Immunotherapy has opened a new era in cancer treatment. Drugs represented by immune checkpoint inhibitors have led to important breakthroughs in the treatment of various solid tumors, greatly improving the survival rate of cancer patients. Many types of immunotherapeutic drugs have become widely available; however, their efficacy is variable, and relatively few patients with advanced cancer experience life-altering durable survival, reflecting the complex and highly regulated nature of the immune system. The research field of cancer immunotherapy (CIT) still faces many challenges in pursuing the broader social goal of "curing cancer." Increasing attention has been paid to strengthening the understanding of the molecular or cellular drivers of resistance to immunotherapy, actively exploring more effective therapeutic targets, and developing combination therapy strategies. Here, we review the key challenges that have emerged in the era of CIT and the possible solutions or development directions to overcome these difficulties, providing relevant references for basic research and the development of modified clinical treatment regimens.
Combined Modality Therapy ; Humans ; Immunologic Factors ; Immunotherapy ; Neoplasms/therapy*

BACKGROUND: Delivery room resuscitation assists preterm infants, especially extremely preterm infants (EPI) and extremely low birth weight infants (ELBWI), in breathing support, while it potentially exerts a negative impact on the lungs and outcomes of preterm infants. This study aimed to assess delivery room resuscitation and discharge outcomes of EPI and ELBWI in China. METHODS: The clinical data of EPI (gestational age [GA] <28 weeks) and ELBWI (birth weight [BW] <1000 g), admitted within 72 h of birth in 33 neonatal intensive care units from five provinces and cities in North China between 2017 and 2018, were analyzed. The primary outcomes were delivery room resuscitation and risk factors for delivery room intubation (DRI). The secondary outcomes were survival rates, incidence of bronchopulmonary dysplasia (BPD), and risk factors for BPD. RESULTS: A cohort of 952 preterm infants were enrolled. The incidence of DRI, chest compressions, and administration of epinephrine was 55.9% (532/952), 12.5% (119/952), and 7.0% (67/952), respectively. Multivariate analysis revealed that the risk factors for DRI were GA <28 weeks (odds ratio [OR], 3.147; 95% confidence interval [CI], 2.082-4.755), BW <1000 g (OR, 2.240; 95% CI, 1.606-3.125), and antepartum infection (OR, 1.429; 95% CI, 1.044-1.956). The survival rate was 65.9% (627/952) and was dependent on GA. The rate of BPD was 29.3% (181/627). Multivariate analysis showed that the risk factors for BPD were male (OR, 1.603; 95% CI, 1.061-2.424), DRI (OR, 2.094; 95% CI, 1.328-3.303), respiratory distress syndrome exposed to ≥2 doses of pulmonary surfactants (PS; OR, 2.700; 95% CI, 1.679-4.343), and mechanical ventilation ≥7 days (OR, 4.358; 95% CI, 2.777-6.837). However, a larger BW (OR, 0.998; 95% CI, 0.996-0.999), antenatal steroid (OR, 0.577; 95% CI, 0.379-0.880), and PS use in the delivery room (OR, 0.273; 95% CI, 0.160-0.467) were preventive factors for BPD (all P < 0.05). CONCLUSION Improving delivery room resuscitation and management of respiratory complications are imperative during early management of the health of EPI and ELBWI.
Birth Weight ; Bronchopulmonary Dysplasia ; China/epidemiology* ; Delivery Rooms ; Female ; Gestational Age ; Humans ; Infant ; Infant, Extremely Low Birth Weight ; Infant, Extremely Premature ; Infant, Newborn ; Male ; Pregnancy

BACKGROUND: Circulating tumor DNA (ctDNA) is a promising biomarker for non-invasive epidermal growth factor receptor mutations (EGFRm) detection in lung cancer patients, but existing methods have limitations in sensitivity and availability. In this study, we used the ΔCt value (mutant cycle threshold [Ct] value-internal control Ct value) generated during the polymerase chain reaction (PCR) assay to convert super-amplification-refractory mutation system (superARMS) from a qualitative method to a semi-quantitative method named reformed-superARMS (R-superARMS), and evaluated its performance in detecting EGFRm in plasma ctDNA in patients with advanced lung adenocarcinoma. METHODS: A total of 41 pairs of tissues and plasma samples were obtained from lung adenocarcinoma patients who had known EGFRm in tumor tissue and were previously untreated. EGFRm in ctDNA was identified by using superARMS. Through making use of ΔCt value generated during the detection process of superARMS, we indirectly transform this qualitative detection method into a semi-quantitative PCR detection method, named R-superARMS. Both qualitative and quantitative analyses of the data were performed. Kaplan-Meier analysis was performed to estimate the progression-free survival (PFS) and overall survival (OS). Fisher exact test was used for categorical variables. RESULTS: The concordance rate of EGFRm in tumor tissues and matched plasma samples was 68.3% (28/41). At baseline, EGFRm-positive patients were divided into two groups according to the cut-off ΔCt value of EGFRm set at 8.11. A significant difference in the median OS (mOS) between the two groups was observed (EGFRm ΔCt ≤8.11 vs. >8.11: not reached vs. 11.0 months; log-rank P = 0.024). Patients were divided into mutation clearance (MC) group and mutation incomplete clearance (MIC) group according to whether the ΔCt value of EGFRm test turned negative after 1 month of treatment. We found that there was also a significant difference in mOS (not reached vs. 10.4 months; log-rank P = 0.021) between MC group and MIC group. Although there was no significant difference in PFS between the two groups, the two curves were separated and the PFS of MC group tended to be higher than the MIC group (not reached vs. 27.5 months; log-rank P = 0.088). Furthermore, EGFRm-positive patients were divided into two groups according to the cut-off of the changes in ΔCt value of EGFRm after 1 month of treatment, which was set at 4.89. A significant difference in the mOS between the two groups was observed (change value of ΔCt >4.89 vs. ≤4.89: not reached vs. 11.0 months; log-rank P = 0.014). CONCLUSIONS Detecting EGFRm in ctDNA using R-superARMS can identify patients who are more likely sensitive to targeted therapy, reflect the molecular load of patients, and predict the therapeutic efficacy and clinical outcomes of patients.
Adenocarcinoma of Lung/genetics* ; Circulating Tumor DNA/genetics* ; ErbB Receptors/genetics* ; Humans ; Lung Neoplasms/genetics* ; Mutation/genetics* ; Protein Kinase Inhibitors

OBJECTIVE: To investigate the expression and clinical significance of microRNA-195 in patients with diffuse large B cell lymphoma(DLBCL). METHODS: Sixty patients with DLBCL were selected from nearly four years in our hospital, and at the same time 30 healthy people with physical examination of the same period and with the same age in our hospital were choosed as control group. Real-time fluorescent quantitative PCR (RT-qPCR) was used to detect the miR-195 expression of the patients and controls, the relationship between miR-195 expression and clinicopathological characteristics of DLBCL and survival time of patients was analyzed. RESULTS: The expression level of miR-195 in DLBCL patients was significantly lower than that in the controls (P<0.001). The expression level of miR-195 closely related with tumor diameter, IPI score and Ann Arbor stage of patients with DLBCL. Overall survival(OS) time of DLBCL patients with highly expressed miR-195 was significantly longer than that of patients with low expression (P<0.001). CONCLUSION miR-195 expression decrease in DLBCL patients, and miR-195 closely relates with tumor characteristics of patients with DLBCL. DLBCL patients with higher expression of miR-195 show longer overall survival time.

Apoptosis ; B7-H1 Antigen/genetics* ; Carcinoma, Non-Small-Cell Lung/genetics* ; Cost-Benefit Analysis ; Humans ; Immune Checkpoint Inhibitors ; Immunotherapy ; Ligands ; Lung Neoplasms/genetics*

Background: IMpower 133 trial first confirmed the efficacy and safety of adding atezolizumab or placebo to first-line treatment with chemotherapy in patients with extensive-stage small-cell lung cancer(SCLC).While,overprice limited its broad use in clinical.The aim of this study was to evaluate the cost-effectiveness of atezolizumab plus chemotherapy in treatment of extensive SCLC as first line in China.Methods: A Markov model was established by extracting data from the IMpower 133 trial with untreated extensive SCLC patients.Utility values were obtained from published studies,and the costs were acquired from real world and literature.Additionally,sensitivity analyses based on a willingness-to-pay(WTP)threshold were performed to identify the uncertain parameters of Markov model.Results: Total costs of atezolizumab group were $48,129,while cost of chemotherapy alone was just $12,920 in placebo group.The quality-adjusted life-years(QALYs)in atezolizumab group was just 0.072 higher than that in placebo group(0.858 QALYs vs.0.786 QALYs).The cost-effectiveness ratio between atezolizumab combination with chemotherapy and chemotherapy alone was$489,013/QAL Y in China.The net benefit of placebo group was significantly higher than atezolizumab group.One-way sensitivity analyses highlighted that utilities of the progression-free survival(PFS)and progression disease state in placebo group were the most influential parameter.Conclusions: Atezolizumab combination therapy was not more cost-effective than chemotherapy alone at a WTP threshold of $25,929/QALY in China.

Background: Base excision repair (BER) plays an important role in the maintenance of genome integrity and anticancer drug resistance. This study aimed to explore the role of BER gene polymorphisms in response to chemotherapy for advanced non-small cell lung cancer (NSCLC) patients treated with platinum-based chemotherapy. Methods: During the period from November 2009 to January 2016, a total of 152 patients diagnosed with NSCLC Stage IIIB and IV in the First Hospital of Jilin University were admitted into this study. The XRCC1 G28152A, MUTYH G972C, HOGG1 C1245G, and PARP1 T2444C polymorphisms of all the patients were detected by mass spectrometry. The logistic regression was used for statictical analysis. All tests were bilateral test, and a P < 0.05 was considered statistically significant. Results: The logistic regression model showed that the response rate of chemotherapy of the PARP1 T2444C polymorphisms, CC genotype (odds ratio [OR]: 5.216, 95% confidence interval [CI]: 1.568-17.352, P = 0.007), TC genotype (OR: 2.692, 95% CI: 1.007-7.198, P = 0.048), as well as the genotype of TC together with CC (OR: 3.178, 95% CI: 1.229-8.219, P = 0.017) were significantly higher than those of TT wild type. There was no relationship between the MUTYH G972C, XRCC1 G28152A, and HOGG1 C1245G gene polymorphisms and chemosensitivity. Conclusions The PARP1 2444 mutation allele C might be associated with the decreased sensitivity to platinum-based chemotherapy in advanced NSCLC. These findings may be helpful in designing individualized cancer treatment.
Antineoplastic Agents ; therapeutic use ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; genetics ; DNA Repair ; DNA-Binding Proteins ; Female ; Genotype ; Humans ; Lung Neoplasms ; drug therapy ; genetics ; Male ; Middle Aged ; Polymorphism, Genetic ; Polymorphism, Single Nucleotide ; Retrospective Studies ; X-ray Repair Cross Complementing Protein 1 ; genetics

OBJECTIVETo explore the curative efficacy of methotrexate(MTX) combined with rituxan for treating patients with primary central nervous system(CNS) lymphoma.

METHODSOne hundred patients with primary CNS lymphoma in our hospital were randomly divided into targeted treatment group(50 cases) and traditional treatment group (50 cases). Targeted treatment group adopted the therapy of high-dose methotrexate combined with rituxan, the traditional treatment group adopted the high-dose methotrexate combined with whole brain radiotherapy. The results of relevant imaging examination, clinical data, imaging, follow-up and the survival time were analysed and compared between these 2 groups.

RESULTSIn the targeted therapy group, there were 33 cases in CR, 9 cases were in stable condition, and 5 cases were in partial response, and 3 cases in the progressive stage. In the group of traditional treatment group, 29 cases reached complete remission, 5 cases were in stable condition, 11 cases were in partial response, and 5 cases were in the progressive stage. In the targeted treatment group and traditional treatment group, the median progression-free survival time was 28 and 11 months, respectively.

CONCLUSIONThe first choice for treatment scheme of PCNSL is high-dose methotrexate chemotherapy combined with whole brain radiotherapy, that showed a certain curative effect, but the adverse reactions are larger, and a big late neuro toxic reaction may occur, while high-dose methotrexate combined PCNSL rituxan treatment shows high curative effect, less adverse reaction and low side effects. This treatment also has a more positive value for the elderly patients with PCNSL.

Objective To investigate the correlation between NRAMP1 gene polymorphisms and susceptibility to tuberculosis ( TB) in Tibetan people in Qinghai. Methods A case-control study was con-ducted in this study, involving 99 Tibetan patients with TB and 89 healthy Tibetans. The single nucleotide polymorphisms of NRAMP1 gene at rs17235409 and rs3731865 sites were detected by using TaqMan probe method. Gene cloning and sequencing typing were performed to analyze the single nucleotide polymorphisms of NRAMP1 gene at the rs17235416 site. SPASS20. 0 software was used to statistically analyze the correla-tion between NRAMP1 gene polymorphisms and susceptibility to TB in Tibetan people. Results No signifi-cant difference in the genotype frequencies of rs3731865 and rs17235409 was found between the two groups (χ2=0. 852, P=0. 356;χ2=0. 279, P=0. 597). The genotype frequencies of TGTG/TGTG and TGTG/del+del/del at the rs17235416 site were 70. 7% ( 70/99 ) and 29. 3% ( 29/99 ) in patients with TB and 86. 5% (77/89) and 13. 5% (12/89) in healthy subjects. There were significant differences in the geno-type frequencies of TGTG/TGTG and TGTG/del+del/del between the two groups (χ2=6. 870, P=0. 009). The genotypes of TGTG/del and del/del at rs17235416 were risk factors for TB ( OR=0. 376; 95%CI:0. 178-1. 794 as compared with the TGTG/TGTG genotype in Tibetan people in Qinghai. Conclusion This study suggested that the NRAMP1 gene polymorphisms at rs3731865 and rs1723409 sites had no correlation with the susceptibility to TB in Tibetans in Qinghai. However, the NRAMP1 gene polymorphisms at rs17235416 site were correlated with the susceptibility to TB. The TGTG/del alleles at the rs17235416 site might be the risk factors for tuberculosis in Tibetans in Qinghai.

BACKGROUNDLittle attention has been paid to the role of subcortical deep gray matter (SDGM) structures in type 2 diabetes mellitus (T2DM)-induced cognitive impairment, especially hippocampal subfields. Our aims were to assess the in vivo volumes of SDGM structures and hippocampal subfields using magnetic resonance imaging (MRI) and to test their associations with cognitive performance in T2DM.

METHODSA total of 80 T2DM patients and 80 neurologically unimpaired healthy controls matched by age, sex and education level was enrolled in this study. We assessed the volumes of the SDGM structures and seven hippocampal subfields on MRI using a novel technique that enabled automated volumetry. We used Mini-Mental State Examination and Montreal Cognitive Assessment (MoCA) scores as measures of cognitive performance. The association of glycosylated hemoglobin (HbA1c) with SDGM structures and neuropsychological tests and correlations between hippocampal subfields and neuropsychological tests were assessed by partial correlation analysis in T2DM.

RESULTSBilaterally, the hippocampal volumes were smaller in T2DM patients, mainly in the CA1 and subiculum subfields. Partial correlation analysis showed that the MoCA scores, particularly those regarding delayed memory, were significantly positively correlated with reduced hippocampal CA1 and subiculum volumes in T2DM patients. Additionally, higher HbA1c levels were significantly associated with poor memory performance and hippocampal atrophy among T2DM patients.

CONCLUSIONSThese data indicate that the hippocampus might be the main affected region among the SDGM structures in T2DM. These structural changes in the hippocampal CA1 and subiculum areas might be at the core of underlying neurobiological mechanisms of hippocampal dysfunction, suggesting that degeneration in these regions could be responsible for memory impairments in T2DM patients.

Aged ; CA1 Region, Hippocampal ; pathology ; physiopathology ; Diabetes Mellitus, Type 2 ; pathology ; physiopathology ; Female ; Hippocampus ; pathology ; physiopathology ; Humans ; Magnetic Resonance Imaging ; Male ; Memory Disorders ; etiology ; pathology ; Middle Aged ; Neuropsychological Tests