principle. Results::The post-ERCP fatigue scores were significantly lower at 4 h (4.1 ± 2.6 vs. 4.8 ± 2.8, t = 4.23, P <0.001) and 20 h (2.4 ± 2.1 vs. 3.4 ± 2.4, t= 7.94, P <0.001) in the CFD group, with least-squares mean differences of 0.48 (95% confidence interval [CI]: 0.26–0.71, P <0.001) and 0.76 (95% CI: 0.57–0.95, P <0.001), respectively. The 4-h pain scores (2.1 ± 1.7 vs. 2.2 ± 1.7, t = 2.60, P = 0.009, with a least-squares mean difference of 0.21 [95% CI: 0.05–0.37]) and positive urine ketone levels (7.7% [39/509] vs. 15.4% [82/533], χ2 = 15.13, P <0.001) were lower in the CFD group. The CFD group had significantly less cholangitis (2.1% [13/634] vs. 4.0% [26/658], χ2 = 3.99, P = 0.046) but not pancreatitis (5.5% [35/634] vs. 6.5% [43/658], χ2 = 0.59, P = 0.444). Subgroup analysis revealed that CFD reduced the incidence of complications in patients with native papilla (odds ratio [OR]: 0.61, 95% CI: 0.39–0.95, P = 0.028) in the multivariable models. Conclusion::Ingesting 400 mL of CFD 2 h before ERCP is safe, with a reduction in post-ERCP fatigue, abdominal pain, and cholangitis during recovery.Trail Registration::ClinicalTrials.gov, No. NCT03075280.

Purpose: This study aims to evaluate the efficacy and safety of a new combination treatment of vinorelbine and pyrotinib in human epidermal growth factor receptor 2 (HER2)–positive metastatic breast cancer (MBC) and provide higher level evidence for clinical practice. Materials and Methods: This was a prospective, single-arm, phase 2 trial conducted at three institutions in China. Patients with HER2-positive MBC, who had previously been treated with trastuzumab plus a taxane or trastuzumab plus pertuzumab combined with a chemotherapeutic agent, were enrolled between March 2020 and December 2021. All patients received pyrotinib 400 mg orally once daily plus vinorelbine 25 mg/m2 intravenously or 60-80 mg/m2 orally on day 1 and day 8 of 21-day cycle. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included the objective response rate (ORR), disease control rate (DCR), overall survival, and safety. Results: A total of 39 patients were enrolled. All patients had been pretreated with trastuzumab and 23.1% (n=9) of them had accepted trastuzumab plus pertuzumab. The median follow-up time was 16.3 months (95% confidence interval [CI], 5.3 to 27.2), and the median PFS was 6.4 months (95% CI, 4.0 to 8.8). The ORR was 43.6% (95% CI, 27.8% to 60.4%) and the DCR was 84.6% (95% CI, 69.5% to 94.1%). The median PFS of patients with versus without prior pertuzumab treatment was 4.6 and 8.3 months (p=0.017). The most common grade 3/4 adverse events were diarrhea (28.2%), neutrophil count decreased (15.4%), white blood cell count decreased (7.7%), vomiting (5.1%), and anemia (2.6%). Conclusion Pyrotinib plus vinorelbine showed promising efficacy and tolerable toxicity as second-line treatment in patients with HER2-positive MBC.

The Qa-1 in mice is homologous to human leukocyte antigen E(HLA-E), and both of them belong to the non-classical major histocompatibility complex I b(MHC-I b) molecules. Qa-1 is capable of presenting self or exogenous antigen peptides to interact with two distinct receptors, namely T cell receptor (TCR) and natural killer cell group 2 member A (or C) (NKG2A/C), thus playing an important role in immune response and regulation. Qa-1-restricted regulatory CD8⁺ T cell (CD8⁺ Treg) is one of the most studied CD8⁺ Treg subgroups, which can maintain immune homeostasis and autoimmune tolerance by exerting immunosuppressive effects. Consequently, Qa-1-restricted CD8⁺Treg cells are closely associated with the occurrence and development of various clinical diseases, such as tumors, infections, autoimmune diseases, and transplant rejections. This paper provides a comprehensive review of the phenotypic characteristics, functional effects, regulatory mechanisms of Qa-1-restricted CD8⁺ Treg cells, as well as the latest research progresses of Qa-1-restricted CD8⁺ Treg cells involved in the pathogenesis of infectious diseases.
Humans ; Animals ; T-Lymphocytes, Regulatory/immunology* ; Histocompatibility Antigens Class I/immunology* ; CD8-Positive T-Lymphocytes/immunology* ; Communicable Diseases/immunology*

Scavenger receptor class B, member 2 (SCARB2) is linked to Gaucher disease and Parkinson's disease. Deficiency in the SCARB2 gene causes progressive myoclonus epilepsy (PME), a rare group of inherited neurodegenerative diseases characterized by myoclonus. We found that Scarb2 deficiency in mice leads to age-dependent dietary lipid malabsorption, accompanied with vitamin E deficiency. Our investigation revealed that Scarb2 deficiency is associated with gut dysbiosis and an altered bile acid pool, leading to hyperactivation of FXR in intestine. Hyperactivation of FXR impairs epithelium renewal and lipid absorption. Patients with SCARB2 mutations have a severe reduction in their vitamin E levels and cannot absorb dietary vitamin E. Finally, inhibiting FXR or supplementing vitamin E ameliorates the neuromotor impairment and neuropathy in Scarb2 knockout mice. These data indicate that gastrointestinal dysfunction is associated with SCARB2 deficiency-related neurodegeneration, and SCARB2-associated neurodegeneration can be improved by addressing the nutrition deficits and gastrointestinal issues.
Animals ; Mice ; Dysbiosis/metabolism* ; Mice, Knockout ; Humans ; Lysosomal Membrane Proteins/genetics* ; Receptors, Scavenger/genetics* ; Gastrointestinal Microbiome ; Myoclonic Epilepsies, Progressive/genetics* ; Vitamin E Deficiency/complications* ; Neurodegenerative Diseases/genetics* ; Bile Acids and Salts/metabolism* ; Male ; Lipid Metabolism ; Intestinal Mucosa/pathology*

Objective To investigate the syndrome differentiation characteristics of children with atopic dermatitis(AD)and the immune imbalance status in children with different syndrome types of AD.Methods A total of 159 AD children and 100 normal control children were enrolled.The peripheral blood eosinophil(Eo)count was measured by impedance method,total serum immunoglobulin E(IgE)by immunoturbidimetric assay,and interferon-gamma(IFN-γ),interleukin-4(IL-4),interleukin-5(IL-5)and interleukin-17(IL-17)were measured by multiple microspheres flow immunofluorescence assay.Results Among 159 AD children,syndrome of heart-fire and spleen-deficiency was most commom,accounting for 38.4%,followed by syndrome of blood-deficiency and wind-dryness(22.0%),syndrome of heat accumulation in heart and spleen(20.1%)and syndrome of spleen-deficiency and dampness-accumulation(19.5%).Compared with normal control group,there was no significant difference in serum IFN-γ level among different syndrome types of AD.The levels of peripheral blood Eo,serum total IgE,IL-4 and IL-17 in AD with heart-fire and spleen-deficiency syndrome were significantly increased(P<0.05).The levels of peripheral blood Eo,IL-4,IL-5 and IL-17 in AD with blood-deficiency and wind-dryness syndrome were significantly increased(P<0.05).The levels of IL-4,IL-5 and IL-17 in AD with heat accumulation in heart and spleen syndrome were significantly increased(P<0.05).The levels of peripheral blood Eo and serum IL-4 in AD with spleen-deficiency and dampness-accumulation syndrome were significantly increased(P<0.05).Conclusion Heart-fire and spleen-deficiency syndrome is the most common type in children with AD,however,the main type under 3 years old is heat accumulation in heart and spleen syndrome.Th2/Th17 immune imbalance are the main pathogenesis in heart-fire and spleen-deficiency syndrome,blood-deficiency and wind-dryness syndrome and heat accumulation in heart and spleen syndrome,and Th2 immune imbalance is the main pathogenesis of spleen-deficiency and dampness-accumulation syndrome.

Objective To study the chemical constituents from ethyl acetate extracts of the strips of Semiliquidambar cathayensis.Methods The strips of S.cathayensis were extracted by 80%ethanol and the extracts were evaporated.Fourteen compounds in ethyl acetate extracts were isolated and purified by various chromatographic techniques,such as silica gel,Sephadex LH-20 column and pre-HPLC,etc.Their structures were identified on the basis of physicochemical properties and spectroscopic analysis.Antioxidant activity test was used to evaluate total extraction,each extraction part and the isolates.Results Fourteen compounds were isolated from the strips of S.cathayensis and identified by NMR as tetradecanoic acid(1),stearic acid(2),sesamin(3),9-octadecenoic acid(4),linoleic acid(5),dibutylphthalate(6),stigmasterol(7),β-sitosterol(8),lupeol(9),oleanolic acid(10),lup-20(29)-ene-3-[3-keto-hexadecanoate](11),peujaponisin(12),C-veratroylglycol(13),and 2,3-dihydroxy-1-(4-hydroxy-3,5-dimethoxyphenyl)-1-propanone(14).Conclusion Compounds 1,3,4,5,6,7,9,11,12,13 and 14 were isolated from this plant for the first time.The EA part,compounds 13(C-veratroylglycol)and 14(2,3-dihydroxy-1-(4-hydroxy-3,5-dimethoxyphenyl)-1-propanone)showed significant antioxidative effects.