Increased Incidence of Severe Adverse Events in Non-Small Cell Lung Cancer Patients with Previous Tuberculosis Episode Treated with PD-1 Inhibitors

Lung cancer is the top cause of cancer deaths globally.Advances in immune checkpoint inhibitors(ICIs)have transformed cancer treatment,but their use in lung cancer has led to more side effects.This study examined if past pulmonary tuberculosis(TB)affects ICIs’effectiveness and safety in lung cancer treatment.We reviewed lung cancer patients treated with ICIs at Beijing Chest Hospital from January 2019 to August 2022.

小细胞肺癌肿瘤组织及血清CD44表达及临床预后意义

背景与目的小细胞肺癌(small cell lung cancer,SCLC)是一种以增殖迅速、易早期远处转移和获得性治疗耐药为特征的高侵袭性恶性肿瘤,临床预后极差。研究发现干细胞标志物CD44与肿瘤复发转移及治疗抵抗有关,而有关CD44在SCLC患者中的表达及其临床预后意义研究不多。本研究拟通过检测SCLC患者肿瘤组织和血清中CD44的表达水平,初步探索其与患者临床特征的关系并评估其判断预后的临床价值。方法将本院47例初治SCLC患者肿瘤组织和血清标本配对,分别应用免疫组化法(immunohistochemistry,IHC)和酶联免疫吸附试验方法(enzyme-linked immunosorbent assay,ELISA)对CD44进行检测,分析其与患者临床特征及预后的关系。结果SCLC患者肿瘤组织和血清中均可检测到干细胞标志物CD44的表达,体能状态(performance status,PS)2分的患者肿瘤组织CD44阳性率明显高于PS 0分-1分的患者(85.71%vs 30%,P=0.017),根据化疗疗效对患者进行分组,疾病进展组肿瘤组织CD44免疫组化得分及血清CD44浓度均明显高于疾病控制组且差异均达到统计学意义(P=0.006,P=0.034),单因素分析肿瘤组织CD44阳性患者无进展生存期(progression-free survival,PFS)较CD44阴性患者PFS明显缩短(5.23个月vs 9.03个月,P=0.036)。结论初治SCLC患者肿瘤组织中CD44的表达水平与PFS相关,CD44在SCLC中的临床意义值得进一步深入研究。

单中心晚期非小细胞肺癌免疫治疗真实世界数据分析

背景与目的近些年,多项临床试验显示免疫检查点抑制剂(immunocheckpoint inhibitor,ICI)为晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)患者带来生存获益,但临床试验有着严格而复杂的纳入与排除标准,其结果不能完全反映真实世界的实际情况。本研究拟探讨真实世界中免疫治疗的临床疗效和安全性以及可能相关的预后因素。方法回顾性分析2017年1月-2019年7月在北京胸科医院接受免疫治疗的晚期NSCLC患者,收集患者基本临床资料、治疗疗效、无进展生存期(progression-free survival,PFS)和药物不良反应等资料,探讨临床疗效、不良反应及可能相关的预后因素。结果研究共纳入34例患者,中位PFS为5.66个月(95%CI:4.48个月-6.84个月),1级-2级不良反应和3级-4级不良反应发生率分别为61.71%(22/34)和14.71%(5/34),共有3例(8.82%)患者出现致死性免疫相关不良反应(immune-related adverse event,ir AE),其中2例为免疫相关肺炎,1例为免疫相关心肌炎。单因素分析显示肿瘤-淋巴结-转移(tumor-node-metastasis,TNM)分期、转移部位与中位PFS相关(P<0.05),多因素分析显示存在肺外转移(OR=6.42,P=0.029)、胸膜转移(OR=14.14,P=0.006)为患者PFS的独立预后因素。结论真实世界中免疫治疗对晚期NSCLC患者具有良好的疗效,但其严重ir AE的发生率也较高。存在肺外转移、胸膜转移是接受免疫治疗的晚期NSCLC患者的不良预后因素。

The expression of vascular endothelial growth factor(VEGF)/endostatin(ES)and VEGF receptor 2(VEGFR2)/ES is associated with NSCLC prognosis

Objective The aim of our study was to detect the expression of angiogenesis inhibitory proteins and angiogenesis promotive proteins in the postoperative tumor tissue of non-small cell lung cancer(NSCLC)patients.We also investigated the relationship of protein expression with clinical characteristics and prognosis.Methods We examined the expression of vascular endothelial growth factor(VEGF),VEGF receptor 2(VEGFR2),and endostatin(ES)proteins in 255 specimens resected from NSCLC patients,using immune histochemistry(IHC).We then evaluated the relationships between the expression of the three proteins and clinical characteristics such as stage,histological type,differentiation,gender,tobacco use,and age.According to the value of VEGF/ES,we divided the cohort into angiogenesis-promoting group A,angiogenesis-inhibiting group A,and balance group A.The survival differences in the three groups were evaluated to determine the prognostic value of VEGF/ES.Similarly,we tested the prognostic value of VEGFR2/ES.Results VEGF-positive expression was observed in 93 patients(36.4%).VEGF expression was not correlated with the clinical characteristics.VEGFR2-positive expression was observed in 103 patients(40.4%).The expression of VEGFR2 was correlated with the clinical stage(χ^(2)=21.414,P=0.045)and histological type(χ^(2)=26.911,P=0.008).ES-positive expression was observed in 140 patients(54.9%).The expression of ES was correlated with the clinical stage(χ^(2)=26.504,P=0.009).When evaluating the prognostic values of VEGF/ES and VEGFR2/ES,the prognosis of the angiogenesis balance group was similar to that of the angiogenesis-inhibiting group.The minimum survival time was observed in the angiogenesis-promoting group.Conclusion VEGF/ES and VEGFR2/ES in resected tumors have prognostic value in postoperative NSCLC patients.The survival time of the population with predominant angiogenic factors was short.

环境化学与四大基础化学教学衔接的探究

环境工程专业必修课程环境化学与该专业四大基础化学课程(无机化学、有机化学、物理化学、分析化学)在教学内容上存在重复现象。为提高课堂教学效率和学生的学习积极性,本教学团队总结分析了环境化学与四大基础化学的相似知识点,采用更新优化教学内容,开展提问式、对比式、讨论式等多种教学方式,引导学生由"已知"探"新知",使知识层层深化,并利用"雨课堂"的教学模式助力教学衔接,提高教学效果。

Investigation of therapeutic modalities of G719X, an uncommon mutation in the EGFR gene in non-small cell lung cancer

Objective G719 X is the most frequently seen uncommon mutation of the epidermal growth factor receptor(EGFR) gene, which is a point mutation at exon 18 with three common subtypes, G719 A/G719 C/G719 S. This study explored the clinicopathological characteristics of the G719 X mutation and investigated the efficacy of EGFR-tyrosine kinase inhibitor(TKI) treatment and chemotherapy in patients with the G719 X mutation; the survival rate after these different treatment modalities were then analyzed in order to provide evidence for clinical treatment.Methods Clinical data of 41 patients with the G719 X mutation admitted in the Beijing Chest Hospital, Capital Medical University from September 2014 to July 2018, were collected and the EGFR mutations were detected by amplification refractory mutation system-polymerase chain reaction(ARMS-PCR). The clinicopathological characteristics of the G719 X mutation were analyzed, and the relationship among the G719 X mutation, the efficacy of different treatment modalities, and the progression-free survival(PFS) was analyzed. Results Of the 41 cases, 24(58.5%) were G719 X single mutations and 17(41.5%) were compound mutations, including G719 X/S768 I, G719 X/L861 Q, G719 X/19 del, and G719 X/c-Met compound mutation. The objective response rate(ORR) of first-line EGFR-TKI therapy was 50%(6/12), the disease control rate(DCR) was 83.3%(10/12), and the median PFS(mPFS) was 9 months. After resistance to EGFR-TKI in the previous treatment, the ORR(71.4%, 5/7) and DCR(100%, 7/7) were still high following EGFR-TKIs, by an mPFS of 8 months. The ORR of chemotherapy was 33.3%(2/6), the DCR was 100%(6/6), and the mPFS was 6 months. Conclusion G719 X is an uncommon mutation of the EGFR gene and is sensitive to many EGFR-TKIs. It can be treated with the second-or third-generation EGFR-TKIs after resistance to the first-generation EGFR-TKIs. G719 X mutation also showed favorable effect to chemotherapy.

Cathode catalyst prepared from bacterial cellulose for ethanol fermentation stillage treatment in microbial fuel cell

Bacterial cellulose doped with P and Cu was used as a catalyst for a microbial fuel cell(MFC) cathode,which was then used to treat ethanol fermentation stillage from food waste.Corresponding output power,coulombic efficiency(CE),and biological toxicity were detected.Through a series of characterization experiments,the addition of the cathode catalyst was found to improve catalytic activity and accelerate the consumption of the substrate.The resulting maximum output power was 572.16 mW·m^(-2).CE and the removal rate of chemical oxygen demand(COD) in the fermentation stillage by P-Cu-BC reached 26% and 64.5%,respectively.The rate of biotoxicity removal by MFC treatment reached 84.7%.The aim of this study was apply a novel catalyst for MFC and optimize the treatment efficiency of fermentation stillage.

Icotinib, an EGFR-TKI, for the treatment of brain metastases in non-small cell lung cancer:a retrospective study

Objective Treatment of brain metastases from non-small cell lung cancer(NSCLC) is a challenge because of the poor prognosis. Icotinib is a new type of oral epidermal growth factor receptor(EGFR) tyrosine kinase inhibitor(TKI) used in the treatment of advanced NSCLC. The aim of this study was to evaluate the efficacy of icotinib in NSCLC patients with brain metastasis.Methods This study reviewed records of 51 NSCLC patients with brain metastases who took icotinib 125 mg, 3 times a day. Response rate, progression free survival, and overall survival were analyzed. SPSS software version 17.0 was used for univariate analysis, and Cox regression analysis to analyze factors affecting survival. Results Thirty-six cases had partial response, 6 cases had stable disease, and 10 cases had progressive disease. In 31 cases, EGFR gene mutation test were performed. EGFR was mutated in 26 cases and was with wild-type in 5 cases. In patients with EGFR mutations, 23 patients responded to icotinib [the disease control rate(DCR) was 88.5%], significantly higher than in patients with wild-type EGFR(1 patient, DCR 20%)(P = 0.005). The overall median progression-free survival(PFS) was 7.6 months. PFS was longer in the patients with EGFR mutations than in those with wild type EGFR(7.8 months vs 1.2 months, P = 0.03). The overall median overall survival(OS) time was 10.7 months. OS was longer in patients with EGFR mutations than in those with wild type EGFR(15.1 months vs 6.7 months, P = 0.003). The main side effects of the treatment were skin rash and diarrhea; no stage 3 or 4 toxic effects occurred. Univariate analysis demonstrated that OS was related to sex, Eastern Cooperative Oncology Group performance status(ECOG PS), smoking history, and EGFR mutation. Multivariate analysis showed that OS was independently related to sex, ECOG PS, and EGFR mutations.Conclusion Icotinib has a favorable effect on NSCLC patients with brain metastases harboring EGFR mutations. Icotinib can be a new choice of treatment for brain metastases in patients with NSCLC harboring EGFR mutations.

Bronchoscopic biopsy for diagnosis of lung cancer in the absence of visible endobronchial abnormalities

Objective Bronchoscopy has been extensively used in the diagnosis of respiratory diseases, and par- ticularly, malignant diseases. However, endoscopists do not normally perform bronchoscopic biopsy in Case lesions are undetected via bronchoscopy. The aim of this study was to evaluate whether performing bron- choscopic biopsy could be established in the diagnosis of lung cancer in case of endobronchial abnormali- ties undetectable to the naked eye. Methods We retrospectively analyzed 109 cases between January 2008 and December 2012. The in- clusion criteria were confirmed lung cancer diagnosis, transbronchial biopsy performed in the absence of visible endobronchial manifestations, brushing, and bronchoalveolar lavage （BAL） according to the images obtained from high-resolution computed tomography （HRCT）. Data regarding age, sex, pathology, tumor stage; the method of diagnosis; location of primary lesion （central, peripheral, or intermediate）; tumor size, mediastinal lymph node metastasis, and the serum carcinoembryonic antigen （CEA） value were collected. The Pearson chi-square test or Fisher＇s exact and McNemar tests were used in the univadate analysis. Results Among the 109 patients, the diagnosis of 37 （33.9%） patients was confirmed through bronchos- copy. Brushing and BAL had higher positive detection rates than biopsy （P = 0.004）. There were no differ- ences in the positive detection rates between the sex, pathology, lesion location, tumor size, lymph node metastasis, and the serum CEA value （P〈 0.05 for all groups）. Conclusion Despite the normal appearance of the endobronchial manifestations, lesions undetectable by bronchoscopy could be indicated. Therefore, we suggest performing bronchoscopic biopsy and that brushing and BAL might increase the positive detection rate of bronchoscepic examination.

Pilot-scale experiments on multilevel contact oxidation treatment of poultry farm wastewater using saran lock carriers under different operation model

A pilot-scale multilevel contact oxidation reactors system, coupled with saran lock carriers,was applied for the treatment of poultry farm wastewater. The removal efficiencies of CODcr, ammonia, and the total nitrogen as well as the elimination performance of CODcr and total nitrogen along the three-level contact oxidation tanks under six designed operational models were investigated. Based on the performance of the nitrogen removal of the saran lock carriers and the distribution of anoxic–aerobic interspace under the suitable operation model, the mechanism of nitrogen removal of the system was also explored. The results revealed that the intermittent aeration under parallel model is the most suitable operation model, while the removal efficiencies of CODcr, ammonia, and the total nitrogen were 86.86%, 84.04%, and 80.96%, respectively. The effluent concentration of CODcr,ammonia, and the total nitrogen were 55.6 mg/L, 8.3 mg/L, and 12.0 mg/L, which satisfy both the discharge standard of pollutants for livestock and poultry breeding industry(GB18596–2001) and the first grade of the integrated wastewater discharge standard(GB 8978–1996). Moreover, the mechanism for the nitrogen removal should be attributed to the plenty of anoxic–aerobic interspaces of the biofilm and the three-dimensional spiral structure of the saran lock carriers, where the oxygen-deficient distribution was suitable for the happening of the simultaneous nitrification and denitrification process. Therefore, the multilevel contact oxidation tanks system is an effective pathway for the treatment of the poultry farm wastewater on the strength of a suitable operation model and novel carriers.

Sludge reduction during brewery wastewater treatment by hydrolyzation-food chain reactor system

During brewery wastewater treatment by a hydrolyzation-food chain reactor(FCR)system,sludge was recycled to the anaerobic segment.With the function of hydrolyzation acidification in the anaerobic segment and the processes of aerobic oxidation and antagonism,preda-tion,interaction and symbiosis among microbes in multi-level oxidation segment,residual sludge could be reduced effectively.The 6-month dynamic experiments show that the average chemical oxygen demand(COD)removal ratio was 92.6% and average sludge production of the aerobic segment was 8.14%,with the COD of the influent at 960–1720 mg/L and hydraulic retention time(HRT)of 12 h.Since the producedsludge could be recycled and hydrolyzed in the anaerobic segment,no excess sludge was produced during the steady running for this system.

Advanced treatment of wet-spun acrylic fiber manufacturing wastewater using three-dimensional electrochemical oxidation

A three-dimensional electrochemical oxidation （3D-EC） reactor with introduction of activated carbon （AC） as particle micro-electrodes was apphed for the advanced treatment of secondary wastewater effluent of a wet-spun acrylic fiber manufacturing plant. Under the optimized conditions （current density of 500 A/m2, circulation rate of 5 mL/min, AC dosage of 50 g, and chloride concentration of 1.0 g/L）, the average removal efficiencies of chemical oxygen demand （CODer）, NH3-N, total organic carbon （TOC）, and ultraviolet absorption at 254 nm （UV2s4） of the 3D-EC reactor were 64.5%, 60.8%, 46.4%, and 64.8%, respectively; while the corresponding effluent concentrations of CODcr, NH3-N, TOC, and UV2s4 were 76.6, 20.1, and 42.5 mg/L, and 0.08 Abs/cm, respectively. The effluent concentration of CODer was less than 100 mg/L, which showed that the treated wastewater satisfied the demand of the integrated wastewater discharge standard （GB 8978-1996）. The 3D-EC process remarkably improved the treatment efficiencies with synergistic effects for CODer, NH3-N, TOC, and UV2s4 during the stable stage of 44.5%, 38.8%, 27.2%, and 10.9%, respectively, as compared with the sum of the efficiencies of a two-dimensional electrochemical oxidation （2D-EC） reactor and an AC adsorption process, which was ascribed to the numerous micro-electrodes of AC in the 3D-EC reactor. Gas chromatography mass spectrometry （GC-MS） analysis revealed that electro- chemical treatment did not generate more toxic organics, and it was proved that the increase in acute biotoxicity was caused primarily by the production of free chlorine.

Pollution characteristics of polycyclic aromatic hydrocarbons in common used mineral oils and their transformation during oil regeneration

The pollution characteristic of polycyclic aromatic hydrocarbons （PAHs） in common used mineral oils, semi-refined oils, refined oils and solid wastes produced during the used mineral oil regeneration process was analyzed. The results showed that total PAHs content in six common used mineral oils was as follows： used engine oil 〉 used quenching oil 〉 used casting oil 〉 used hydraulic oil 〉 used antimst oil 〉 used industrial lubricating oil. Furthermore, this order was dependent on the source of PAHs and oil working temperatures. Additionally, total PAt-Is content in regenerated oils was as follows： semi-refined oil 〉 refined oil 〉 crude oil, which was related to the catalytic cracking process of crude oil and adsorption refining process of semi-refined oil. The ranking of total PAHs content in regenerated wastes varied depending on the regeneration technology used as follows： waste adsorption sand 〉 acid sludge 〉 waste clay 〉 precipitation sludge 〉 cracked residue. In all types of used mineral oils and regenerated wastes, the maximum and minimum proportions of the total PAHs content were composed of 2-3 ring-PAHs and 5-6 ring-PAHs, respectively. The majority of PAHs in the used mineral oils entered into regenerated wastes during regeneration process, while a small number remained in the regenerated oil.

Wastewater-nitrogen removal using polylactic acid/starch as carbon source： Optimization of operating parameters using response surface methodology

Nitrogen removal from ammonium-containing wastewater was conducted using polylactic acid （PLA）/ starch blends as carbon source and carrier for fimctional bacteria. The exclusive and interactive influences of operating parameters （i.e., temperature, pH, stirring rate, and PLA-to-starch ratio （PLA proportion）） on nitrification （Y1）, denitrification （Y2）, and COD release rates （Y3） were investigated through response surface methodology. Experimental results indicated that nitrogen removal could be successfully achieved in the PLA/starch blends through simultaneous mtnncatlon anti clenltnncatlon. The carbon release rate of the blends was controllable. The sensitivity of Y1, Y2, and Y3 to different operating parameters also differed. The sequence for each response was as follows： for Y1, pH 〉 stirring rate 〉 PLA proportion 〉 temperature; for Y2, PH 〉 PLA proportion 〉.temperature.〉 stirring rate; and for Y3, stirring rate 〉pH 〉 PLA proportion 〉 temperature. In this study, the following optimum conditions were observed： temperature, 32.0℃; pH 7.7; stirring rate, 200.0 r · min^-1 and PLA proportion 0.4. Under these conditions Y1 Y2 and Y3 were 134.0 μg-N·g-blend^-1·h^-1, 160.9μg-N-g-blend^-1·h^-1, and 7.6 × 10^3 μg-O·g-blend^-1·h^-1, respectively. These results suggested that the PLA/starch blends may be an ideal packing material for nitrogen removal.