Objective To explore the efficacy of a new anti-heart failure drug,Entresto,in the prevention of cardiotoxicity caused by doxorubicin(DOX).Methods Male adult ICR mice were randomly divided into three groups(n = 8):control group,DOX group and DOX plus Entresto group.Cardiac function of mice was measured by echocardiography.H9c2 cells were pretreated with Entresto(0-48 μmol/L)for 24 hours in the presence or absence of DOX(1 mmol/L),and then cell viability,oxidative stress,apoptosis and mitochondrial function were evaluated.Results As compared with the control group,leakage of CK,CK-MB and LDH increased significantly in the DOX group(P<0.01),and left ventricular systolic dysfunction occurred.Entresto administration reversed these changes in the DOX group.The level of ROS and the number of apoptotic cells in cardiomyocytes in the DOX plus Entresto group were lower than those in the DOX group(P<0.05).As compared with the DOX group,the level of ROS and the number of apoptotic cells in H9c2 cells decreased significantly in the Entresto plus DOX group(P<0.05),and mitochondrial membrane potential increased significantly(P<0.05).Entresto reversed the inhibitory effect of DOX on SIRT1/PGC-1α/MFN2 signaling pathway.Conclusions Entresto improves DOX-induced cardiotoxicity by inhibiting ROS-mediated oxidative stress and apoptosis,and its mechanism may be related to SIRT1/PGC-1α/MFN2 signal transduction pathway.

Objectives:To explore the causal relationship between body mass index,uric acid and congestive heart failure(CHF),and provide genetic evidence to support the association between uric acid-mediated body mass index and the risk of CHF. Methods:Using the published data set of genome-wide association studies(GWAS)in East Asia,inverse variance weighting(IVW)method was used as the main analysis method,and MR-Egger method,weighted median model(WME),simple model and weighted model were used to analyze the causal relationship between body mass index,uric acid and CHF.MR-Egger regression was used to detect pleiotropy,Cochran Q test was used to detect heterogeneity,leave-one-out sensitivity was used to detect bias,funnel plot was drawn to detect bias,and MR-PRESSO package was used to remove outlier single nucleotide polymorphism(SNP).After Mendelian analysis,the mediating effect ratio was calculated,and the reverse Mendelian randomization study results between body mass index,uric acid and CHF were analyzed. Results:IVW method showed that body mass index(OR=1.685,95%CI:1.417-2.003,P<0.001)and uric acid(OR=1.225,95%CI:1.087-1.380,P<0.001)were risk factors of CHF in two-sample Mendelian analysis.Body mass index(OR=1.204,95%CI:1.139-1.273,P<0.001)was a risk factor for uric acid.The mediating effect of uric acid was 7.23%.The P values of MR-Egger regression intercept terms were all>0.05,that is,there was no pleiotropy of the selected SNP,and the causal inference method was valid.The Cochran Q test P values of body mass index and uric acid,and body mass index and CHF were<0.01,indicating heterogeneity.IVW analysis of CHF and body mass index in reverse Mendelian analysis was OR=0.977,95%CI:0.947-1.008,P>0.05 and CHF and uric acid was OR=1.000,95%CI:0.963-1.038,P>0.05,so the reverse causal inference was not valid.However,the analysis of uric acid and body mass index showed pleiotropy,so the causal inference method was invalid. Conclusions:There is a causal and positive correlation between body mass index and CHF.There is a causal relationship and positive correlation between uric acid and CHF.However,uric acid is an incomplete mediator between body mass index and CHF.

Objective:To investigate the clinical outcomes of Ortho-Bridge Combination System (OBCS) to achieve precise ulna-shortening osteotomy (USO) in the treatment of ulnar impaction syndrome.Methods:A retrospective study was conducted to analyze the 25 patients with ulnar impaction syndrome who had been treated at Institute of Orthopedic Trauma Research, The 920th Hospital of Joint Logistic Support Force of Chinese People's Liberation Army between January 2020 to March 2022. The patients all underwent USO using OBCS. They were 14 females and 11 males with an age of (43.2 ± 10.1) years. Their CT scans were retrieved for preoperative planning and design of a personalized USO. Intraoperatively, OBCS was fixated to the ulna before USO. After the bone was resected according to preoperative planning, the gap between the osteotomy sites was closed with compression, and OBCS was finally fixated with locking screws. The time for bone union after resection, complications, range of motion and grip strength were recorded. The clinical outcomes were evaluated by visual analogue scale (VAS) and Mayo wrist score.Results:All patients completed their operations successfully using OBCS. Their follow-up time was (13.5 ± 1.2) months. The ulnar variation was corrected and osteotomy ends got united in all patients, without nonunion, angulation, or rotation. The wrist VAS significantly decreased from 6.0 (5.0, 6.5) points before operation to 2.0 (1.0, 2.0) points at the last follow-up ( P<0.05). At the last follow-up, the Mayo wrist score [(85.4 ± 8.9) points], grip strength [(39.4 ± 1.2) kg], wrist flexion-extension (111.9° ± 12.6°), wrist pronation-supination (133.2° ± 15.7°), and ulnar radial deviation (35.3° ± 2.8°) were significantly increased compared with the preoperative values [(69.2 ± 13.3) points, (31.3 ± 5.2) kg, 102.0° ± 16.0°, 128.0° ± 15.5°, and 32.2° ± 2.8°] ( P<0.05). Conclusion:In the treatment of ulnar impaction syndrome, OBCS can facilitate the process of USO, correct ulnar variance, and avoid complications like rotation and angulation to improve functions of the wrist.

Objective:To investigate the efficacy of digital reconstruction technology in assisted design of lobulated deep inferior epigastric perforator flap (DIEPF) for surgical reconstruction of large defect in lower extremity.Methods:From January 2017 to January 2022, a study was carried out to retrospectively analyse 8 patients who had massive soft tissue defects in lower extremities were admitted in the Department of Orthopaedic Surgery of the 920 Hospital of Joint Logistic Support Force of Chinese PLA. The size of defects varied from 16.0 cm×12.0 cm-28.0 cm×22.0 cm. CTA scans were performed over abdominal aorta and the arteries of lower extremities. Three-dimensional model of DIEPF and vascular pedicles were reconstructed by Mimics software. According to the shape and size of the wound, targeted perforators were determined on the 3D images, and precisely mapped in a digitised rectangular coordinate system. The lobulated flap was then digitally designed in the 3D coordinate system. Flaps were harvested according to preoperative digital designs for the reconstruction of large defects in the lower extremities. The donor site was sutured directly. The flaps and recovery of lower extremities were observed though postoperative follow-ups and were conducted through visits of outpatient clinics and distance interviews via telephone and WeChat. Recoveries of lower extremities were evaluated using Maryland ankle-foot function scoring system.Results:The 3D reconstructed models of the vessels in donor sites were successfully completed for all patients. The harvests of lobulated DIEPF were successfully guided by the digital designs. Fifteen lobes of lobulated DIEPF survived successfully in all 8 patients. All donor sites were closed in the stage-I. Necrosis occurred at the distal tip of a lobulated flap due to a local venous occlusion, and healed after debridement and re-suture. Four patients received further flap debulking surgery. Time of postoperative follow-ups had ranged 15-27 months, with an average of 20 months. At the last follow-up, all the flaps had satisfactory appearance with linear scars at the donor sites. All fractures were healed. Five patients achieved Maryland's ankle-foot function score in excellent, 2 in good, and 1 was acceptable.Conclusion:Digital reconstruction technology can accurately map the perforators and reasonably assist the design of lobulated flaps. A lobulated DIEPF offers a wider area for flap excision and allows a primary closure of the donor sites. Combination of the 2 advantages of a lobulated DIEPF can be effectively applied in reconstruction of a large-sized defect in lower extremity.

ObjectiveTo investigate effect of astragaloside Ⅳ on the proliferation， migration， and invasion of colorectal cancer HCT116 cells and the underlying molecular mechanism. MethodColorectal cancer HCT116 cells were classified into blank group （DMSO） and low-dose （15.7 mg·L^-1）， medium-dose （31.4 mg·L^-1）， and high-dose （62.8 mg·L^-1） astragaloside Ⅳ groups. After drug treatment， the morphological changes of HCT116 cells were observed under an inverted microscope. Cell viability was detected by cell counting kit-8 （CCK-8） assay， and the migration and invasion of cells were detected based on scratch assay and Transwell assay. The expression of cyclin-dependent kinase inhibitor （p21）， CyclinD₁， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein （Bax） in the cells was examined by Western blot. ResultCompared with the blank group， cells in the three astragaloside Ⅳ groups demonstrated slow growth， low density， inconsistent morphology， nuclear shrinkage， degradation of cytoplasm， and high death rate. Moreover， cell viability decreased in a concentration-dependent manner in the astragaloside Ⅳ groups. Cell migration and invasion were inhibited （P<0.05， P<0.01）， and the inhibition rate was in positive correlation with the concentration of the astragaloside Ⅳ. The expression of pro-apoptotic protein Bax in low-dose， medium-dose and high-dose astragaloside Ⅳ groups increased gradually in a concentration-dependent manner， while the expression of p21， CyclinD₁ and anti-apoptotic protein Bcl-2 decreased gradually in a concentration-dependent manner compared with those in the blank group （P<0.05， P<0.01）. ConclusionAstragaloside Ⅳ can suppress the proliferation， migration， and invasion of colorectal cancer HCT116 cells and promote the apoptosis， thus inhibiting the occurrence and development of colorectal cancer.

Objective To investigate the effect of imatinib on the growth of A549 non-small cell lung cancer transplanted tumors and the expression of PDGFB and PDGFRβ proteins in tumor tissues and stroma in nude mice and to explore the underlying tumor suppression mechanism. Methods A transplantation tumor model of A549 non-small cell lung cancer was established in nude mice. The mice were then randomly divided into four groups: control group (0.9%NaCl), low-dose imatinib group (50 mg/(kg·d)), medium-dose imatinib group (100 mg/(kg·d)), and high-dose imatinib group (200 mg/(kg·d)). The effect of different concentrations of imatinib administered by continuous gavage on tumor growth was observed for 28 days. HE staining was performed to observe the pathological changes of tumor tissues. The expression of PDGF/PDGFR pathway-related proteins and the phosphorylation levels of AKT and ERK1/2 proteins in tumor tissues were detected by Western blot analysis. Double immunofluorescence staining was used to detect the expression of PDGFB and PDGFRβ proteins in the tumor stroma. Results Imatinib inhibited the growth of A549 non-small cell lung cancer cells in nude mice, suppressed the expression of PDGFB in tumor tissues, and decreased the phosphorylation levels of PDGFRβ, AKT, and ERK1/2. The expression of PDGFB and PDGFRβ in tumor stromal fibroblasts of the administered group was significantly lower than that of the control group. Conclusion Imatinib exhibits a pronounced inhibitory effect on A549 xenografts of nude mice with non-small cell lung cancer, and its antitumor mechanism may involve the downregulation of PDGFB and PDGFRβ expression in tumor stromal fibroblasts.

Objective:To introduce the concept and procedures of precise flap surgery in construction of knee defects and to report the preliminary clinical outcomes.Methods:The data of 16 patients with knee defects at 17 sides were retrospectively analyzed who had been treated under the guidance of the concept of precise flap surgery at Department of Orthopedic Surgery, The 920th Hospital of Joint Logistic Support Force of PLA from August 2014 to March 2022. There were 12 males and 4 females, aged 44(34, 54) years. The wounds were at the left side in 8 cases, at the right side in 7 ones and at bilateral sides in one, and their sizes ranged from 5 cm×3 cm to 15 cm×11 cm. The time from injury to surgery was 8.5(6.0, 13.0) days. Optimal repair protocols were chosen after the donor and recipient sites were evaluated according to the methods of precise flap surgery: a retrograde anterolateral thigh flap in 7 sides, a descending genicular artery perforator flap in 3 ones, a saphenous artery flap in 2 ones, and a superior genicular lateral artery perforator flap, a popliteal artery perforator flap, a medial sural perforator propeller flap, a peroneal artery perforator propeller flap, and a randomized flap in one, respectively. The flap sizes ranged from 10 cm×6 cm to 15 cm×15 cm. The outcomes and complications of skin flap repair, and functional recovery of the affected limb were recorded.Results:All the flaps at 17 sides survived after surgery; 3 cases developed distal edge necrosis which responded to dressing change. The follow-ups for the 16 patients were 14.5(10.0, 28.0) months. All the flaps presented with good color, texture and contour. Flap bulking, local osteomyelitis, and scar ulcer was found in one case respectively. According to the revascularization assessments in the digital replantation criteria by Hand Surgery Society, Chinese Medical Association, all the flaps at 17 sides were excellent. Accoding to the knee functional evaluation of Hospital for Special Surgery (HSS) at the last follow-up, the 17 affected limbs scored 86(80,91) points, yielding 9 excellent, 7 good and 1 fair sides.Conclusion:Although the defects and donor sites around the knee vary greatly, precise flap surgery may lead to effective control of the variations, choice of an optimal reconstruction protocol, and precise wound repair.

【Objective】 To research the genetic polymorphism of HPA 1-6/10/15/21 in platelet donors in Zhongshan area, and establish a gene bank of platelet donors with HPA locus. 【Methods】 The HPA 1-6/10/15/21 system genotyping was performed by Real time fluorescent PCR combined with TaqMan probe technology on 192 platelet donors in Zhongshan area, and the genotype frequency and gene frequency were calculated. 【Results】 Only HPA-aa genotype was found within HPA-4/10, and no allele HPA-b had been detected. The majority of HPA-1, 2, 5, 6 and 21 genotypes were aa. HPA-3 and HPA-15 showed high heterozygosity, with genotype frequency of 0.307 3, 0.494 8 and 0.197 9 for HPA- 3aa, HPA-3ab and HPA-3bb, while 0.270 8, 0.505 2 and, 0.224 0 for HPA -15aa, HPA-15ab and HPA-15bb, respectively. 【Conclusion】 The distribution characteristics of HPA 1-6 /10/15/21 of platelet donors in Zhongshan shows regional differences compared with similar researches from other regions. The establishment of HPA gene bank is helpful to avoid alloimmunization caused by incompatible platelet transfusion.

Objective:To estimate the preliminary result of circumflex scapular perforator propeller flap in reconstruction of axillary scar contractures.Methods:From January 2016 to June 2021, circumflex scapular perforator propeller flaps were used in 7 cases for reconstruction of soft tissue defect after axillary scar contractures. Patients were 5 males and 2 females. Age ranged from 23 to 38 years old, mean age of 27.7 years old. According to Kurtzman and Stern classification of axillary scar contractures, there were 1 case with type 1a, 1 with type 1b, 2 with type 2, and 3 with type 3. The preoperative range of motion of the shoulder joint were 40°-85°, with an average of 63.7°. All the patients were underwent scar release and circumflex scapular perforator propeller flap transfer. All flaps were transferred as the manner of perforator propeller flap. All the donor sites were closed directly. The defects after releasing ranged from 5.0 cm×7.0 cm to 11.0 cm×9.0 cm, and the flaps ranged from 16.0 cm×7.0 cm to 24.0 cm×9.0 cm. Flap survival, complications of donor site and recipient site were recorded after surgery. The range of motion of the shoulder joint, donor and recipient sites were reviewed in outpatient clinic.Results:All flaps survived uneventfully after surgery, besides 1 case complicated with distal venous congestion. The follow-up time ranged from 6 to 23 months, with an average of 12 months. The texture and contour of the flaps were good in all. At last follow-up, the range of motion of the shoulder joints were 90°-120°, with an average of 107°. Mild scar hyperplasia occurred in 2 cases.Conclusion:The circumflex scapular perforator propeller flap is an effective protocol in reconstruction of axillary scar contractures.

Objective:To investigate the clinical value of digital technology in repair of soft tissue defect in hand by anterior tibial artery perforator flap.Methods:From January 2015 to February 2021, 9 patients with soft tissue defects in hand were repaired with anterior tibial artery perforator flap assisted by digital technology in flap design, including 6 males and 3 females aged from 19 to 63 years with a mean age of 33 years. The size of defects varied from 2.0 cm×1.5 cm to 4.0 cm×3.0 cm, with exposed bones or tendons. Preoperative CTA scan of lower limb was performed and three-dimensional image was reconstructed with Mimics 20.0. The anterior tibial artery perforator flap was designed according to the shape and size of the defect, then the resection of flap was digitally simulated. The flap based on the digital design was harvested and the defect was repaired in the operation. The size of flap was 2.5 cm×2.0 cm~4.5 cm×3.5 cm. Outpatient clinic follow-up was performed to evaluate the survival of flaps. Disability of Arm, Shoulder and Hand(DASH) was used for function evaluation.Results:All flaps were harvested successfully and all donor sites were closed directly. After surgery, 8 flaps survived completely. One flap developed venous occlusion that showed partial necrosis of the flap, and it was rescued after exploration and re-anastomosis. The follow-up period ranged from 6 to 21 months, with an average of 13 months. The DASH scores of the affected limb were 2 to 15 points at the last follow-up, with an average of 6.4 points. Mild scar hyperplasia occurred at donor site in 1 case without sensory abnormality.Conclusion:The digital technology is able to accurately locate the perforators by allowing an individualised design of the anterior tibial artery perforator flap. The flap is suitable for repair of small and medium-sized soft tissue defect in hand, and the digital technology has certain value in clinical application.