OBJECTIVES: To propose a hypothesis that aloe-emodin may inhibit scar tissue fibrosis through thrombospondin-1(THBS1)-PI3K-Akt pathway. METHODS: By cultivating fibroblasts derived from scar tissue after cleft palate surgery in humans, aloe emodin of different concentrations (10, 20, 30, 40 and 50 μmol/L) was added to the cells which activity was detected. At the same time, transcriptome sequencing was performed on scar tissue and cells, and bioinformatics methods were used to explore potential targets and signaling pathways of scar tissue fibrosis. RESULTS: Aloe-emodin had a concentration dependent inhibitory effect on fibroblast proliferation,with the 40 μmol/L concentration group showing the most significant effect. The results of tissue and cell sequencing indicated that differentially expressed genes were significantly enriched in extracellular matrix-receptor interaction pathway, and shared a common differential gene which was THBS1. The ORA analysis results indicated that differentially expressed genes, including THBS1, were significantly enriched in the PI3K-Akt signaling pathway. CONCLUSIONS Aloe emodin may inhibit the PI3K-Akt pathway by downregulating THBS1, thereby reducing the proliferation activity of fibroblasts derived from postoperative palatal scar tissue.
Thrombospondin 1/genetics* ; Humans ; Signal Transduction/drug effects* ; Fibroblasts/cytology* ; Proto-Oncogene Proteins c-akt/metabolism* ; Fibrosis ; Phosphatidylinositol 3-Kinases/metabolism* ; Cicatrix/metabolism* ; Cell Proliferation/drug effects* ; Anthraquinones/pharmacology* ; Cells, Cultured

Objective:To investigate the clinical effects of combined tissue flap transplantation in repairing giant chest wall defects.Methods:This study was a retrospective observational study. From August 2013 to December 2020, 31 patients with chest wall tumor or radiation ulcer after radical resection of chest wall tumor and conformed to the inclusion criteria were admitted to the Department of Breast Oncoplastic Surgery of Hunan Cancer Hospital, including 12 males and 19 females, aged 25-71 years. After resection of tumor or ulcer and wound debridement, the area of secondary chest wall defect was 300-600 cm 2 with length of 16-35 cm and width of 16-32 cm. According to the actual situation of the patients and the preoperative design, the chest wall defects were repaired with the flexible combination of perforator flaps and myocutaneous flaps from different donor sites, and the area of the combined tissue flap was 260-540 cm 2 with length of 20-30 cm and width of 13-20 cm. Free posteromedial thigh perforator flap+free anterolateral thigh myocutaneous flap were used in 2 patients, free deep inferior epigastric artery perforator flap+free anterolateral thigh myocutaneous flap were used in 5 patients, free deep inferior epigastric artery perforator flap+pedicled rectus abdominis myocutaneous flap+free anterolateral thigh myocutaneous flap were used in 7 patients, free deep inferior epigastric artery perforator flap+pedicled rectus abdominis myocutaneous flap+pedicled latissimus dorsi myocutaneous flap were used in 2 patients, and bilateral free anterolateral thigh myocutaneous flaps were used in 15 patients. For the remaining small area of superficial tissue defect after being repaired by combined tissue flaps, skin graft was used to repair or delayed local flap transfering was performed after the tissue flaps survived and edema subsided. The appropriate blood vessels in the donor and recipient sites were selected for anastomosis to reconstruct the blood supply of tissue flaps. The wounds in the donor sites of tissue flaps that can be directly sutured were sutured directly; for those that cannot be sutured directly, the skin grafting or delayed suture was performed. The anastomosis of blood vessels in the recipient sites, operation length, and postoperative hospital stay were recorded. The survivals of tissue flaps and skin grafts, the shape and texture of reconstructed chest wall, the wound healing, scar formation, and function of donor sites of tissue flaps, and the scar formation of the donor sites of skin grafts were observed after operation. Tumor recurrence and death of recurrent patients were followed up after operation. Results:The blood vessels in the recipient sites were anastomosed as follows: proximal internal thoracic vessels for 24 times, distal internal thoracic vessels for 12 times, trunk of thoracodorsal vessels for 4 times, anterior serratus branches of thoracodorsal vessels for 8 times, and thoracoacromial vessels for 12 times. The operation length was 6.0 to 8.5 hours, and the postoperative hospital stay was 9 to 21 days. Necrosis at the edge of partial tissue flaps occurred in 4 patients after operation, which healed after dressing change, and the tissue flaps and skin grafts of the other patients survived completely. The shape and texture of the reconstructed chest wall were good. Four patients had poor wound healing in the donor sites of abdominal tissue flaps, which healed after dressing change and local drainage. Only linear scar was left in the donor sites of all tissue flaps, and there was no obvious dysfunction in the donor sites of tissue flaps. Mild hypertrophic scar was left in the donor sites of skin grafts. During follow-up of 9 to 36 months after operation, 6 patients had tumor recurrence, and the recurrence time was 5 to 20 months after operation. After comprehensive treatment for patients with tumor recurrence, 3 patients died.Conclusions:Transplantation of combined tissue flaps in repairing the giant chest wall defects can shorten the time of total operation and hospital stay, and avoid multiple operations. After operation, patients had good chest wall appearance, with reduced tumor recurrence in patients with chest wall tumor.

Objective:To establish a brain metastasis (BM) prediction model for limited-stage small cell lung cancer (LS-SCLC) patients who achieved complete response (CR) or partial response (PR) after thoracic chemoradiotherapy, and to explore the value of prophylactic cranial irradiation (PCI) in different risk groups.Methods:Clinical data of 274 patients with LS-SCLC who achieved CR/PR after thoracic chemoradiotherapy in Tianjin Medical University Cancer Institute & Hospital from January 2010 to December 2021 were retrospectively analyzed, including 144 cases in the PCI group and 130 in the non-PCI group. The nomogram was developed based on variables determined by univariate and multivariate analyses in the non-PCI group. The bootstrap method, receiver operating characteristics (ROC) curve, calibration curve and decision curve analysis (DCA) were employed to evaluate the predictive power and clinical benefits of the model. Patients were stratified into high- and low-risk groups based on risk scores. The brain metastases-free survival (BMFS), progression-free survival (PFS), extracranial progression-free survival (ePFS) and overall survival (OS) were compared between patients with and without PCI in different risk-stratified populations using the log-rank test.Results:The nomogram included five variables: systemic immune inflammation index (SII), lymphocyte-to-monocyte ratio (LMR), pro-gastrin-releasing peptide precursor (ProGRP), neuron-specific enolase (NSE), and blood calcium. The area under the ROC curve (AUC) of the nomogram in predicting 1- and 2-year BMFS was 0.761 and 0.822. In the low-risk group, there was no significant difference in the BMFS ( P=0.374), PFS ( P=0.551), ePFS ( P=0.508) and OS ( P=0.767) between the PCI and non-PCI groups. In the high-risk group, PCI could significantly increase the BMFS ( P<0.001) and PFS ( P=0.022), while there was no significant difference in the ePFS ( P=0.963) and OS ( P=0.632). And propensity score-matching (PSM) analysis showed similar results. Conclusions:PCI does not improve OS in LS-SCLC patients regardless of high or low risk of BM. However, PCI significantly prolong the BMFS and PFS in patients at a high risk of BM.

Objective:To analyze the failure mode after immunotherapy and the prognostic significance of combined radiotherapy for advanced non-small cell lung cancer (NSCLC).Methods:Clinical data of 220 advanced NSCLC patients receiving immune checkpoint inhibitors (ICI) as the first-line therapy in Tianjin Medical University Cancer Institute and Hospital from January 2017 to December 2021 were retrospectively analyzed. The baseline characteristics, the first-line treatment regimen, modes and locations of failure, radiotherapy purpose, location and prescription dose of all patients were collected. The main parameter was the overall survival (OS). Survival analysis was conducted by Kaplan-Meier method. Survival comparison was performed by log-rank test.Results:A total of 220 patients were enrolled in the study in which 65 cases (29.5%) exhibited a state of oligometastasis. Among 72 patients who received radiotherapy, 29 cases (40%) received chest radiotherapy and 53 cases (74%) received metastatic radiotherapy. The median follow-up time was 25.6 months. Up to the last follow-up, disease progression had been observed in 140 patients, with 84 patients (38.2%) of them demonstrating a state of oligometastasis. Among 120 patients with disease progression and confirmed location of progression, 62 patients (51.7%) failed in first-line immunotherapy because of the primary lesion progression (mainly in the chest cavity), 34 patients (28.3%) due to the appearance of new metastases, and the remaining 24 patients(20.0%) due to primary lesion progression and new distant metastases. Among 72 patients treated with the first-line immunotherapy combined with local radiotherapy, 17 patients (24%) received planned radiotherapy, another 17 patients (24%) received salvage radiotherapy, and the remaining 38 patients (53%) received radiotherapy to relieve symptoms. The prognosis of patients significantly differed according to the purpose of radiotherapy ( P=0.030). The median OS of patients who did not receive radiotherapy was 29.1 months, those who received planned radiotherapy did not reach the median OS, and the median OS of those who received salvage radiotherapy was 28.7 months, and the median OS of those who received local radiotherapy to relieve symptoms was only 19.0 months. Conclusions:The progression of primary lesions is the main failure mode of the first-line immunotherapy. Chest cavity is the main location of tumor progression. Local radiotherapy for intrathoracic lesions may improve the survival benefit further for advanced NSCLC patients after the first-line immunotherapy.

OBJECTIVE To study the content changes of 5 chemical compositions in water extract and ethanol precipitate of different processed products of Psoralea corylifolia， and to preliminarily evaluate its hepatotoxicity. METHODS The water extracts from crude product of P. corylifolia and processed products by Leigong method， running water rinsing method， and salt stir-frying method were prepared， as well as the ethanol precipitates of processed products by Leigong method and salt stir-frying method were prepared. The contents of psoralenoside， isopsoralenoside， psoralen， isopsoralen and bakuchiol were determined by high- performance liquid chromatography and compared. The median lethal concentration （LC50） and maximum non-lethal concentration （MNLC） of each sample to wild-type zebrafish juveniles were calculated after 72 h of treatment with different concentrations of water extracts from raw product and processed products by running water rinsing method， Leigong method and salt stir-frying method， different concentrations of ethanol precipitates from processed products by Leigong method and salt stir-frying method， and the acetaminophen was used as the positive control. The basic morphology of wild-type zebrafish juveniles and the liver phenotype of transgenic zebrafish juveniles were observed after 72 h of treatment with the above samples （MNLC）. Pearson correlation analysis was used to evaluate the correlation between component content and hepatotoxicity. RESULTS Compared with the water extract of raw products， the contents of psoralenoside and isopsoralenoside in the water extract of different processed products were generally decreased （P＜0.05）， while the contents of psoralen， isopsoralen and bakuchiol in the ethanol precipitate of Leigong method and salt stir-frying products were significantly increased （P＜0.05）. The LC50 of water extracts of crude product and processed products by running water rinsing method， Leigong method， salt stir-frying method， and ethanol precipitates of processed products by Leigong method and salt stir- frying method were 2.45， 5.00， 5.38， 1.55， 2.36， 0.64 g/L （calculated by crude drug）， and MNLC were 2.21， 4.53， 5.02， 1.37， 2.13， 0.53 g/L （calculated by crude drug）. Compared with the blank control group， the zebrafish juveniles in each sample treatment group showed different degrees of deformity， the liver relative fluorescence intensity was significantly weakened （P＜0.05 or P＜ 0.01）. Fat-soluble components such as bakuchiol， isopsoralen and psoralen were highly correlated with liver fluorescence intensity （R 2＞0.7）. CONCLUSIONS The processed products of P. corylifolia mainly compose of psoralenoside and isopsoralenoside after water extraction， the contents of psoralen， isopsoralen and bakuchiol increase after alcohol precipitation， and the hepatotoxicity is positively correlated with the contents of liposoluble compositions in P. corylifolia.

Objective:To explore the application of the classification of the accompanying vein of deep inferior epigastric artery and vascular anastomotic strategy in breast reconstruction.Methods:The data of patients who underwent breast reconstruction after breast cancer surgery with unilateral free lower abdominal flap transplantation in Hunan Cancer Hospital from October 2015 to January 2021 were retrospectively analyzed. During surgery, free deep inferior epigastric artery perforator (DIEP) flap or free muscle-sparing rectus abdominis musculocutaneous flap was used for breast reconstruction, and the recipient vessel was internal mammary vessel. The anatomy of the accompanying vein of the deep inferior epigastric artery can be divided into three types: independent type, including one branch type and two branch type; Y-shaped structure; H-shaped structure. Direct anastomosis was used for independent veins. There were five methods of vascular anastomoses for Y-shaped and H-shaped accompanying vein: (1) direct anastomosis; (2) the Y-shaped common stem segment was removed and the two accompanying veins were anastomosed respectively; (3) ligate the communicating branch and anastomose the two accompanying veins respectively; (4) the communicating branch was reserved and the two accompanying veins were anastomosed respectively; (5) ligate the smaller accompanying vein and anastomose the larger accompanying vein. Methods 1 and 2 were suitable for Y-shaped accompanying veins, and methods 3 to 5 were suitable for H-shaped accompanying veins. The excessively long inferior abdominal artery segment was removed during the operation. The complications of intraoperative vascular anastomosis were counted, and the survival of flap, aesthetics of breast reconstruction and tumor recurrence were followed up.Results:A total of 173 female patients were included, ranging from 26 to 60 years, with an average age of 41.2 years. There were 92 cases of immediate breast reconstruction and 81 cases of delayed breast reconstruction. 109 cases of free DIEP flap and 64 cases of free muscle-sparing rectus abdominis musculocutaneous flap were harvested. The length of the flap was (26.9±1.9) cm, the width of the flap was (11.3±0.7) cm, the length of the vascular pedicle was (10.5±0.4) cm. The anatomical type of the deep inferior epigastric artery with only one accompanying vein accounted for 16 cases, and the veins were anastomosed directly. The anatomical type of Y-shaped accompanying vein accounted for 14 cases, of which 5 cases were anastomosed directly using method 1, 3 cases were anastomosed directly using method 1 after partial resection of the third costal cartilage to create a groove, and 6 cases were anastomosed using method 2. The H-shaped accompanying vein of the deep inferior epigastric artery was found in 143 cases. In 96 cases, vascular anastomosis were accomplished using method 3, 19 cases were anastomosed using method 4 and 28 cases were anastomosed using method 5. In 97 cases, the excessively long segment of the deep inferior epigastric artery were trimmed before vascular anastomosis. The average length of the trimmed segment was (2.7±0.7) mm. There were 6 cases of vascular anastomotic complications during operation, of which 2 patients were treated with method 1. Venous entrapment occurred during operation and was relieved after changing into method 2. The venous anastomosis methods adopted in the other 4 cases included 1 case of method 2, 1 case of method 3, and 2 cases of method 4, all of which were relieved of vessel entrapment by timely adjusting the placement of vessel pedicles. Postoperative flap necrosis occurred in 1 case. The vein anastomosis was direct Y-shaped vein anastomosis. The remaining 172 cases were completely successful. The patients were followed up for 10 to 36 months, with an average of 18.7 months. The reconstructed breast shape was good, the texture was soft, without flap contracture and deformation. Only linear scar remained in the donor site of the flap, which had no significant effect on the function of the abdominal wall. No tumor recurrence was observed.Conclusion:By flexibly adjusting the vascular anastomosis strategy according to the classification of the accompanying vein of the deep inferior epigastric artery, the blood supply of the free lower abdominal flap transfer in breast reconstruction can be guaranteed to the greatest extent.

In December 2021, a 37-year-old female patient was admitted to the Department of Oncology Plastic Surgery, Hunan Cancer Hospital, 32 months after bilateral mastectomy. After admission, it was planned to perform bilateral breast reconstruction with bilateral free deep inferior epigastric artery perforator (DIEP) flap and bilateral free posterior medial thigh perforator flap. The ipsilateral lower abdominal flap and posterior medial thigh flap were stacked to reconstruct the ipsilateral breast, and the vascular pedicle of profunda artery perforator was anastomosed with the distal end of internal mammary vessel, the deep inferior epigastric artery was anastomosed with the proximal end of the internal mammary vessel. During the operation, the blood supply of the flap was good, and the donor sites of the thigh and abdomen were closed directly. The postoperative course of the patient was stable, the flap survived well, and the donor site healed well. After 1 month follow-up, the appearance and function of the donor area of abdomen and thigh were good, no obvious complications were found, and the reconstructed breast shape was satisfactory. This case suggests that the combined transplantation of free DIEP flap and posterior medial thigh perforator flap is suitable for the reconstruction of large breast.

On June 15, 2021, a female patient with right breast cancer aged 43 years old was admitted in Hunan Cancer Hospital. She received left mastectomy 13 years ago and left breast reconstruction with pedicled rectus abdominis myuocutaneous flap 6 years ago. After admission, she received right mastectomy and immediate right breast reconstruction with bilateral free medial arm perforator flaps. The lateral side of the breast was reconstructed with the ipsilateral medial arm flap. The superior ulnar collateral vessels were anastomosed with the proximal end of the lateral thoracic artery and distal end of the lateral thoracic vein. And the contralateral medial arm flap was used to reconstruct the medial part of the breast. The superior ulnar collateral vessels were anastomosed with the proximal and distal ends of the internal mammary vessels. After revascularization, the blood supply of the flap was good, and the donor sites were closed directly. The postoperative course of the patient was stable, the flap survived well, and the donor area healed well. In the two-month follow-up, the appearance and function of the flap donor area was good, there were no obvious complications, while the reconstructed breast shape was not satisfactory. This case suggests that the combined transplantation of bilateral free arm medial perforator flaps is suitable for small and medium-sized breast reconstruction, but not enough for large-volume breast reconstruction.

Objective:To explore the application of the classification of the accompanying vein of deep inferior epigastric artery and vascular anastomotic strategy in breast reconstruction.Methods:The data of patients who underwent breast reconstruction after breast cancer surgery with unilateral free lower abdominal flap transplantation in Hunan Cancer Hospital from October 2015 to January 2021 were retrospectively analyzed. During surgery, free deep inferior epigastric artery perforator (DIEP) flap or free muscle-sparing rectus abdominis musculocutaneous flap was used for breast reconstruction, and the recipient vessel was internal mammary vessel. The anatomy of the accompanying vein of the deep inferior epigastric artery can be divided into three types: independent type, including one branch type and two branch type; Y-shaped structure; H-shaped structure. Direct anastomosis was used for independent veins. There were five methods of vascular anastomoses for Y-shaped and H-shaped accompanying vein: (1) direct anastomosis; (2) the Y-shaped common stem segment was removed and the two accompanying veins were anastomosed respectively; (3) ligate the communicating branch and anastomose the two accompanying veins respectively; (4) the communicating branch was reserved and the two accompanying veins were anastomosed respectively; (5) ligate the smaller accompanying vein and anastomose the larger accompanying vein. Methods 1 and 2 were suitable for Y-shaped accompanying veins, and methods 3 to 5 were suitable for H-shaped accompanying veins. The excessively long inferior abdominal artery segment was removed during the operation. The complications of intraoperative vascular anastomosis were counted, and the survival of flap, aesthetics of breast reconstruction and tumor recurrence were followed up.Results:A total of 173 female patients were included, ranging from 26 to 60 years, with an average age of 41.2 years. There were 92 cases of immediate breast reconstruction and 81 cases of delayed breast reconstruction. 109 cases of free DIEP flap and 64 cases of free muscle-sparing rectus abdominis musculocutaneous flap were harvested. The length of the flap was (26.9±1.9) cm, the width of the flap was (11.3±0.7) cm, the length of the vascular pedicle was (10.5±0.4) cm. The anatomical type of the deep inferior epigastric artery with only one accompanying vein accounted for 16 cases, and the veins were anastomosed directly. The anatomical type of Y-shaped accompanying vein accounted for 14 cases, of which 5 cases were anastomosed directly using method 1, 3 cases were anastomosed directly using method 1 after partial resection of the third costal cartilage to create a groove, and 6 cases were anastomosed using method 2. The H-shaped accompanying vein of the deep inferior epigastric artery was found in 143 cases. In 96 cases, vascular anastomosis were accomplished using method 3, 19 cases were anastomosed using method 4 and 28 cases were anastomosed using method 5. In 97 cases, the excessively long segment of the deep inferior epigastric artery were trimmed before vascular anastomosis. The average length of the trimmed segment was (2.7±0.7) mm. There were 6 cases of vascular anastomotic complications during operation, of which 2 patients were treated with method 1. Venous entrapment occurred during operation and was relieved after changing into method 2. The venous anastomosis methods adopted in the other 4 cases included 1 case of method 2, 1 case of method 3, and 2 cases of method 4, all of which were relieved of vessel entrapment by timely adjusting the placement of vessel pedicles. Postoperative flap necrosis occurred in 1 case. The vein anastomosis was direct Y-shaped vein anastomosis. The remaining 172 cases were completely successful. The patients were followed up for 10 to 36 months, with an average of 18.7 months. The reconstructed breast shape was good, the texture was soft, without flap contracture and deformation. Only linear scar remained in the donor site of the flap, which had no significant effect on the function of the abdominal wall. No tumor recurrence was observed.Conclusion:By flexibly adjusting the vascular anastomosis strategy according to the classification of the accompanying vein of the deep inferior epigastric artery, the blood supply of the free lower abdominal flap transfer in breast reconstruction can be guaranteed to the greatest extent.

In December 2021, a 37-year-old female patient was admitted to the Department of Oncology Plastic Surgery, Hunan Cancer Hospital, 32 months after bilateral mastectomy. After admission, it was planned to perform bilateral breast reconstruction with bilateral free deep inferior epigastric artery perforator (DIEP) flap and bilateral free posterior medial thigh perforator flap. The ipsilateral lower abdominal flap and posterior medial thigh flap were stacked to reconstruct the ipsilateral breast, and the vascular pedicle of profunda artery perforator was anastomosed with the distal end of internal mammary vessel, the deep inferior epigastric artery was anastomosed with the proximal end of the internal mammary vessel. During the operation, the blood supply of the flap was good, and the donor sites of the thigh and abdomen were closed directly. The postoperative course of the patient was stable, the flap survived well, and the donor site healed well. After 1 month follow-up, the appearance and function of the donor area of abdomen and thigh were good, no obvious complications were found, and the reconstructed breast shape was satisfactory. This case suggests that the combined transplantation of free DIEP flap and posterior medial thigh perforator flap is suitable for the reconstruction of large breast.