1.Pathogenesis Reasoning Chain-of-thought Supervision for Large Language Models: Syndrome Manifestation Recognition and Multidimensional Evaluation in Spleen-stomach Disorders
Shu-Han YANG ; Yu-Xin HU ; Xin-Yu YU ; Yu-Ying TU ; Yi-Chang ZANG ; Pan-Fei LI
Progress in Biochemistry and Biophysics 2026;53(5):1240-1263
ObjectiveThe essence of syndrome manifestation recognition in traditional Chinese medicine (TCM) is to infer the body’s latent pathogenesis state from clinical observational information, rather than to perform simple label matching. However, previous studies have largely modeled this task as syndrome pattern classification within a fixed label space, which does not adequately reflect the cognition process of TCM syndrome differentiation centered on pathogenesis reasoning, and is also insufficient to capture the openness, semantic variability, and cross-disease reusability of syndrome manifestation expression. This study aimed to investigate whether introducing pathogenesis reasoning chain-of-thought (PR-CoT) supervision into large language models (LLMs) could improve the quality and cognitive consistency of syndrome manifestation recognition and support cross-disease transfer. MethodsSyndrome manifestation recognition was formulated as a conditional generation task under the framework of clinical observational information (X)→pathogenesis structure (Z)→syndrome pattern output (Y), where Z serves as an explicit intermediate structural variable linking the clinical evidence and syndrome judgment. Within this framework, a PR-CoT-supervised dataset for syndrome manifestation recognition was constructed based on medical case records of spleen-stomach disorders. After preprocessing, information extraction, manual proofreading, and data cleaning, the dataset comprised 4 800 training cases, 400 development cases, and 400 test cases. Each sample was annotated with a structured PR-CoT consisting of three progressive levels: clinical information summarization, comprehensive pathogenesis analysis, and syndrome pattern output. Supervised fine-tuning was conducted on open-source LLMs, with an end-to-end model serving as the baseline. Qwen3-32B was used as the primary experimental model, and Qwen3-14B as the scale comparison model. A progressive multidimensional evaluation framework was further established, comprising a structural parsing level, a semantic similarity level, and an expert blind review level. At the structural parsing level, syndrome pattern expressions were decomposed into structural elements and evaluated using Precision, Recall, F1 score, and Jaccard similarity. At the semantic similarity level, independent LLMs scored the theoretical proximity between predicted and reference syndrome patterns. At the expert blind review level, three TCM experts independently evaluated model outputs on two dimensions: syndrome differentiation consistency and terminology standardization of syndrome patterns. In addition, zero-shot cross-disease transfer evaluation was conducted on gynecological and heart-system disorder test sets. ResultsAt the structural parsing level, PR-CoT supervision did not lead to a stable improvement in the element-wise overlap of syndrome pattern structural components. Compared with the corresponding baselines, neither Qwen3-32B nor Qwen3-14B showed consistent advantages in structural matching metrics after the introduction of PR-CoT supervision. In contrast, at the semantic similarity level, PR-CoT supervision produced stable positive gains across different model scales and evaluation systems. The average semantic score of Qwen3-32B increased from 6.425 8 in the baseline model to 6.585 0 after PR-CoT supervision, and that of Qwen3-14B increased from 5.870 0 to 5.964 2. At the expert blind review level, the overall score of Qwen3-32B (PR-CoT) was 7.026 0±0.107 7, higher than 6.416 3±0.288 9 for its baseline. In zero-shot cross-disease testing, the PR-CoT model still showed advantages in semantic evaluation and expert evaluation on both gynecological and heart-system disorder test sets, indicating a certain degree of transferability. ConclusionThe benefits of PR-CoT supervision are mainly reflected in TCM semantic consistency and clinical plausibility, rather than in improved hard matching of structural elements. These findings support understanding syndrome manifestation recognition as a process of generating and expressing latent pathogenesis structures, rather than as a classification task within a traditional fixed label space. By introducing pathogenesis reasoning as an explicit intermediate structure into the modeling process and combining it with a progressive multidimensional evaluation framework, this study provides a methodological pathway for intelligent TCM syndrome differentiation that integrates theoretical alignment, interpretability, and multi-level evaluation.
2.Pathogenesis Reasoning Chain-of-thought Supervision for Large Language Models: Syndrome Manifestation Recognition and Multidimensional Evaluation in Spleen-stomach Disorders
Shu-Han YANG ; Yu-Xin HU ; Xin-Yu YU ; Yu-Ying TU ; Yi-Chang ZANG ; Pan-Fei LI
Progress in Biochemistry and Biophysics 2026;53(5):1240-1263
ObjectiveThe essence of syndrome manifestation recognition in traditional Chinese medicine (TCM) is to infer the body’s latent pathogenesis state from clinical observational information, rather than to perform simple label matching. However, previous studies have largely modeled this task as syndrome pattern classification within a fixed label space, which does not adequately reflect the cognition process of TCM syndrome differentiation centered on pathogenesis reasoning, and is also insufficient to capture the openness, semantic variability, and cross-disease reusability of syndrome manifestation expression. This study aimed to investigate whether introducing pathogenesis reasoning chain-of-thought (PR-CoT) supervision into large language models (LLMs) could improve the quality and cognitive consistency of syndrome manifestation recognition and support cross-disease transfer. MethodsSyndrome manifestation recognition was formulated as a conditional generation task under the framework of clinical observational information (X)→pathogenesis structure (Z)→syndrome pattern output (Y), where Z serves as an explicit intermediate structural variable linking the clinical evidence and syndrome judgment. Within this framework, a PR-CoT-supervised dataset for syndrome manifestation recognition was constructed based on medical case records of spleen-stomach disorders. After preprocessing, information extraction, manual proofreading, and data cleaning, the dataset comprised 4 800 training cases, 400 development cases, and 400 test cases. Each sample was annotated with a structured PR-CoT consisting of three progressive levels: clinical information summarization, comprehensive pathogenesis analysis, and syndrome pattern output. Supervised fine-tuning was conducted on open-source LLMs, with an end-to-end model serving as the baseline. Qwen3-32B was used as the primary experimental model, and Qwen3-14B as the scale comparison model. A progressive multidimensional evaluation framework was further established, comprising a structural parsing level, a semantic similarity level, and an expert blind review level. At the structural parsing level, syndrome pattern expressions were decomposed into structural elements and evaluated using Precision, Recall, F1 score, and Jaccard similarity. At the semantic similarity level, independent LLMs scored the theoretical proximity between predicted and reference syndrome patterns. At the expert blind review level, three TCM experts independently evaluated model outputs on two dimensions: syndrome differentiation consistency and terminology standardization of syndrome patterns. In addition, zero-shot cross-disease transfer evaluation was conducted on gynecological and heart-system disorder test sets. ResultsAt the structural parsing level, PR-CoT supervision did not lead to a stable improvement in the element-wise overlap of syndrome pattern structural components. Compared with the corresponding baselines, neither Qwen3-32B nor Qwen3-14B showed consistent advantages in structural matching metrics after the introduction of PR-CoT supervision. In contrast, at the semantic similarity level, PR-CoT supervision produced stable positive gains across different model scales and evaluation systems. The average semantic score of Qwen3-32B increased from 6.425 8 in the baseline model to 6.585 0 after PR-CoT supervision, and that of Qwen3-14B increased from 5.870 0 to 5.964 2. At the expert blind review level, the overall score of Qwen3-32B (PR-CoT) was 7.026 0±0.107 7, higher than 6.416 3±0.288 9 for its baseline. In zero-shot cross-disease testing, the PR-CoT model still showed advantages in semantic evaluation and expert evaluation on both gynecological and heart-system disorder test sets, indicating a certain degree of transferability. ConclusionThe benefits of PR-CoT supervision are mainly reflected in TCM semantic consistency and clinical plausibility, rather than in improved hard matching of structural elements. These findings support understanding syndrome manifestation recognition as a process of generating and expressing latent pathogenesis structures, rather than as a classification task within a traditional fixed label space. By introducing pathogenesis reasoning as an explicit intermediate structure into the modeling process and combining it with a progressive multidimensional evaluation framework, this study provides a methodological pathway for intelligent TCM syndrome differentiation that integrates theoretical alignment, interpretability, and multi-level evaluation.
3.Analysis of scalp fungal communities in severe alopecia areata patients by ITS sequencing
Chunlan ZHANG ; Yilong LEI ; Ruixuan CHENG ; Dawei DUAN ; Xin DU ; Wenming ZHOU ; Dandan ZANG ; Feng WANG
Acta Universitatis Medicinalis Anhui 2026;61(3):576-582
ObjectiveTo compare the differences in fungal community composition between lesional and non-lesional scalp areas in patients suffering from severe alopecia areata (AA), and compare these with healthy scalp areas in control subjects. Additionally, to preliminarily explore the changes in scalp fungal communities in severe AA patients and their potential underlying immunological mechanisms. MethodsA total of 20 severe AA patients and 18 healthy controls were enrolled. Skin swab samples were collected from lesional and non-lesional scalp areas of severe AA patients, as well as from the normal scalp of healthy controls. The fungal internal transcribed spacer (ITS) region was amplified and analyzed using high-throughput sequencing. ResultsThe lesional scalp areas of severe AA patients exhibited higher α-diversity and species richness in fungal communities. Notably, the relative abundance of Ascomycota, along with genera such as Mycosphaerella, Aspergillus, Penicillium, and Wallemia, significantly increased in the bald regions. In contrast, Acremonium and Schizophyllum were more predominant in the non-lesional areas of severe AA patients. ConclusionDistinct region-specific differences in scalp fungal microbiota in severe AA patients suggests that fungal dysbiosis may play a potential role in the pathogenesis of alopecia areata. These findings provide new insights into the disease characteristics of severe AA from the perspective of scalp microecology.
4.Clinical and pathological characteristics of adrenal cortical carcinoma:a single-center retrospective study
Qing-Zheng WU ; Ming-Xiu YANG ; Bing LI ; Shu-Ying LI ; Zi-Xin GUO ; Yi-Jun LI ; Ya-Qi YIN ; Ya-Jing WANG ; Kang CHEN ; Li ZANG ; Wei-Jun GU ; Yi-Ming MU ; Zhao-Hui LYU
Medical Journal of Chinese People's Liberation Army 2025;50(7):786-792
Objective To investigate the clinical and pathological characteristics of adrenal cortical carcinoma(ACC),compare differences between hypercortisolism and non-functional ACC,and assess the diagnostic value of indicators such as Ki-67 index.Methods The clinical data of 57 ACC patients admitted to the First Medical Center of Chinese PLA General Hospital from January 2015 to March 2025 were retrospectively analyzed.According to the results of endocrine function assessment,47 of these patients were divided into hypercortisolism group(n=19)and non-functional group(n=28).The differences in clinical and pathological characteristics between the two groups were compared,and non-parametric tests and Spearman correlation analysis were used to explore the relationship between Ki-67 index and tumor stage as well as imaging features.Results Among the 57 patients,there were 20 males and 37 females,with a male-to-female ratio of 1:1.85.The age ranged from 16 to 76 years,and the age at diagnosis was(48.7±13.3)years.The tumor diameter was(10.53±4.14)cm.The tumors were located on the right side in 12 cases(21.1%),on the left side in 34 cases(59.6%),and bilaterally in 11 cases(19.3%).Among them,16 cases(28.1%)were complicated with glucose metabolism disorders,31 cases(54.3%)had hypertension,and 20 cases(35.1%)had hypokalemia.According to ENSAT staging,there were 0 cases in stage Ⅰ,15 cases(26.3%)in stage Ⅱ,24 cases(42.1%)in stage Ⅲ,and 18 cases(31.6%)in stage Ⅳ.Endocrine function assessment was completed in 47 of the 57 patients,including 28 cases(59.6%)of non-functional ACC and 19 cases(40.4%)of hypercortisolism(including 1 case of hypercortisolism combined with increased sex hormone secretion).Compared with non-functional group,hypercortisolism group had a significantly higher prevalence of hypertension(P=0.014),later ENSAT stage(P=0.010),and a higher proportion of hypervascularization(P=0.048).The median Ki-67 index was 20%(10%-40%),showing no significant correlation with either the maximum tumor diameter or SUVmax value,but it was related to ENSAT staging,with Ki-67 index in stageⅣ patients being significantly higher than that in stage Ⅱ(P=0.032).Immunohistochemistry results showed that the positive rate of Inhibin-α was 84.8%,and the positive rate of Melan-A was 40.9%.Conclusions ACC is a rare malignant endocrine tumor.ACC patients with hypercortisolism are more likely to be complicated with hypertension,have later staging,and more common hypervascular manifestations.Clinically,their endocrine function should be prioritized for assessment,and more active treatment strategies should be adopted.Diagnosis should be combined with imaging characteristics(such as hypervascularization)and immunohistochemical indicators(Ki-67,Inhibin-α,Melan-A).The significant increase in Ki-67 is in the advanced stage can serve as an important prognostic indicator to guide individualized treatment.
5.Clinical characteristics of clinical and subclinical Cushing's syndrome caused by primary bilateral macronodular adrenal hyperplasia
Huai-Jin XU ; Bing LI ; Kang CHEN ; Hui-Xin ZHOU ; Ya-Jing WANG ; Li ZANG ; Xian-Ling WANG ; Yu CHENG ; Jin DU ; Qing-Hua GUO ; Wei-Jun GU ; Zhao-Hui LYU ; Jian-Ming BA ; Jing-Tao DOU ; Yi-Ming MU
Medical Journal of Chinese People's Liberation Army 2025;50(7):800-807
Objective To investigate the clinical characteristics of patients with clinical and subclinical Cushing's syndrome caused by primary bilateral macronodular adrenal hyperplasia(PBMAH).Methods A retrospective analysis was performed on the clinical data of 198 patients with Cushing's syndrome caused by PBMAH diagnosed in the First Medical Center of Chinese PLA General Hospital from January 2004 to October 2024.According to clinical manifestations,the patients were classified into clinical type Cushing's syndrome(n=61)and subclinical type Cushing's syndrome(n=137),and the clinical characteristics of the two types were compared.Results The mean age at diagnosis of patients with PBMAH-induced Cushing's syndrome was(53.5±10.4)years,including 118 males and 80 females,with a male-to-female ratio of 1.475:1.Compared with the subclinical type,the clinical type had a higher proportion of females,higher levels of serum cortisol,24-hour urine free cortisol(24 h UFC),and inhibited serum cortisol after low-dose dexamethasone suppression.Additionally,the clinical type had lower plasma ACTH,larger adrenal nodules and a higher risk of surgery(P<0.05)compared with those in subclinical type.The incidences of hypertension,dyslipidemia,obesity,diabetes mellitus,hypokalemia,vitamin D deficiency,osteoporosis,coronary heart disease,and cerebrovascular disease in patients with Cushing's syndrome caused by PBMAH were 87.9%,50.5%,37.1%,36.9%,27.8%,25.9%,18.7%,18.7%and 12.1%,respectively.Among them,compared with subclinical type patients,clinical type patients had higher incidence of hypokalaemia,vitamin D deficiency and osteoporosis(P<0.05),while there were no statistically significant differences in the incidences of other comorbidities between the two types(P>0.05).The results of postoperative follow-up for PBMAH patients showed that the short-term biochemical remission rate of unilateral total adrenalectomy was 41.5%(22/53)and the long-term biochemical remission rate was 32.0%(8/25).The short-term biochemical remission rate of unilateral partial(or nodular)adrenalectomy was 52.9%(9/17),and the long-term biochemical remission rate was 14.3%(1/7).All patients who underwent unilateral total adrenalectomy plus contralateral partial resection developed adrenal insufficiency(3/3),and 1 patient(1/3)relapsed 3.4 years after surgery.Conclusion Clinical and subclinical types of Cushing's syndrome caused by PBMAH have their distinct clinical characteristics.Surgery is an effective treatment for PBMAH,but a certain proportion of patients fail to achieve biochemical remission after non-bilateral total adrenalectomy.
6.Neuroimaging aided diagnosis and transcranial magnetic stimulation interventions for autism spectrum disorder
Xuchu WENG ; Jin JING ; Jianhong LUO ; Xujun DUAN ; Yufeng ZANG ; Xin WANG ; Jiuxing LIANG ; Lixia YUAN ; Xingjie YANG ; Lei LI ; Lizi LIN ; Haiqing XU ; Zhuoming CHEN ; Saijun HUANG ; Qiang CHEN ; Quanying YI ; Maoping LIANG ; Yanjuan CHEN
Chinese Mental Health Journal 2025;39(8):661-670
Autism spectrum disorder(ASD),characterized by unknown etiology and high heterogeneity,ne-cessitates precise diagnostic and intervention strategies.Neuroimaging techniques have shown great promise in un-covering the neural mechanisms of ASD,providing a foundation for aided diagnosis and transcranial magnetic stim-ulation(TMS)interventions.This review highlights that integrating multimodal neuroimaging and developing indi-vidualized indices with developmental specificity can significantly improve the accuracy of ASD diagnosis and clas-sification.Furthermore,TMS interventions guided by functional connectivity derived from functional magnetic reso-nance imaging(fMRI)offer a personalized approach to ASD treatment.
7.Effect analysis of innovative model on perioperative pain management in prostate cancer patients with hematuria undergoing prostatic artery embolization
Xin WANG ; Ji-xian ZANG ; Xiao-yang SU ; Chun-meng PENG ; Sha-sha LIU ; Ao-mei LI
National Journal of Andrology 2025;31(8):728-731
Objective:To investigate the effect of innovative perioperative pain management on prostate cancer patients with he-maturia undergoing prostatic artery embolization(PAE).Methods:A total of 60 patients undergoing PAE in the Interventional Ther-apy Department of General Hospital of Eastern Theater Command from May 2024 to January 2025 were selected by convenience sam-pling method and randomly divided into the intervention group and the control group,with 30 patients in each group.The control group received traditional pain management of nursing.An innovative perioperative pain management was performed in intervention group in-cluding preoperative"body-mind-pain"holistic assessment and preparation,intraoperative humanistic care and real-time support,post-operative multimodal analgesia and rehabilitation,dynamic monitoring and closed-loop feedback.The pain degree after 6 hours,1 day,3 days and 1 week of the operation,and the quality of life after 1 week of operation,as well as nursing satisfaction at discharge were compared between the two groups.Results:The VAS scores of the intervention group were significantly lower than those of the con-trol group after 6 hours,1 day,3 days and 1 week of operation(P<0.05).One week after the operation,the quality of life in the ob-servation group was higher than that of the control group significantly(P<0.05).The nursing satisfaction of the observation group was significantly higher than that of the control group at discharge(P<0.05).Conclusion:The application of innovative perioperative pain management can alleviate pain of patients with PAE,which improves the quality of life and nursing satisfaction of patients,and is conducive to the rehabilitation of patients.
8.Development of a nomogram-based risk prediction model for chronic obstructive pulmonary disease incidence in community-dwelling population aged 40 years and above in Shanghai
Yixuan ZHANG ; Yiling WU ; Jinxin ZANG ; Xuyan SU ; Xin YIN ; Jing LI ; Wei LUO ; Minjun YU ; Wei WANG ; Qi ZHAO ; Qin WANG ; Genming ZHAO ; Yonggen JIANG ; Na WANG
Shanghai Journal of Preventive Medicine 2025;37(8):669-675
ObjectiveTo develop a nomogram-based risk prediction model for chronic obstructive pulmonary disease (COPD) incidence among the community-dwelling population aged 40 years old and above, so as to provide targeted references for the screening and prevention of COPD. MethodsBased on a natural population cohort in suburban Shanghai, a total of 3 381 randomly selected participants aged ≥40 years underwent pulmonary function tests between July and October 2021. Cox stepwise regression analysis was used to develop overall and gender-specific risk prediction models, along with the construction of corresponding risk nomograms. Model predictive performance was evaluated using the C-indice, area under the curve (AUC) values, and Brier score. Stability was assessed through 10-fold cross-validation and sensitivity analysis. ResultsA total of 3 019 participants were included, with a median follow-up duration of 4.6 years. The COPD incidence density was 17.22 per 1 000 person-years, significantly higher in males (32.04/1 000 person-years) than that in females (7.38/1 000 person-years) (P<0.001). The overall risk prediction model included the variables such as gender, age, education level, BMI, smoking, passive smoking, and respiratory comorbidities. The male-specific model incorporated the variables such as age, BMI, respiratory comorbidities, and smoking, while the female-specific model included age, marital status, respiratory comorbidities, and pulmonary tuberculosis history. The C-indices for the overall, male-specific, and female-specific models were 0.829, 0.749, and 0.807, respectively. The 5-year AUC values were 0.785, 0.658, and 0.811, with Brier scores of 0.103, 0.176, and 0.059, respectively. Both 10-fold cross-validated C-indices and sensitivity analysis (excluding participants with a follow-up duration of <6 months) yielded C-indices were above 0.740. ConclusionThis study developed concise and practical overall and gender-specific COPD risk prediction models and corresponding nomograms. The models demonstrated robust performance in predicting COPD incidence, providing a valuable reference for identifying high-risk populations and formulating targeted screening and personalized management strategies.
9.Study on artificial intelligence-based ultrasound diagnosis and auxiliary decision-making for ovarian tumors
Chunli QIU ; Yanlin CHEN ; Yuanji ZHANG ; Haotian LIN ; Xiaoyi PAN ; Siying LIANG ; Xiang CONG ; Xin LIU ; Zhen MA ; Cai ZANG ; Xin YANG ; Dong NI ; Guowei TAO
Chinese Journal of Ultrasonography 2025;34(7):608-615
Objective:To apply artificial intelligence(AI)in classifying ovarian tumors on ultrasound images,and compare the diagnostic results of several sonographers with varying seniority levels.Methods:A total of 645 patients diagnosed with adnexal masses via gynecological ultrasound examination at Qilu Hospital of Shandong University from January 2021 to December 2024 were enrolled. Three deep learning architectures,i.e.,Alexnet,Densenet121,and Resnet50 were developed and used to internally test the classification effectiveness of ovarian tumors,while the optimal model was selected for external testing. Two junior sonographers and two senior sonographers were recruited to independently diagnose ovarian tumors in the external test dataset. Subsequently,the benign and malignant results of the model's predictions were disclosed to each sonographer,and their revised diagnoses on the same external test data in combination with the best AI model were recorded.Results:The optimal model achieved an accuracy of 0.941,sensitivity of 0.936,and specificity of 0.944 on the internal test dataset,and maintained robust performance on the external test dataset with accuracy of 0.891,sensitivity of 0.880,and specificity of 0.907. Compared to junior sonographers,the optimal model demonstrated significantly higher sensitivity in discriminating benign from malignant ovarian tumors(0.880 vs. 0.723,0.602;all P<0.05). No statistically significant difference was observed in diagnostic accuracy between the optimal model and senior sonographer 1( P=0.05). With assistance from the optimal model,junior sonographers achieved significant improvements in both sensitivity and specificity(sensitivity:0.723 vs. 0.843,0.602 vs. 0.819;specificity:0.778 vs. 0.833,0.685 vs. 0.741;all P<0.05). Conclusions:The optimal model achieves comparable performance to that of senior sonographers in ovarian tumor classification. With model assistance,the diagnostic performance of junior sonographers is significantly improved.
10.Functional perforator flap: concept and clinical applications.
Hu JIAO ; Mengqing ZANG ; Lu ZHOU ; Shengyang JIN ; Jiadong PAN ; Miao WANG ; Xin WANG ; Yuanbo LIU
Chinese Journal of Reparative and Reconstructive Surgery 2025;39(9):1076-1085
OBJECTIVE:
To review the clinical applications of functional perforator flaps in restoring human body functions.
METHODS:
An extensive literature review was conducted on both domestic and international publications to summarize the clinical use of functional perforator flaps for functional restoration.
RESULTS:
Perforator flaps are among the most commonly used flaps in reconstructive surgery. Beyond providing soft tissue repair, they are increasingly employed to reconstruct diverse bodily functions, leading us to propose the concept of the "functional perforator flap". Although various forms of functional perforator flaps are currently utilized, reports are predominantly scattered case studies, lacking systematic organization. Commonly used functional perforator flaps can be categorized into five types: chimeric perforator flaps, perforator flaps for nerve function restoration, perforator flaps for lymphatic drainage enhancement, flow-through perforator flaps, and perforator flaps for restoring bone and joint motion. These flaps significantly broaden the application scope of perforator flaps, elevating the goal of reconstruction from mere wound repair to achieving repair concurrent with functional reconstruction.
CONCLUSION
The application of various functional perforator flap designs significantly improves wound reconstruction outcomes and represents an effective approach for managing complex defects. Future developments will undoubtedly see more forms of functional perforator flaps reported to meet increasingly sophisticated reconstructive demands.
Humans
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Perforator Flap/blood supply*
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Plastic Surgery Procedures/methods*
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Soft Tissue Injuries/surgery*
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Skin Transplantation/methods*
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Wound Healing

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