BACKGROUND:In recent years,with the development of biological scaffold materials and bioprinting technology,tissue-engineered bone has become a research hotspot in bone defect repair. OBJECTIVE:To summarize the current treatment methods for bone defects,summarize the biomaterials and bioprinting technology for preparing tissue-engineered bone scaffolds,and explore the application of biomaterials and printing technology in tissue engineering and the current challenges. METHODS:Search terms were"bone defect,tissue engineering,biomaterials,3D printing technology,4D printing technology,bioprinting,biological scaffold,bone repair"in Chinese and English.Relevant documents published from January 1,2009 to December 1,2022 were retrieved on CNKI,PubMed and Web of Science databases.After being screened by the first author,high-quality references were added.A total of 93 articles were included for review. RESULTS AND CONCLUSION:The main treatment methods for bone defects include bone transplantation,membrane-guided regeneration,gene therapy,bone tissue engineering,etc.The best treatment method is still uncertain.Bone tissue engineering technology is a new technology for the treatment of bone defects.It has become the focus of current research by constructing three-dimensional structures that can promote the proliferation and differentiation of osteoblasts and enhance the ability of bone formation.Biological scaffold materials are diverse,with their characteristics,advantages and disadvantages.A single biological material cannot meet the demand for tissue-engineered bone for the scaffold.Usually,multiple materials are combined to complement each other,which is to meet the demand for mechanical properties while taking into account the biological properties of the scaffold.Bioprinting technology can adjust the pore of the scaffold,build a complex spatial structure,and is more conducive to cell adhesion,proliferation and differentiation.The emerging 4D printing technology introduces"time"as the fourth dimension to make the prepared scaffold dynamic.With the synchronous development of smart materials,4D printing technology provides the possibility of efficient repair of bone defects in the future.

The biological clock(also known as the circadian rhythm)is the fundamental reliance for all organisms on Earth to adapt and survive in the Earth's rotation environment.Circadian rhythm is the most basic regulatory mechanism of life activities,and plays a key role in maintaining normal physiological and biochemical homeostasis,disease occurrence and treatment.Recent studies have shown that the biologi-cal clock plays an important role in the development of oral tissues and in the occurrence and treatment of oral diseases.Since there is cur-rently no guiding literature on the research methods of biological clock in stomatology,researchers mainly conduct research based on pub-lished references,which has led to controversy about the research methods of biological clock in stomatology,and there are many confusions about how to rationally apply the research methods of circadia rhythms.In view of this,this expert consensus summarizes the characteristics of the biological clock and analyzes the shortcomings of the current biological clock research in stomatology,and organizes relevant experts to summarize and recommend 10 principles as a reference for the rational implementation of the biological clock in stomatology research.

Objective To observe the effects of Ditan Yizhi Decoction on learning and memory ability,structure of hippocampal tissue,neuronal morphology of hippocampus,and the expression of endoplasmic reticulum autophagy-related protein FAM134B in hippocampal tissue;To explore the mechanism of its therapeutic effect on vascular dementia.Methods Totally 32 SD rats were randomly divided into sham-operation group,model group,donepezil group and Ditan Yizhi Decoction group,with 8 rats in each group.The model group,donepezil group and Ditan Yizhi Decoction group were prepared with a modified permanent ligation method of bilateral common carotid arteries to create a rat model of vascular dementia,the common carotid artery was separated in the sham-operation group,but not ligated.After modeling,the donepezil group was given donepezil hydrochloride,Ditan Yizhi Decoction group was given Ditan Yizhi Decoction,and the sham-operation group and model group were given equal volume of distilled water for gavage for 4 consecutive weeks.Morris water maze experiment was used to evaluate the learning and memory ability,HE staining and Nissl staining were used to observe the morphological changes of hippocampus,ultrastructure of hippocampal neurons was observed using transmission electron microscopy,Western blot was used to detect the protein expression of FAM134B and p-FAM134B in hippocampal tissue.Results Compared with the sham-operation group,the escape latency period was prolonged of the rats in model group,and the number of crossing the original platform and the duration of stay in the target quadrant was reduced(P<0.01),the gap between neurons in CA1 region of the hippocampus increased,the cell morphology was irregular,the boundaries were blurred,the neurons shrinked,the Nissl bodies dissolved and broke,the number decreased,the endoplasmic reticulum arrangement was scattered,mitochondria swelled and deformed,and the expressions of FAM134B and p-FAM134B protein in hippocampal tissue increased(P<0.01).Compared with the model group,the escape latency period of rats in donepezil group and Ditan Yizhi Decoction group were significantly shortened,and the number of crossing the original platform and the duration of stay in the target quadrant were increased(P<0.01),the morphology and quantity of neurons in CA1 region of the hippocampus were more regular,with a decrease in neuronal pyknosis,an increase in the number of Nissl bodies,and a reduction in dissolution and fragmentation,the swelling and deformation of the endoplasmic reticulum were restored,and the expression of FAM134B and p-FAM134B protein in hippocampal tissue increased(P<0.01).Moreover,the effects of Ditan Yizhi Decoction group were better than those of the donepezil group(P<0.01).Conclusion Ditan Yizhi Decoction can improve the learning and memory ability and the morphology of neurons in vascular dementia rats.The mechanism may related to increasing the expression and phosphorylation of FAM134B protein,thereby promoting endoplasmic reticulum autophagy.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective To evaluate the clinical value of neutrophil CD64(nCD64)index as a novel biomark-er in the differential diagnosis of acute and chronic brucellosis.Methods A total of 38 patients with acute bru-cellosis and 48 patients with chronic brucellosis diagnosed in the People's Hospital of Xinjiang Uygur Autono-mous Region from February 2021 to July 2023 were included.Peripheral blood of the patients was collected and nCD64 index was detected by flow cytometry,and the correlation between nCD64 index and disease severi-ty was analyzed.Receiver operating characteristic(ROC)curve was used to analyze the sensitivity and the specificity of nCD64 index in differentially diagnosing acute and chronic brucellosis.Meanwhile,Rose-Bengal Plate Test(RBPT)and Standard Tube Agglutination Test(SAT)were used as controls to evaluate the clini-cal diagnostic value of the three.Results The nCD64 index of acute brucellosis patients was higher than that of chronic brucellosis patients(U=216.00,P<0.001),and the index was positively correlated with the sever-ity of the disease(r=0.670,P<0.001).The ROC curve analysis results showed that the area under the curve of nCD64 index in the differential diagnosis of acute and chronic brucellosis was 0.882(95%CI:0.811-0.952,P<0.001),the cut-off value was 2.81,and sensitivity,specificity,positive predictive value,negative predictive value and accuracy were 83.3%,81.6%,80.4%,81.9%and 82.6%,respectively.The efficacy of nCD64 index in differential diagnosis of nCD64 index was significantly better than those of the qualitative tests of RBPT and SAT.Conclusion nCD64 index has favourable sensitivity and specificity in the differential diag-nosis of acute and chronic brucellosis,and tends to reflect the severity of the disease.It has clinical value in the differential diagnosis of acute brucellosis and chronic brucellosis,and plays an important role in the early diag-nosis and treatment effect monitoring of brucellosis.

Objective To investigate the characteristics of changes in interleukin(IL)-33 and regulatory T(Treg)cells in brucellosis,to verify the regulatory effect of IL-33 on Treg cells,so as to clarify the immune mechanism of IL-33 on Treg cells in brucellosis.Methods The peripheral blood of 39 patients with brucellosis treated in the People's Hospital of Xinjiang Uygur Autonomous Region from January to December 2021(the brucellosis group)and 42 healthy controls(the healthy control group)who underwent physical examination during the same period were collected.The serum IL-33 level was detected by AimPlex kit,and the proportion of Treg cells was detected by flow cytometry.Peripheral blood mononuclear cell(PBMC)was extracted and cultured in vitro to observe the proportion and mRNA expression levels of forkhead box protein P3(Foxp3)after stimulation and blocking of IL-33.Results Compared with the healthy control group,the level of IL-33 and the proportion of Treg cells in brucellosis group were significantly increased,with statistical significance(P＜0.05).In vitro tests showed that the Foxp3 proportion and mRNA expression level of PBMC in the two groups were significantly increased after IL-33 stimulation,and significantly decreased after IL-33 blocking,with statistical significance(P＜0.001).Conclusion IL-33 and Treg cells increased significantly in brucellosis patients,and IL-33 promoted the immune function of Treg cells.Blocking IL-33 is expected to be a potential target for immunotherapy of brucellosis.

Objective:To quantify the diagnostic index of probe-based confocal laser endomicroscopy (pCLE) for diagnosing Helicobacter pylori ( HP)-associated chronic atrophic gastritis (HpCAG), and to evaluate the efficacy of the quantified diagnostic index for HpCAG. Methods:The study was divided into two stages. The first stage prospectively included patients undergoing gastroscopy, endoscopic biopsy and 13C breath test from November 2021 to September 2022 at the Second Affiliated Hospital of Baotou Medical College. The capillary diameter (CD), cells spacing (CS), gland spacing (GS), and gland area (GA) in the pCLE field of offline video was measured with Image J. The diagnostic criteria of HpCAG by quantitative indicators under pCLE was established by analyzing the area under the receiver operating characteristic (ROC) curve (AUC). In the second stage, the cases with pCLE examination and 13C breath test at the Second Affiliated Hospital of Baotou Medical College from October 2021 to October 2022 were included. The cases that overlapped with the first stage were excluded. The trial was single-blind, with endoscopists and pathologists blind to each other's diagnoses. The diagnosis of pCLE was conducted according to the criteria obtained in the first stage, and the consistency between pCLE diagnosis and the results of histopathology and 13C breath test was analyzed. Results:The first stage enrolled 191 specimens from 35 patients. According to the pathological results of endoscopic biopsy and 13C breath test results, patients and gastric mucosa samples were divided into 4 groups, HP-positive CAG group ( n=59), HP-positive non-CAG group ( n=52), HP-negative CAG group ( n=40), and HP-negative non-CAG group ( n=40). ROC curve analysis results showed that in HP-positive patients, the optimal critical value of GS to distinguish between CAG and non-CAG gastric mucosa was 29.68 μm, and the AUC was the largest among the 4 parameters. In HP-negative patients, the optimal critical value of GS for distinguishing gastric mucosa from CAG and non-CAG was 23.57 μm, and the AUC was the largest among the 4 parameters. In patients with non-CAG, the optimal critical value for GS to distinguish HP-positive and HP-negative gastric mucosa was 20.57 μm, and the AUC was the largest among the 4 parameters. In patients with CAG, the optimal critical values of CD, CS, GS and GA to distinguish between HP-positive and HP-negative gastric mucosa were 13.23 μm, 1.38 μm, 34.03 μm and 6 066.5 μm 2, respectively, and the AUC were 0.608, 0.888, 0.849 and 0.900, respectively. Finally, GS was selected to distinguish between HpCAG and non-HpCAG gastric mucosa, and the optimal critical value was 31.71 μm. However, considering that it was difficult to measure the distance of 31.71 μm by the ruler below the image, the critical value was changed to 30 μm, so GS>30 μm was used as the diagnostic criteria for HpCAG in pCLE, and the diagnostic sensitivity and the specificity were 91.5% and 76.0%, respectively. In the second phase 224 specimens from 80 patients were observed. The sensitivity, the specificity, the positive predictive value, the negative predictive value and accuracy of pCLE (GS>30 μm) in the diagnosis of HpCAG were 96.5% (164/170), 88.9% (48/54), 96.5% (164/170), 88.9% (48/54) and 94.6% (212/224), respectively, with excellent diagnostic agreement with histopathology and 13C breath test (Kappa=0.854). Conclusion:The quantitative monitoring of gastric mucosal microstructure can be achieved under pCLE, and the quantifying indicators are helpful to improve the accuracy of HpCAG diagnosis.

Objective To compare the short-term efficacy and occurrence of complication of endoscopic laminar fenestration (Endo-LOVE) and percutaneous endoscopic transforaminal decompression (PETD) in patients with degenerative lumbar lateral recess stenosis (LSLRS). Methods A total of 160 patients with LSLRS were enrolled as study objects, and were randomly assigned to control group (treated with PETD) and observation group (treated with Endo-LOVE), with 80 patients in each group. Surgical indicators, occurrence of complications, and therapeutic effects were observed and compared between the two groups. Bone lateral recess angle, soft lateral recess angle, Oswestry Disability Index (ODI) score, pain score, and Japanese Orthopaedic Association (JOA) score were compared before and after surgery. Results The observation group had less intraoperative blood loss, and shorter operative and hospital stays than the control group (P < 0.05). There were no statistically significant differences in the incidence of complications such as lower limb numbness, fever, and postoperative low back pain between the two groups (P>0.05). There were no statistically significant differences in preoperative bone lateral recess angle or soft lateral recess angle between the two groups (P>0.05). At 72 hours postoperatively, both angles increased in both groups compared with preoperative values, and the observation group had larger angles than the control group (P < 0.05). There were no statistically significant differences in preoperative pain score, ODI score, or JOA score between the two groups (P>0.05). At 3 months postoperatively, JOA scores increased and pain scores as well as ODI scores decreased in both groups compared with preoperative values, with the observation group having higher JOA scores and lower pain scores as well as ODI scores than the control group (P < 0.05). The excellent and good rate was 96.25%(77/80) in the observation group, which was higher than 87.50%(70/80) in the control group (P < 0.05). Conclusion Compared with the PETD approach, the Endo-LOVE approach for the treatment of LSLRS offers shorter operative time, less intraoperative blood loss, and better short-term efficacy.

ObjectiveTo perform a predictive analysis of the quality marker（Q-Marker） for the anticoagulant activity of Kunning granules. MethodThe chemical components of Kunning granules were analyzed by ultra high performance liquid chromatography-quadrupole-time of flight tandem mass spectrometry（UHPLC-Q-TOF-MS/MS） on a Waters ACQUITY UPLC HSS T3 column（2.1 mm×100 mm， 1.8 μm） with the mobile phase of acetonitrile（A）-25 mmol∙L^-1 ammonium acetate aqueous solution（B） for gradient elution （0-5 min， 5%-22%A； 5-10 min， 22%-30%A； 10-15 min， 30%-95%A； 15-20 min， 95%-5%A； 20-30 min， 5%A）， flow rate of 0.2 mL∙min^-1， column temperature at 30 ℃， injection volume of 1 μL， electrospray ionization（ESI）， positive and negative ion detection modes. Interaction analysis between the targets of chemical components and the targets of abnormal uterine bleeding（AUB） was performed by network pharmacology， and the key components were screened through network topology analysis. The fingerprints of 10 batches of Kunning granules were established by high performance liquid chromatography（HPLC）， the anticoagulant activity of the granules was determined by blood coagulation method and fibrinogen plate method， and the spectrum-effective relationship was established. The components co-occurring in the topological analysis and spectrum-effective relationship were selected as Q-Markers， and their anticoagulant activities were verified and confirmed. ResultA total of 475 chemical components were identified from Kunning Granule， of which 22 key components such as salvianolic acid B， paeoniflorin， naringin and neohesperidin， were the potential material basis for the treatment of AUB. The spectrum-effective analysis showed that peaks 7（paeoniflorin）， 9（naringin）， 10（neohesperidin） and 11（salvianolic acid B） were the optimal principal components， and in vitro activity test showed that these four components could better characterize their anticoagulant activity. ConclusionSalvianolic acid B， paeoniflorin， neohesperidin and naringin may be Q-Markers for the anticoagulant activity of Kunning granules.

【Objective】 To investigate the effects of biomimetic bone trabecular with the same porosity and pore size and regular porous structure on the adhesion, proliferation, and differentiation of osteoblasts, so as to provide theoretical basis for the improvement of osseointegration performance of titanium alloy implants. 【Methods】 The biomimetic bone trabecular and regular porous structures with the same porosity and pore size were generated by computer-aided software, and then processed into disc-shaped Ti6Al4V scaffolds with a diameter of 10 mm and a height of 3 mm by selective laser melting technology. MC3T3-E1 cells, the precursor cells of mouse osteoblasts in the logarithmic growth phase, were seeded on two kinds of scaffolds and divided into biomimetic bone trabecular group and regular porous structure group. After 3 hours of culture, acridine orange staining and phalloidin /DAPI staining were used to evaluate the number of cell adhesion. After 3 days of culture, the scaffolds were examined by scanning electron microscopy to evaluate the adhesion state of cells. After 1, 3, and 5 days of culture, the scaffolds were taken for CCK8 detection to observe the proliferation of cells. After 7 and 14 days of differentiation, alkaline phosphatase (ALP) activity was detected. After 14 days of differentiation, the expressions of osteogenesis-related genes (ALP, OCN, RUNX2) were detected by RT-PCR. After 30 days of differentiation, the scaffolds were stained with alizarin red and 100 g/L cetylpyridinium chloride was used to dissolve mineralized nodules. Calcium salt deposition was qualitatively and quantitatively detected to evaluate cell differentiation. 【Results】 The results of acridine orange and phalloidin /DAPI staining showed that the biomimetic trabecular Ti6Al4V scaffold adhered to more MC3T3-E1 cells than the regular porous structure, and the cytoskeleton of the former scaffold was more densely distributed. The results of scanning electron microscopy showed that the pseudopodia of MC3T3-E1 cells on the biomimetic bone trabecular Ti6Al4V scaffold were longer and the extension state was better than that of the regular porous structure. CCK8 test showed that the proliferation of MC3T3-E1 cells on the biomimetic trabecular bone titanium alloy scaffold was significantly higher than that on the regular porous structure on the 3rd and 5th day, and the difference gradually increased with the increase of time, with statistical significance (P<0.05). The results of cell differentiation test showed that ALP activity on the bionic trabecular scaffold was higher than that on the regular porous structure (P<0.05). The expressions of osteogenic genes (ALP, OCN, RUNX2) in MC3T3-E1 cells on the biomimetic bone trabecular titanium alloy scaffold were significantly higher than those on the regular porous structure (P<0.05). After 30 days of induction, the amount of calcium salt deposited in the bionic trabecular titanium alloy scaffold was significantly larger than that in the regular porous structure (P<0.05). 【Conclusion】 The biomimetic bone trabecular with a porosity of 65% and an equivalent pore size of 600 μm is more conducive to the adhesion, proliferation and differentiation of mouse osteoblast precursor cells MC3T3-E1 on the titanium alloy scaffold than the regular porous structure with the same porosity and pore size. It is theoretically more conducive to improving the osseointegration performance of titanium alloy implants.