Immune checkpoint inhibitors (ICI) have transformed the treatment landscape of advanced non-small cell lung cancer (NSCLC). Biomarkers are essential for guiding precision immunotherapy. Tissue-based programmed death ligand 1 (PD-L1) expression and tumor mutational burden (TMB) are currently widely used biomarkers for selecting patients for immunotherapy. However, tissue specimens are often difficult to reach and couldn't overcome spatial and temporal heterogeneity. Blood biomarkers offer an alternative non-invasive solution that could provide a complete insight on patient's immune status and tumor as well, and show their potential in predicting the outcome as well as in monitoring response to immunotherapy. In this article, we summarize current knowledge on blood biomarkers in NSCLC patients treated with ICI, and we hope to provide more references for development of novel biomarkers.
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Objective: To study the prevalence and antimicrobial susceptibility of Ureaplasma urealyticum (Uu) and Mycoplasma hominis (Mh) in Changsha, and provide laboratory evidence for clinical drug use. Methods: A retrospective study was conducted to analyze 53 006 specimens of suspected genital mycoplasma infection in Xiangya Second Hospital of Changsha District and Hunan Wangwang Hospital from 2010 to 2017, and to analyze the infection rate and drug resistance rate of Uu and Mh. Results: From 2010 to 2017, a total of 53 006 specimens were detected, where there were 16 830 cases of Uu infection, the infection rate was 31.75%; 2 471 cases of Mh infection, the infection rate was 4.66%; and 1 071 cases of Uu and Mh mixed infection, the infection rate was 2.02%. Male Uu infection rate was 19.48%(5 989/30 749), which was lower than the female infection rate 48.71%(10 841/22 257) (χ²=5 091, P<0.001); male Mh infection rate was 3.16%(973/30 749), lower than female infection rate 6.73%(1 498/22 257) (χ²=369,P<0.001). The population of genital mycoplasma infection is concentrated between 20 and 40 years old, accounting for 71.76% (12 077/16 830). The drug resistance rates of Uu and Mh to doxycycline and minocycline were less than 2%, while the drug resistance rate to quinolones was higher; The resistance rate of Uu to macrolide antibiotics such as erythromycin, josamycin and clarithromycin were less than 2%, while the resistance rate to azithromycin, erythromycin and roxithromycin were higher, 29.74%(5 006/16 830) and 53.74%(9 045/16 830), respectively, and the resistance rate of Mh to macrolide antibiotics (except josamycin) was higher than 90%.Between 2010 and 2017, a gradually increasing resistance of ureaplasmas to azithromycin, from 3.81% (46/1 206) in 2010 to 53.15% (1 503/2 828) in 2017, and decreasing resistance to gatifloxacin and thiamphenicol were observed, from 76.78% (926/1 206) and 60.28% (727/1 206) in 2010 decreased to 34.23% (968/2 828) and 37.87% (1 071/2 828) in 2017, respectively. The resistance rate of Mh to gatifloxacin and thiamphenicol were decreased, from 68.93% (122/177) and 41.81% (74/177) in 2010 to 53.54% (159/297) and 21.21% (63/297) in 2017, respectively. Conclusions Doxycycline, minocyclinum and josamycin are good treatment options for genital mycoplasma in Changsha. The resistance rate of Uu to azithromycin is increasing, suggesting that the abuse of azithromycin is present in Changsha, and indicating that better management of antibiotics is necessary.

Bone is one of the most metastatic sites of advanced malignant tumors. With the continuous improvement of diagnosis and treatment of malignant tumors, the survival time of patients is prolonged and incidence of bone metastases also increases. Lung cancer is the leading cause of cancer-related mortality worldwide. It is estimated that the incidence of bone metastases in patients advanced lung cancer is about 30%-40%. The traditional diagnosis of bone metastases in lung cancer is based on clinical symptoms, X ray, computed tomography (CT), magnetic resonance imaging (MRI) and pathology. Recently, a large number of exploratory studies have reported blood biomarkers as indicators of bone metastasis screening and efficacy evaluation. In this review, we summarize the progress of biomarkers in diagnosis of bone metastases of lung cancer.
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Biomarkers, Tumor ; metabolism ; Bone Neoplasms ; metabolism ; physiopathology ; secondary ; Humans ; Lung Neoplasms ; pathology ; Osteogenesis

Objective To investigate the relationship between the composition of vaginal microbiota and the course of cervical precancerous lesion.Methods A total of 64 vaginal swabs were collected from 22 healthy women, 18 CINⅠ patients and 24 CINⅡ/Ⅲ patients who visited Obstetrics and Gynecology of the Second Xiangya Hospital of Central South University during July 2014 and July 2015.The Bacterial genomic DNA was extracted and the V3 and V4 hypervariable regions of 16S rRNA were amplified and high-throughput sequenced.The abundance and composition of vaginal microbiota were analyzed by Uparse, Mothur and LefSe statistical software.Results There was no significant difference in Alpha diversity index between CINⅡ/Ⅲ group(Chao:63±32;ACE:72±38;Simpson:0.70±0.27;Shannon:0.70±0.63) and control group ( Chao:48±24;ACE:54±25;Simpson:0.71±0.27;Shannon:0.65±0.58)(W=192,P=0.11;W=189,P=0.10;W=281,P=0.72;W=241,P=0.62).The ACE(85±37) and Chao(66±25) values of CINⅠgroup were significantly different from those of the control group (ACE:54±25;Chao:48±24)(W=99,P=0.006;W=113,P=0.02).At the phylum level, 78.69%(309 020/392 722) of the vaginal microbiota in the control group was Firmicutes, 16%(62 846/392 722) was Actinobacteria.Firmicutes was reduced to 64.86%(208 422/321 318) and Actinobacteria increased to 27.71%(89 040/321 318) in CINⅠgroup.The composition of vaginal microbiotain in CINⅡ/Ⅲ group was similar to those of control group.At the genus level, the composition of vaginal microbiota were similar between CINⅡ/Ⅲ group and control group, with Lactobacillus as predominant genus[71.81%(307 658/418 424)], Gardnerella[12.91%(55 299/428 424)], others such as Prevotella, atopobium were less.In the CINⅠ group, the abundance of Lactobacillus was decreased to 56.26%(180 787/321 318), Gardnerella was increased to 19.62%(63 057/321 318), and Listeria was increased to 7.7%(24 746/321 318).The composition of vaginal microbiota in the most samples was classified as CSTⅢ and CSTⅠ, with Lactobacillus inersand and Lactobacillus crispatus were dominant respectively.There was no significant difference in the composition of vaginal microbiota between the three groups(χ2=2.72, P=0.949).LEfSe analysis showed that the abundance of bacteria in CIN group and control group were varied.At the genus level, there were significant differences in the abundance of Geobacter, Atopobium and Ureaplasma (P<0.05, P<0.05, P<0.01, respectively).At the species level, there was significant difference in the abundance of Ureaplasma urealyticum serotype 9 (P<0.01).Conclusion The diversity and the composition of vaginal microbiota were similar between CIN patients and healthy women, but the abundances of some bacteria were varied, with Ureaplasma increased in patients with CIN.

Background and objective Treatment options for patients with squamous cell carcinoma of the lung (SCC) are limited in chemotherapy. However, not all patients could benefit form standard platinum regimen. Considering the dismal prognosis of patients with advanced SCC, a greater focus on selecting sensitive chemotherapy regimens remains of up-most importance to improve outcomes in this disease. In this study, we used matrix-assisted laser desorption/ionization time-of-flight mass spectrometry to detect pre-chemotherapy serum peptides in advanced lung squamous cell carcinoma patients accepting paclitaxel combined with platinum chemotherapy and to analyze the correlation between serum peptides and che-motherapy efcacy. Methods Patients with advanced lung squamous cell carcinoma received paclitaxel combining with plati-num chemotherapy and evaluated the efcacy every two cycles. Evaluation of complete response (CR) or partial response (PR) patients defined as sensitive group, progressive disease (PD) patients defined as resistant group. Serum samples were collected from patients with lung squamous cell carcinoma. Eighty-one patients were randomly divided into training group (sensitive group Ⅰ and resistant group Ⅰ) and validation group (sensitive group Ⅱ and resistant group Ⅱ) according to the ratio of 3:1. Se-rum samples were pretreated and Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) was used to detect serum peptide fingerprints. ClinProTools software was used to analyze the differences between the sensitive group Ⅰ and the resistant group Ⅰ. Three kinds of biological algorithms (SNN, GA, QC) built in CPT software were used to establish the curative effect prediction model respectively and the optimal algorithm was selected. The validation group was used for blind verification. Results Thirty sensitive patients and 31 resistant patients were enrolled in the training group. Ten sensitive patients and 10 resistant patients were included in the validation group. The training group had 96 differentially expressed peptides in the sensitive and resistant patients, with 16 statistically significant peptides (P<0.001). The predictive model was established by 5 polypeptides (1,897.75 Da, 2,023.93 Da, 3,683.36 Da, 4,269.56 Da, 5,341.29 Da). The recognition rate of this model was 89.18% and the cross validation rate was 95.11%. The accuracy of the model was 85%, the sensitivity was 90.0% and the specificity was 80.0%. The median PFS in the sensitive group was better than patients in the resistant group (7.2 months 95%CI: 4.4-14.5 vs 1.8 months 95%CI: 0.7-3.5). The results showed that the differential peptides 4,232.04 Da and 4,269.56 Da were correlated with PFS in patients with lung squamous cell carcinoma (P<0.001). Conclusion MALDI-TOF-MS was used to detect the difference of serum peptides between sensitive and resistant groups. The preliminary curative effect prediction model was used to predict the efcacy of paclitaxel combined with platinum regimen. However, this model need further investigations to verify the accuracy and the sensitivity.

Lung cancer, of which approximately 85% are non-small cell lung cancer (NSCLC), is one of the most prevalent cancers and the most leading cause of cancer mortality. Despite recent improvements in its treatment, the prognosis remains dismal. Previous studies have clearly proved that estrogen and estrogen receptors (ER) are involve in the pathogenesis and development of lung cancer. More and more evidences showed antiestrogen therapy may reverse the drug-resistance of platinum based chemotherapy in NSCLC patients and can enhance curative effect of epidermal growth factor receptor tyrosine kinase inhibitor. We will review recent progress in the function of estrogen in NSCLC and the treatment based on the ER sig-naling pathways for NSCLC in this article.

Background and objectivehTis study aimed at using matrix-assisted laser desorption ionization - time of lfight mass spectrometer (matrix-assisted laser desorption ionization time-of-lfight mass spectrometry, MALDI-TOF-MS) screening the difference serum peptides during epidermal growth factor tyrosine kinase inhibitors (EGFR-TKIs) treatment and exploring their signiifcance of advanced NSCLC patients.MethodsCollect 102 serum samples from 34 advanced NSCLC pa-tients, which are before TKI treatment, best effect of treatment and atfer progession. Peptides were extracted from the samples and then detected by MALDI-TOF-MS system to get the mass spectra. hTe mass spectra data was analyzed by the Clinpro-ToolTM sotfware to identify the different serum peptides, and then analyzed the clinical signiifcance of peptides.Results Among the 34 patients who received TKI treatment, there were none evaluated as complete response (CR), 11 patients evalu-ated as PR and 23 patients evaluated as stable disease (SD), with the PFS was 8.0 months (95%CI: 6.6-11.2); overall survival (OS) was 11.4 months (95%CI: 10.6-16.5). Atfer detected the serum from three different points of time, the result showed that they were totally different; 87 different peptide peaks were identiifed atfer analysis self-paired serum between the time of best effect and baseline, which included one statistically different [P<0.001, area under curve (AUC)≥0.9] peptide; 96 different peptide peaks were identiifed atfer analysis serum between the time of progression and baseline, which included 3 statistically different (P<0.001, AUC≥0.9) peptides; 115 different peptide peaks were identiifed atfer analysis serum between the time of progression and best effect, which included 4 statistically different (P<0.001, AUC≥0.9) peptides.ConclusionhTeserum peptides of NSCLC patients in the process of TKI treatment are dynamic and the different peptides may be associated with treatment effect and disease progression. However, the features and clinical signiifcance of different peptides need to be vali-dated in the future.

Objective:Cytosolic 5'-nucleotidase (CN-Ⅱ), a nucleotide kinase, exhibits both 5'-nucleotidase and nucleoside phos-photransferase activities. Abnormal CN-Ⅱexpression may be correlated with the resistance of nucleoside analogs in anticancer drugs. This study was designed to investigate CN-Ⅱexpression in human non-small cell lung cancer (NSCLC) tissues and its correlation with the clinicopathological parameters as well as the prognosis of patients treated with gemcitabine. Methods:Immunohistochemistry was used to detect CN-Ⅱexpression in 116 cases of paraffin-embedded NSCLC samples. The correlations with the clinicopathological pa-rameters and the response to gemcitabine chemotherapy of CN-Ⅱwere analyzed through the Chi-square test. Log-rank test was used to determine whether or not CN-Ⅱexpression is correlated with the overall survival of patients. Results:The positive rate of CN-Ⅱwas 53.4% in 116 NSCLC tissues. No significant correlation existed between CN-Ⅱ expression and the clinicopathological parameters. Among the 67 of the 116 patients who received gemcitabine chemotherapy, those with tumor progression (positive rate of 57.6%) exhib-ited higher CN-Ⅱexpression than those with therapeutic efficacy (positive rate of 30.4%, P=0.008) and disease-control chemotherapy (positive rate of 36.7%, P=0.013). The progression-free survival was 4.5 and 5.5 months in the CN-Ⅱ-positive and CN-II-negative groups, respectively, with significant differences (95%CI:4.452 to 6.148, P=0.041). Correspondingly, the overall survival was 9.5 and 11.0 months in the two groups (95%CI:8.667 to 13.333, P=0.282). Conclusion:CN-Ⅱmay be a prognostic factor for gemcitabine chemotherapy in NSCLC patients.

Background and objective Small-cell lung cancer (SCLC) is an aggressive disease for which the mainstay of treatment is cytotoxic chemotherapy. Despite good initial responses most patients will relapse or progress atfer the ifrst-line therapy. hTe evidence of a beneift from second-line chemotherapy is limited in patients with relapsed/advanced SCLC. Some drugs are recommended by guidelines, but more regimens are formulated based on experience in clinical. So we conducted this retrospective study in order to compare the effcacy and safety of different second-line treatment regimens. Methods We totally analyzed 309 patients received second-line treatment in our retrospective study. 157 patients received best supportive care (BSC), and the rest 152 patients received second-line chemotherapy. hTe Kaplan-Meier method survival curves and Log-rank test were used to analysis the differences among different groups. hTe endpoints were objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Results Patients administered second-line chemotherapy lived signiifcantly longer, with a total OS from ifrst-line therapy of 11.5 mo compared to 6.0 mo in patients with best supportive care alone (P<0.001), and the ORR, DCR, PFS and OS of the former (including the sensitive dis-ease and resistance/refractory disease patients) were obviously better than that of the latter. hTe ORR and DCR of the patients who received second-line chemotherapy is 39.5%and 59.2%, respectively. hTe median PFS and OS from second-line chemo-therapy were 3.3 mo and 5.3 mo. hTe patients who received second-line chemotherapy were divided by types of second-line regimens. hTe sensitive disease patients were from group A (VP-16-based rechallenge) and group B1 (CPT-11-based regimen). hTe ORR of the two groups were 48.6%and 35.3%, and the DCR were 68.6%and 58.8%, respectively. hTere was no statistically signiifcant difference (P=0.264;P=0.400). hTe median PFS from second-line chemotherapy of the two groups were 4.0 mo and 3.0 mo, and the second-line median OS were 6.5 mo and 4.5 mo. hTere was no statistic difference (P=0.432;P=0.508). hTe resistance/refractory disease patients were divided into group B2 (CPT-11-based regimen), group C (PTX/DXL-based regi-men) and group D (TPT-based regimen). hTere was no statistic difference in second-line ORR, DCR and median PFS among the three groups (P value is 0.521, 0.528 and 0.775, respectively);hTe median OS from second-line chemotherapy of the group D is longer than that of group B2 and group C, with statistical difference (P=0.043;P=0.030). hTe differences of grade III-IV hematologic toxicities among the four subgroups were not statistically different. hTe incidence of diarrhea in non-hematologic toxicities in patients who received irinotecan as second-line chemotherapy was higher than other three subgroups (P=0.029). Conclusion Patients who progressed atfer the completion of ifrst-line chemotherapy can gain survival beneift. hTe response and the PFS of the different second-line chemotherapies were similar. hTe patients who received the TPT-based regimen may gain longer overall survival than other resistance/refractory disease patients.

Background and objective Gemcitabine and taxanes are effective agents commonly used in advanced squamous lung cancer. hTe best treatment sequence, however, is unclear to our knowledge. So we conducted this retrospective study in order to compare the effcacy and toxicities of ifrst-line Gemcitabine+/-platinum followed by second-line taxanes+/-platinum with the reverse sequence. Methods We totally analyzed 105 patients with stage IIIb-IV squamous lung cancer in our retrospective study. hTere were 49 patients receiving gemcitabine+/-platinum ifrst-line followed by taxanes+/-plati-num second-line (G-T group), and 56 patients receiving taxanes+/-platinum ifrst-line followed by gemcitabine+/-platinum second-line (T-G group). hTe primary endpoint of the study was overall survival (OS), and the secondary endpoints included progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR) and toxicities. Results hTe me-dian OS were 18.5 mo in G-T group and 19.0 mo in T-G group (P=0.520). hTe median PFS1 was 5.0 mo and 4.0 mo with ifrst-line gemcitabine+/-platinum and taxanes+/-platinum, respectively (P=0.584). hTe median PFS2 was 2.7 mo and 2.5 mo with second-line gemcitabine+/-platinum and taxanes+/-platinum (P=0.432). hTe ORR1 of G-T group and T-G group were 36.73%and 33.92%(P=0.577), and DCR1 were 79.59%and 89.29%(P=0.186);the ORR2 of G-T group and T-G group were 4.08%and 5.36%(P=0.085), and DCR2 were 51.02%and 66.07%, respectively (P=0.118). Hematologic toxicities was more frequent in G-T group, the patients experienced more grade 3-4 lower hemoglobin (P=0.027) and thrombocytopenia (P=0.002). Conclusion hTe effcacy of ifrst line gemcitabine+/-platinum followed by second line taxanes+/-platinum and the reverse sequence was similar, and the toxicities was tolerable. Both sequential patterns were effective in advanced squamous lung cancer.