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Objective: To explore medium and long term efficacy of oblique lateral interbody fusion (OLIF) in treating lumbar specific infection., Methods: From October 2017 to January 2021, 24 patients with lumbar specific infection were treated by OLIF combined with vertebral screw internal fixation, including 15 males and 9 females, aged from 27 to 61 years old with an average of (43.0±15.0) years old;the courses of disease ranged from 6 to 24 months with an average of (14.0±7.0) months;7 patients with L 2 -L 3 , 12 patients with L 3 -L 4 and 5 patients with L 4 -L 5 ;19 patients with tuberculosis infection and 5 patients with brucella infection. The amount of intraoperative blood loss, operative time and complications were recorded, and erythrocyte sedimentation rate(ESR), C-reactive protein (CRP), visual analogue scale (VAS), Japanese Orthopaedic Association(JOA) score and American Spinal Injury Association (ASIA) rating were compared before and one month after opertaion., Results: All patients were followed up from 9 to 24 months with an average of (13.0±6.0) months. Operative time was (132.5±21.4) min, and intraoperative blood loss was (227.3±43.1) ml. ESR and CRP were decreased from (82.34±18.62) mmol·h -1 and (53.08±21.84) mg·L -1 before operation to (33.52±17.31) mmol·h -1 and (15.48±8.36) mg·L -1 at one month after operation, respectively ( P <0.05). VAS was decreased from (7.52±1.36) before opertaion to (1.74±0.87) at one month after operation ( P <0.05). JOA was increased from (17.86±3.95) before operation to (24.72±3.19) at one month after operation ( P <0.05). Four patients had neurological symptoms before operation, and were classified to grade D according to ASIA classification, who were recovered to grade E at 1 month after operation. One patient was suffered from psoas major muscle injury after operation, and returned to normal at 3 weeks. One patient was suffered from abdominal distension and difficulty in defecation, and relieved after gastrointestinal decompression and enema. No complications such as abdominal organ injury and poor wound healing occurred in all patients., Conclusion: OLIF combined with vertebral screw internal fixation is a new minimally invasive surgical method for the treatment of lumbar specific infection, especially the lesion located on the middle lumbar vertebra. It has advantages of less trauma, short operation time, less blood loss, convenient operation, complete removal of the lesion, safety and effectiveness, and has good medium-and long-term efficacy for lumbar specific infection.

In addition to the classical resistance mechanisms, receptor tyrosine-protein kinase AXL is a main mechanism of resistance to third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) osimertinib in EGFR-mutated non-small cell lung cancer (NSCLC). Developing an effective AXL inhibitor is important to sensitize osimertinib in clinical application. In this study we assessed the efficacy of brigatinib, a second-generation of anaplastic lymphoma kinase (ALK)-TKI, as a novel AXL inhibitor, in overcoming acquired resistance to osimertinib induced by AXL activation. We established an AXL-overexpression NSCLC cell line and conducted high-throughput screening of a small molecule chemical library containing 510 anti-tumor drugs. We found that brigatinib potently inhibited AXL expression, and that brigatinib (0.5 μM) significantly enhanced the anti-tumor efficacy of osimertinib (1 μM) in AXL-mediated osimertinib-resistant NSCLC cell lines in vitro. We demonstrated that brigatinib had a potential ability to bind AXL kinase protein and further inhibit its downstream pathways in NSCLC cell lines. Furthermore, we revealed that brigatinib might decrease AXL expression through increasing K48-linked ubiquitination of AXL and promoting AXL degradation in HCC827OR cells and PC-9OR cells. In AXL-high expression osimertinib-resistant PC-9OR and HCC827OR cells derived xenograft mouse models, administration of osimertinib (10 mg·kg -1 ·d -1 ) alone for 3 weeks had no effect, and administration of brigatinib (25 mg·kg -1 ·d -1 ) alone caused a minor inhibition on the tumor growth; whereas combination of osimertinib and brigatinib caused marked tumor shrinkages. We concluded that brigatinib may be a promising clinical strategy for enhancing osimertinib efficacy in AXL-mediated osimertinib-resistant NSCLC patients., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Twenty-nine 12 N-substituted aloperine derivatives were synthesized and screened for suppression on PD-L1 expression in H460 cells, as a continuation of our work. Systematic structural modifications led to the identification of compound 6b as the most active PD-L1 modulator. Compound 6b could significantly down-regulate both constitutive and inductive PD-L1 expression in NSCLC cells, and successively enhance the cytotoxicity of co-cultured T cells against tumor cells at the concentration of 20 μM. Also, it exhibited a moderate in vivo anticancer efficacy against Lewis tumor xenograft with a stable PK and safety profile. The mechanism study indicated that 6b mediated the degradation of PD-L1 through a proteasome pathway, rather than a lysosome route. These results provided the powerful information for cancer immunotherapy of aloperine derivatives with unique endocyclic skeleton by targeting PD-L1 to activate immune cells to kill cancer cells., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Cisplatin has been reported to promote the expression of programmed cell death ligand-1 (PD-L1) in some cancer cells. However, the underlying mechanism through which PD-L1 is transcriptionally regulated by cisplatin in hepatocellular carcinoma (HCC) cells remains largely unknown. In the present study, we found that the expression of hepatocyte growth factor (HGF), p-Akt, p-ERK, and PD-L1 was increased in cisplatin-treated SNU-368 and SNU-739 cells. HGF stimulation also increased PD-L1 expression in these cells. Moreover, Inhibition of HGF/c-MET, PI3K/Akt, and MEK/ERK signaling pathways can dramatically block cisplatin or HGF-induced PD-L1 expression in SNU-368 and SNU-739 cells. In vivo, combination PHA665752 with cisplatin significantly reduced tumor weight with increased infiltration of CD8 +  T cells in the tumor. Taken together, our study suggested that HGF/c-Met axis-induced the activation of PI3K/Akt and MEK/ERK pathways contributes to cisplatin-mediated PD-L1 expression. These findings may provide an alternative avenue for the treatment of HCC., (© 2021 International Federation for Cell Biology.)

Objective: To investigate the expression of Long non-coding RNA ADIPOQ and its facilitating effects on proliferation and invasion of colorectal cancer by modulating the expression of TP53 via sponging with miR-219c-3p., Patients and Methods: qRT-PCR was performed to detect the expressions of ADIPOQ and TP53 in human colorectal cancer tissues and cells. CCK-8 assay was performed to evaluate the Caco-2 cells proliferation and transwell assay was performed to evaluate the Caco-2 cells migration. The relationship between ADIPOQ and miR-219c-3p was detected by statistical analysis. Target prediction and Luciferase activity assay were conducted to investigate the binding site and interaction between ADIPOQ and miR-219c-3p. Further, we cloned the mice TP53 3'-UTR into the Luciferase reporter vector and constructed miR-219c-3p binding mutants to verify the inhibited regulation of miR-219c-3p to the TP53 expression., Results: The results suggested that the expression of ADIPOQ and TP53 was downregulated in human colorectal cancer tissues and Caco-2 cells. qRT-PCR and CCK-8 assay showed that ADIPOQ expression is correlated with the proliferation of colorectal cancer cells. Transwell assay showed that ADIPOQ regulated the migration ability of colorectal cancer cells. The bioinformatics prediction and Luciferase assay demonstrated that ADIPOQ serves as ceRNA for miR-219c-3p to further regulate the expression of TP53., Conclusions: For the first time, we found that lncRNA-ADIPOQ was downregulated in human colorectal cancer cells, which could facilitate tumor proliferation, migration and invasion as a ceRNA by sponging with miR-219c-3p.

Multicistronic vectors can increase transgene expression and decrease the imbalance of gene expression in the Chinese hamster ovary (CHO) cell expression system. Small, self-cleaving 2A peptides have a high cleavage efficiency and are essential for constructing high-expression multicistronic vectors. In this study, we investigated the effects of two different 2A peptides on transgene expression in CHO cells via their mediating action on tricistronic vectors. The enhanced green fluorescent protein (eGFP) and red fluorescent protein (RFP) genes were linked by the porcine teschovirus-1 (P2A) and Thosea asigna virus (T2A) peptides in a multicistronic vector. We transfected CHO cells with these vectors and screened for the presence of blasticidin-resistant colonies. Flow cytometry and real-time quantitative PCR (qPCR) were used to detect the expression levels of eGFP and RFP and the copy numbers of stably transfected cells. The results showed that P2A could enhance eGFP and RFP expression by 1.48- and 1.47-fold, respectively, compared to T2A. The expression levels of the genes were not proportional to their copy numbers. In conclusion, we found that P2A can effectively drive transgene expression in CHO cells and a potent 2A peptide can be used for recombinant protein production in the CHO cell system.

Objective: Epithelial ovarian cancer (EOC) is a common gynecologic malignancy characterized by extensive peritoneal metastasis and high mortality rate. ABHD11 Antisense RNA1 (ABHD11-AS1) has recently been identified as a regulator of growth and metastasis in multiple tumors, including EOC. However, the biological function and potential mechanism of ABHD11-AS1 in EOC remains poorly understood., Methods: Immunohistochemistry, western blot, and qRT-PCR analysis were used to determine the expression pattern of ABHD11-AS1 and epidermal growth factor receptor (EGFR) in both EOC tissues and cell lines, respectively. Colony formation, transwell and wound healing assays were performed to evaluate the roles of EGFR and ABHD11-AS1 on the capacity of cell proliferation, migration, and invasion. Western blot analysis was performed to measure the regulation of EGFR pathway on STAT3. Moreover, chromatin immunoprecipitation was employed to demonstrate the interaction between ABHD11-AS1 and STAT3. RNA immunoprecipitation was subjected to prove the direct binding between ABHD11-AS1 and EZH2. Immunofluorescence staining was performed to measure the expression and localization of TIMP2. EOC mouse model was conducted for validating the role of ABHD11-AS1 in vivo., Results: EGFR and ABHD11-AS1 were highly expressed in EOC tissues and cell lines. Knockdown of EGFR or ABHD11-AS1 inhibited cell growth, migration, and invasion of EOC cells. Expression of ABHD11-AS1 was regulated by the activation of EGFR signaling pathway, mediated by STAT3. Besides, ABHD11-AS1 was shown to silence TIMP2 by binding to chromatin-modifying enzyme EZH2. Furthermore, inhibition of EGFR pathway or ABHD11-AS1 repressed the tumor growth of EOC., Conclusion: We defined the regulatory relationship between the EGFR signaling pathway, ABHD11-AS1, EZH2, and TIMP2 suggesting that ABHD11-AS1 may act as an oncogene and a potential target for antitumor therapies in ovarian cancer., (© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background : Ovarian cancer (OC) is the gynecologic malignant tumor with high mortality. Accumulating evidence indicates that M2-like tumor-associated macrophages (TAMs) can secret EGF to participate in ovarian cancer growth, migration, and metastasis. An EGF-downregulated lncRNA, LIMT (lncRNA inhibiting metastasis), was identified as a critical regulator of mammary cell migration and invasion. Nevertheless, whether EGF secreted from M2-like TAMs regulates LIMT expression in ovarian cancer progression remains largely unknown. Methods : The human OC cell lines OV90 and OVCA429 were recruited in this study. The differentiation of the human monocyte cell line THP-1 into M2-like TAMs was confirmed using flow cytometry within the application of phorbol 12-myristate 13-acetate (PMA). ELISA was performed to detect EGF concentration in co-culture system of M2-like TAMs and OC cell lines. Moreover, CCK-8, flow cytometry and immunofluorescence staining of Ki67 were performed to assess the capacity of cell proliferation. Besides, cell migration and invasion were determined by wound healing and transwell assays. Furthermore, the expression levels of epithelial-mesenchymal transition (EMT) markers and EGFR/ERK signals were analyzed by qRT-PCR and western blot. Female athymic nude mice (8-12 weeks of age; n = 8 for each group) were recruited for in vivo study. Results : In the present study, THP-1 cells exhibited the phenotype markers of M2-like TAMs with low proportion of CD14 + marker and high proportion of CD68 + , CD204 + , CD206 + markers within the application of PMA. After co-culturing with M2-like TAMs, EGF concentration in the supernatants was significantly increased in a time-dependent manner. Besides, OC cells presented better cell viability, higher cell proliferation, and stronger migration and invasion. The expression of EMT-related markers N-cadherin, Vimentin and EGFR/ERK signals were markedly up-regulated, while E-cadherin was significantly decreased. However, these effects induced by co-culture system were reversed by the application of AG1478 (an EGFR inhibitor) or LIMT overexpression. Furthermore, the endogenous expression of LIMT was decreased in OC cell lines compared with the control group. Also, the in vivo experiments verified that the inhibition of EGFR signaling by AG1478 or overexpression of LIMT effectively repressed the tumor growth. Conclusion : Taken together, we demonstrated that EGF secreted by M2-like TAMs might suppress LIMT expression via activating EGFR-ERK signaling pathway to promote the progression of OC.

Nickel phosphide-embedded graphene, prepared by the hydrothermal reaction of red phosphorus, nickel chloride, and graphene oxide in a mixture of ethylene glycol-water, is investigated as the counter electrode of DSSCs. It is demonstrated that the DSSC with the nickel phosphide-embedded graphene as the new counter electrode presents an excellent performance competing with that of the Pt electrode.

Objective: Explore the relationship between lumbar Epidural Pressure (LEDP) and CSFP through clinical studies and to determine whether LEDP can represent CSFP., Methods: We selected 150 cases of cerebral diseases at random for this study. A special mini transducer was implanted into the lumbar epidural space between the third and the 4th lumbar vertebra by means of a No. 18 Touhy needle for monitoring of LEDP. In the meantime, a traditional lumbar puncture was made between the 4th and the 5th lumbar vertebrae and CSFP, which was taken as the standard value, was measured using an ordinary catheter. The transducer was adjusted until the LEDP was equal to CSFP and was designated LEDP0. The LEDP0 was monitored continuously and was translated into a continuous curve. In each and every case, a lumbar puncture was repeated at 24, 48, 72 and 96 hours to obtain CSFP for comparison and to explore the relationship between LEDP0 and CSFP. While monitoring LEDP0, we observed the variation in pressure when the patient breathed, coughed, changed posture, and also if the clinical symptoms changed with intracranial hypertension., Result: The values of the intracranial pressure measured by these two methods were identical., Conclusion: LEDP responded to the changes of CSFP.