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BACKGROUND: The surge in omicron variants has caused nationwide breakthrough infections in mainland China since the December 2022. In this study, we report the neutralization profiles of serum samples from the patients with breast cancer and the patients with liver cancer who had contracted subvariant breakthrough infections. METHODS: In this real-world study, we enrolled 143 COVID-19-vaccinated (81 and 62 patients with breast and liver cancers) and 105 unvaccinated patients with cancer (58 and 47 patients with breast and liver cancers) after omicron infection. Anti-spike receptor binding domain (RBD) IgGs and 50% pseudovirus neutralization titer (pVNT50) for the preceding (wild type), circulating omicron (BA.4-BA.5, and BF.7), and new subvariants (XBB.1.5) were comprehensively analyzed. RESULTS: Patients with liver cancer receiving booster doses had higher levels of anti-spike RBD IgG against circulating omicron (BA.4-BA.5, and BF.7) and a novel subvariant (XBB.1.5) compared to patients with breast cancer after breakthrough infection. Additionally, all vaccinated patients produced higher neutralizing antibody titers against circulating omicron (BA.4-BA.5, and BF.7) compared to unvaccinated patients. However, the unvaccinated patients produced higher neutralizing antibody against XBB.1.5 than vaccinated patients after Omicron infection, with this trend being more pronounced in breast cancer than in liver cancer patients. Moreover, we found that there was no correlation between anti-spike RBD IgG against wildtype virus and the neutralizing antibody titer, but a positive correlation between anti-spike RBD IgG and the neutralizing antibody against XBB.1.5 was found in unvaccinated patients. CONCLUSION: Our study found that there may be differences in vaccine response and protective effect against COVID-19 infection in patients with liver and breast cancer. Therefore, we recommend that COVID-19 vaccine strategies should be optimized based on vaccine components and immunology profiles of different patients with cancer.
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Anticuerpos Neutralizantes , Anticuerpos Antivirales , Neoplasias de la Mama , Vacunas contra la COVID-19 , COVID-19 , Neoplasias Hepáticas , SARS-CoV-2 , Humanos , Femenino , COVID-19/inmunología , COVID-19/epidemiología , COVID-19/prevención & control , COVID-19/virología , Neoplasias Hepáticas/virología , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/epidemiología , Neoplasias de la Mama/inmunología , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/virología , SARS-CoV-2/inmunología , Anticuerpos Neutralizantes/sangre , Anticuerpos Neutralizantes/inmunología , Persona de Mediana Edad , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , China/epidemiología , Vacunas contra la COVID-19/inmunología , Adulto , Anciano , Glicoproteína de la Espiga del Coronavirus/inmunología , Masculino , Brotes de Enfermedades , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunologíaRESUMEN
Objective: To identify the factors influencing the completion rate of the course of rabies vaccinations without considering the economic factors or the drug supplies. Methods: Rabies vaccination data from the Fourth Medical Center of the PLA General Hospital from January 1 to December 31, 2020, were collected. This includes demographics, information on injury-causing animals, vaccination schemes, and injury assessments. Data on completed the course of rabies vaccinations were compared with data on uncompleted. Internal analysis of Zagreb regimen and Essen regimen was performed. The key factor affecting the completion of the course of rabies vaccinations was analyzed. Results: A total of 1633 patients completed the course of rabies vaccinations, while 462 patients did not. There were differences between the two groups in terms of the vaccination scheme, age, and previous history of rabies vaccinations. The results of a multivariate analysis of variance showed that only the vaccination scheme was significantly correlated with the completion rate of the course of rabies vaccinations. The internal analysis of the vaccination schemes showed that the duration of the vaccination scheme directly affected the completion rate of the course of rabies vaccinations, and the vaccination duration was negatively correlated with the completion rate of rabies vaccinations. Conclusion: The completion rate of the course of rabies vaccinations with Zagreb regimen was higher than Essen regimen. The completion rate was closely correlated with the vaccination scheme, but the duration of the vaccination scheme was the key factor. There was a linear relationship between the vaccination duration and the completion rate of the course of vaccinations, which can be represented by the following linear equation: the completion rate of the course of rabies vaccinations (%) = 98.342-0.999 × vaccination duration (d). Duration is the critical factor affecting the completion rate. To improve the completion rate of vaccination, it is recommended to use a shorter vaccination duration regimen.
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PURPOSE: To investigate the regulatory roles of neutrophil elastase (NE) and matrix metalloproteinase-9 (MMP-9) in lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. METHODS: To construct LPS-induced ALI mouse models, wild-type C57BL/6 mice were administered 5.0 mg/kg of LPS through endotracheal, and/or 1.0 mg/kg of ONO-5046, and/or 20.0 mg/kg of chemically modified tetracycline-3 (CMT-3) by gavage. The levels of MMP-9, tissue inhibitor of metalloprotease-1, interleukin (IL)-6 were detected by real time RT-PCR at 6 h, 24 h and 48 h, and tumor necrosis factor (TNF), lung wet-dry weight ratio, white blood cell (WBC) count and polymorphonuclear (PMN) count in bronchoalveolar lavage fluid (BALF) were tested at 48 h after administration. The 5-day survival analysis of the ALI mice was also performed. RESULTS: Both ONO-5046 and CMT-3, regardless of being used individually or combined, significantly reduced the levels of MMP-9, IL-6, and TNF in lung tissue as well as in BALF, and the WBC and PMN count in BALF. Combined treatment with ONO-5046 and CMT-3 remarkably improved the survival rate of ALI mice. CONCLUSION: Neutrophil elastase synergizes with matrix metalloproteinase-9 to promote and regulate the release of inflammatory mediators and the infiltration of inflammatory cells, consequently affecting the survival of lipopolysaccharide-induced acute lung injury mice.
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Lesión Pulmonar Aguda/enzimología , Glicina/análogos & derivados , Elastasa de Leucocito/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Sulfonamidas/administración & dosificación , Tetraciclinas/administración & dosificación , Lesión Pulmonar Aguda/sangre , Lesión Pulmonar Aguda/inducido químicamente , Animales , Líquido del Lavado Bronquioalveolar/citología , Modelos Animales de Enfermedad , Glicina/administración & dosificación , Mediadores de Inflamación/metabolismo , Interleucina-6/metabolismo , Recuento de Leucocitos , Elastasa de Leucocito/efectos de los fármacos , Lipopolisacáridos , Metaloproteinasa 9 de la Matriz/análisis , Metaloproteinasa 9 de la Matriz/efectos de los fármacos , Ratones Endogámicos C57BL , Neutrófilos , Análisis de Supervivencia , Factores de Tiempo , Inhibidor Tisular de Metaloproteinasa-1/metabolismo , Factores de Necrosis Tumoral/metabolismoRESUMEN
ABSTRACT PURPOSE: To investigate the regulatory roles of neutrophil elastase (NE) and matrix metalloproteinase-9 (MMP-9) in lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. METHODS: To construct LPS-induced ALI mouse models, wild-type C57BL/6 mice were administered 5.0 mg/kg of LPS through endotracheal, and/or 1.0 mg/kg of ONO-5046, and/or 20.0 mg/kg of chemically modified tetracycline-3 (CMT-3) by gavage. The levels of MMP-9, tissue inhibitor of metalloprotease-1, interleukin (IL)-6 were detected by real time RT-PCR at 6 h, 24 h and 48 h, and tumor necrosis factor (TNF), lung wet-dry weight ratio, white blood cell (WBC) count and polymorphonuclear (PMN) count in bronchoalveolar lavage fluid (BALF) were tested at 48 h after administration. The 5-day survival analysis of the ALI mice was also performed. RESULTS: Both ONO-5046 and CMT-3, regardless of being used individually or combined, significantly reduced the levels of MMP-9, IL-6, and TNF in lung tissue as well as in BALF, and the WBC and PMN count in BALF. Combined treatment with ONO-5046 and CMT-3 remarkably improved the survival rate of ALI mice. CONCLUSION: Neutrophil elastase synergizes with matrix metalloproteinase-9 to promote and regulate the release of inflammatory mediators and the infiltration of inflammatory cells, consequently affecting the survival of lipopolysaccharide-induced acute lung injury mice.
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Animales , Sulfonamidas/administración & dosificación , Tetraciclinas/administración & dosificación , Elastasa de Leucocito/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Lesión Pulmonar Aguda/enzimología , Glicina/análogos & derivados , Factores de Tiempo , Líquido del Lavado Bronquioalveolar/citología , Análisis de Supervivencia , Lipopolisacáridos , Interleucina-6/metabolismo , Mediadores de Inflamación/metabolismo , Elastasa de Leucocito/efectos de los fármacos , Inhibidor Tisular de Metaloproteinasa-1/metabolismo , Metaloproteinasa 9 de la Matriz/análisis , Metaloproteinasa 9 de la Matriz/efectos de los fármacos , Factores de Necrosis Tumoral/metabolismo , Modelos Animales de Enfermedad , Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/sangre , Glicina/administración & dosificación , Recuento de Leucocitos , Ratones Endogámicos C57BL , NeutrófilosRESUMEN
The aim of this study was to explore the association of CpG islands methylation of liver kinase B1 (LKB1) with primary lung cancer and smoking, providing a theoretical basis for the demethylating drug to treat lung cancer by detecting the LKB1 promoter CpG methylation. mRNA expression of LKB1 were detected by in situ hybridization and methylation status on Hap II locus of the promoter of LKB1 was analyzed by methylation-specific polymerase chain reaction (PCR). 7 of 80 LKB1 positive cases had methylation on CpG islands while 18 of 44 LKB1 negative cases had methylation on CpG islands. The difference was significant between CpG island methylation and LKB1 expression. 8 of 54 cases of early and middle lung cancer were detected LKB1 promoter CpG island methylation while 30 controls were not detected, the difference was significant. 5 of 64 more-than-5-year cases had methylation on CpG islands while 20 of 60 less-than-5-year cases had methylation. The difference was significant between of 5-year survival and CpG island methylation of LKB1. 22 of 74 smoking cases of lung cancer had methylation on CpG islands of LKB1 while only 3 of 50 non-smoking cases had methylation. The difference of smoking and CpG island methylation of LKB1 was significant. LKB1 promoter CpG islands aberrant methylation is closely associated with the occurrence, development and prognosis of lung cancer, especially with smoking history including clinical early diagnosis and prognosis. CpG islands methylation in the promoter of LKB1 is likely important one of the mechanism of smoking-associated lung cancer.
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OBJECTIVE: To improve the management of the early neurogenic pulmonary edema(NPE)in patients with non-traumatic cerebral hemorrhage. METHODS: Totally 140 eligible patients with non-traumatic cerebral hemorrhage who were treated in the emergency department of our hospital from October 2008 to October 2014 were divided into two groups:NPE group(n=25)and non-NPE group(n=115). The clinical data were analyzed and compared. RESULTS: Although the mean arterial pressure was similar between these two groups,the median pH and the bicarbonate ion(HCO(3)(-))were significantly lower in the NPE group than in the non-NPE group(pH:7.32 vs.7.39,P=0.002;HCO(3)(-),20.6 mmol/L vs.22.7 mmol/L,P=0.01). Multivariate regression analysis indicated that younger age and higher glucose level were significantly correlated with the early onset of NPE in the NPE group than in the non-NPE group(age:50.1 years vs.65.1 years,P=0.0008;glucose,15.4 mmol/L vs.10.78 mmol/L,P=0.001).There were only 3 patients in all with non-traumatic cerebral hemorrhage happened the fulminant NPE in 1 hour. Within 24 hours after patients visited the emergency room,the condition was improved in 20 of 25 patients in the NPE group. However,5 patients died,among whom 3 patients with fulminant NPE(onset within 1 hour)died due to acute respiratory distress syndrome and complicated with multiple organ failure,and 2 died of cerebral hernia. CONCLUSIONS: NPE is a rare and severe complication in patients with non traumatic cerebral hemorrhage. The possibility of NPE should be considered in relatively young patients with higher glucose and lower blood pH value. Timely prevention and treatment can improve the outcomes.
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Edema Pulmonar , Servicio de Urgencia en Hospital , Glucosa , HumanosRESUMEN
BACKGROUND AND AIMS: Currently, the distinction between AMI and cardiac noncoronary artery disease (CNCD) remains a challenge in clinical practice. Our aim was to evaluate the diagnostic role of high-sensitivity cardiac troponin T (hs-cTnT) level at presentation and its change within the first hour to distinguish AMI from CNCD. METHODS: hs-cTnT was measured at presentation and after 1 h in 110 consecutive Chinese patients with symptoms suggestive of AMI within 12 h from symptom onset. Receiver-operating characteristics (ROC) analysis was used to estimate the diagnostic accuracy of hs-cTnT. RESULTS: Patients with AMI had higher presentation values of hs-cTnT and higher absolute changes in the first h than patients with CNCD. The diagnostic accuracy of hs-cTnT at presentation for the distinction between patients with AMI and CNCD as quantified by the area under the receiver-operating characteristics curve (AUC) was 0.88. The discriminatory power of Δhs-cTnT 0-1 h was higher for absolute (AUC, 0.89; 95% CI, 0.83-0.94) compared to relative (AUC, 0.64; 95% CI, 0.60-0.73) changes. Combining presentation values of hs-cTnT at presentation with absolute changes in the first h increased the AUC to 0.93 (p < 0.001 for comparison with AUC of 0 h hs-cTnT). CONCLUSIONS: Overall, our results suggest that the combined use of presentation values of hs-cTnT and its absolute change in the first hour discriminates well between patients with AMI and CNCD, further confirming the role of hs-cTnT as a biomarker for the early diagnosis of AMI.
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Infarto del Miocardio/diagnóstico , Troponina T/sangre , Anciano , Biomarcadores/sangre , Diagnóstico Diferencial , Diagnóstico Precoz , Femenino , Cardiopatías/sangre , Cardiopatías/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/sangre , Estudios Prospectivos , Curva ROCRESUMEN
Myocardial infarction (MI) is one of the leading causes of death worldwide and Mesenchymal Stem Cells (MSCs) transplantation has been considered a promising therapy. Recently, it was reported that the therapeutic effectiveness of MSCs is dependent on the age of the donor, yet the underlying mechanism has not been thoroughly investigated. This study was designed to investigate whether this impaired therapeutic potency is caused by an increased susceptivity of MSCs from old donors to reactive oxygen species (ROS). The MSCs were isolated from the subcutaneous inguinal region of young (8-10 weeks) and old (18 months) Sprague-Dawley (SD) rats. By exposing these MSCs to H2O2, we found that the adhesion of MSCs from old donors was damaged more severely. Specifically, decreased expression of integrin and reduced phosphorylation of focal adhesion kinase Src and FAK were observed. Furthemore, H2O2 triggered an increased apoptosis of MSCs from old donors. To study the viability and therapeutic potency of MSCs from young and old donors in vivo, these MSCs were transplanted into acute MI model rats. We observed a more rapidly decreased survival rate of the old MSCs in the infarct region, which may be caused by their increased susceptivity to the micro-environmental ROS, as transplantation of the old MSCs with N-acetyl-L-cysteine (NAC), a ROS scavenger, protected them. The low viability of engrafted old MSCs consequently impaired their therapeutic effectiveness, judging by the histology and function of heart. Our study may help to understand the mechanism of MSCs-host interaction during MI, as well as shed light on the design of therapeutic strategy in clinic.
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Envejecimiento/fisiología , Trasplante de Células Madre Mesenquimatosas , Infarto del Miocardio/terapia , Estrés Oxidativo/fisiología , Especies Reactivas de Oxígeno/toxicidad , Acetilcisteína/uso terapéutico , Animales , Apoptosis , Adhesión Celular , Depuradores de Radicales Libres/uso terapéutico , Corazón/efectos de los fármacos , Corazón/fisiopatología , Peróxido de Hidrógeno/toxicidad , Integrinas/metabolismo , Masculino , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/fisiología , Infarto del Miocardio/fisiopatología , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Sprague-DawleyRESUMEN
OBJECTIVE: To investigate regulatory effect of Acheron (Achn) on proliferation and apoptosis of human vascular endothelial cell. METHODS: (1) Eahy926 cells were cultured in serum-free DMEM medium (96-well plates) and were divided into Achn inhibition group (transfected with plasmid psi-Achn), psi4.1 group (transfected with psi4.1 empty vector), Achn induction group (transfected with pcDNA-Achn), pcDNA3.1 group (transfected with pcDNA3.1 empty vector), cotransfection group [cotransfected with pcDNA-Achn + psi-calcium/calmodulin-dependent serine protein kinase (CASK)], blank control group (treated with PBS) according to the random number table (the same method below). The cell proliferation was determined by MTT assay at post transfection hour (PTH) 1, 24, 48, 72, with expression of absorbance value. (2) Total protein of Eahy926 cells were extracted and quantitated by BCA assay, and then they were divided into Achn antibody precipitation group (100 µg protein), CASK antibody precipitation group (100 µg protein), IgG antibody group (100 µg protein), Western blot group (20 µg protein). Achn and CASK protein levels were determined by immunoprecipitation and Western blot. (3) Synchronously cultured Eahy926 cells were divided into LPS induction group (treated with 5 mol/L LPS), Achn transfection group (transfected with pcDNA-Achn), cotransfection group (cotransfected with psi-CASK and pcDNA-Achn), KCl group (treated with 5 mol/L KCl), and blank control group (treated with 5 mol/L PBS). Cells in transfection groups were stimulated by LPS for 12 hours after PTH 24. Caspase-3 protein level was detected by immunohistochemistry. (4) Synchronously cultured Eahy926 cells were divided into Achn inhibition group (transfected with psi-Achn vector), Achn induction group (transfected with pcDNA-Achn vector), and blank control group (treated with PBS). Apoptosis rate was determined by FITC/PI with flow cytometry. Data were processed with one-way analysis of variance and t test. RESULTS: (1) The cell proliferation in Achn inhibition group was lower than that in psi4.1 group from PTH 24, and the differences were statistically significant at PTH 48, 72 (with t value respectively 10.777, 6.112, P values all below 0.05). The cell proliferation in Achn induction group during PTH 24-72 were higher that in pcDNA3.1 group (with t value respectively 5.367, 6.053, 9.831, P values all below 0.05). The cell proliferation in cotransfection group at PTH 48, 72 were significantly lower than that in Achn induction group (with t value respectively 5.481, 9.517, P values all below 0.05). (2) Achn protein was detected in CASK antibody precipitation group while CASK protein was also detected in Achn antibody precipitation group. (3) Caspase-3 level in Achn transfection group was lower [(15.6 ± 0.5)%] as compared with that in LPS induction group [(32.8 ± 2.6)%, t = 10.083, P < 0.05], and that in cotransfection group showed further inhibition [(7.0 ± 2.0)%, t = 9.827, P < 0.01]. (4) Apoptosis rate in Achn inhibition group [(45.6 ± 10.9)%] was higher than that in blank control group [(13.2 ± 4.3) %, t = 7.043, P < 0.05]; while that in Achn induction group [(5.3 ± 2.9)%] was lower than that in blank control group (t = 6.499, P < 0.05). CONCLUSIONS: Achn can promote human vascular endothelial cell proliferation, and inhibit its apoptosis induced by LPS or burn serum, and the effect is related to CASK.
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Apoptosis , Autoantígenos/metabolismo , Proliferación Celular , Células Endoteliales/citología , Ribonucleoproteínas/metabolismo , Autoantígenos/genética , Línea Celular , Guanilato-Quinasas/metabolismo , Humanos , Ribonucleoproteínas/genética , Transfección , Antígeno SS-BRESUMEN
OBJECTIVE: To study the effect of intensive insulin therapy on serum high mobility group box 1 (HMGB1) levels and its relationship with the prognosis in early phase of severe trauma. METHODS: Eighty severe trauma patients [injury severity score (ISS)≥ 16] were divided into groups according to injury to matched anatomical regions. Forty patients of intensive therapy group were given early intensive insulin therapy, while another 40 patients of the conventional treatment group received routine treatment based on clinical experience with insulin treatment. The insulin dose and the blood glucose levels were recorded within 72 hours after treatment. The relationship between HMGB1 levels and prognosis was analyzed by testing serum HMGB1 levels at 24, 36, 48, 60 or 72 hours after treatment, and clinical terminal events such as multiple organ dysfunction syndrome (MODS) and death rate within 1 week were recorded. Results The insulin dose of intensive therapy group was significantly greater than that of conventional treatment group following the blood glucose levels were significantly lower than those of the conventional treatment group after treatment for 72 hours. The levels of HMGB1 (µg/L) lowered after intensive insulin therapy for 36 hours , and were significantly lower than those of conventional treatment group at 36, 48, 60 and 72 hours after intensive treatment (36 hours: 41.3 ± 9.5 vs. 52.7 ± 11.5, 48 hours: 48.6 ± 17.6 vs. 124.1 ± 22.9, 60 hours: 47.7 ± 23.3 vs. 132.9 ± 33.4, 72 hours: 54.3 ± 26.3 vs. 140.6 ± 16.5, P <0.05 or P <0.01). The incidence of MODS and mortality in intensive therapy group was respectively significantly lower than that of the conventional treatment group (20.0% vs. 55.0%, 10.0% vs. 30.0%, both P <0.05). In conventional treatment group the patients with HMGB1 ≥ 132.26 µg/L ( n =22) occurred MODS, and those with HMGB1<132.26 µg/L ( n =18) did not occur MODS. The HMGB1 levels in death patients ( n =12) were ≥ 132.26 µg/L. CONCLUSION: Early intensive insulin treatment could probably reduce MODS and mortality by inhibiting stress hyperglycemia and serum HMGB1 levels effectively. Serum HMGB1 of severe trauma patients can be used for the clinical indicator of prognosis.
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Proteína HMGB1/metabolismo , Insulina/uso terapéutico , Heridas y Lesiones/tratamiento farmacológico , Heridas y Lesiones/metabolismo , Adolescente , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Índice de Severidad de la Enfermedad , Heridas y Lesiones/diagnóstico , Adulto JovenRESUMEN
The purpose of the present study is to test whether chemically extracted acellular nerve segments can be used to repair the sciatic nerve gap. Fifteen canines were divided into acellular nerve allografting group (ANG, six canines), autografting group (AG, six canines), and fresh nerve allografting group (FNG, three canines). The sciatic nerves on the right side of the animals were exposed, and 5-cm-long segments of the nerves were removed from the midthigh level and replaced by the three types of grafts. At 6 months after grafting, all animals in the ANG and AG had similar patterns of right posterior limb gait cycle and right ankle movements. Moreover, the animals in the ANG and AG had similar nerve regeneration, with dense regeneration fibers in the distal tibial nerves and obvious motor end plates in the target muscle. But in FNG, the area surrounding the graft was scarred as the result of inflammation, and there was a brown central area where there was little nerve regeneration. All of the above shows that chemical acellular nerve allografting can be used to repair a gap as long as 5 cm in the continuity of the sciatic nerve in canines and has similar effects to autografting.