Background and purpose:Non-small cell lung cancer (NSCLC) patients who have good curative effect on epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) will inevitably acquired drug resistance. It will effect the survival directly. In contrast, few studies have found that EGFR-TKI effectively acquired drug resistance in patients with clinical characteristics. We investigated clinical characteristics of NSCLC patients who experienced acquired drug resistance during geiftinib therapy. Methods:To review the treatment from the beneift of patients with non-small cell lung cancer. All of the data were obtained from Jan. 2007 to Jan. 2014 in Xinjiang tumor hospital. The treatment for failure of acquired drug resistance of clinical manifestations, time to progress (TTP) and post-progression survival (PPS) were retrospectively analyzed. Results:The total collection of 417 patients. Median TTP was 10.2 months (95%CI:9.5-10.9). The TTP of women adenocarcinoma patients who didn’t smoke signiifcantly extended. When acquired drug resistance happened, 63.3%of patients appeared worse symptoms. The progress of the disease is as follows:209 cases (58.4%) from the primary lesion, 137 cases (38.3%) before the transfer, 194 cases (54.2%) of new happened. Patients of epidermal growth factor receptor (EGFR) wild type had more tendencies of symptomatic deterioration and new central nervous system (CNS) transfer than patients of EGFR mutation type. Patients of exon 19 deletion and L858R mutations on the new transfer were different (41.4%vs 6.3%, P=0.02). PPS was 8.9 months (95%CI:7.4-10.4). Smoking history, performance status (PS) score, new CNS lesions and the subsequent chemotherapy is independent factors of PPS. Conclusion:This study suggests that the clinical manifestations of acquired drug resistance according to EGFR mutation status and EGFR mutation genotype may be different. In addition, after the treatment of acquired drug resistance in patients with non-small cell lung cancer, the subsequent clinical beneift from chemotherapy are also associated with PPS.

Objective To study the efficacy of combining Entecavir with TACE to treat patients with primary hepatocellular carcinoma with undetectable levels of HBV-DNA.Methods From Aug 2011 to Sep 2013, patients with HBV-related hepatocellular carcinoma but with undetectable levels of HBV DNA who underwent TACE were divided into the treatment group (treated with Entecavir antiviral therapy) and the control group.The endpoints of the study were HBV reactivation rates, liver function, and survival rates.Results Using our predefined inclusion and exclusion criteria, 64 patients with primary liver cancer were divided into the treatment group (n =32) and the control group (n =32).The transaminase and bilirubin levels were raised and the albumin level was reduced at 5 days after TACE.However, there were no significant differences between the 2 groups (P ＞0.05).At 12-month follow-up after TACE, 8 (25.0％) patients developed HBV reactivation in the control group and 2 (6.3％) in the treatment group, the difference was significant (P ＜ 0.05).The level of transaminase was significantly higher in the HBV reactivation group when compared with the no HBV reactivation group (P ＜ 0.05).The overall 6-and 12-month survival rates in the treatment group and the control group were 93.8％ and 84.4％ vs 90.6％ and 59.4％ respectively.There were significant differences in the 12-month survival rates (P ＜ 0.05).Conclusion Entecavir combined with TACE to treat patients with HBV-related primary liver cancer with undetectable HBV-DNA effectively reduced HBV reactivation and improved survival at 12 months.

BACKGROUND:Human and rat ovarian granulosa cels in dominant folicles have the phenomenon of expressing stem cel characteristics. OBJECTIVE:To investigate the expression of stem cel-related factors in rat ovarian granulosa cels. METHODS: After the paraffin sections of rat ovarian tissue, immunohistochemical method was used to detect CD34, CD133, ABCG2/Bcrp1, Pou5f1/Oct-4 expressions. Granulosa cels culturedin vitro were harvested by folicular puncture method, and then the immunohistochemical method was used to detect the expression of FSHR receptor in order to identify the purity of granule cels. In the cultured granulosa cels, CD44 and C-Kit expressions were detected immunohistochemicaly, RT-PCR was used to detect ABCG2/Bcrp1, Pou5f1/Oct-4, Nanog gene expressions in ovarian tissue and granulosa cels. RESULTS AND CONCLUSION:Immunohistochemistry detection on paraffin sections showed that a part of ovarian granulosa cels expressed CD34, CD133, ABCG2/Bcrp1 and Pou5f1/Oct-4, and the expression of Pou5f1/Oct-4 protein gradualy increased in the development of ovarian folicles, significantly enhanced during the luteal phase, and then disappeared after the formation of corpus albicans, displaying a periodic expression characteristics. FSHR receptor positive identification rate of primary cels harvested by the foliclar puncture method was more than 95%. Granulosa cels culturedin vitrowere mainly long spindle-shaped or diamond, and some cels presented with aggregation growth and expressed CD44 and C-Kit. RT-PCR test results showed that there were no Nanog in the ovarian tissue and cultured granulosa cels, low expression of Pou5f1/Oct-4 in the ovarian tissue, strong expression of ABCG2/Bcrp1 in the ovarian tissue, weak expression of Pou5f1/Oct-4 in the cultured granulosa cels, and strong expression of ABCG2/Bcrp1 in the cultured granulosa cels. These findings suggest that a part of granulosa cels in the rat ovarian have the characteristics of stem cels.

Objective:To explore the role of hippocampal γ oscillation abnormality in sepsis-associated encephalopathy (SAE).Methods:Seventy male Sprague-Dawley rats (2-3 months) were randomly (random number) divided into three groups according to the random digital table method: sham, CLP, and CLP + dopamine 4 (D4) receptor agonists RO-10-5824 group. The SAE animal model was established by cecal ligation and puncture (CLP). On day 10-14 after surgery, the open field, novel object recognition, and fear conditioning tests were performed. After that, the hippocampus was collected to measure expressions of parvalbumin (PV) and D4 receptor. In another set of experiment, CA1 local field potential (LFP) were recorded, and the relationship between LFP and time with novel object was analyzed. Independent sample t-test was used for pairwise comparisons, and multiple comparisons were performed by one-way ANOVA, followed by the Tukey multiple comparisons test. Correlation was analyzed using Pearson correlation. Statistical significance was assumed when P<0.05. Results:Compared with the sham group, hippocampal PV (77.54±4.61)%, D4 expression (56.36±3.88)% and γ oscillation power (41.1±8.62)%, object exposure time (36±3) s, new object recognition rate (49±4)%, and scene stiffness time (56±7) s were decreased significantly ( P<0.05). However, RO-10-5824 treatment could increase hippocaml γ oscillation power (92.3±6.7)%, and reverse the decreased new object exposure time (44±3) s and new object recognition rate (63±4)%. Correlation analysis showed that hippocampal γ oscillation power was positively associated with new object exposure time ( r=0.609 2, P=0.015 9). There was no difference in total distance traveled or time spent in the center among groups ( P>0.05). Conclusion:Hippocampal γ oscillation abnormality might play a key role in cognitive impairment associated with SAE.

Portal vein tumor thrombus (PVTT) is a common finding in patients with advanced hepatocellular carcinoma (HCC),and the presence of PVTT usually indicates a poor prognosis.At present,two PVTT classifications are adopted in clinical practice;they are VP classification of Japan and eastern hepatobiliary classification (Cheng's classification).There are some differences in PVTT classification between the above two typing criterion.Certain correlation exists between patient's prognosis and PVTT typing;for example,PVTT of type Ⅰ0 carries the best prognosis,while PVTT of type Ⅳ indicates the worst prognosis.The choice of treatment plan is limited by the type of PVTT for a given patient.Therefore,the optimal therapeutic regimen should be formulated based on the type of PVTT in order to control HCC and to benefit the patient.

This research was aimed at establishing the pilot-scale purification technology of lipopeptide from marine-derived Bacillus marinus. We studied lipopeptide surfactivity interferences on scale-up unit technologies including acid precipitation, methanol extraction, solvent precipitation, salting out, extraction, silica gel column chromatography and HZ806 macroporous absorption resin column chromatography. Then, the unit technologies were combined in a certain order, to remove the impurities gradually, and to gain purified lipopeptide finally, with high recovery rate throughout the whole process. The novel pilot-scale purification technology could effectively isolate and purify lipopeptide with 87.51% to 100% purity in hectograms from 1 ton of Bacillus marinus B-9987 fermentation broth with more than 81.73% recovery rate. The first practical hectogram production of highly purified lipopeptide derived from Bacillus marinus was achieved. With this new purification method, using complex media became possible in fermentation process to reduce the fermentation cost and scale-up the purification for lipopeptide production. For practicability and economy, foaming problem resulting from massive water evaporation was avoided in this technology.

[摘 要] 目的：探讨免疫检查点抑制剂（ICI）治疗非小细胞肺癌（NSCLC）患者发生免疫检查点抑制剂相关性肺炎（CIP）的发生情况和免疫治疗疗效的关系，分析接受ICI治疗的NSCLC患者的预后相关因素。方法：回顾性分析2020年3月至2023年3月在新疆医科大学附属肿瘤医院接受ICI治疗145例NSCLC患者的临床资料，将患者分为CIP组和非CIP组，随后将发生CIP的患者分为轻度（1、2级）CIP和重度（3、4级）CIP两个亚组，通过Kaplan-Meier法比较生存曲线，分析CIP的发生及严重程度对于患者PFS及OS的影响。通过单因素及多因素COX风险比例回归模型分析与PFS和OS相关的预后因素。结果：145例患者中有26例患者出现CIP，发生率为17.93％，重度CIP发生率为3.45%。CIP组患者PFS明显长于非CIP组患者（12.3 vs 7.6个月，P<0.05），CIP组与非CIP组的OS比较差异无统计学意义（16.2 vs 15.8个月，P>0.05)。亚组分析显示，轻度CIP和重度CIP相比，PFS（12.2 vs 12.9个月）及OS（16.1 vs 17.8个月）均无统计学意义（均P>0.05）。多因素COX回归分析显示，CIP[HR=0.55，95%CI（0.33, 0.90），P=0.02]、免疫疗程>6个[HR=0.51，95%CI（0.31, 0.85），P=0.01]是影响患者PFS的有利预后因素，免疫疗程>6个[HR=0.4，95%CI（0.18, 0.88），P=0.02]是影响OS的有利预后因素。结论：CIP的发生率为17.93％，CIP的发生与PFS的延长密切相关。免疫疗程>6个是影响NSCLC患者PFS、OS的有利预后因素。