Objective:To investigate the efficacy of a decellularized extracellular matrix (dECM)-quaternized chitosan (QCS)-gelatin (Gel) composite scaffold loaded with growth factors in repairing diabetic foot wounds in a rat model.Methods:A dECM-QCS-Gel composite scaffold (referred to as GDQ scaffold) was fabricated using a 3D bioprinter. Forty 8-week-old male Sprague-Dawley (SD) rats were selected to establish a diabetic foot wound model with a diameter of approximately 1 cm. Based on the treatment methods for diabetic foot wounds, the rats were divided into five groups: Control group (no treatment), Exosome group (wound covered with exosome suspension), Exosome+GDQ group (wound covered with GDQ scaffold loaded with exosome suspension), GDQ group (wound covered with GDQ scaffold alone), and Growth factor+GDQ group (wound covered with GDQ scaffold loaded with recombinant human basic fibroblast growth factor suspension). The wound healing rate was measured. Histological analysis was performed by HE staining and Masson staining. ELISA kits were used to determine the levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, and IL-10 in wound tissues from each group. Protein expression levels of MIP-1 and MIP-2 genes were also assessed.Results:The wound healing rate of the growth factor+GDQ group on the 21st d was 94.89%±1.21%, which was higher than that of the exosome+GDQ group ( P<0.05). With increasing repair time, the expression levels of TNF-α, IL-1β and IL-6 in each group all decreased, while IL-10 increased in all groups ( P<0.05). Among them, the exosome+GDQ group (TNF-α: 46.54±1.26 pg/ml, IL-1β: 225.79±7.29 pg/ml, IL-6: 142.81±4.02 pg/ml and IL-10: 117.36±0.95 pg/ml, P<0.001) and the growth factor+GDQ group (TNF-α : 40.01±1.64 pg/ml, IL-1β: 209.15±2.98 pg/ml, IL-6: 138.50±2.61 pg/ml and IL-10: 127.66±1.23 pg/ml, P<0.05); The levels of TNF-α and IL-1β in the exosome+GDQ group were both lower than those in the exosome+GDQ group ( P<0.05), and IL-10 was higher than that in the exosome+GDQ group ( P<0.05). On the 7th d the control group showed the highest expression levels of MIP-1α and MIP-2. All other groups had lower levels, with the growth factor+GDQ group showing the lowest among them. On the 21st d, the inflammatory protein expression in the growth factor+GDQ group had further decreased and remained lower than in all other experimental groups. Conclusions:The GDQ composite scaffold, when combined with bioactive factors, can synergistically reduce inflammation in diabetic foot wounds and promote wound healing. The scaffold loaded with basic fibroblast growth factor demonstrated superior therapeutic efficacy compared to the scaffold loaded with exosomes.

BACKGROUND:With the increasing degree of population aging in China,the incidence of osteoporosis is rising annually.This growing demand for screening and diagnosis poses significant challenges to the healthcare system,increasing the time costs,financial burdens,and radiation exposure risks for patients.OBJECTIVE:To develop a novel interpretable prediction method based on traditional CT examination data and demographic data,aiming to reduce the number of patient examinations and enable multiple screenings from one examination.METHODS:A two-stage interpretable framework for osteoporosis prediction was designed.In the first stage,a human-computer collaborative method was used for annotating CT images,with an innovative vertebra 7-point CT value measurement technique.Patient's sex and age were used as key demographic features to enrich the model's input.In the second stage,the LightGBM model was enhanced by SHapley Additive exPlanations for quantitative analysis of feature importance,improving the interpretability of predictions and increasing clinical trust.Systematic experiments validated the effectiveness of the framework and the stability of the optimal feature set through the comparative analysis of different feature combinations with six machine learning models.To further assess the generalization ability of the model,the model was further tested on an external dataset.RESULTS AND CONCLUSION:The experiment compared six machine learning models suitable for medical applications,and the results showed that LightGBM model achieved an F1 score of 0.902 2 and an area under the curve of 0.938 7,outperforming the other models.In terms of interpretability,the clinical application credibility and operability of the model was increased by ranking and visualizing the contribution of input features to the results.Additionally,this study realized a prototype system,and testing results indicated that the system is user-friendly,capable of quickly processing data to provide prediction results,with visualized outcomes demonstrating good interpretability.This system effectively assists doctors in clinical decision-making and provides robust support for the screening and preliminary diagnosis of osteoporosis.

Objective:To investigate the efficacy of a decellularized extracellular matrix (dECM)-quaternized chitosan (QCS)-gelatin (Gel) composite scaffold loaded with growth factors in repairing diabetic foot wounds in a rat model.Methods:A dECM-QCS-Gel composite scaffold (referred to as GDQ scaffold) was fabricated using a 3D bioprinter. Forty 8-week-old male Sprague-Dawley (SD) rats were selected to establish a diabetic foot wound model with a diameter of approximately 1 cm. Based on the treatment methods for diabetic foot wounds, the rats were divided into five groups: Control group (no treatment), Exosome group (wound covered with exosome suspension), Exosome+GDQ group (wound covered with GDQ scaffold loaded with exosome suspension), GDQ group (wound covered with GDQ scaffold alone), and Growth factor+GDQ group (wound covered with GDQ scaffold loaded with recombinant human basic fibroblast growth factor suspension). The wound healing rate was measured. Histological analysis was performed by HE staining and Masson staining. ELISA kits were used to determine the levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, and IL-10 in wound tissues from each group. Protein expression levels of MIP-1 and MIP-2 genes were also assessed.Results:The wound healing rate of the growth factor+GDQ group on the 21st d was 94.89%±1.21%, which was higher than that of the exosome+GDQ group ( P<0.05). With increasing repair time, the expression levels of TNF-α, IL-1β and IL-6 in each group all decreased, while IL-10 increased in all groups ( P<0.05). Among them, the exosome+GDQ group (TNF-α: 46.54±1.26 pg/ml, IL-1β: 225.79±7.29 pg/ml, IL-6: 142.81±4.02 pg/ml and IL-10: 117.36±0.95 pg/ml, P<0.001) and the growth factor+GDQ group (TNF-α : 40.01±1.64 pg/ml, IL-1β: 209.15±2.98 pg/ml, IL-6: 138.50±2.61 pg/ml and IL-10: 127.66±1.23 pg/ml, P<0.05); The levels of TNF-α and IL-1β in the exosome+GDQ group were both lower than those in the exosome+GDQ group ( P<0.05), and IL-10 was higher than that in the exosome+GDQ group ( P<0.05). On the 7th d the control group showed the highest expression levels of MIP-1α and MIP-2. All other groups had lower levels, with the growth factor+GDQ group showing the lowest among them. On the 21st d, the inflammatory protein expression in the growth factor+GDQ group had further decreased and remained lower than in all other experimental groups. Conclusions:The GDQ composite scaffold, when combined with bioactive factors, can synergistically reduce inflammation in diabetic foot wounds and promote wound healing. The scaffold loaded with basic fibroblast growth factor demonstrated superior therapeutic efficacy compared to the scaffold loaded with exosomes.

BACKGROUND:With the increasing degree of population aging in China,the incidence of osteoporosis is rising annually.This growing demand for screening and diagnosis poses significant challenges to the healthcare system,increasing the time costs,financial burdens,and radiation exposure risks for patients.OBJECTIVE:To develop a novel interpretable prediction method based on traditional CT examination data and demographic data,aiming to reduce the number of patient examinations and enable multiple screenings from one examination.METHODS:A two-stage interpretable framework for osteoporosis prediction was designed.In the first stage,a human-computer collaborative method was used for annotating CT images,with an innovative vertebra 7-point CT value measurement technique.Patient's sex and age were used as key demographic features to enrich the model's input.In the second stage,the LightGBM model was enhanced by SHapley Additive exPlanations for quantitative analysis of feature importance,improving the interpretability of predictions and increasing clinical trust.Systematic experiments validated the effectiveness of the framework and the stability of the optimal feature set through the comparative analysis of different feature combinations with six machine learning models.To further assess the generalization ability of the model,the model was further tested on an external dataset.RESULTS AND CONCLUSION:The experiment compared six machine learning models suitable for medical applications,and the results showed that LightGBM model achieved an F1 score of 0.902 2 and an area under the curve of 0.938 7,outperforming the other models.In terms of interpretability,the clinical application credibility and operability of the model was increased by ranking and visualizing the contribution of input features to the results.Additionally,this study realized a prototype system,and testing results indicated that the system is user-friendly,capable of quickly processing data to provide prediction results,with visualized outcomes demonstrating good interpretability.This system effectively assists doctors in clinical decision-making and provides robust support for the screening and preliminary diagnosis of osteoporosis.

Objective:Exploring the clinical efficacy of using ultra-thin lobulated anterolateral thigh perforator flap(ALTPF) with retrograde separation of perforating vessels from the superficial and deep junction layer of the superficial fascia to repair large soft tissue defects in the foot.Methods:From August 2021 to November 2022, 8 patients (5 males and 3 females) were admitted to the Second Department of Hand and Foot Surgery, the Affiliated Central Hospital of Dalian University of Technology. The patients were 28 to 52 years old in age. The soft tissue defects were located in dorsal and plantar foot. At the plantar foot, the wound involved the weight-bearing area with explosion of bone, tendon or internal fixtures. The area of soft tissue defects was 6.0 cm × 5.0 cm - 16.0 cm × 8.0 cm, and the sizes of ALTPF were 8.0 cm ×5.5 cm - 18.0 cm × 8.5 cm. Preoperative high frequency CUD combined with CTA angiography were employed to locate the 2 flap perforator vessels. By keeping the perforator vessels at center and according to the soft tissue defect area and the wound shape, an ALTPF with a proper size and shape was designed in anterolateral thigh. The perforator were separated in the boundary layer between superficial and deep fascia, where it helped to obviously thin the flap. After the flap was harvested, it was further lobulated between the 2 perforators into 2 lobes after having confirmed the effective blood supply. Finally the lobulated ALTPF was transferred to covered the defect in foot. Cautions should be taken to ensure that the flap covered the weight-bearing area of foot. All the donor sites were directly sutured. Postoperative follow-up was conducted to observe the survival of flaps and the functional recovery of the reconstructed site, also to evaluate the clinical effect. Postoperative follow-up included outpatient visits and reviews over WeChat or telephone. Recovery of the ankle motor function was evaluated according to the American Orthopedic Foot and Ankle Societ (AOFAS) ankle-hind foot score scale.Results:All 8 ALTPF survived. Over 6 to 18 months (10.8 months in average) of follow-up, the transferred flaps had good blood supply, soft in texture, with good elasticity and thin in appearance. Appearance and function of donor sites recovered well, except 1 patient who had mild scar hyperplasia. The plantar flap had good abrasion resistance. No flap damage, bleeding or granulation tissue hyperplasia occurred when walking. The mean score of AOFAS ankle-hind foot score achieved 95.6.Conclusion:The application of ultra-thin lobulated ALTPF with retrograde separation of perforating vessels from the superficial fascia at the junction layer for repairing large soft tissue defects in the foot has good clinical efficacy.

Objective:To retrospectively analyze the treatment of 25 cases of lower necrotizing fasciitis.Methods:A total of 25 patients with lower limb necrotizing fasciitis (13 males and 12 females), with mean age 63 years old (48-75 years old) in Dalian Municipal Central Hospital from September 2016 to December 2020. After admission, the patient′s general physical condition was strictly evaluated, the relevant preoperative examination was improved, and the necrotizing fasciitis laboratory risk index (LRINEC) score was performed. In the absence of surgical contraindication, multiple debridement was performed, leaving the necrotic tissue removed for general bacterial culture and drug sensitivity test in parallel. After debridement, eight patients showed a large area of skin necrosis, and amputation was selected. The other 17 patients chose limb protection treatment after debridement, and adopted debridement and free skin grafting. After surgery, patients were encouraged to strengthen rehabilitation exercise to restore limb function to the maximum extent.Results:With followed up 0.6 to 3.0 years, with an average of 1.8 years. Methods include outpatient return visit, WeChat contact or telephone inquiry. The skin survived in 17 patients with mean healing time (27.5 ± 6.9) d. Eighteen patients were multiple bacterial infections and seven patients were single bacterial infections. All patients had no joint dysfunction caused by scar contracture, and reinfection in the skin grafting area.Conclusions:Necrotizing fasciitis requires early diagnosis and early treatment, with correct choice of treatment method is closely related to the patient′s prognosis.

Objective To investigate the clinical effect of free bilateral anterolateral femoral perforator flap in repairing large area soft tissue defects of foot and ankle. Methods From July, 2013 to December, 2017, 30 pa-tients (19 males and 11 females) with large soft tissue defects of ankle and foot were treated , aged 21-52 years. The defects were located in the middle and distal part of the foot and ankle, the wounds were all exposed with bone, ten-don or internal fixator, and the area of skin defect was 15 cm × 22 cm-19 cm× 28 cm. All of them were repaired by free bilateral anterolateral femoral perforator flaps. The perforating branch of bilateral flap was determined by CDU or DSA before operation. According to the area of skin defect and the shape of wound, an appropriate perforating branch flap was designed in the anterolateral thigh region. One perforating branch flap was used as the proximal series flap, the proximal vessel pedicle was anastomosed with the recipient region arteriovenous flap. The other perforating branch flap was used as the distal series flap, the artery and vein were anastomosed between the two flaps. The total area of the two flaps was 17 cm × 25 cm-23 cm × 32 cm. The survival of the flap and the functional recovery of the repair site were observed and the clinical effect was evaluated. Results There was no vascular crisis after operation, and the flaps survived. Followed-up for 5-28(mean, 13.5)months showed that the flap had good blood flow, soft texture and good elasticity, among which 4 cases were slightly bloated and improved after plastic operation. After operation, 26 cases were excellent (90-100 points), 4 cases were good (75-89 points), and the average score of AOFAS was 93.8 points. Conclusion The traffic accident of anterolateral perforating branch and the attention in the process of flap cutting and series were summarized.

Objective: To investigate the methods for qualitative pathological assessment of dynamic changes in liver fibrosis/cirrhosis after antiviral therapy in patients with chronic hepatitis B (CHB), since antiviral therapy can partially reverse liver fibrosis and cirrhosis caused by hepatitis B and semi-quantitative, rather than qualitative, pathological assessment is often used for the research on liver fibrosis regression. Methods: Previously untreated CHB patients with liver fibrosis and cirrhosis were enrolled, and liver biopsy was performed before treatment and at 78 weeks after the antiviral therapy based on entecavir. The follow-up assessment was performed once every half a year. Based on the proportion of different types of fibrous septum, we put forward the new qualitative criteria called P-I-R classification (predominantly progressive, predominantly regressive, and indeterminate) for evaluating dynamic changes in liver fibrosis. This classification or Ishak fibrosis stage was used to evaluate the change in liver fibrosis after treatment and Ishak liver inflammation score was used to evaluate the change in liver inflammation after treatment. Results: A total of 112 CHB patients who underwent liver biopsy before and after treatment were enrolled, and among these patients, 71 with an Ishak stage of ≥3 and qualified results of live biopsy were included in the final analysis. Based on the P-I-R classification, 58% (41/71) were classified as predominantly progressive, 29% (21/71) were classified as indeterminate, and 13% (9/71) were classified as predominantly regressive; there were no significant differences between the three groups in alanine aminotransferase, aspartate aminotransferase, albumin, HBeAg positive rate, HBV DNA, and liver stiffness (P < 0.05). After treatment, the proportion of predominantly progressive, indeterminate, or predominantly regressive patients changed to 11% (8/71), 11% (8/71), and 78% (55/71), respectively. Among the 35 patients who had no change in Ishak stage after treatment, 72% (25/35) were classified as predominantly regressive and had certain reductions in the Laennec score, percentage of collagen area, and liver stiffness. Conclusion This new P-I-R classification can be used to assess the dynamic changes in liver fibrosis after antiviral therapy in CHB patients.

BACKGROUND:Studies have shown that nerve grafts with Schwann cels can repair peripheral nerve defect and Schwann cels have an important role in nerve regeneration. OBJECTIVE: To observe the rehabilitation status of neutral function after sciatic nerve injury in rats bridged by nerve grafts with Schwann cels. METHODS: A rat model of sciatic nerve injury was established, and schwann cels were primarily cultured. Then, the rat model was repaired with polylactic-co-glycolic acid copolymer-extracelular matrix gel-Schwann cels complex. According to different concentrations of Schwann cels, there were five cel groups from 105/L to 109 RESULTS AND CONCLUSION: The nerve conduction velocities in the cel groups were al higher than that in the control group at 3, 6, 12 weeks after modeling (P < 0.01), and it was highest in the 10 and a control group. The nerve conduction velocity was detected respectively at 3, 6, 12 weeks after modeling; the e tibialis anterior muscle gravity was detected and histological observation was done at 12 weeks. 8/L (P < 0.05). At 12 weeks, hematoxylin-eosin staining of the tibialis anterior muscle showed that the number of normal muscle fibers was higher in the cel groups than the control group (P < 0.05). In the 108/L and 109 and had similar length, thickness and density. These findings indicate that polylactic-co-glycolic acid complex with 10/L groups, the morphology of tibialis anterior muscle recovered wel; the muscle fibers were in strip-like and wavy shapes, grew in the same direction, 8/L Schwann cels is better to promote sciatic nerve regeneration.