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.

Objective:To observe the neuroprotective effect of wind medicine (Puerariae Lobatue Radix and Acori Tatarinowii Rhizoma) in combination with Panax ginseng total saponin (PNS) on cerebral ischemia-reperfusion rats; To elucidate the mechanism of "wind medicine increasing effect".Methods:Totally 140 male SD rats were divided into sham-operation group, model group, PNS group, Puerariae Lobatue Radix group, Acori Tatarinowii Rhizoma group, Puerariae Lobatue Radix + PNS group, Acori Tatarinowii Rhizoma + PNS group according to the random number table method, with 20 rats in each group. Except for the sham-operation group, the cerebral ischemia/reperfusion rat model was established using the modified Longa line bolus method in the remaining groups. After 7 d of administration of the appropriate pharmacologic intervention in each group, neurological dysfunction was evaluated by Zea-longa score after final administration, cerebral infarct volume was determined by TTC staining; blood brain barrier (BBB) permeability of brain tissue on the ischemic side was detected by Evans blue content; BBB ultrastructure of each group of rats was observed by transmission electron microscopy; Claudin 5 protein expression level was detected by immunohistochemistry; Zonula occludens-1 (ZO-1), major facilitator supeffamily domain-containing protein 2a (Mfsd2a), Occludin, P-glycoprotein (P-gp), Monocarboxylate Transporters-1 (MCT1) and breast cancer resistance protein (BCRP) protein expression levels were detected by Western-blot.Results:Compared with the model group, the rat neurological function scores were reduced in each administration group ( P<0.05), infarct volume was reduced ( P<0.05), EB content of brain tissue decreased ( P<0.05), protein expressions of Claudin 5, ZO-1, Mfsd2a and Occludin in brain tissue were elevated ( P<0.05), the protein expressions of P-gp, BCRP and MCT1 were reduced ( P<0.05), and the protein expressions of Claudin 5, Mfsd2a, and Occludin was higher in the Puerariae Lobatue Radix + PNS group and Acori Tatarinowii Rhizoma + PNS group than that of each group of medication alone ( P<0.05), and the protein expression of MCT1 was lower than that of each group of medication alone ( P<0.05); the protein expression level of ZO-1 in the Puerariae Lobatue Radix + PNS group was higher than that of the group of medication alone ( P<0.05); P-gp protein expression was lower in Acori Tatarinowii Rhizoma + PNS group than in the PNS group and Acori Tatarinowii Rhizoma group ( P<0.05). Conclusion:Wind medicine (Puerariae Lobatue Radix and Acori Tatarinowii Rhizoma) may potentiate the neuroprotective effect of PNS on cerebral ischemia-reperfusion rats, and the mechanism may be related to the protection of BBB structural integrity and maintenance of central barrier properties, while regulating substance transport proteins and increasing the intracerebral content of the drug.

Objective: To investigate the clinical manifestations, pathological features, and treatment of oral and maxillofacial pyogenic granulomas induced by camrelizumab. Methods: A case of pyogenic granuloma of the gums and lips caused by camrelizumab was reported along with a literature review. Results: After 4 months of treatment with camrelizumab for liver cancer, the patient developed systemic reactive capillary hyperplasia (RCH), followed by multiple masses on the lower lip and gingiva. After periodontal therapy, the masses on the lower lip and the gingiva were removed, and camrelizumab administration was stopped. The pathological result was gingival pyogenic granuloma/granulomatous hemangioma. No new masses were found in the oral cavity during postoperative follow-up. A review of the literature showed that RCH is the most common adverse drug reaction to camrelizumab but it occurs infrequently in the oral cavity. At present, the etiology of RCH has not been clarified, but the research has shown that camrelizumab may trigger tissue proliferation into hemangiomas by activating vascular endothelial cells, and the combined use of camrelizumab is safer than single use. RCH is self-limiting and most cases resolve spontaneously after discontinuation of the drug. If the mass causes dysfunction, surgical excision is feasible. Conclusion Camrelizumab can cause oral and maxillofacial reactive capillary hyperplasia complicated by pyogenic granuloma.

Objective:To explore the application effect of integrated mode of medical and nursing in colostomy patients.Methods:Using the convenient sampling method, a total of 60 patients who underwent colostomy in the Second Affiliated Hospital of Wenzhou Medical University from January 2019 to April 2020 were selected as the research objects. The patients who hospitalized from January to August 2019 were included in the control group, and the patients who hospitalized from September 2019 to April 2020 were included in the observation group, with 30 cases in each group. The patients in the control group were treated with routine nursing mode, and the patients in the observation group were treated with integrated mode of medical and nursing. Before discharge, 1, 3 and 6 months after the operation, the status of independent replacement of colostomy bags, scores of the Stoma Self-care Scale-Early Version and the incidence of stoma complications were compared between the two groups.Results:There was no statistically significant difference in the number of patients who changed colostomy bags independently before discharge and 1, 3 and 6 months after the operation between the two group ( P>0.05) . There was no statistically significant difference in the number of cases of periostomy dermatitis, ostomy and mucosal separation and stoma depression between the two groups of patients after surgery ( P>0.05) . The score of the Stoma Self-care Scale-Early Version of the observation group were higher than that of the control group at 3 and 6 months after surgery, and the difference was statistically significant ( P<0.05) . Conclusions:The integrated mode of medical and nursing can improve the self-care ability of patients at 3 and 6 months after the operation , which is worthy of clinical application.

Objective To provide a simple, convenient, and safe anesthesia method for the establishment of a M1 segment of middle cerebral artery occlusion model in rhesus monkey or other large laboratory animals.Method Twenty male rhesus monkeys weighing 7-11 kg (ages 7-9 years) from Academy of Military Medical Sciences were used in this study.Sumianxin injection combined with 0.1 mg/kg ketamine was given before endotracheal intubation (ID:4.5-5.5#).The animals were then transported to an interventional operation room, where the intravenous access was established and a urinary catheter was inserted into the urinary bladder.Mechanical ventilation was used during the surgery, propofol was continuously injected in a speed of 2-4 mg/kg/h, and Sumianxin-ketamine could be given if necessary to maintain adequate anesthesia depth.The dose was adjusted according to vital signs of the rhesus such as body movements, physiological parameters, and demand of surgery.Brain MRI examination was performed before and after thrombolysis.Anesthetic injection was suspended and the animals were allowed to have a spontaneous breathing every time before the MRI text.Heart rates, temperature, non-invasive blood pressure, and SpO2 were monitored during the whole surgery.Blood samples were taken from the radial artery for blood gas analysis after anesthesia induction and during operation.Results All the 20 animals underwent the operation successfully, no animal had restlessness, respiratory depression, arrhythmia and other serious complications.At the end of the study, animals awake soon.Fifteen of them survived longer than 24 hours, only 5 died from serious cerebral hemorrhage and larger cerebral infarction.Conclusions General endotracheal anesthesia is safe for rhesus monkeys during such interventional operation and MRI examination.

Objective To evaluate the relationship between inflammatory responses induced by perioperative infection and surgical stress and postoperative cognitive dysfunction in mice. Methods One hundred forty?four healthy male C57BL∕6 mice, aged 8-12 weeks, weighing 20-25 g, were divided into 4 groups ( n=36 each) using a random number table: control group ( group C) , surgery group ( group S) , infection group ( group I) , and infection+surgery group ( group I+S) . In group S, the open reduction and internal fixation was performed after tibial fracture was induced. Lipopolysaccharide ( LPS) 100 μg∕kg was injected intraperitoneally at the same time every day for 5 consecutive days starting from 1 day before surgery in group I. In group I+S, LPS 100 μg∕kg was injected intraperitoneally at the same time every day for 5 consecutive days starting from 1 day before surgery, and the open reduction and internal fixation was per?formed after tibial fracture was induced at 2 h after LPS injection on the day of surgery. Contextual fear con?ditioning test was performed on 1 and 3 days after surgery, and cognitive function was assessed. The rate of freezing time was calculated. The peripheral venous blood samples were collected for determination of plas?ma interleukin?6 ( IL?6) and IL?1β concentrations by enzyme?linked immunosorbent assay. The animals were then sacrificed, and the hippocampi were isolated for determination of IL?6, IL?1β and prostaglandin E2 ( PGE2 ) contents in hippocampal tissues by enzyme?linked immunosorbent assay. Results Compared with group C, the rate of freezing time was significantly decreased on 1 and 3 days after surgery, and the contents of IL?6, IL?1βand PGE2 in hippocampal tissues were significantly increased on 1 and 3 days after surgery in S and I+S groups, the concentrations of plasma IL?6 and IL?1βwere significantly increased on 1 day after surgery, and the concentration of plasma IL?1βwas significantly increased on 3 days after surgery in group S, the concentrations of plasma IL?6 and IL?1β were significantly increased on 1 and 3 days after surgery in I and I+S groups ( P<0?01) , and no significant change was found in the rate of freezing time on 1 and 3 days after surgery in group I ( P>0?05) . Compared with group S or group I, the rate of freezing time was significantly decreased on 1 and 3 days after surgery, and the concentrations of IL?6 and IL?1βin plasma and contents of IL?6, IL?1β and PGE2 in hippocampal tissues were significantly increased on 1 and 3 days after surgery in group I+S ( P<0?01) . Conclusion Inflammatory responses induced by periopera?tive infection and surgical stress can aggravate postoperative cognitive dysfunction in mice.

Objective To summarize the postoperative complications of reconstruction of mandible defect with titanium reconstruction plate.Methods A total of 111 cases of the mandibular defect caused by various reasons and repaired by titanium reconstruction plate in the Department Oral and Maxillofacial Surgery of the affiliated Hospital of Qingdao University from 2003 to 2012 were collected and followed up.The complications were analyzed.Results Thirty-seven percent of 111 cases showed long term complications.The titanium fracture was the main complication(16％[18/111]),followed by stress-shielding (9％[10/111]),infection(8％[9/111]),and titanium plate exposure(4％[4/111]).Titanium plate fracture occurred within 8 months and 3 years after surgery.The simple titanium plate reconstruction had the highest rate of plate fracture(30％[15/50]).Stress-shielding in non-vascularized bone graft was more significant than that in vascularized bone graft(P＜0.05).When replaced by mini-titanium plate,the stress-shielding effect disappeared gradually.When the retention of mandibular margin height was less than 1 cm with the use of reconstruction plate,the postoperative complications were prone to occur.Conclusions Bone graft is the best way to reconstruct mandibular defect,and simple reconstruction plate repair is applied only as a transitional means for high degree of malignancy,obvious recurrence tendency tumor or special reasons such as age etc,which are not suitable for bone graft.The reconstruction plate fixation is not recommended for bone graft,especially non-vascularized bone graft.The retention of mandibular margin with reconstruction plate fixation is open to discussion.

Objective To evaluate the efficacy of oxycodone or hydromorphone combined with propofol for colonoscopy.Methods A total of 150 patients of both sexes,aged 18-64 yr,weighing 45-85 kg,of ASA physical status Ⅰ or Ⅱ,undergoing colonoscopy,were randomly divided into 3 groups (n=50) using a random number table:fentanyl combined with propofol group (group F),oxycodone combined with propofol group (group O) and hydromorphone combined with propofol (group H).In F,O and H groups,fentanyl 1 μg/kg,oxycodone 0.1 mg/kg and hydromorphone 0.02 mg/kg were injected over 60 s,respectively,and then propofol 1.5 mg/kg was injected intravenously.After eyelash reflex disappeared,a colonoscope was placed.When body movement occurred during examination,half of the initial dose of propofol was added.The time for induction of anesthesia,operation time,emergence time,recovery time,occurrence of adverse cardiovascular events,nausea and vomiting and respiratory depression,and amount of propofol consumed were recorded.Results There was no significant difference between the three groups in the time for induction of anesthesia,operation time,emergence time,recovery time,adverse cardiovascular events,respiratory depression,and amount of propofol consumed.Compared with group F,the incidence of nausea and vomiting and respiratory depression was significantly decreased,and the degree was reduced in H and O groups.No significant difference was found between group O and group H in the incidence of nausea and vomiting and respiratory depression and the degree.Conclusion Oxycodone or hydromorphone combined with propofol can be safely and effectively used for colonoscopy and the efficacy is better than that of fentanyl combined with propofol.

Using mutation PCR, we cloned the target gene containing 421-480nt (141-160aa) and 598-639nt (200-213aa) of VP1 gene of foot and mouth disease virus (FMDV) into the deleted region (508-532aa) of Nsp2 gene of a highly pathogenic porcine reproductive and respiratory syndrome virus derived vaccine strain (HuN4-F112) that was used as vector. The recombinant cDNA was in vitro transcribed followed by transfection of BHK-21 cells for 36 h. Then, the supernatant of the cell culture was continuously seeded to monolayer of MARC-145 cells for recovery of the recombinant virus. CPE was obviously visible after a couple of passages in the seeded MARC-145, and the rescued virus (designated as rPRRSV-F112-O/VP1ep) was identified by Mlu I digestion, sequencing and immunofluorescence assay. Meanwhile, expression of inserted FMDV epitopes was also detected by indirect immunofluorescence assay with polyclonal antibodies against VP1 protein of FMDV. The analysis of biological characteristics shows that the titer of the rescued recombinant PRRSV (TCID50 = -log10(-6.75)/0.1 mL) was similar to its direct parental virus rHuN4-F112-delta508-532, but higher than rHuN4-F112.
Animals ; Antigens, Viral ; immunology ; Base Sequence ; Capsid Proteins ; immunology ; Cell Line ; Cysteine Endopeptidases ; genetics ; Epitopes ; genetics ; Foot-and-Mouth Disease ; immunology ; prevention & control ; Foot-and-Mouth Disease Virus ; genetics ; immunology ; Molecular Sequence Data ; Mutation ; Porcine respiratory and reproductive syndrome virus ; genetics ; immunology ; Recombination, Genetic ; Swine ; Transfection ; Vaccines, Attenuated ; genetics ; immunology ; Viral Envelope Proteins ; genetics ; immunology ; Viral Vaccines ; genetics ; immunology

OBJECTIVETo reconstruct mandibular defect using tissue engineering bone with bone marrow stem cells (BMSCs) cell sheets and investigate the effect of cell sheets on osteogenesis.

METHODSBMSCs were isolated with the method of density gradient centrifugation from canine and cultured. BMSCs were induced to differentiate to osteoblasts. BMSCs induced were fabricated to BMSCs cell sheets. The poly (lactic-co-glycolic acid) (PLGA) wrapped with cell sheets were implanted into the mandibular defect in the left side (experimental side). PLGA wrapped without cell sheets were implanted into the right side (control side) of mandibles. 16 dogs were evenly divided into 4 groups, and one group of them was executed in 4, 8, 12, 16 weeks for gross investigation and histological observation.

RESULTSThe osteogenesis of experimental side was better than that of control side. 16 weeks after implantation, most areas of the mandibular defect were replaced by fresh bone tissue. Compact bone similar to normal bone tissue formed in the lingual defect of mandible and had bony union with the bone stump. The optical density of the fresh bone in the experimental side was higher than that of the control side, there was a significant difference between the two methods (P<0.05). Plenty of lamellar bones formed in experimental side and Haversian system, as well as red marrow, were observed.

CONCLUSIONTissue engineering bone with the structure of lamellar bones can be formed by the technology of BMSCs cell sheets.

Animals ; Bone Marrow Cells ; Bone and Bones ; Dogs ; Lactic Acid ; Mandible ; Osteoblasts ; Osteogenesis ; Polyesters ; Polyglycolic Acid ; Polymers ; Tissue Engineering