Objective To investigate the role of quercetin(QUE)in ferroptosis during intestinal ischemia-reperfusion(IR)injury and elucidate its underlying mechanisms.Methods ① Potential target genes of QUE were predicted using the TCMSP,PharmMapper,and SwissTargetPredictive databases.Target genes associated with intestinal IR injury and ferroptosis were collected from GeneCards,PharmGKB,and OMIM databases.After overlapping genes were identified and analyzed,protein-protein interaction(PPI)networks were constructed using the STRING database and then visualized with Cytoscape 3.10.0.Molecular docking was performed to validate the binding conformations between QUE and key targets.② In vivo experiments were conducted to verify QUE's protective effects against intestinal IR injury.Thirty-six SPF-grade male C57BL/6J mice(6～8 weeks old,body weight:22±2 g)were randomly divided into Sham,Sham+QUE,IR,IR+QUE,IR+QUE+erastin(IR+QUE+Era),and IR+QUE+kevetrin hydrochloride(IR+QUE+KH)groups,with 6 mice in each group.Mouse model of intestinal IR injury was induced by 45 min ischemia of the superior mesenteric artery followed by 60 min reperfusion.HE staining was used to observe histopathological changes in the intestinal tissues.ELISA was employed to the serum or intestinal contents of diamine oxidase(DAO),pro-inflammatory cytokines(TNF-α,IL-6,IL-1β),and ferroptosis markers[glutathione(GSH)and Fe2+].Western blotting was utilized to detect the protein expression of glutathione peroxidase 4(GPX4),acyl-CoA synthetase long-chain family member 4(ACSL4),and tumor protein 53(p53).Results ① Network pharmacology identified 460 QUE targets,1 552 intestinal IR injury targets,and 1 967 ferroptosis-related targets,and 92 overlapping genes were identified as potential therapeutic targets.Molecular docking revealed a strong binding affinity between QUE and p53(binding energy:-6.8 kcal/mol).② In vivo experiments demonstrated that the IR+QUE group exhibited reduced intestinal damage and lower Chiu's score(P<0.05),decreased serum DAO content but elevated intestinal DAO content(P<0.05),decreased levels of TNF-α,IL-6,and IL-1β in the serum and intestinal tissues(P<0.05),reduced Fe2+accumulation,and increased GSH content(P<0.05),and up-regulated GPX4(P<0.05)and down-regulated ACSL4 and p53 expression(P<0.05)at protein level when compared with the IR group.While,the administration of ferroptosis agonist Era,or p53 agonist KH resulted in diminished therapeutic effects of QUE(P<0.05)when compared with the IR+QUE group.Conclusion QUE alleviates intestinal IR injury by inhibiting ferroptosis,which may be associated with its down-regulating p53 expression.

Objective To investigate whether remimazolam attenuates intestinal ischemia-reperfusion(I/R)injury in mice by regulating ferroptosis through connexin-43(CX43).Methods Molecular docking was applied to predict the binding affinity of remimazolam to CX43.A total of 72 SPF-grade adult male C57BL/6J mice(6～8 weeks old,weighing 20～25 g)were subjected.Thirty of them were randomly divided into sham operation group(Sham group),I/R group 1,and I/R+10,20 and 40 mg/kg remimazolam groups(RM10,RM20 and RM40 groups),with 6 mice in each group.Another 30 mice were randomly assigned into 5 groups(n=6),I/R group 2,erastin group(E group),I/R+40 mg/kg remimazolam group 2(RM40 group 2),I/R+Fer-1 group(Fer-1 group),and erastin+40 mg/kg remimazolam group(ERM group).The left 12 mice were randomly and equally grouped into I/R+RM+oe-NC group(oe-NC group)and I/R+RM+oe-CX43 group(oe-CX43 group).The Fer-1 group was given an intraperitoneal injection of 5 mg/kg Fer-1 in 1 h prior to reperfusion,the E group was given 10 mg/kg erastin intraperitoneally 1 d before modeling,and all the remimazolam groups,the oe-NC group and the oe-CX43 group were injected intravenously with corresponding doses of remimazolam 30 min pre-modeling,while the oe-NC and oe-CX43 groups were injected with empty vector virus and overexpression of CX43 vector virus,respectively,48 h before the administration of remimazolam.A mouse intestinal I/R injury model was constructed by clamping the superior mesenteric artery for 45 min and reperfusion for 30 min.The small intestine tissues were harvested and observed for pathological changes,and the intestinal mucosal damage was assessed with Chiu's score.The contents of Fe2+,total iron,malondialdehyde(MDA),glutathione(GSH),and superoxide dismutase(SOD)were detected by colorimetric assay;the production of reactive oxygen species(ROS)was determined by DHE probe;the expression of ferroptosis-related genes was determined by RT-qPCR;and the expression levels of CX43,GPX4,and SLC7A11 were detected by Western blotting.Results Molecular docking indicated that remimazolam had a binding energy of-6.699 kcal/mol with CX43 protein,suggesting good binding affinity between them.Compared with the Sham group,the I/R group 1 showed increases in Chiu's scores and CX43 expression(P<0.05),along with pathological damage to intestinal tissues,and elevated contents of Fe2+,total iron,ROS and MDA(P<0.05),and down-regulated GPX4 and SLC7A11(P<0.05).Compared with the I/R group 1,Chiu's score was reduced in the RM40 group,and CX43 was significantly down-regulated(P<0.05),contents of Fe2+,total iron,ROS,and MDA were decreased(P<0.05),and expression levels of GPX4 and SLC7A11 were enhanced(P<0.05),and severity of intestinal histological damage was attenuated in both the RM40 and Fer-1 groups.Compared with the E group,the ERM group had the decreases in CX43 expression level(P<0.05),Fe2+,total iron,ROS,and MDA contents(P<0.05),and increases in GPX4 and SLC7A11 expression levels(P<0.05),with the improvement in intestinal tissue.Compared with the oe-NC group,overexpression of CX43 resulted in the increased CX43 expression,elevated contents of Fe2+,total iron,ROS and MDA(P<0.05)and decreased expression of GPX4 and SLC7A11(P<0.05),leading to the exacerbated injury in intestinal tissue.Conclusion Remimazolam attenuates intestinal I/R injury by inhibiting ferroptosis through down-regulating CX43 expression.

Objective:To investigate the role of group 3 innate lymphoid cells (ILC3) in skin wound healing, and to explore the underlying mechanisms.Methods:Twenty-four 5-week-old male C57BL/6 mice were randomly and equally allocated into 3 groups: the skin wound + ILC3 inhibitor group (referred to as ILC3 inhibitor group), the skin wound group, and the control group, with 8 mice in each group. Four days before the establishment of the wound model, mice in the ILC3 inhibitor group were intraperitoneally injected with 1 &mu;g of ILC3 inhibitor every 2 days for a total of 2 doses, mice in the skin wound group were injected with an equal volume of physiological saline solution, and mice in the control group were fed normally. To establish a mouse skin wound model, a full-thickness circular incision with a diameter of 0.6 cm was made around the midpoint of the dorsal midline using a biopsy punch after the intraperitoneal injection of anesthetics, which was histologically confirmed to be a full-thickness injury. The size of the wounds was observed and recorded, photographs of the wounds were taken on days 0, 1, 3, 5, 7, and 9 after wounding, and corresponding wound healing rates were calculated. On day 9 after wounding, tissue samples were collected from the wound edges, and subjected to flow cytometry analysis to quantify ILC3 infiltrating around the skin wound, and hematoxylin and eosin (HE) staining was performed to assess the healing status of the skin wounds. Real-time quantitative polymerase chain reaction (qRT-PCR) was conducted to determine the mRNA expression of vitamin D receptor (VDR), Notch1, tumor necrosis factor-alpha (TNF-α), interleukin (IL) -17A, IL-17F, and IL-22 in the wound-edge tissues, and Western blot analysis to determine their protein expression. Statistical analysis was carried out by using one-way analysis of variance and t test. Results:On day 9 after wounding, the skin wound group showed an increased number of ILC3 in the wound-edge tissues (5.31% ± 1.47% vs. 3.10% ± 0.54%, P < 0.01), increased mRNA and protein expression of TNF-α, IL-22, IL-17A, and IL-17F (all P < 0.05), but decreased mRNA and protein expression of VDR (both P < 0.05) compared with the control group; the protein expression of Notch1 was significantly higher in the skin wound group than in the control group ( P < 0.05), but there was no significant difference in its mRNA expression between the two groups ( P > 0.05). On days 1, 3 and 5, the wound healing rates were significantly higher in the ILC3 inhibitor group (45.17% ± 9.90%, 61.58% ± 11.61%, 75.61% ± 9.12%, respectively) than in the skin wound group (25.87% ± 10.96%, 47.78% ± 13.81%, 64.55% ± 10.29%, respectively, all P < 0.05). On day 9, the ILC3 inhibitor group showed a decreased number of ILC3 around the wound (2.69% ± 0.95%, P < 0.01), decreased mRNA and protein expression of TNF-α, IL-22, IL-17A, and IL-17F in the wound-edge tissues (all P < 0.05), but increased mRNA and protein expression of Notch1 and VDR in the wound-edge tissues (all P < 0.05) compared with the skin wound group. On day 9 after wounding, histopathological examination with HE staining revealed continuous and intact epithelial structure, as well as dense and neatly arranged collagen fibers in the ILC3 inhibitor group, and the structures of hair follicles, blood vessels, and sebaceous glands were similar to those in the control group. Conclusions:Skin ILC3 infiltrated local wounds and were involved in the skin wound healing process through inflammatory factors such as TNF-α, IL-17A, IL-17F, and IL-22. Downregulating the number of ILC3 may promote skin wound healing by activating VDR and Notch1, as well as inhibiting the TNF-α signaling pathway and the expression of downstream inflammatory factors.

Objective:To evaluate the clinical and ultrasonographic features for early diagnosis and prediction of lateral cervical lymph node metastasis of medullary thyroid microcarcinoma.Methods:From Jan 2010 to Jan 2020 233 patients undergoing primary surgery were categorized as "medullary thyroid microcarcinoma" and "medullary thyroid macrocarcinoma". The preoperative clinical and ultrasonographic characteristics, the diagnostic positive rate of preoperative serum calcitonin and fine needle aspiration (FNA) were investigated between two groups. All patients with medullary thyroid microcarcinoma were divided on the basis of wether there was lateral cervical lymph node metastasis.Results:There were statistically significant differences in initial diagnostic method(χ 2=32.290, P=0.000), TNM staging(χ 2=50.300, P=0.000) between medullary thyroid microcarcinoma and medullary thyroid macrocarcinoma. Medullary thyroid microcarcinoma showed more malignant ultrasonic features. The diagnostic accuracy of preoperative serum calcitonin was higher than FNA for medullary thyroid micro carcinoma(χ 2=47.933, P=0.000). Multivariate regression analysis demonstrated that the abutment/perimeter ≥1/4( OR=25.475, 95%CI: 2.320-279.771), preoperative serum calcitonin >65 ng/L( OR=32.663, 95%CI:2.433-438.409) were the independent factor for lateral cervical lymph node metastases of medullary thyroid microcarcinoma. Conclusions:The combination of ultrasonography and serum calcitonin helps establish early diagnosis of medullary thyroid microcarcinoma. Medullary thyroid microcarcinoma with the abutment/perimeter ≥1/4, serum calcitonin >65 ng/L predicts lateral cervical lymph node metastases.

Objective:To investigate the preliminary effects of sub-pectoral fascial breast augmentation and reconstruction.Methods:Six patients (10 breasts) of mammary dysplasia, mastatrophy, prophylactic mastectomy, unilateral breast defect with contralateral mastatrophy were included in the study from Oct. 2019 to July 2021. The mean patient age was 29 years (range, 20 to 35 years). All the textured and smooth cohesive gel implants were inserted under pectoralis major fascia by endoscopic-assisted, incisions were including axillary, around areola and inferior mammary fold approaches. The prophylactic mastectomy cases were performed nipple sparing mastectomy and sub-pectoral fascial breast restoration with implants. The fat and fascia tissue were well reserved to give a satisfying coverage of the appropriate implant. Negative pressure drainage and moulding dressing were used after the surgery.Results:Ten breast augmentation and restoration with a mean implant size of 200 cc (range, 180-300 cc). Less immediate postoperative pain and bleeding were reported. Patients were followed up for an average of 10 months (range, 6 to 21 months). There were no cases of major malpositions, double-bubble and bottom out symptoms. The overall outcome was with better symmetry and satisfaction with time passed by, and no secondary surgical procedures needed.Conclusions:Primary and satisfactory results have been obtained in subfascial breast augmentation and restoration for indications. With the endoscopic-assisted accurate pectoral fascial dissection, and well reserved soft tissue coverage, this technique could avoid the pectoralis major muscle ablation and keep the advantages of sub-glandular plane.

Objective:To discuss the diagnostic value of superb microvacular imaging (SMI) in renal solid tumors of different sizes.Methods:A total of 142 patients with 146 renal tumors detected by ultrasound in Tianjin Medical University Cancer Institute and Hospital from September 2017 to March 2019 were retrospectively analyzed. The maximum diameter of lesions was 0.8-7.3 cm, and patients were divided into the maximum diameter ≤3.0 cm group (61 patients, 64 lesions) and the maximum diameter >3.0 cm group (61 patients, 82 lesions). All of the tumors were separately evaluated by SMI and color Doppler flow imaging (CDFI) with Adler grade, vascular morphology and peripheral blood flow.Results:In the group with maximum diameter ≤3.0 cm, 50 lesions were malignant and 14 were benign. In the group with maximum diameter >3.0 cm, 62 lesions were malignant and 20 were benign. In the group with maximum diameter ≤3.0 cm, there were no significant differences in location, boundary, echo, homogeneity and small cystic area between malignant tumors and benign tumors ( P>0.05). In the group with maximum diameter >3.0 cm, there were significant differences in echo, homogeneity and small cystic area between malignant tumors and benign tumors ( P<0.05). For all of the benign tumors, there were no significant difference between CDFI and SMI in evaluating Adler grade, vascular morphology and peripheral blood flow ( P>0.05). For malignant tumors with maximum diameter ≤3.0 cm, 43 lesions with Adler grade 2-3 were detected by SMI, which was higher than CDFI (32, P<0.05). There were 38 lesions with dendritic and irregular vascular morphology detected by SMI, which was higher than CDFI (7, P<0.05). The detected rate of peripheral annular or semi-annular blood flow in lesions was 80.0% (40/50), higher than CDFI (18/50, P<0.05). While in malignant tumors with maximum diameter >3 cm, the lesion with peripheral annular or semi-annular blood flow detected by SMI was 38, higher than 22 of CDFI ( P<0.05). The area under the receiver operating characteristic (ROC) curve for CDFI and SMI diagnosis of renal solid tumors with the maximum diameter ≤3.0 cm was 0.627 (sensitivity: 54.0%, specificity: 71.4%) and 0.791 (sensitivity: 94.0%, specificity: 64.3%), respectively, with statistically significant difference ( P=0.039). The area under the ROC curve for CDFI and SMI diagnosis of renal solid tumors with the maximum diameter>3.0 cm was 0.852 (sensitivity: 85.5%, specificity: 85.0%) and 0.860 (sensitivity: 91.9%, specificity: 80.0%), respectively, without statistically significance ( P=0.858). Conclusions:SMI is superior to CDFI in detecting low-velocity blood flow and microvessels in both malignant and benign renal tumors, and can effectively improve the display rate of peripheral blood flow in malignant tumors. Otherwise, SMI can provide better diagnostic efficiency for renal tumors with the maximum diameter ≤3.0 cm.

Objective:To discuss the diagnostic value of superb microvacular imaging (SMI) in renal solid tumors of different sizes.Methods:A total of 142 patients with 146 renal tumors detected by ultrasound in Tianjin Medical University Cancer Institute and Hospital from September 2017 to March 2019 were retrospectively analyzed. The maximum diameter of lesions was 0.8-7.3 cm, and patients were divided into the maximum diameter ≤3.0 cm group (61 patients, 64 lesions) and the maximum diameter >3.0 cm group (61 patients, 82 lesions). All of the tumors were separately evaluated by SMI and color Doppler flow imaging (CDFI) with Adler grade, vascular morphology and peripheral blood flow.Results:In the group with maximum diameter ≤3.0 cm, 50 lesions were malignant and 14 were benign. In the group with maximum diameter >3.0 cm, 62 lesions were malignant and 20 were benign. In the group with maximum diameter ≤3.0 cm, there were no significant differences in location, boundary, echo, homogeneity and small cystic area between malignant tumors and benign tumors ( P>0.05). In the group with maximum diameter >3.0 cm, there were significant differences in echo, homogeneity and small cystic area between malignant tumors and benign tumors ( P<0.05). For all of the benign tumors, there were no significant difference between CDFI and SMI in evaluating Adler grade, vascular morphology and peripheral blood flow ( P>0.05). For malignant tumors with maximum diameter ≤3.0 cm, 43 lesions with Adler grade 2-3 were detected by SMI, which was higher than CDFI (32, P<0.05). There were 38 lesions with dendritic and irregular vascular morphology detected by SMI, which was higher than CDFI (7, P<0.05). The detected rate of peripheral annular or semi-annular blood flow in lesions was 80.0% (40/50), higher than CDFI (18/50, P<0.05). While in malignant tumors with maximum diameter >3 cm, the lesion with peripheral annular or semi-annular blood flow detected by SMI was 38, higher than 22 of CDFI ( P<0.05). The area under the receiver operating characteristic (ROC) curve for CDFI and SMI diagnosis of renal solid tumors with the maximum diameter ≤3.0 cm was 0.627 (sensitivity: 54.0%, specificity: 71.4%) and 0.791 (sensitivity: 94.0%, specificity: 64.3%), respectively, with statistically significant difference ( P=0.039). The area under the ROC curve for CDFI and SMI diagnosis of renal solid tumors with the maximum diameter>3.0 cm was 0.852 (sensitivity: 85.5%, specificity: 85.0%) and 0.860 (sensitivity: 91.9%, specificity: 80.0%), respectively, without statistically significance ( P=0.858). Conclusions:SMI is superior to CDFI in detecting low-velocity blood flow and microvessels in both malignant and benign renal tumors, and can effectively improve the display rate of peripheral blood flow in malignant tumors. Otherwise, SMI can provide better diagnostic efficiency for renal tumors with the maximum diameter ≤3.0 cm.

Objective:To investigate the application effect of reverse abdominal wall advancement flap in repairing chest wall soft tissue defect after breast tumor resection.Methods:From October 2020 to April 2021, the Department of Plastic Surgery and Breast Surgery of Hainan Cancer Hospital cooperated to repair the chest wall wounds of 4 female patients with unilateral giant breast tumors after primary lesion resection. Patients aged 40-63 years old, with an average of 51.5 years old. The size of the tumor estimated by physical examination was 7 cm × 6 cm-15 cm × 20 cm. The flaps were closely monitored after surgery, and complications were recorded. Local recurrence was followed-up.Results:The wound size of 4 patients after mastectomy was 16 cm×14 cm-20 cm×18 cm. Abdomen separation range reached anterior axillary line laterally and contralateral clavicle midline medially. Inferiorly, 1 case reached umbilical level, 1 case reached 2 cm below the umbilicus, and 2 cases reached 3 cm below the umbilicus. Three cases were diagnosed as breast lobulated tumors, and 1 case invasive lobular carcinoma. Among the 4 cases, 3 flaps survived completely and healed by first intention, while another flap healed under blister scab. There was no necrosis, infection, hematoma, seroma, or vascular crisis of the flap. All patients were satisfied. Three patients received radiotherapy and one received radiotherapy combined with oral chemotherapy. All patients were followed up for 3-6 months. No local recurrence was discovered. The abdomen was tighter than before operation, but no stiffness was found. There was no abdominal pain, abdominal wall bulging or abdominal hernia.Conclusions:Reverse abdominal wall advancedment flap was used to repair soft tissue defect of the chest wall after breast tumor resection. The operation was simple and fast, with no need for additional donor site incision. Quick recovery allowed shorter interval between surgery and next scheduled treatments.

Objective:To investigate the application effect of reverse abdominal wall advancement flap in repairing chest wall soft tissue defect after breast tumor resection.Methods:From October 2020 to April 2021, the Department of Plastic Surgery and Breast Surgery of Hainan Cancer Hospital cooperated to repair the chest wall wounds of 4 female patients with unilateral giant breast tumors after primary lesion resection. Patients aged 40-63 years old, with an average of 51.5 years old. The size of the tumor estimated by physical examination was 7 cm × 6 cm-15 cm × 20 cm. The flaps were closely monitored after surgery, and complications were recorded. Local recurrence was followed-up.Results:The wound size of 4 patients after mastectomy was 16 cm×14 cm-20 cm×18 cm. Abdomen separation range reached anterior axillary line laterally and contralateral clavicle midline medially. Inferiorly, 1 case reached umbilical level, 1 case reached 2 cm below the umbilicus, and 2 cases reached 3 cm below the umbilicus. Three cases were diagnosed as breast lobulated tumors, and 1 case invasive lobular carcinoma. Among the 4 cases, 3 flaps survived completely and healed by first intention, while another flap healed under blister scab. There was no necrosis, infection, hematoma, seroma, or vascular crisis of the flap. All patients were satisfied. Three patients received radiotherapy and one received radiotherapy combined with oral chemotherapy. All patients were followed up for 3-6 months. No local recurrence was discovered. The abdomen was tighter than before operation, but no stiffness was found. There was no abdominal pain, abdominal wall bulging or abdominal hernia.Conclusions:Reverse abdominal wall advancedment flap was used to repair soft tissue defect of the chest wall after breast tumor resection. The operation was simple and fast, with no need for additional donor site incision. Quick recovery allowed shorter interval between surgery and next scheduled treatments.

Objective To compare the diagnostic efficiency of superb micro-vascular imaging ( SMI) and power Doppler imaging ( PDI) in differentiating different size breast tumors . Methods Retrospective analysis were performent in a total of 170 cases of breast tumors of 144 patients screened with SMI and PDI in our hospital from August 2016 to July 2017 ,and pathological results were finally obtained . These tumors were divided into two groups according to the maximum diameter 2 .0 cm . SMI and PDI diagnostic efficiency were compared by showing blood flow distribution ,vascular morphology and Alder grade . Results There were 68 benign tumors and 102 malignant tumors .When the maximum diameter was no more than 2 .0 cm ,there were no significant difference in the blood flow distribution ,vascular morphology and Alder grade between PDI and SMI of benign tumors( all P > 0 .05) ;However ,there were significant differences in the vascular morphology and Alder grade of malignant tumors( all P < 0 .05) ,but no difference in blood flow distribution( P = 0 .174) ;The area under the curve of ROC by PDI and SMI were 0 .724 and 0 .844 ,thus , the difference was statistically significant( P = 0 .024) . When the maximum diameter was more than 2 .0 cm ,the between PDI and SMI differences in blood flow distribution ,vascular morphology and Alder grade were not statistically significant ( all P > 0 .05) in benign tumors ,but there was statistical difference in vascular morphology ( P = 0 .001) in malignant tumors ,and there was no significant difference in blood flow distribution ,Alder grade in malignant tumors between PDI and SMI ( all P > 0 .05) . The area under the curve of ROC by PDI and SMI were 0 .768 and 0 .802 ,the difference was not statistically significant ( P = 0 .447) . Conclusions SMI can show the blood flow characteristics more clearly in breast tumors . When the maximum diameter is no more than 2 .0 cm ,SMI diagnostic efficiency is better than PDI .