ObjectiveTo explore the academic characteristics of contemporary renowned Chinese medicine masters in treating diabetic kidney disease （DKD） from the perspectives of principles， methods， formulas， and medications. MethodsIn strict accordance with the Systematic Review of Text and Opinion （SrTO） process developed by the Joanna Briggs Institute （JBI）， an Australian evidence-based healthcare center， the databases including China National Knowledge Infrastructure （CNKI）， VIP Database， Wanfang Data， and China Biomedical Literature Service System （SinoMed） were searched. Based on predefined inclusion and exclusion criteria， text information extraction， quality evaluation， and text information synthesis were conducted sequentially. The data were analyzed and presented in the form of text and figures. ResultsA total of 215 articles related to 43 contemporary renowned experts in the fields of Chinese medicine nephrology and endocrinology were included. The study found that the academic thoughts of these masters in the treatment of DKD are extensive， involving multiple levels such as disease understanding， therapeutic strategies， formula application， and medication use. In terms of disease understanding， the primary pathogenesis is characterized by deficiency in the root and excess in the manifestation. It is emphasized that internal factors， such as congenital endowment deficiency， interact with external factors such as improper diet， emotional disturbances， invasion of exogenous pathogens， and delayed or inappropriate treatment， to jointly induce the disease. This further gives rise to various pathogenetic theories， including obstruction of renal collaterals by blood stasis， toxin-induced damage to renal collaterals， latent wind disturbing the kidney， and internal heat leading to mass formation. In terms of therapeutic strategies and medication use， the principal treatment method is to replenish Qi and nourish Yin. Stage-based and syndrome-differentiated treatments are advocated. Flexible use of insect-derived drugs and wind-dispelling drugs is emphasized， along with proficiency in applying classical formulas and drug pairs. Integrated internal and external treatments， as well as the combined application of multiple therapeutic approaches， are commonly employed for comprehensive management. Meanwhile， the concept of "preventive treatment of disease" is upheld， and individualized long-term management of patients is advocated. ConclusionThrough the SrTO process， the academic thoughts of contemporary renowned Chinese medicine masters in the treatment of DKD have been systematically and standardly synthesized， providing a scientific and standardized basis for future theoretical exploration.

ObjectiveTo explore the academic characteristics of contemporary renowned Chinese medicine masters in treating diabetic kidney disease （DKD） from the perspectives of principles， methods， formulas， and medications. MethodsIn strict accordance with the Systematic Review of Text and Opinion （SrTO） process developed by the Joanna Briggs Institute （JBI）， an Australian evidence-based healthcare center， the databases including China National Knowledge Infrastructure （CNKI）， VIP Database， Wanfang Data， and China Biomedical Literature Service System （SinoMed） were searched. Based on predefined inclusion and exclusion criteria， text information extraction， quality evaluation， and text information synthesis were conducted sequentially. The data were analyzed and presented in the form of text and figures. ResultsA total of 215 articles related to 43 contemporary renowned experts in the fields of Chinese medicine nephrology and endocrinology were included. The study found that the academic thoughts of these masters in the treatment of DKD are extensive， involving multiple levels such as disease understanding， therapeutic strategies， formula application， and medication use. In terms of disease understanding， the primary pathogenesis is characterized by deficiency in the root and excess in the manifestation. It is emphasized that internal factors， such as congenital endowment deficiency， interact with external factors such as improper diet， emotional disturbances， invasion of exogenous pathogens， and delayed or inappropriate treatment， to jointly induce the disease. This further gives rise to various pathogenetic theories， including obstruction of renal collaterals by blood stasis， toxin-induced damage to renal collaterals， latent wind disturbing the kidney， and internal heat leading to mass formation. In terms of therapeutic strategies and medication use， the principal treatment method is to replenish Qi and nourish Yin. Stage-based and syndrome-differentiated treatments are advocated. Flexible use of insect-derived drugs and wind-dispelling drugs is emphasized， along with proficiency in applying classical formulas and drug pairs. Integrated internal and external treatments， as well as the combined application of multiple therapeutic approaches， are commonly employed for comprehensive management. Meanwhile， the concept of "preventive treatment of disease" is upheld， and individualized long-term management of patients is advocated. ConclusionThrough the SrTO process， the academic thoughts of contemporary renowned Chinese medicine masters in the treatment of DKD have been systematically and standardly synthesized， providing a scientific and standardized basis for future theoretical exploration.

ObjectiveType 2 diabetes mellitus (T2DM) often causes severe hepatic metabolic complications, dominated by metabolic associated fatty liver disease (MAFLD). Persistent hepatic steatosis and oxidative stress further trigger steatohepatitis and progressive liver damage, increasing the mortality risk of diabetic patients. Aerobic exercise effectively improves hepatic lipid metabolism and antioxidant capacity, but poor patient adherence restricts its long-term clinical application. Mitochondrial-derived mitochondrial open reading frame of the 12S rRNA type-c (MOTS-c) is a key peptide regulating insulin sensitivity and hepatic redox homeostasis. This study aimed to explore the protective mechanism of MOTS-c against T2DM-related liver injury and its combined beneficial effect with aerobic exercise via the NRF2/PPARγ signaling axis. This study aimed to investigate whether MOTS-c cooperates with aerobic exercise to alleviate T2DM-associated hepatic oxidative stress and metabolic dysfunction by activating the NRF2/PPARγ axis, and to clarify the molecular and transcriptomic characteristics of their combined intervention. MethodsStable MOTS-c overexpression and knockdown HepG2 cell lines were constructed using lentiviral transfection. An oleic acid-induced cellular lipid accumulation model and NRF2-knockout cell model were applied to verify the NRF2-dependent mechanism ofMOTS-c. Intracellular lipid deposition, triglyceride levels, antioxidant enzyme activities, and the expression of NRF2/PPARγ pathway-related genes and proteins were detected. In vivo, a T2DM rat model with obvious hepatic steatosis was established via a high-fat and high-sucrose diet combined with streptozotocin injection. Model rats received aerobic exercise, MOTS-c intraperitoneal injection, or combined intervention. We detected systemic glycolipid metabolic indicators, hepatic histopathological changes, and the expression of core proteins in the hepatic NRF2/PPARγ axis. Hepatic transcriptomic sequencing was performed to screen differentially expressed genes (DEGs) and enrich key pathways co-regulated by MOTS-c and aerobic exercise. ResultsCellular results showed that MOTS-c overexpression significantly reduced oleic acid-induced lipid deposition, enhanced antioxidant enzyme activity, and upregulated NRF2 and PPARγ expression. Conversely, MOTS-c knockdown aggravated hepatic lipid accumulation and oxidative damage and inhibited NRF2/PPARγ pathway activation. NRF2 knockout completely eliminated the protective effects of MOTS-c on lipid metabolism and redox balance, confirming its NRF2-dependent regulatory mechanism. In T2DM rats, both MOTS-c supplementation and aerobic exercise effectively improved insulin resistance, corrected glycolipid metabolic disorders, and alleviated hepatic steatosis, while consistently activating the hepatic NRF2/PPARγ axis. Compared with single intervention, the combined treatment showed a better improvement trend in hepatic metabolic and oxidative injury, without definitive synergistic effects. Transcriptomic analysis revealed that the co-regulated DEGs of MOTS-c and aerobic exercise were primarily enriched in lipid metabolism and PPAR signaling pathways, with multiple antioxidant and lipid-regulating genes significantly modulated by combined intervention. ConclusionMOTS-c exhibits obvious exercise-mimetic hepatoprotective effects in T2DM. It activates the hepatic NRF2/PPARγ axis to strengthen antioxidant defense, stabilize lipid metabolism, and relieve T2DM-associated hepatic steatosis and oxidative damage. Furthermore, MOTS-c produces additive beneficial effects with aerobic exercise, showing a superior intervention trend on diabetic liver dysfunction. This study identifies the NRF2/PPARγ axis as the core mechanism of MOTS-c-regulated hepatic protection, elucidates the transcriptomic basis of combined intervention, and provides a reliable theoretical basis and potential therapeutic target for clinical intervention in T2DM-complicated MAFLD.

Objectives:This study aims to evaluate the causal relationship between plasma proteins and myocardial infarction(MI)using two-sample bidirectional Mendelian randomization(MR)analysis,identify key biomarkers,and validate their expression.Methods:The study utilized publicly available genome-wide association study(GWAS)data of 4 907 plasma proteins as the exposure factor,with single nucleotide polymorphisms(SNPs)as instrumental variables,and four MI datasets as outcomes.Two-sample MR analysis was performed using the inverse variance weighted(IVW)method,complemented by simple model,weighted model,weighted median estimator(WME),and MR-Egger regression methods to assess the causal relationship between exposure factors and outcomes.Venn diagrams and word clouds were used to screen proteins associated with MI as candidate biomarkers.Reverse MR analysis was conducted to evaluate reverse causality.Sensitivity analysis was performed to assess the robustness of the results.Immunohistochemistry(IHC)was used to validate the expression of proteasome activator subunit 1(PSME1)and vacuolar protein sorting 29(VPS29)in the aorta of mice,and enzyme-linked immunosorbent assay(ELISA)was used to verify the expression of PSME1 and VPS29 in plasma from patients with acute myocardial infarction(AMI).Results:The two-sample MR analysis indicated that PSME1 was significantly negatively associated with myocardial infarction in all four datasets,with OR(95%CI)of 0.684(0.557-0.839),0.990(0.987-0.993),0.579(0.448-0.748),and 0.993(0.990-0.996),respectively,with all P<0.001.Similarly,VPS29 also showed a significant negative association with MI in all four datasets,with OR(95%CI)of 0.902(0.862-0.945),0.998(0.997-0.999),0.866(0.808-0.929),and 0.998(0.997-0.999),respectively,with all P<0.001.Reverse MR analysis did not detect reverse causality,and sensitivity analysis confirmed the robustness of the results.IHC results showed significantly reduced expression of PSME1 and VPS29 in the aortas of AMI mice with an atherosclerotic background compared to control mice(both P<0.05).ELISA results indicated significantly lower plasma levels of PSME1 and VPS29 in AMI patients compared to healthy controls(both P<0.05).Conclusions:Higher levels of PSME1 and VPS29 are negatively associated with the risk of MI,suggesting that PSME1 and VPS29 may serve as protective biomarkers for cardiovascular diseases.

BACKGROUND:The cryopreservation technology enables tissues/cells to be stored for a long time in a low-temperature environment while maintaining the integrity of their activity and function,which is of great significance for the construction of cell therapy,tissue engineering and biological sample banks.Cryoprotective agents often contain dimethyl sulfoxide and serum.To avoid the toxic side effects of dimethyl sulfoxide,the complexity of serum components and immune responses,although some finished cryoprotective agents have been marketed,they are faced with many difficulties such as high cost and limited application.Therefore,there is an urgent need to develop a cryoprotective agent with clear components and the ability to solve the above problems.OBJECTIVE:To evaluate the effects of a novel cryoprotectant on cryopreservation efficiency of different tissue and cell sources.METHODS:By applying the novel cryoprotectant as an experimental group with the commercially available and widely used cryoprotectant(control group)to umbilical cord Wharton's jelly tissue,umbilical cord mesenchymal stem cells,umbilical cord blood/peripheral blood mononuclear cells,NK and CIK cells,comparative analyses were conducted in terms of cell morphology,number,viability,surface markers,differentiation potential,and cell-killing toxicity assay before cryopreservation and after resuscitation thawing.We confirmed the cryopreservation effect of the new cryoprotectant and its potential application value.RESULTS AND CONCLUSION:(1)The novel cryoprotectant facilitated the normal growth of cryopreserved Wharton's jelly tissue upon recovery,exhibiting mesenchymal stem cell morphology.No significant differences were observed between the experimental and control groups in terms of cell recovery rate,surface markers,and differentiation potential.(2)There was no significant difference in the number and viability of cells between the experimental group and the control group after cryopreservation of cord blood/peripheral blood mononuclear cells,and the cryo-resuscitated cell numbers and viability of derived NK cells/CIK cells did not show significant difference between the experimental and control groups.(3)For NK cells derived and differentiated from cord blood/peripheral blood mononuclear cells,there was no significant difference in the proportion of CD56+CD16+cell subpopulations between the experimental group and the control group.For CIK cells derived and differentiated from cord blood/peripheral blood mononuclear cells,there was no significant difference in the proportions of CD3+CD8+and CD3+CD56+cell subpopulations between the experimental group and the control group.(4)In terms of cytotoxicity testing,when the effective-target ratio of immune cells and melanoma cell line Mel624 was 20:1,whether it was NK cells/CIK cells derived from cord blood or peripheral blood mononuclear cells,there was no significant difference in the tumoricidal activity of cells between the experimental group and the control group.These findings suggest that the novel cryoprotectant can replace existing commercially available and widely used cryoprotectants,and is applicable to Wharton's jelly tissue,umbilical cord mesenchymal stem cells,umbilical cord blood/peripheral blood mononuclear cells,as well as NK and CIK cells,providing a solid technical foundation for the scaling,standardization,and commercialization of universal cryoprotectants.

Objective:To investigate the clinical manifestation, therapy, and prognosis of Susac syndrome and enhance the understanding of this disease.Methods:A case summary was made.The clinical data of two siblings with Susac syndrome treated at Children′s Medical Center, Peking University First Hospital in January 2024 were summarized.Reported cases of pediatric Susac syndrome were reviewed.Results:The onset of the disease in the two siblings was at the age of 3.00 and 6.75 years, with recurrent headaches, tinnitus, hearing loss and encephalopathy symptoms.Cranial magnetic resonance imaging showed multiple cerebral microbleeding and microinfarction lesions, " snowball like" in the corpus callosum and diffuse white matter edema in the brain.Audiometry revealed sensorineural hearing loss.In one case, ophthalmic fluorescein angiography revealed ischemic changes due to branch retinal artery occlusions.No pathogenic variants were detected in gene testing.This child was diagnosed with Susac syndrome, and the symptoms were improved after treatment with Corticosteroids and Rituximab.No relapse was observed during the 9-month follow-up.A total of 20 pediatric cases of Susac syndrome were retrieved, including 18 reported previously and 2 cases from this study.There were 2 boys and 18 girls, with the age of onset ranging from 2.5 to 17.0 years.The common initial symptoms included headache (19 cases), vertigo and tinnitus or hearing loss (9 cases), and vision impairment or visual field defect (4 cases). The symptoms were improved after immunotherapy.Conclusions:With a low incidence, Susac syndrome is rare in children and difficult to diagnose.There may be a genetic predisposition in such disease.Early diagnosis and immunotherapy can low the relapse and improve the prognosis.

Objective To analyze the characteristics of brain functional networks in patients with post-stroke aphasia(PSA)during a Chinese word-picture matching task.Methods A total of 18 PSA patients in Dongzhimen Hospital from January,2018 to December,2021 were enrolled as PSA group,and nine healthy controls matched for sex,age and education were included as the control group.The Chinese Rehabilitation Research Center Aphasia Examination(CRRCAE)and task-state electroencephalogram(EEG)data based on a Chinese word-picture matching paradigm were collected.Source-space reconstruction was applied to EEG signals to construct functional connectivity matrices.Graph-theoretical analysis was used to com-pute global network properties,and network-based statistics were used to identify subnetwork differences be-tween groups.Correlations between global network properties and CRRCAE subscales were further analyzed.Results The global properties of each frequency band were higher in the control group(unmatched)than in PSA group and the control group(matched)(P<0.01).Subnetworks connections enhanced in the alpha band in the frontal,temporal,parietal,occipital lobes and limbic system(23 nodes,31 edges,P<0.05),and weakened connections in the frontal,temporal,limbic system and basal ganglia(20 nodes,26 edges,P<0.01)in PSA group;in the beta band,subnetwork connections enhanced in the frontal,temporal lobes,basal ganglia and limbic system(15 nodes,23 edges,P<0.01);in the theta band,subnetwork connections weakened in the left frontal and temporal lobes(10 nodes,11 edges,P<0.05),and enhanced in the right frontal and temporal lobes(7 nodes,7 edges,P<0.05).Under the matched condition,the global properties of the alpha and beta bands in PSA group were positive-ly correlated with reading(r=0.511 to 0.650,all P<0.05),and the local efficiency and average clustering coeffi-cient of the theta band were negatively correlated with repetition(r=-0.500 to-0.505,all P<0.05);under the unmatched condition,the local efficiency and average clustering coefficient of the alpha and beta bands in PSA group were positively correlated with reading(r=0.522 to 0.642,all P<0.05),and the global efficiency and lo-cal efficiency of the alpha band were positively correlated with auditory comprehension(r=0.486 to 0.496,all P<0.05).The comparison between the task state and the resting state further revealed that compensatory connec-tion enhanced in the alpha band in the frontal lobe and limbic system(6 nodes,5 edges,P<0.05)and in the beta band in the frontal,temporal,parietal,occipital lobes and limbic system(38 nodes,52 edges,P<0.01)in PSA pa-tients.Conclusion The core network damage characteristics of PSA patients are abnormally decreased global properties across multiple frequency bands and frequency-specific abnormal network reorganization,suggesting the overall brain network efficiency decline coexists with local compensation.This provides an objective basis for the neuroelec-trophysiological evaluation and targeted intervention of PSA.

Objective:To evaluate the role of ferroptosis in reduction of intestinal ischemia-reperfusion injury (IRI) by sodium butyrate pretreatment in mice.Methods:Thirty SPF healthy male C57BL/6 mice, aged 6-8 weeks, weighing 20-23 g, were divided into 5 groups ( n=6 each) using a random number table method: sham operation group (S group), intestinal IRI group (IR group), intestinal IRI + sodium butyrate pretreatment group (IN group), intestinal IRI + sodium butyrate pretreatment+ FER-1 group (INF group), and intestinal IRI + sodium butyrate pretreatment + Erastin group (INE group). The intestinal IRI model was established by occluding the superior mesenteric artery for 45 min followed by reperfusion for 30 min in S group. In IN, INF and INE groups, sodium butyrate was administered by gavage at a dose of 500 mg/kg daily at 1 week before developing the model, while the equal volume of normal saline was given by gavage in the other two groups. The ferroptosis inhibitor FER-1 5 mg/kg and ferroptosis agonist Erastin 30 mg/kg were intraperitoneally injected at 1 h prior to ischemia in INF and INE groups. Mice were sacrificed after anesthesia at the end of reperfusion to obtain small intestinal tissues for examination of the pathological changes (using light microscopy) which were scored according to Chiu and for determination of the contents of Fe 2+, malondialdehyde (MDA), glutathione (GSH) and glutathione disulfide(GSSG) (by enzyme-linked immunosorbent assay), expression of glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11), and ferritin heavy chain 1 (FTH1) (by Western blot). The ratio of GSH to GSSG was calculated. Results:Compared to S group, Chiu′s scores and contents of MDA and Fe 2+ were significantly increased, the expression of GSH, GPX4, FTH1 and SLC7A11 was down-regulated, and the GSH/GSSG ratio was decreased in IR group ( P<0.001). Compared to IR group, Chiu′s scores and contents of MDA and Fe 2+ were significantly decreased, the expression of GSH, GPX4, FTH1 and SLC7A11 was up-regulated, and the GSH/GSSG ratio was increased in IN and INF groups ( P<0.001). Compared to IN group, Chiu′s scores and contents of MDA and Fe 2+ were significantly increased, the expression of GSH, GPX4, FTH1 and SLC7A11 was down-regulated, and the GSH/GSSG ratio was decreased in INE group ( P<0.001). Conclusions:Ferroptosis is involved in sodium butyrate pretreatment-induced reduction of intestinal I/RI in mice.

Objective:To evaluate the role of ferroptosis in reduction of intestinal ischemia-reperfusion injury (IRI) by sodium butyrate pretreatment in mice.Methods:Thirty SPF healthy male C57BL/6 mice, aged 6-8 weeks, weighing 20-23 g, were divided into 5 groups ( n=6 each) using a random number table method: sham operation group (S group), intestinal IRI group (IR group), intestinal IRI + sodium butyrate pretreatment group (IN group), intestinal IRI + sodium butyrate pretreatment+ FER-1 group (INF group), and intestinal IRI + sodium butyrate pretreatment + Erastin group (INE group). The intestinal IRI model was established by occluding the superior mesenteric artery for 45 min followed by reperfusion for 30 min in S group. In IN, INF and INE groups, sodium butyrate was administered by gavage at a dose of 500 mg/kg daily at 1 week before developing the model, while the equal volume of normal saline was given by gavage in the other two groups. The ferroptosis inhibitor FER-1 5 mg/kg and ferroptosis agonist Erastin 30 mg/kg were intraperitoneally injected at 1 h prior to ischemia in INF and INE groups. Mice were sacrificed after anesthesia at the end of reperfusion to obtain small intestinal tissues for examination of the pathological changes (using light microscopy) which were scored according to Chiu and for determination of the contents of Fe 2+, malondialdehyde (MDA), glutathione (GSH) and glutathione disulfide(GSSG) (by enzyme-linked immunosorbent assay), expression of glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11), and ferritin heavy chain 1 (FTH1) (by Western blot). The ratio of GSH to GSSG was calculated. Results:Compared to S group, Chiu′s scores and contents of MDA and Fe 2+ were significantly increased, the expression of GSH, GPX4, FTH1 and SLC7A11 was down-regulated, and the GSH/GSSG ratio was decreased in IR group ( P<0.001). Compared to IR group, Chiu′s scores and contents of MDA and Fe 2+ were significantly decreased, the expression of GSH, GPX4, FTH1 and SLC7A11 was up-regulated, and the GSH/GSSG ratio was increased in IN and INF groups ( P<0.001). Compared to IN group, Chiu′s scores and contents of MDA and Fe 2+ were significantly increased, the expression of GSH, GPX4, FTH1 and SLC7A11 was down-regulated, and the GSH/GSSG ratio was decreased in INE group ( P<0.001). Conclusions:Ferroptosis is involved in sodium butyrate pretreatment-induced reduction of intestinal I/RI in mice.

Objective:To explore the clinical efficacy of anterolateral thigh perforator flap (ALTPF) in treatment of extensive wound of Degree IV burns in limbs.Methods:A retrospective analysis was conducted on 9 patients who had extensive wound of Degree IV burns in limbs caused by stove burns admitted to Department of Burns and Plastic Surgery, the 988th Hospital of the Joint Logistics Support Force of the Chinese PLA between January 2017 and January 2024. Among the patients, there were 8 males and 1 female, aged between 36 and 63 years. Three patients had the wound from anterior leg to dorsal foot, 3 from leg down to ankle, 1 from forearm to hand and 2 from arm to forearm. Area of burns ranged from 20 cm × 15 cm to 30 cm × 25 cm, and all patients were treated by free ALTPF. According to whether the main artery at the recipient site was feasible for direct anastomosis with the vessels carried in flap, 4 patients were treated by bilateral parallel ALTPFs, and 5 were treated by unilateral ultra-long internally supercharged ALTPF. A total of 13 ALTPFs were harvested, with individual flap size at 20 cm × 8 cm to 46 cm × 12 cm. Donor sites were directly sutured. Time for flap harvesting, flap survival and wound healing time were records. Scheduled postoperative follow-up was conducted at outpatient clinic and via telephone interviews to evaluate functional recovery. Follow-up assessments included evaluation of flap condition, two-point discrimination (TPD), recovery of joint function at recipient sites, flap appearance and donor site recovery.Results:The time for flap harvest was 1.0 to 4.5 hours. All 13 ALTPFs successfully survived. The time from surgery to healing of recipient sites was 18 to 72 days, and all donor sites healed. Over the postoperative follow-up that lasted for 6 to 34 months, the recipient sites had found with good cosmetic outcomes, without osteomyelitis or deep tissue infection. Four ALTPFs in 2 patients were found swelling, which were revised at 6 months after surgery. Four ALTPFs in other 2 patients had pigment deposition at edges. One ALTPF was scalded, which healed after dressing changes but left with patchy scars. The remaining ALTPFs were soft, elastic, free from pain and well-perfused, with regained protective sensation at S 3. However, all of the ALTPFs failed to detect TPD. Six patients with lower limb injuries were evaluated using the American Orthopedic Foot and Ankle Society (AOFAS) ankle hindfoot scoring system: 2 patients were rated as excellent and 4 were rated as good. Three patients with upper limb injuries were evaluated using Evaluation Trial Standards of Upper Limb Partial Functional of Hand Surgery of Chinese Medical Association: 1 patient was rated as excellent and 2 were rated as good. Only linear scars left at the 13 donor sites, with normal blood supply to the distal limbs, and without restrictions in range of motion of knee joints nor muscle strength of quadriceps. Conclusion:The ALTPF offers advantages such as anatomical consistency, reliable blood supply and flexible combination in treatment of extensive wound of Degree Ⅳ burns in limbs. It is an ideal surgical procedure for treatment of large soft tissue defects of extremities.