[Gene mutation characteristics of clinical stage â A lung adenocarcinoma and their relations with patients' long-term prognosis].

Objective: To explore the gene mutation characteristics and the relationship between gene mutations and long-term prognosis in clinical stage ⅠA lung adenocarcinoma patients. Methods: A retrospective analysis was conducted on 63 clinical stage ⅠA lung adenocarcinoma patients who underwent surgical resection at the Cancer Hospital of the Chinese Academy of Medical Sciences from January 2007 to October 2012, with documented postoperative recurrence or metastasis, as well as those who had a follow-up duration of 10 years or more without recurrence or metastasis. Whole exome sequencing (WES) technology was used to analyze the gene mutation profiles in tumor tissues and univariate and multivariate Cox regression analysis were used to clarify the influencing factors for patient prognosis. Results: After long term follow-up, 13 out of the 63 patients (21%) experienced recurrence or metastasis. WES technology analysis revealed that the most common tumor related gene mutations occurred in epidermal growth factor receptor (EGFR), with a mutation rate of 65.1% (41/63), followed by tumor protein p53 (TP53), fatatypical cadherin 1 (FAT1), low density lipoprotein receptor-related protein 1B (LRP1B), mechanistic target of rapamycin (MTOR), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma (PIK3CG), and SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4 (SMARCA4), with mutation rates of 30.2% (19/63), 20.6% (13/63), 15.9% (10/63), 15.9% (10/63), 15.9% (10/63), and 15.9% (10/63), respectively. Multivariate Cox regression analysis showed that PIK3CG mutations (HR=21.52, 95% CI: 3.19-145.01),smoothened (SMO) mutations (HR=35.28, 95% CI: 3.12-398.39), catenin beta 1 (CTNNB1) mutations (HR=332.86, 95% CI: 15.76-7 029.05), colony stimulating factor 1 receptor (CSF1R) mutations (HR=8 109.60, 95% CI: 114.19-575 955.17), and v-Raf murine sarcoma viral oncogene homolog B (BRAF) mutations (HR=23.65, 95% CI: 1.86-300.43) were independent risk factors affecting the prognosis of clinical stage ⅠA lung adenocarcinoma patients. Conclusions: PIK3CG, SMO, CTNNB1, CSF1R, BRAF gene mutations are closely related to long-term recurrence or metastasis in clinical stage ⅠA lung adenocarcinoma. Patients with these gene mutations should be given closer clinical attention.

[Dyspnea with multiple bilateral lung opacities on CT scan].

A 58-year-old man was admitted with a typical presentation of acute left heart failure. However, the patient showed a partial response to the anti-heart failure therapy. Following admission, a continuous fever was monitored, and a CT scan revealed that multiple opacities on bilateral lungs had progressed. Bronchoscopy was performed, and Coxiella burnetii was detected by Metagenomic next-generation sequencing (mNGS) in bronchoalveolar lavage (BALF), and transbronchial lung biopsy showed organizing pneumonia. Considering that the patient had a history of rabbit breeding and delivery, with some newborn rabbits dying before he became ill, organizing pneumonia secondary to Q fever pneumonia was diagnosed. Anti-Q fever treatment was initiated and the patient's temperature returned to normal. Glucocorticoid was administered after adequate treatment for Q fever. The patient's symptom of dyspnea relieved soon and opacities on CT scan were absorbed remarkably. The final diagnosis was organizing pneumonia secondary to Q fever pneumonia accompanied with left heart failure.

[Opportunities and challenges in accurate early diagnosis and treatment of lung cancer/pulmonary nodules].

Lung cancer remains the most prevalent and lethal malignancy in our country. Early diagnosis and treatment are crucial for improving patient prognosis in lung cancer/pulmonary nodules. Recent advancements in non-invasive/minimally invasive liquid biopsy, multi-omics, and artificial intelligence technologies have significantly enhanced the accuracy of early lung cancer/pulmonary nodule diagnosis. However, an early diagnostic method with both high sensitivity and specificity is yet to be established. Furthermore, addressing the methods and extent of early precision surgery, local precision therapy, perioperative combined treatment, and postoperative recurrence and metastasis monitoring are urgent challenges in the early management of lung cancer/pulmonary nodules. Integrating the advantages of various treatment strategies and formulating personalized and precise treatment plans is key to further improving patient survival. In the future, while exploring new therapeutic strategies, it is necessary to continuously search for biomarkers to identify the population that will benefit from the treatment effectively. Additionally, large-sample randomized controlled clinical studies should be conducted to investigate the benefits of long-term patient survival under a diverse range of treatment strategies.

[Clinical characteristics and surgical outcomes in pediatric progressive restrictive strabismus].

Objective: To investigate the clinical features, imaging manifestations, histopathological characteristics, and surgical outcomes in pediatric progressive restrictive strabismus. Methods: A retrospective case series study was conducted, including data from 9 cases (9 eyes) of pediatric progressive restrictive strabismus treated at Tianjin Eye Hospital from June 2017 to October 2022. The study compared the degree of globe protrusion in both eyes, changes in eyelid fissure height during internal and external rotation in the primary gaze, summarized clinical characteristics, and analyzed intraoperative conditions, surgical outcomes and postoperative histopathological results of strabismus correction surgery. Statistical analysis was performed using Wilcoxon signed-rank test and Friedman two-way analysis of variance. Results: All 9 cases involved unilateral onset, with 4 males and 5 females. Three cases affected the right eye, and six affected the left eye. Onset age ranged from 2 to 40 months. The degree of globe protrusion in the affected eyes was 13.00 (12.00, 13.00) mm for the right eye and 12.00 (12.00, 13.50) mm for the left eye, with no statistically significant difference (Z=-1.00, P=0.317). There were no significant changes in eyelid fissure height during internal rotation [8.00 (7.25, 8.00) mm], primary gaze [7.50 (7.00, 8.00) mm], and external rotation [8.00 (7.75, 8.00) mm] in the affected eyes (χ²=1.00, P=0.607). No apparent abnormalities were observed in head CT or MRI scans, serum, or immunological tests. However, orbital CT or MRI scans indicated thickening of different extraocular muscle bellies. Six out of nine cases underwent strabismus correction surgery, and postoperative examination revealed restriction in eye movement despite achieving orthophoria in the primary gaze. Tissue pathology of three cases showed increased collagen fiber proliferation in one, scattered bundles of smooth muscle fibers amid diffuse collagen fiber proliferation in another, and abnormal proliferation of striated muscle fibers with varying diameters, increased paired box (PAX)7-positive satellite cells expressing slow muscle myosin in the third case. Conclusions: Pediatric progressive restrictive strabismus presents with restrictive changes, without significant alterations in globe protrusion and eyelid fissure height. Imaging examinations reveal thickening of the extraocular muscle bellies in the affected eye. Although strabismus correction surgery improves eye position, postoperative eye movement remains restricted. Histopathological findings in some cases show abnormal proliferation of skeletal muscle fibers or collagen fibers.

[A comparative study of the curative effects between butterfly-shaped flap and propeller flap based on the dorsal branch of digital artery in repairing the wound in volar aspect of finger].

Objective: To compare the curative effects of butterfly-shaped flap based on the dorsal branch of digital artery (hereinafter referred to as butterfly-shaped flap) and propeller flap based on the dorsal branch of digital artery (hereinafter referred to as propeller flap) in repairing the wound in volar aspect of finger. Methods: A retrospective cohort study was conducted. From August 2018 to April 2022, 16 patients with finger palmar wounds admitted to Ruijin Hospital of Shanghai Jiao Tong University School of Medicine and 7 patients with finger palmar wounds admitted to General Hospital of PLA Central Theater Command met the inclusion criteria, including 14 males and 9 females, aged 25 to 64 years. After debridement or resection of skin benign tumor, the wounds ranged from 0.5 cm×0.5 cm to 1.5 cm×1.5 cm. According to the different rotation axes of flap pedicle during wound repair, the patients were divided into butterfly-shaped flap group (8 cases) and propeller flap group (15 cases), and their wounds were repaired by butterfly-shaped flap (with area of 0.5 cm×0.5 cm-1.5 cm×1.3 cm) or propeller flap (with area of 0.7 cm×0.5 cm-1.5 cm×1.5 cm) , respectively. In propeller flap group, wounds in the donor sites were repaired by full-thickness skin grafts taken from the palms of wrists or the groin. The surgical time, postoperative complications, flap survival, and wound healing time of patients in the two groups were recorded. Data were statistically analyzed with independent sample t test, Mann Whitney U test, or Fisher's exact probability test. Results: The surgical time and postoperative wound healing time of patients in butterfly-shaped flap group ((43±9) min and (13.1±0.8) d, respectively) were both significantly shorter than those in propeller flap group ((87±16) min and (16.7±4.6) d, respectively, with t values of -7.03 and -2.86, respectively, P<0.05). The postoperative flap survival and complications of patients between the two groups were both similar (P>0.05). Conclusions: For repairing the wound in volar aspect of finger, the butterfly-shaped flap has more advantages in comparison with the traditional propeller flap. The butterfly-shaped flap has a short surgical time and fast postoperative recovery, which is worthy of clinical promotion.

[Treatment and prognosis analysis of 488 patients with FIGO 2018 stage â ¢c squamous cervical cancer].

Objective: To analyze the treatment and prognosis of patients with International Federation of Gynecology and Obstetrics (FIGO) 2018 stage Ⅲc cervical squamous cell carcinoma. Methods: A total of 488 patients at Zhejiang Cancer Hospital between May, 2013 to May, 2015 were enrolled. The clinical characteristics and prognosis were compared according to the treatment mode (surgery combined with postoperative chemoradiotherapy vs radical concurrent chemoradiotherapy). The median follow-up time was (96±12) months ( range time from 84 to 108 months). Results: (1) The data were divided into surgery combined with chemoradiotherapy group (surgery group) and concurrent chemoradiotherapy group (radiotherapy group), including 324 cases in the surgery group and 164 cases in the radiotherapy group. There were significant differences in Eastern Cooperation Oncology Group (ECOG) score, FIGO 2018 stage, large tumors (≥4 cm), total treatment time and total treatment cost between the two groups (all P<0.01). (2) Prognosis: ① for stage Ⅲc1 patients, there were 299 patients in the surgery group with 250 patients survived (83.6%). In the radiotherapy group, 74 patients survived (52.9%). The difference of survival rates between the two groups was statistically significant (P<0.001). For stage Ⅲc2 patients, there were 25 patients in surgery group with 12 patients survived (48.0%). In the radiotherapy group, there were 24 cases, 8 cases survived, the survival rate was 33.3%. There was no significant difference between the two groups (P=0.296). ② For patients with large tumors (≥4 cm) in the surgery group, there were 138 patients in the Ⅲc1 group with 112 patients survived (81.2%); in the radiotherapy group, there were 108 cases with 56 cases survived (51.9%). The difference between the two groups was statistically significant (P<0.001). Large tumors accounted for 46.2% (138/299) vs 77.1% (108/140) in the surgery group and radiotherapy group. The difference between the two groups was statistically significant (P<0.001). Further stratified analysis, a total of 46 patients with large tumors of FIGO 2009 stage Ⅱb in the radiotherapy group were extracted, and the survival rate was 67.4%, there was no significant difference compared with the surgery group (81.2%; P=0.052). ③ Of 126 patients with common iliac lymph node, 83 patients survived, with a survival rate of 65.9% (83/126). In the surgery group, 48 patients survived and 17 died, with a survival rate of 73.8%. In the radiotherapy group, 35 patients survived and 26 died, with a survival rate of 57.4%. There were no significant difference between the two groups (P=0.051). (3) Side effects: the incidence of lymphocysts and intestinal obstruction in the surgery group were higher than those in the radiotherapy group, and the incidence of ureteral obstruction and acute and chronic radiation enteritis were lower than those in the radiotherapy group, and there were statistically significant differences (all P<0.01). Conclusions: For stage Ⅲc1 patients who meet the conditions for surgery, surgery combined with postoperative adjuvant chemoradiotherapy and radical chemoradiotherapy are acceptable treatment methods regardless of pelvic lymph node metastasis (excluding common iliac lymph node metastasis), even if the maximum diameter of the tumor is ≥4 cm. For patients with common iliac lymph node metastasis and stage Ⅲc2, there is no significant difference in the survival rate between the two treatment methods. Based on the duration of treatment and economic considerations, concurrent chemoradiotherapy is recommended for the patients.

[Research and application of the SARS-CoV-2 vaccine based on adenovirus vector technology platform].

During the global efforts to prevent and control the COVID-19 pandemic, extensive research and development of SARS-CoV-2 vaccines using various technical approaches have taken place. Among these, vaccines based on adenovirus vector have gained substantial knowledge and experience in effectively combating potential emerging infectious diseases, while also providing novel ideas and methodologies for vaccine research and development (R&D). This comprehensive review focuses on the adenovirus vector technology platform in vaccine R&D, emphasizing the importance of mucosal immunity induced by adenoviral vector-based vaccine for COVID-19 prevention. Furthermore, it analyzes the key technical challenges and obstacles encountered in the development of vaccines based on the adenovirus vector technology platform, with the aim of providing valuable insights and references for researchers and professionals in related fields.

Bioinformatics-based design of a fusion vaccine with CTLA-4 variable region to combat Brucella

Brucellosis has become a global zoonotic disease, seriously endangering the health of people all over the world. Vaccination is an effective strategy for protection against Brucella infection in livestock in developed countries. However, current vaccines are pathogenic to humans and pregnant animals, which limits their use. Therefore, it is very important to improve the safety and immune protection of Brucella vaccine. In this study, different bioinformatics approaches were carried out to predict the physicochemical properties, T/B epitope, and tertiary structure of Omp2b and Omp31. Then, these two proteins were sequentially linked, and the Cytotoxic T lymphocyte associated antigen-4 (CTLA-4) variable region was fused to the N-terminal of the epitope sequence. In addition, molecular docking was performed to show that the structure of the fusion protein vaccine had strong affinity with B7 (B7-1, B7-2). This study showed that the designed vaccine containing CTLA-4 had high potency against Brucella, which could provide a reference for the future development of efficient brucellosis vaccines.

IFITM3 restricts virus-induced inflammatory cytokine production by limiting Nogo-B mediated TLR responses.

Interferon-induced transmembrane protein 3 (IFITM3) is a restriction factor that limits viral pathogenesis and exerts poorly understood immunoregulatory functions. Here, using human and mouse models, we demonstrate that IFITM3 promotes MyD88-dependent, TLR-mediated IL-6 production following exposure to cytomegalovirus (CMV). IFITM3 also restricts IL-6 production in response to influenza and SARS-CoV-2. In dendritic cells, IFITM3 binds to the reticulon 4 isoform Nogo-B and promotes its proteasomal degradation. We reveal that Nogo-B mediates TLR-dependent pro-inflammatory cytokine production and promotes viral pathogenesis in vivo, and in the case of TLR2 responses, this process involves alteration of TLR2 cellular localization. Nogo-B deletion abrogates inflammatory cytokine responses and associated disease in virus-infected IFITM3-deficient mice. Thus, we uncover Nogo-B as a driver of viral pathogenesis and highlight an immunoregulatory pathway in which IFITM3 fine-tunes the responsiveness of myeloid cells to viral stimulation.

[Application of acellular bovine pericardium patch in implant based immediate breast reconstruction].

Objective: To examine the clinical effect of acellular bovine pericardium patch in implant based immediate breast reconstruction. Methods: The clinicopathological information of 141 breast cancer patients, who admitted to Department of Breast Reconstruction and Oncoplastic Surgery, Tianjin Medical University Cancer Hospital, underwent immediate mammoplasty with implants combined with acellular bovine pericardium patches were analyzed from June 2016 to October 2019. All patients were female, with the age of (38.8±8.5) years (range: 13 to 60 years). The body mass index was (21.9±2.5) kg/m2 (range: 16.0 to 32.3 kg/m2). There were 39 cases of duct carcinoma in situ, 46 cases of stage Ⅰ, 40 cases of stage Ⅱ and 16 cases of stage Ⅲ. All patients received nipple-areola-sparing mastectomy or skin-sparing mastectomy with sentinel lymph node biopsy or axillary lymph node dissection, and prosthesis implantation with sub-pectoralis combined with breast patch. The correlation of clinicopathological characters and complications was assessed by t test, χ2 test, Fisher's exact probability method and Logistic regression. Pre-and post-operative aesthetic, quality of life scores were recorded. Results: The operation time (M(IQR)) was 3.6(1.5) hours (range: 3.0 to 6.5 hours). The early postoperative complication rate was 22.0% (31/141), prosthesis removal was the main postoperative complication, accounting for 64.5% (20/31) of the total complications, of which 15 cases occurred in the first 30 patients. The follow-up time was 28(8) months (range: 20 to 53 months), The most frequent long-term complications were capsular contracture and implant displacement, with the incidence of 11.2% (14/125) and 10.4% (13/125), respectively. Multivariate analysis showed that prosthesis volume ≥300 ml (OR=8.173, 95%CI: 1.302 to 51.315, P=0.021) and peri-areolar incision (OR=7.809, 95%CI: 2.162 to 28.211, P<0.01) were independent relative factors for the occurrence of short-term postoperative local complications. After 2 years of operation, the score of breast appearance satisfaction was 71.7±15.5, postoperative effect satisfaction was 90.4±9.5, psychological satisfaction was 90.7±17.1, sexual satisfaction was 70.1±25.1. The immediate postoperative satisfaction rate at discharge was 95.4% (134/141), and 17.6% (22/125) of patients had the intention to received revision surgery. Conclusions: Prosthesis volume ≥300 ml and peri-areolar incision were independent realtive factors for short-term local complications after bovine pericardium patch combined with prosthesis implantation in the immediate breast reconstruction. After completing the learning curve, the postoperative complications of the procedure could be decreased.

[The composition of ascites lymphocytes in high-grade serous ovarian cancer and its correlation with clinical features].

Objective: To explore the composition of ascites lymphocytes in high-grade serous ovarian carcinoma (HGSOC) and its correlation with clinical features. Methods: A total of 59 newly-diagnosed HGSOC patients, aged (58±11) years old, who were treated at the Department of Obstetrics and Gynecology of Peking University Third Hospital from July 2019 to December 2020 were included, collecting ascites and peritoneal irrigation fluid respectively. Detect the proportion of T, B, NK cell and its subpopulations by flow cytometry, and analyze its correlation with the clinical characteristics of patients. Results: Among 59 patients, 48 patients (81.4%) had ascites, and 11 patients (18.6%) had no ascites. Compared with the peritoneal irrigation fluid, the CD3+T (70.2%±15.6% vs 78.1%±6.7%, P=0.014), CD8+T (38.3%±11.2% vs 47.7%±10.1%, P=0.014) and CD16-CD56bright NK [2.0% (0.8%, 3.6%) vs 4.2% (1.5%, 7.1%), P=0.026] cells were significantly decreased in the ascites, while the CD16+CD56dim NK cells was significantly increased [6.8% (2.8%, 15.7%) vs 2.6% (1.6%, 4.3%), P=0.008]. In patients with ascites volume ≥1 000 ml, CD16-CD56bright NK cells were significantly increased than those ascites volume<1 000 ml [3.1% (1.2%, 3.9%) vs 0.8% (0.4%, 2.3%), P=0.002]. Age was significantly positively correlated with the level of CD4+T cells (r=0.332, P=0.021) and the ratio of CD4+T/CD8+T (r=0.379, P=0.008) in ascites. In ascites from patients with poor response to treatment, the proportion of CD4+T cells was increased significantly than those with better response (64.7%±4.2% vs 48.3%±11.7%, P=0.002). Conclusion: The formation of ascites in newly diagnosed high-grade serous epithelial ovarian cancer patients would affect the lymphocyte composition in the abdominal cavity microenvironment, which is related to the patient's age, cancer progression and treatment response.

Acellular bovine pericardium matrix in immediate breast reconstruction compared with conventional implant-based breast reconstruction.

BACKGROUND: Acellular Bovine Pericardium Matrix (ABPM) is a new material in implant-based breast reconstruction (IBBR). Few studies have reported on its outcome and complications worldwide and most studies were without a control group. Our aim was to compare its use in IBBR with the other two conventional implant-based reconstruction methods. METHODS: A retrospective review of patients undergoing IBBR from January to December 2018 was performed. Patients were assigned to the ABPM-assisted IBBR (group A), latissimus dorsi-assisted IBBR (group B) and two-stage IBBR (group C). Patients' post-operative complications, cost-effectiveness and Quality of Life were compared. RESULTS: 100 patients with 100 breasts were included in the study. No complications occurred in group C (n = 11). No significant differences were noted between group A (n = 44) and group B (n = 45) in terms of overall complications (9.1% vs 11.1%, p = 0.973). Group B had the longest operative duration (310.8 ± 62.3 min, p<0.001). The cost of hospitalization forthe three groups was $8051.3 ± 849.2, $7566.0 ± 1172.7 and $7896.5 ± 1762.2, respectively (p = 0.128). The postoperative Breast-Q scores  were similar across the three groups. CONCLUSIONS: ABPM demonstrated acceptable complication rates, cost-effectiveness and quality of life outcomes when compared to LD-assisted IBBR and two-stage IBBR.

Value of intravoxel incoherent motion and diffusion kurtosis imaging in predicting peritumoural infiltration of soft-tissue sarcoma: a prospective study based on MRI-histopathology comparisons.

AIM: To investigate the performance of intravoxel incoherent motion (IVIM) and diffusion kurtosis imaging (DKI) in the identification of peritumoural infiltration of soft-tissue sarcoma (STS). MATERIALS AND METHODS: From July 2018 to January 2020, 34 STS patients who underwent 3-T magnetic resonance imaging (MRI), including IVIM and DKI, were reviewed. The standard apparent diffusion coefficient (ADC), true diffusion (D), pseudo-diffusion coefficient (D∗), perfusion fraction (f), mean kurtosis (MK), and mean diffusion (MD) of each lesion were analysed independently by two observers. An MRI-histopathology control method was used to ensure the correspondence of MRI sections with histopathological sections. Differences in STS with and without infiltration were evaluated. The area under the curve (AUC) was used to determine the best cut-off point for different parameters. Interobserver agreement was assessed using the intraclass correlation coefficient. RESULTS: Standard ADC, D, MK, and MD values reliably distinguished STS that had positive and negative infiltration. The MD value had the best diagnostic performance. Use of an MD cut-off value of 2.35 × 10-3 mm2/s to distinguish positive and negative infiltration had an AUC of 0.85, accuracy of 88.2%, sensitivity of 94.4%, and specificity of 81.3%. The two independent observers had nearly perfect agreement for all parameters. CONCLUSION: The standard ADC and D value of IVIM, and the MK and MD values of DKI reliably identify the presence of peritumoural infiltration of STS.

[Multimodality navigation for liver resection of complicated alveolar echinococcosis].

Objective: To investigate the clinical application of multimodality navigation for liver resection in the treatment of complicated alveolar echinococcosis (AE). Methods: From October 2019 to February 2020, the clinical data and perioperative results of patients with AE treated by surgery in our department were retrospectively studied. Hepatic parenchyma disconnection plane and liver resection were navigated and performed with three-dimensional reconstruction and HITACHI real-time multi-image fusion interventional navigation system (RVS). Results: All of six patients were successful performed radical liver resection without mortality. The operation time was (301±106)min and the median blood loss was 200 ml. Two patients needed blood transfusion intraoperative (33.33%). The postoperative hospital stay was (10.8±2.8) day, and the cost of hospitalization was (82 584±995.61) yuan. Clavien-Dindo grade Ⅲ complication occurred in one patient. Conclusions: Multimodality navigation might provide precise intraoperative navigation of the surgical plane and effectively assist liver resection for the treatment of complicated AE.

[The heritage and development of visual physiology in China in the past 70 years].

Vision is the receptive and cognitive process of converting light and pattern signals into nerve impulse signals. The main role of visual physiology is to elucidate the neural mechanism of vision. As an important part of visual physiology, visual electrophysiological examination, like electrocardiogram and electroencephalogram, is used to diagnose diseases through the bioelectrical phenomena generated during the activities of body organs and tissues. Since the founding of the People's Republic of China, remarkable achievements have been made in basic research, translational research and clinical research of visual physiology with more than 70 years of heritage and efforts. But there are still many unknown areas that need further exploration. Looking back at the development history will encourage us to forge ahead and make more contributions to visual physiology in China. Congratulations on the 70th anniversary of the founding of Chinese Journal of Ophthalmology. （Chin J Ophthalmol， 2020， 56: 481-488）.

Synergistic protection of RGCs by olfactory ensheathing cells and alpha-crystallin through regulation of the Akt/BAD Pathway.

BACKGROUND: Our recent in vivo studies have shown that olfactory ensheathing cells (OECs) and α-crystallin can promote retinal ganglion cell (RGC) survival and axonal regeneration synergistically after optic nerve injury. However, the mechanism is still unknown. OBJECTIVES: Here, we studied the synergistic effect and mechanism of OECs and α-crystallin on RGC survival after H2O2-induced oxidative damage and a crushing injury to the optic nerve in an adult rat model. METHODS: After H2O2-induced oxidative damage, RGC-5 cells were treated with OECs, α-crystallin or a combination of OECs and α-crystallin. Apoptosis of RGC-5 cells was assessed by flow cytometry. Phosphorylated Akt, BAD, and cleaved-caspase3 were detected by Western blot after optic nerve injury in vivo and H2O2-induced RGC-5 oxidative damage in vitro. RESULTS: The results showed that OECs and α-crystallin could both independently inhibit RGC-5 apoptosis (P<0.01), increase the phosphorylation of both Akt and BAD, and decrease the activation of caspase-3 (P<0.01). However, the effect of the combination of both was more significant than either alone. CONCLUSION: These findings indicate that inhibition of superoxide damage to RGCs through regulation of the Akt/BAD pathway is one of the mechanisms by which OECs and α-crystallin promote optic nerve recovery after injury.

Knockdown of FBP1 enhances radiosensitivity in prostate cancer cells by activating autophagy.

For patients with clinically early-stage localized prostate cancer, radiotherapy is another treatment that can achieve radical treatment in addition to radical prostatectomy. Despite this, there are still a large number of patients with prostate cancer who have a biochemical recurrence after undergoing radiotherapy, or even clinical recurrence, leading to treatment failure. Although the expression of the fructose-1,6-bisphosphatase 1 (FBP1) gene has been found to be absent in various tumors and is associated with a poor prognosis in tumor patients. However, the expression and role of FBP1 in prostate cancer are not clear. The purpose of this study was to investigate the role and mechanism of FBP1 in the radiotherapy resistance of prostate cancer. By analyzing the microarray data of prostate cancer radiotherapy resistant cells and parental cells (GSE53902), we found that FBP1 expression in DU145 radiotherapy resistant cells was significantly higher than in the DU145 parental cells. In addition, we searched for the expression of FBP1 in 492 prostate cancer samples from TCGA and found that its expression in prostate cancer was significantly higher than that in normal tissues. Knockdown of FBP1 expression significantly inhibited the proliferation of prostate cancer cells, promoted DNA damage-mediated apoptosis, and enhanced the sensitivity of prostate cancer cells to radiotherapy. Further mechanism analysis revealed that FBP1 knockdown could activate autophagy mediated by the AMPK-mTOR signaling pathway, while inhibition of the AMPK-mTOR signaling pathway could reverse FBP1 knockdown-mediated autophagy and apoptosis, as well as radiosensitization. In conclusion, this study clarified that FBP1 is an oncogene in prostate cancer, and the main mechanism for knockdown of FBP1 to increase radiosensitivity is to enhance autophagy mediated by the AMPK-mTOR signaling pathway. Therefore, FBP1 may be a potential target for enhancing prostate cancer radiotherapy.

Circ-DB participates in the progression of gastric cancer by competitively binding microRNA-34a to regulate the expression of MET.

OBJECTIVE: To figure out the possible role and mechanism of circ-DB in the pathogenesis of gastric cancer (GCa). PATIENTS AND METHODS: 32 cases of postoperative GCa tissue samples and adjacent ones were collected and divided into groups of ≥ 5 cm and < 5 cm according to tumor diameter. Circ-DB, microRNA-34a, and MET expressions were detected by real time-quantitative PCR (RT-qPCR) in GCa tissues and adjacent tissues. To determine the main mode of action of circ-DB, the subcellular localization of circ-DB was examined by dividing the cells into the nucleus and cytoplasmic fractions. The binding of microRNA-34a to circ-DB was demonstrated by a Dual-Luciferase reporter gene assay. The expression of circ-DB in HGC-27 and AGS cells was overexpressed and knocked down to evaluate the migration function of the cells by transwell. The protein expression of MET, as well as the target gene of microRNA-34a, was detected by Western blot. RESULTS: The expression of circ-DB and MET in GCa tissues was significantly higher than that in the corresponding adjacent tissues. Circ-DB was positively correlated with MET expression, while microRNA-34a expression was negatively correlated with circ-DB and MET expression. Circ-DB was mainly located in the cytoplasm, and the Dual-Luciferase reporter gene demonstrated that microRNA-34a can bind to circ-DB. The down-regulation of circ-DB expression inhibited the migration of HGC-27 and AGS cells. In vitro cell experiments showed that low expression of circ-DB inhibited cell migration, which could be recovered by the co-transfection with microRNA-34a inhibitor. CONCLUSIONS: Circ-DB may regulate MET level through microRNA-34a and affect the proliferative ability and migration of GCa cells.