Objective To investigate the effect ot ionizing radiation (IR) on the expressions of HMGB1 in the radiation-sensitive and radiation-resistant human cervical cancer cells and to analysis the role of HMGB1 in the regulation of radiosensitivity.Methods Human cervical cancer cells HeLa and its radioresistant strain HeLaR cells were irradiated with different doses of X-rays.The cells were collected at different time points after irradiation.The expressions of protein and mRNA of HMGB1 were detected by Western blot and real-time quantitative PCR.Results At the protein level,the expression of HMGB1 in HeLaR cells was significantly reduced at 6-36 h after 2,5 and 10 Gy X-ray irradiation (t =3.574-9.754,P ＜0.05),and then it was recovered to the control level at 48 h after IR.On the contrary,the expression of HMGB1 in HeLa cells was significantly increased at 6,12,48 h after 2 Gy IR (t =3.945-4.864,P＜0.05),at 6,36,48hafter5 GyIR (t=-2.875-3.295,P＜0.05),and at 36,48 h after 10 Gy IR (t =-4.480,-4.517,P ＜ 0.05).At mRNA level,the trend of HMGB1 expression alteration was consistent with that of protein expression.Conclusions The changes of HMGB1 expression can be differently induced by X-rays in the human cervical cancer radiation-sensitivity cells and radiation-resistant cells.HMGB1 may be involved in the radioresistance of human cervical cancer.

Objective To explore the effect of apatinib in first-line treatment of advanced liver cancer. Methods Retrospective analysis was performed on 35 patients with advanced liver cancer treated in our department from July 2017 to January 2020. All patients were given apatinib mesylate tablet 250-500 mg orally with QD. The patients with effective disease control (including CR, PR and SD) were given administration until PD or intolerance or death occurred. The primary endpoints were PFS and OS, and the secondary endpoints were DCR and ORR. The side effect was observed. Results There was one case of CR, 17 cases of PR and 11 cases of SD. The ORR and DCR were 51.43% and 82.86%. The median PFS and OS were 9.7 and 11.1 months. The main adverse reactions included hand-foot syndrome, hypertension, proteinuria, etc. Most grade 3-5 adverse reactions were reversible with good safety. Conclusion Apatinib can significantly improve the clinical benefits of liver cancer patients. It is an alternative first-line treatment for advanced liver cancer.

Objective:To screen the factors influencing overall survival (OS) of patients undergoing radical resection for colorectal cancer (CRC) and to construct a prognostic model for OS of patients after CRC.Methods:The clinical data of 350 patients with stage Ⅰ-Ⅳ CRC who underwent radical resection in the People's Hospital of Wuhan University from March 2017 to December 2019 were collected retrospectively. Patients were divided into subgroups 0 ( n=70), 1 ( n=172), and 2 ( n=108) according to different preoperative systemic inflammation score (SIS). The relationship between different SIS, neutrophil to lymphocyte ratio (NLR), lymphocyte to monocyte ratio (LMR), systemic immune inflammation index (SII) and prognosis of CRC patients undergoing radical surgical resection were analyzed, and Cox regression models were used to perform univariate and multifactorial analyses of factors affecting patient prognosis, and column line graph models were constructed based on the results of multifactorial analyses. Results:By the deadline of follow-up, 80 of 350 CRC patients died, and the 5-year OS rate was 77.14%. The 5-year survival rates of patients in SIS group 0, group 1 and group 2 were 95.71%, 79.65% and 61.11% respectively, with a statistically significant difference ( χ2=30.19, P<0.001). Statistically significant differences in age ( χ2=19.40, P<0.001), tumor site ( χ2=8.18, P=0.017), T stage ( χ2=10.01, P=0.007), TNM stage ( χ2=14.80, P=0.001), tumor diameter ( χ2=13.91, P=0.001) and carcino-embryonic antigen (CEA) level ( χ2=10.12, P=0.006) among patients in SIS group 0, group 1 and group 2. The 5-year OS rates of patients in the low NLR and high NLR groups were 82.67% and 56.16% respectively, with a statistically significant difference ( χ2=24.96, P<0.001) ; the 5-year OS rates of patients in the low LMR and high LMR groups were 66.85% and 88.17% respectively, with a statistically significant difference ( χ2=22.45, P<0.001) ; the 5-year OS rates of patients in the low SII and high SII groups were 86.14% and 69.02% respectively, with a statistically significant difference ( χ2=14.76, P<0.001). Univariate analysis showed that age ( HR=2.58, 95% CI: 1.54-4.32, P<0.001), T stage ( HR=2.41, 95% CI: 1.24-4.68, P=0.009), N stage ( HR=3.03, 95% CI: 1.85-4.94, P<0.001), TNM stage ( HR=3.61, 95% CI: 2.15-6.04, P<0.001), nerve invasion ( HR=1.97, 95% CI: 1.27-3.08, P=0.002), vascular invasion ( HR=2.31, 95% CI: 1.49-3.59, P<0.001), preoperative SIS 1 score ( HR=5.09, 95% CI: 1.57-16.56, P=0.007), SIS 2 score ( HR=11.05, 95% CI: 3.42-35.65, P<0.001), NLR ( HR=2.97, 95% CI: 1.90-4.64, P<0.001), LMR ( HR=0.31, 95% CI: 0.19-0.52, P<0.001), and SII ( HR=2.50, 95% CI: 1.54-4.06, P<0.001) were all independent influence factors affecting the postoperative prognosis of CRC patients undergoing radical surgical resection; multivariate analysis showed that age >60 years ( HR=2.27, 95% CI: 1.31-3.91, P=0.003), TNM stage Ⅲ-Ⅳ ( HR=7.08, 95% CI: 1.89-26.59, P=0.004), and preoperative SIS 2 score ( HR=4.02, 95% CI: 1.09-14.83, P=0.037) were all independent risk factors affecting the postoperative prognosis of CRC patients undergoing radical surgical resection. The nomogram model built based on the screened variables has high prediction accuracy: the C-index of the nomogram was 0.75. Conclusion:Age>60 years old, TNM stage Ⅲ-Ⅳ, SIS 2 score are all independent risk factors for postoperative prognosis of colorectal cancer. The nomograph model constructed by this method has high prediction accuracy.

In the past decade, rapid breakthroughs have been made in the systemic treat-ment of advanced unresectable hepatocellular carcinoma. Single systemic therapy has little effect on controlling tumor local recurrence and distant metastasis, and the combination modality therapy is the treatment for the majority of patients with advanced hepatocellular carcinoma. The change of tumor microenvironment is the research hotspot of antitumor therapy at present. Targeted therapy, immunotherapy and radiotherapy can lead to a change in the tumor microenvironment of primary hepatic carcinoma. The synergistic effect of combined therapy is particularly important. The authors report the clinical efficacy of programmed death ligand-1 inhibitor plus vascular endothelial growth factor inhibitor in the first-line treatment of a patient with advanced unresectable hepatocellular carci-noma. The results show that partial response being achieved according to the modified response evaluation criteria in solid tumors, and the survival time is more than 20 months with no obvious adverse reactions and high quality of life.

OBJECTIVETo investigate the effect of stable knockdown of DNA methyltransferase 3b (DNMT3b) on the proliferation and apoptosis of bladder cancer cells.

METHODSLentivirus expressing DNMT3b siRNA or the negative control siRNA was infected in human bladder cancer BIU-87 cells. MTT assay and flow cytometry were used to detect cell proliferation and apoptosis, respectively. The inhibitory effect of DNMT3b knockdown on xenograft tumors in nude mice was observed. Real-time PCR and Western blotting were carried out to investigate the expression level of cell apoptosis related genes. Methylation specific PCR was used to examine the methylation in the promoter region of the cell apoptosis related genes.

RESULTSThe results of real-time PCR and Western blotting showed that DNMT3b mRNA and protein level were stably knocked down in BIU-87 cells. Stable DNMT3b knockdown suppressed BIU-87 cell growth and the tumor formation ability of the cells in nude mice. DNMT3b knockdown promoted the apoptosis of BIU-87 cells, increased the mRNA and protein expression of the cell growth and apoptosis related genes including DAPK, Bax and RASSF1A, and significantly decreased the methylation of these genes.

CONCLUSIONStable DNMT3b knockdown can affect the methylation of the cell growth and apoptosis related genes to regulate their expression, which might be a possible mechanism for suppressed cell growth and enhanced apoptosis of BIU-87 cells.

Animals ; Apoptosis ; Cell Cycle ; Cell Line, Tumor ; Cell Proliferation ; DNA (Cytosine-5-)-Methyltransferases ; genetics ; Gene Knockdown Techniques ; Humans ; Mice ; Mice, Nude ; Neoplasm Transplantation ; RNA, Small Interfering ; Real-Time Polymerase Chain Reaction ; Urinary Bladder Neoplasms ; genetics ; pathology

Objective:To investigate the treatment, safety and prognosis of advanced non-small cell lung cancer patients with leptomeningeal metastasis and performance status score more than 3.Methods:The clinical data of 6 NSCLC patients with leptomeningeal metastasis admitted to the People's Hospital of Wuhan University from November 2016 to September 2018 were analyzed retrospectively. The curative effect and adverse reactions were observed, and the prognosis was analyzed.Results:There were 5 females and 1 male among 6 patients. The median age was 57 years old (46-74 years old). All 6 patients were diagnosed as stage Ⅳ lung adenocarcinoma. There were 3 patients with epidermal growth factor receptor (EGFR) exon 21 mutation, 2 patients with exon 19 mutation and one with anaplastic lymphoma kinase (ALK) fusion mutation. The time window of leptomeningeal metastasis occurred after the progression of adenocarcinoma of lung: 3 cases was more than 12 months, the other 3 cases was less than 12 months, and the average was 20.3 month. Performance status score was more than 3 when leptomeningeal metastasis occurred. The brain magnetic resonance imaging of 6 patients showed linear enhancement of leptomeningeal, cancer cells were found in cerebrospinal fluid in one case, 4 cases were treated with a combination of bevacizumab and EGFR-tyrosine kinase inhibitor (EGFR-TKI), 1 case was treated with oral administration of EGFR-TKI, 1 case was treated with oral administration of EGFR-TKI combined with temozolomide. The median overall survival (mOS) was 9 months (2-13 months), and the median progression free survival was 6 months (2-11 months).Conclusion:Lung adenocarcinoma may be prone to leptomeningeal metastasis; for NSCLC patients with leptomeningeal metastasis and performance status score more than 3, a combination of EGFR-TKI and bevacizumab has good tolerance, high safety and considerable curative effect.

Objective:To investigate the clinical characteristics and prognosis of patients with cutaneous intravascular large B-cell lymphoma (IVLBCL).Methods:The data of 30 cutaneous IVLBCL published between January 1989 and May 2019 in China were systematically reviewed. The clinical manifestation, biochemical and imaging characteristics and diagnostic features of patients were summarized, and then the survival of different groups was also analyzed.Results:The median onset age was 61.5 years old (25.0-83.0 years old), and there were 22 (73.3%) females. All 30 patients presented with cutaneous lesions. Initial symptoms showed cutaneous lesions in 16 (53.3%) patients; and B symptom, respiratory symptoms or central nervous system (CNS) occurred in 14 (46.7%) patients with late cutaneous lesions. Cutaneous lesions were heterogeneous, and 76.7% (23/30) lesions located in lower abdomen and proximal limbs. And 76.2% (16/21) were positive in image examination, and 78.3% (18/23) had two or more extranodal organs invasion. The median time from onset to visit was 2.5 months (0.4-24.0 months), and clinical misdiagnosis rate was 56.7%(17/30). All IVLBCL patients were confirmed by biopsy, including 6 cases (27.3%, 6/22) of bone marrow involvement, 1 case (3.3%) of hemophagocytic syndrome-associated variant, and 29 cases (96.7%) of classical variant. Finally, 81.8% (18/22) patients received anthracycline-based combined chemotherapy. Compared with non-chemotherapy group, the median OS time of chemotherapy group was prolonged [11.0 months (2.0-60.0 months) vs. 2.0 months (0.7-24.0 months), P = 0.002]. Patients with CNS symptoms had shorter median OS time compared with patients without CNS symptoms [2.0 months (0.7-6.0 months) vs. 11.0 months (1.0-60.0 months), P < 0.01]. The median OS time in the group of cutaneous lesions as initial symptom combined with other symptoms was longer than that in group of late cutaneous lesions and other symptoms as initial symptom [unreached (2.0-60.0 months) vs. 3.0 months (1.5-24.0 months), P = 0.032]. Conclusions:Cutaneous IVLBCL is a rare disease with atypical clinical characteristics in China. Prompt attention and biopsy in time will be helpful for early diagnosis. Accompanied with CNS symptoms suggests poor prognosis; and timely chemotherapy can improve the prognosis of the patients.

Objective: To investigate the clinical efficacy of modified tracer minimally invasive fixation in robot-assisted pedicle screw placement. Methods: A prospective randomized controlled study was conducted to analyze the clinical data of 41 patients with thoracolumbar fresh fracture at the orthopaedics department of Karamay Central Hospital from July 2017 to December 2017. There were 20 males and 21 females, aged 25-55 years, with an average of 40.6 years. According to AO fracture typing, there were 28 patients with type A and 13 patients with type B. The patients underwent robot-assisted pedicle screw placement. Random number table method was used to divide the patients into the conventional group (20 patients) and modified group (21 patients). The conventional group was treated with conventional tracer fixation, and the modified group modified tracer minimally invasive fixation. A total of 92 pedicle screws were implanted in the conventional group and 96 pedicle screws were implanted in the modified group. The size of wound, wound bleeding, time of fixing the tracer, complications (spinal cord injury and nerve root injury when fixing the tracer), development of the tracer fixator and artifacts were recorded. The accuracy of nail placement was evaluated by 320-slice CT scan and Gertzbein-Robbins criteria. Results: There was no significant difference in age, sex, diagnosis, transverse diameter of pedicle and e angle between the two groups (P>0.05). The wound size, wound bleeding, and time of fixing the tracer in the modified group were (6.00±1.26)mm, (1.38±0.22)ml and (1.42±0.17)minutes, respectively, while those of the conventional group were (40.16±5.71)mm, (11.61±1.15)ml, and (5.12±0.64)minutes respectively (P<0.05). No spinal cord or nerve root injury occurred in either group when the tracer was fixed. In the process of three-dimensional image acquisition and automatic registration, the tracer fixator in the modified group developed with Kirschner needle without artifacts, and the tracer in minimally invasive fixator had good fluoroscopy effect. The modified group included 94 pedicle screws of type A and two of type B according to Gertzbein-Robbins criteria. The conventional group included 89 pedicle screws of type A and three of type B according to Gertzbein-Robbins criteria. There was no significant difference in the screw placement accuracy between the two groups (P>0.05). Conclusion In the robot-assisted pedicle screw placement, the modified tracer minimally invasive fixation method is safe and less traumatic, with no side effect on the accuracy of pedicle screw placement.

Objective: To investigate the salvage strategy and efficacy for patients with locally recurrent esophageal squamous cell carcinoma after definitive radiochemotherapy. Methods: A total of 126 patients who met the inclusion criteria were enrolled in this study and divided into the salvage surgery, salvage radiochemotherapy and best supportive care. Results: Fifty-eight of 126 patients received salvage esophagectomy, 52 underwent salvage radiochemotherapy and the remaining 16 patients received best supportive care. The 1-, 3-, 5-year overall survival rates of patients receiving salvage therapy were 51%, 16% and 4% for the three groups, whereas all patients in the best supportive care group died within 12.0 months (P<0.001). The 1-, 3-, 5-year survival rates in the salvage surgery and salvage radiochemotherapy groups were 48%, 20% and 7%, and 51%, 11% and 3%, respectively (P=0.473). Multivariate analysis by Cox proportional hazard model showed that T staging of recurrent tumors and salvage regimen were the independent prognostic factors in patients with locally recurrent esophageal cancer (both P<0.001). Postoperative infection occurred in 16% of the patients in the salvage surgery group, and the incidence of esophagotracheal fistula and mediastinoesophageal fistula was 10% and 6% in the salvage radiochemotherapy group. Conclusions A survival benefit can be elicited by salvage surgery or salvage radiochemotherapy in patients with locally recurrent esophageal cancer after definitive radiochemotherapy. Nevertheless, extensive attention should be paid to the management of postoperative complications in clinical practice.