Identification of the exosomal PD-L1 inhibitor to promote the PD-1 targeting therapy of gastric cancer.

Programmed death 1/programmed death-ligand 1 (PD-1/PD-L1) targeting therapy is widely applied in clinics for gastric cancer treatment. Nevertheless, the clinical response is not well acceptable due to the exosomal PD-L1. Hence, abrogation of the exosomal PD-L1 may be a strategy to sensitize the gastric cancer cell to PD-1 targeting therapy. With the aid of CD63 targeting antibody and PD-L1 targeting aptamer, HTRF based assay was established to quantify the exosomal PD-L1, and applied to our in-house compound library, resulting in the identification of moclobemide. Further optimization of moclobemide lead to EP16, which can inhibit the generation of exosomal PD-L1 with IC50 = 0.108 µM. By applying EP16 to gastric cancer cell line coupled with T-cell activity related experiment, it was validated to activate T-cell and can promote the response of PD-1 targeting therapy for gastric cancer treatment in vitro and in vivo. Collectively, our findings give a promising tool to promote the sensitivity of anti-PD-1 for gastric cancer treatment, and EP16 can serve as a leading compound for exosomal PD-L1 abrogation.

The complete mitochondrial genome sequence of Fragaria orientalis (Rosaceae).

Fragaria orientalis Lozinsk. is valuable germplasm material for cross breeding in Fragaria. In this study, we assembled the complete mitochondrial genome of F. orientalis using a combination of Illumina data and Nanopore data. The mitochondrial genome was 275,143 bp in length, including 29 protein-coding genes, 20 tRNA genes, and three rRNA genes, with a total GC content 45.23%. Seven protein-coding genes contained introns, and three were trans-spliced. Phylogenetic analysis indicated that F. orientalis is making a sister clade to the Amygdaloideae species. The complete mitochondrial genome of F. orientalis reported in this study will improve our understanding of Fragaria evolution.

Vacuum-assisted closure vs. bilateral pectoralis major muscle flaps for deep sternal wounds infection.

BACKGROUND: Deep sternal wound infection (DSWI) is a life-threatening complication after cardiac surgery. The aim of this study was to retrospectively evaluate the outcomes of reconstructing infected poststernotomy wounds with either vacuum-assisted closure (VAC) after previous debridement or bilateral pectoralis major muscle flaps (BPMMFs). METHODS: In total, 565 patients with postoperative DSWI were enrolled in this study from January 1, 2014, to June 1, 2018. Of these patients, 247 received BPMMFs. To address the indicated biases, a 1:1 propensity score-matched cohort was created based on age, body mass index, preoperative diabetes mellitus, chronic obstructive pulmonary disease (COPD), internal thoracic artery grafting (ITAG), type of cardiac surgery, time before treatment for DSWI and wound classification. After matching, 132 patients who had similar risk profiles were enrolled in the study population (66 in the VAC group: 66 in the BPMMF group). RESULTS: At 21.9±12.1 (median: 24, IQR: 14-28) months of follow-up, the survival rate was 93.9% in the BPMMF group and 74.4% in the VAC group (P<0.01). Compared with the VAC group, the BPMMF group had a significantly decreased length of hospital stay (P<0.01). At the spirometry assessment, the forced expiratory volume in the 1st second (FEV1), vital capacity (VC), and FEV1/VC ratio showed no significant differences in survival between the VAC group and BPMMF group. CONCLUSIONS: In our study, compared with VAC therapy, BPMMFs guaranteed better early- and late-term outcomes, as shown by less length of hospital stay, a higher rate of long-term survival and unimpaired respiratory function.

Gao's double-way approach for laparoscopic D2 radical surgery for gastric cancer.

Laparoscopic D2 radical surgery for gastric cancer is minimally invasive but complex. In this path: (1) Repeated operation of lesser curvature side; (2) The gastrohepatic ligament is relatively fixed. Hence, it is not easy to expose the suprapancreatic area; and (3) It is not easy to dissect No. 1, 12 lymph nodes. This area may not be sufficiently cleaned or surrounding vessels may be injured during a resection. So it is critical to choose position fixing, and a clear, fast and convenient operation path. The author, based on his experience, has established a set of procedural steps called "Gao's double-way", lesser omentum approach and traditional greater omentum approach, which are described in detail in this article. The path of this first approach is described as a "W" type of dissection. The second way is the traditional greater omentum approach, whose path is described as a "M" type of dissection. This will enable laparoscopic surgeons to select a suitable path. This new approach not only simplifies the surgery but also provides more space for the subsequent operation, thereby making the surgery more simple, safe and easy.

Sternal reconstruction of deep sternal wound infections following median sternotomy by single-stage muscle flaps transposition.

OBJECTIVE: To assess clinical effectiveness of using bilateral pectoralis major or plus rectus abdominis muscle flaps in treating deep sternal wound infection (DSWI) following median sternotomy. METHODS: Between January 2009 and December 2013, 19 patients with DSWI after median sternotomy for cardiac surgery were admitted to our hospital, including 14 males (73.7%) and 5 females (26.3%), aged 55±13 (18-78) years. According to the Pairolero classification of infected median sternotomies, 3 (15.8%) patients were type II, and the other 16 (84.2%) were type III. Surgical procedure consisted of adequate debridement of infected sternum, costal cartilage, granulation, steel wires, suture residues and other foreign substances. Sternal reconstruction used the bilateral pectoralis major or plus rectus abdominis muscle flaps to obliterate dead space. The drainage tubes were placed and connected to a negative pressure generator for adequate drainage. RESULTS: There were no intraoperative deaths. In 15 patients (78.9%), bilateral pectoral muscle flaps were mobilized sufficiently to cover and stabilize the defect created by wound debridement. 4 patients (21.0%) needed bilateral pectoral muscle flaps plus rectus abdominis muscle flaps because their pectoralis major muscle flaps could not reach the lowest portion of the wound. 2 patients (10.5%) presented with subcutaneous infection, and 3 patients (15.8%) had hematoma. They recovered following local debridement and medication. 17 patients (89.5%) were examined at follow-up 12 months later, all healed and having stable sternum. No patients showed infection recurrence during the follow-up period over 12 months. CONCLUSION: DSWI following median sternotomy may be effectively managed with adequate debridement of infected tissues and reconstruction with bilateral pectoralis major muscle or plus rectus abdominis muscle flap transposition.

Nude mice model of human hepatocellular carcinoma via orthotopic implantation of histologically intact tissue.

AIM: To establish a nude mice model of human hepatocellular carcinoma (HCC) via orthotopic implantation of histologically intact tissue, in order to study biologic features of HCC in vivo and to direct clinical treatment respectively. METHODS: Histologically intact fresh specimens of HCC were orthotopically implanted in nude mice (BALB/c, nu/nu). Survival rate and growth curve were investigated with B-ultrasound. Morphological characteristics of pathology and spontaneous metastatic rates were detected with microscopy. Expression of multidrug resistance genes studied with immunohistochemical method and RT-PCR, and other biologic features of implanted tumor were observed and compared with human HCC specimens. RESULTS: Out of the specimens from two patients with HCC, only one specimen survived in nude mice. The orthotopic implantation tumor survival rate, spontaneous intrahepatic metastatic rate, pulmonary metastatic rate and bone metastases rate were 100%, 75.0%, 37.5% and 37.5% respectively in the first passage. AFP was kept on secreting and increasing with the size of the tumor. The morphological characteristics and biologic features were similar to the donor's, the protein and mRNA of MDR1 and LRP were expressed in tumors of the model and the donor, and there was no significant difference between them (P>0.05). CONCLUSION: The model of nude mice with orthotopic implantation of histologically intact HCC tissue is an ideal model to study biologic features of HCC in vivo and to direct clinical treatment.