Tumor is a system-biology illness.Treatment of this intractable disease by any single medicine has not been realistic.In this review, we analyze the anti-tumor network of Tumor Necrosis Factor-related Apoptosis-indu-cing Ligand ( TRAIL ) by a system-biology technology and try to providecin individualized treatment strategy for TRAIL based therapy .

The reversible phosphorylation plays an important regulatory role in various pathological and physiological processes. Src Homology 2 domain containing protein tyrosine phosphatase (SHP2),a featured member of the protein tyrosine phosphatase family,is identified as the first PTP proto-oncogene. SHP2 is associated with breast cancer,leukemia,lung cancer,liver cancer,gastric cancer,laryngeal cancer,oral cancer and other types of cancer. Signalling pathways involving SHP2 have also been discovered. It has been recently reported that the high expression of SHP2 in lung cancer regulates cancer cell proliferation,metastasis and drug resistance. SHP2 may be a potential thera?peutic target because it is implicated in many diseases. This article focuses on the research progress in functions of SHP2 in lung cancer.

Aim To investigate the antinociception, tolerance and withdrawal abstinence of δ/μ/κ opioid receptor triple agonist KUST201 ( DPI-125 ) in rats. Methods Male Sprague-Dawley rats were used to de-termine the time course of analgesic effects and ED50 effects of co-administration of naltrindole were assessed as well. In withdrawal experiments, KUST201 was ad-ministrated twice daily for 3 d with increasing doses each day. On the 4th day, the rats were given a single dose, challenged with naloxone 3 h later, and signs of abstinence were monitored. Results The ED50 values of KUST201 were 0. 34 mg·kg-1 in tail-pinch test and 0. 68 mg · kg-1 in hot-plate test. The antinociception actions of KUST201 started to decrease 1 h after ad-ministration, and disappeared after 2 h. In chronic tol-erance experiments, the antinociception actions started to decrease on d 3 , and completely disappeared on d 7 . Naltrindole could reduce the antinociceptive action of KUST201. In withdrawal experiments, abstinence scores increased significantly in the dose range between 2~8 times of tail-pinch ED50 . Conclusion Compared with previously reported δ/μ/κ triple agonist DPI-3290 , KUST201 exhibits similar antinociceptive effects in rats. The chronic tolerance to KUST201 actions de-velops less quickly, but the abstinence scores of KUST201 are slightly higher. The activation of δ-opi-oid receptor can synergistically enhance the antinoci-ception mediated by μ-receptor.

Objective By constructing the differential expression profile of lncRNA/mRNA in peripheral blood plasma of patients with Keshan disease (KSD) and dilated cardiomyopathy (DCM),to explore the commonality and characteristics of the two diseases in molecular mechanism.Methods Ten patients with chronic KSD were selected in the severe disease area of KSD in Shandong Province,and 10 cases of DCM and 10 healthy subjects (control group) were selected in non-KSD area.Blood of elbow vein was collected and plasma was separated.RNA-seq technology was used to construct the differential lncRNA/mRNA expression profile between KSD and control group,DCM and control group,and co-expression and specific expression of partial genes in KSD and DCM were analyzed through Wien analysis.The lncRNA-mRNA co-expression network maps of specific part of KSD,specific part of DCM and common part of the two diseases were constructed,and Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were applied to distinguish the biological function of the two diseases.Results Compared with control group,102 dysregulated mRNAs and 22 dysregulated lncRNAs showed the same trend in KSD and DCM.And 3 606 mRNAs and 451 lncRNAs were only differentially expressed in KSD group,217 mRNAs and 137 lncRNAs were only differentially expressed in DCM group.The differentially expressed lncRNA/mRNA shared between the KSD and DCM groups were mainly about viral transcription,immuno-inflammatory response,oxidative stress signaling pathways.The KSD specific lncRNA/mRNA mainly participated in cell membrane damage and viral myocarditis.The DCM specific lncRNA/mRNA mainly regulated mitochondrial structure and oxidative phosphorylation related enzymes.Conclusion The differentially expressed lncRNA/mRNA shared in KSD and DCM groups are mainly involved in viral transcription,oxidative stress signaling pathways;KSD specific lncRNA/mRNA are mainly related to cell membrane damage and viral myocarditis;DCM specific lncRNA/mRNA mainly regulate mitochondrial structure.

Objective:Through differential miRNA expression profiles and bioinformatics in the peripheral blood of patients with Keshan disease (KD) and healthy control, to explore the possible pathogenesis of KD.Methods:Ten patients with chronic KD (KD group) were selected in the severe disease area of KD in Wulian County, and 10 healthy subjects (control group) were selected in non-KD area of Dongchangfu District, Shandong Province. Blood sample of elbow vein was collected and plasma was separated. RNA-seq technology was used to construct the differential expression profiles of miRNA in KD and control groups. Target mRNAs were screened using Starbase, miRTarBase, miRDB and TargetScan. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted to investigate the possible pathogenesis of KD.Results:Compared the control group and KD group, 132 differentially expressed miRNAs were screened out, including 90 upregulated and 42 downregulated miRNAs. Through Starbase, miRTarBase, miRDB and TargetScan, 53 miRNAs were obtained, 737 targeted mRNAs were obtained. GO analysis showed that the differential genes were mainly involved in the biological processes of Ras protein signal transduction, transmembrane transport, cell cycle regulation, cell adhesion, etc. KEGG pathway analysis showed that the differential genes were mainly involved in viral infection, endocytosis, adhesion spot and actin regulation.Conclusion:In this study, RNA-seq technology is used to obtain differential miRNA expression profiles of KD patients and healthy control, and target pathogenic genes and signaling pathways that may be related to KD are screened out.

Objective:To investigate the clinical effect of free posterior tibial artery perforator flap in repair of forefoot soft tissue defect.Methods:From January 2017 to January 2021, a retrospective study was conducted on 13 patients with forefoot soft tissue defect, metatarsal head exposed, and forefoot transverse arch integrity, including 9 males and 4 females. The age was (40.0±13.0) years old. Cause of injury: 8 cases of traffic accident injury, 5 cases of heavy object smashing injury. Seven cases had forefoot skin defect and toe damage, and 6 cases had forefoot skin avulsion injury, open toe fracture with tendon, blood vessel and nerve injury. The wound area was 4.5 cm×3.0 cm-8.0 cm×6.0 cm. VSD treatment was performed in the first stage, and free posterior tibial artery perforator flap was used for the second stage. The flap area was 5.5 cm×4.0 cm-9.0 cm×7.0 cm. Outpatient reviews scheduled at 1, 2, 3, and 6 months after surgery, through outpatient clinic, telephone or WeChat. The flaps were evaluated according to appearance, texture, sensory recovery, and the American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hind foot function scoring system.Results:All 13 flaps survived. The follow-up lasted for 6 to 24 months. The feet were in good shape, walking with weight beries, and the flaps had satisfactory appearance without wear and tear. Five cases were S 3, 6 were S 2, and 2 were S 1. According to AOFAS ankle-hindfoot function score, 4 had excellent scores, 7 were in good, and 2 in fair. Conclusion:The free posterior tibial artery perforator flap has relatively constant perforators, and the pedicle of the middle and upper perforators is longer, and the flap can build part of the sensation. Posterior artery perforator flap is a good flat for repairing the soft tissue defects of the metatarsal head of the forefoot.

Objective:To investigate the clinical effect of turbocharged large free anterolateral thigh flaps (ALTF) by anastomosis with a superior perforator of the flap in reconstruction of large soft tissue defects of limbs.Methods:From June 2017 to June 2021, 6 patients with large soft tissue defects of limbs with exposed joints and tendons were treated in the Department of Hand and Foot Surgery of the Affiliated Hospital of Qingdao University with turbocharged large free ALTFs. The pressurised blood supply of ALTF was achieved by anastomosing a superior perforating branch carried in the flap. Such large and turbocharged ALTFs were used to repair large soft tissue defects with exposed joints and tendons in limbs. Of the 6 patients, there were 4 males and 2 females, and aged 32-60(46.0±8.1) years old. Cause of injury: 5 by traffic accident and 1 by machine crush. Four patients had soft tissue defects in lower limbs: 2 with open tibia and fibula fractures, 1 had patellar defect and fibula fracture, and 1 associated with fibula fracture. The other 2 patients had soft tissue defect in upper limbs with bone and tendon exposed but without fracture. The sizes of wound were 25.0 cm×12.0 cm-35.0 cm×19.0 cm. In the primary surgery, Vacuum sealing drainage (VSD) was applied. In the second stage, free ALTFs were used to cover the wound. The area of flap incision was increased by anastomosing the superior perforators and as the consequence, the size of flaps was achieved to 26.0 cm×13.0 cm-36.0 cm×15.0 cm. Donor site of 6 cases were reduced by direct suture, and the remaining wound was covered by free skin graft. Postoperative follow-ups were conducted at outpatient clinic reviews at 1, 2, 3 and 6 months after surgery, and followed by telephone or WeChat interviews. The results of the operation were evaluated according to the appearance, texture and sensory recovery of the flap.Results:All 6 flaps survived and the patients completed the postoperative follow-up that lasted for 6-24 (16.7±5.0) months. No necrosis of flap occurred after surgery. The appearance and texture of the flaps were satisfactory without wear and tear. Sensation recover was evaluated by the standered of British Medical Research Council (BMRC), 4 patients recovered to S 3 and 2 patients to S 2. The Mayo score of the elbow joint was good in 2 patient with upper extremity injuries. Of the other 4 patients with lower limb injuries, the knee function evalued by Hospital for Special Surgery(HSS) score were excellent in 3 patients and good in 1 patient, and the American Orthopedic Foot and Ankle Societ(AOFAS) ankle-hind foot function score was excellent in 2 patients and good in 2 patients. There was no infection or function loss at all donor sites. Conclusion:The perforator of an ALTF is relatively constant, and the flap can partially restore sensation. The superior perforator is reliable and the incision area of the flap can be enlarged by anastomosing the superior perforator vessels. It is a better way to reconstruct a large soft tissue defects in limbs.

Objective:To analyze the influencing factors of gout patients and explore whether there is an interaction between serum uric acid and diastolic blood pressure affecting the onset of tophi.Methods:A total of 4 798 gout patients were retrospective selected in the outpatient Department of the Gout Clinical Medical Center of the Affiliated Hospital of Qingdao University from September 2016 to May 2020. It was divided into tophi group and non-tophi group to compare the differences in indicators. A logistic regression model was used to analyze the influencing factors of tophi, and an interaction model was constructed to analyze the interactions.Results:Multivariate logistic regression analysis showed significant associations between age, diastolic blood pressure, alcohol consumption history, gout family history, blood uric acid, urea nitrogen, and creatinine clearance and tophi formation. The results of blood uric acid-related interaction analysis showed a significant interaction between blood uric acid and diastolic blood pressure( Pinteraction=0.014), and the risk of developing tophi in low diastolic blood pressure and high diastolic blood pressure group increased by 34.4%( OR=1.344, 95% CI 1.105-1.635, P=0.003) and 95.4%( OR=1.954, 95% CI 1.558-2.450, P<0.001) in the high blood uric acid group compared with the low blood uric acid group. The results of diastolic blood pressure and blood uric acid subgroup analysis showed that there was no statistical difference in the risk of developing tophi in people with low uric acid levels( P=0.238), but in people with high uric acid levels, the risk of developing tophi was 67%( OR=1.670, 95% CI 1.379-2.022, P<0.001) higher than that in the low uric acid group. Conclusion:Age, diastolic blood pressure, combined alcohol consumption history and gout family history, blood uric acid, renal function are related to the occurrence of tophi. High uric acid and high diastolic blood pressure have interaction on the occurrence of tophi. Attention and proactive intervention shall be applied to this group of patients.