[摘 要] 目的：通过对比免疫相关不良反应（irAE）发生前后血常规中主要指标的变化，为鉴别诊断irAE及感染性炎症提供新依据。方法：回顾性分析201例2018年8月至2022年6月在河南省肿瘤医院接受抗PD-1抗体治疗后出现irAE的肿瘤患者的临床资料，包括抗PD-1抗体治疗前、发生irAE前及irAE后血常规的主要指标，采用配对t检验分析治疗前后血常规指标值的统计学差异。采用定性变量的配对c2检验分析治疗前后血常规指标值的阳性率（高于正常值的比例）的统计学差异。结果：从201例患者中观察到了258次irAE，其中27例（13.4%）患者发生了2种及以上类型的irAE，214次（82.94%）irAE未引起发热；irAE发生后与抗PD-1抗体治疗前相比，白细胞计数（t=1.087, P=0.278）、中性粒细胞计数（t=0.959, P=0.338）及中性粒细胞百分比（t=0.817，P=0.414）未见明显升高，且三指标高于正常值的病例数分别为28 vs 38（χ2=1.737，P=0.187）、32 vs 44（χ2=2.222，P=0.136）、45 vs 55（χ2=1.240，P=0.265）,差异均无统计学意义。结论：irAE发生后患者外周血白细胞计数、中性粒细胞计数及中性粒细胞百分比无明显变化，这对鉴别诊断感染性炎症可能具有参考意义。

Objective: To evaluate the efficacy of lung cancer screening in urban areas of Henan province by low-dose computed tomography (LDCT) from 2013 to 2017. Methods: A cluster sampling method was used to select the residents of 40-74 years old in Henan province to investigate the risk factors and conduct lung cancer risk assessment. Subjects with high risk of lung cancer received LDCT for screening. Results: A total of 179 002 residents completed the lung cancer risk assessment, and 35 672 subjects were identified as high risk of lung cancer, with a high risk rate of 19.93%. A total of 13 383 subjects with high risk received LDCT, and the screening rate was 37.52%. There were 786 cases diagnosed as positive nodules, and the detection rate was 5.87%. Among them, 755 cases of solid/partial solid nodule were ≥5 mm, 23 cases of non-solid nodules were ≥8 mm, 8 cases were intratracheal nodules, and 115 cases were diagnosed as suspicious lung cancer. The detection rate in males was 6.74%, which was higher than 5.02% in females. The detection rate was positively related with age (P<0.05). Conclusions The application of LDCT is a useful screening method which can elevate the early detection rate of positive nodules and other related diseases in lungs. In the future, males and older populations should be paid more attention to improve screening efficacy.

Objective: To investigate the function of anti-PD-1 (scFv)/IL-15/IL-15Rα-sushi fusion protein (PD-S15) to specifically bind to PD-1 in vitro and to explore its effect on NK/T cell proliferation. Methods: The human anti-PD-1 (scFv) gene sequence and human IL-15/IL-15Rα-sushi fusion gene sequence were synthesized chemically. The recombinant expression plasmid pUC57-PD-S15 was constructed by enzyme digestion and ligation of the two target genes, and then transiently transfected into HEK293T cells by lipofectamineTM 2000. The supernatants of cell culture medium were acquired, and the expression of PD-S15 fusion protein in cell culture supernatants was detected by Wb assay. PBMCs and TILs were cultured in mediums with different proportion of PD-S15/X-VIVOTM15, respectively. Then, the capacity of PD-S15 fusion protein to bind to PD-1 in vitro and its effect on the proliferation of PBMCs and the proportion of CD3+CD8+, CD3+CD4+ and CD3-CD56+ subsets were detected by flow cytometry. The effect of PD-S15 fusion protein on the proliferation of TILs was detected by cytometry. Results: The successful construction of pUC57-PD-S15 eukaryotic expression plasmid was confirmed by double enzyme digestion and sequencing, and then successfully transfected into HEK293T cells. The relative molecular weight of the target protein was approximately 55 000, and was in line with expectations. PD-S15 fusion protein could specifically combine with PD-1 in vitro (P<0.05) and stimulate NK/T cell proliferation (P<0.05). Compared with classical TILs culture method, the efficiency of activation and amplification of T cells in vitro by PD-S15 culturemethodwasbetter (P<0.01). Conclusion: PD-S15 fusion protein can specifically target PD-1 and rapidly expand NK/T cells in vitro, which lays a foundation for the selective expansion of CD8+PD-1+ antigen-specific T lymphocytes from tumor tissues and even peripheral blood.

OBJECTIVETo investigate the association between obesity and the risk of lung cancer and evaluate a dose-response relationship between body mass index (BMI) and incidence risk of lung cancer in the Chinese population.

METHODSA systematic literature search for BMI and incidence risk of lung cancer in the Chinese population, as well as through the reference lists of retrieved articles. The literature databases including Chinese National Knowledge Infrastructure, Wanfang, PubMed, Embase and Google Scholar. Time range was from the founding of each database to September 2014 and a total of 93 research papers were collected. Meta-analysis was conducted to calculate pooled odds ratio and corresponding 95% CI. Generalized least-squares regression methods were used to make a dose-response meta-analysis between BMI and incidence risk of lung cancer.

RESULTSSeven studies were included in the meta-analysis, with a number of 2 351 lung cancer cases. Results showed that obesity was inversely associated with lung cancer incidence (OR = 0.68, 95% CI: 0.59-0.79) (heterogeneity test: I² = 0, P = 0.594). The association did not change with stratification by study design, sex, smoking status, BMI measurement method and study population. A linear dose-response association between BMI and risk of lung cancer was visually significant, and lung cancer risk would be reduced 21% for per 5 kg/m² BMI increase (OR = 0.79, 95% CI: 0.71-0.89) (heterogeneity test: q = 22.43, P = 0.002).

CONCLUSIONThe results of this meta-analysis indicated that higher BMI was a protective factor against lung cancer, but smoking may play a stronger role as a confounding factor for the most important role with lung cancer incidence.

Asian Continental Ancestry Group ; Body Mass Index ; China ; Humans ; Incidence ; Lung Neoplasms ; Obesity ; Odds Ratio ; Protective Factors ; Risk ; Smoking

OBJECTIVETo evaluate the efficiency and safety of rituximab and dexamethasone combined with cyclophosphamide for treating patients with relapsed and refractory immune thrombocytopenia (ITP).

METHODSTwelve patients with relapsed and refractory immune thrombocytopenia were prospectively enrolled in this study, and received rituximab 375 mg/m(2) once a week for 4 weeks, dexamethasone 40 mg once a day for consecutive 4 days, and cyclophosphamide 500 mg/m(2) biweekly for 2 weeks. The levels of IFN-r and IL-4 in peripheral blood of patients were measured by enzyme-linked immunosorbent assay (ELISA), and the percentages of Breg, Treg and Th17 cells were detected by flow cytometry before and after treatment. Efficiency was evaluated according to platelet counts, and side effects were observed.

RESULTSSix out of 12 patients reached to complete remission and 4 patients reached to partial remission, with the total response rate 83.33%. The platelet counts [(115.42 ± 76.60) × 10(9)/L] after treatment were significantly higher than that before treatment [(115.42 ± 76.60) × 10(9)/L] (P < 0.001). The ratio of IFN-r/ IL4 after treatment (5.89 ± 2.30) was very significantly lower than that before treatment (7.00 ± 2.73) (P = 0.002). The percentage of Breg cells after treatment [(21.27 ± 4.28)%] were much significantly higher than that before treatment [(15.48 ± 1.67)%] (P < 0.001). The ratio of Treg/Th17 after treatment (3.07 ± 1.50) was significantly higher than that before treatment (0.98 ± 0.45) (P < 0.001). Infusion reaction was observed in 1 patient, secondary hypertension and hyperglycemia were in 1 patient, and pneumonia in 2 patients.

CONCLUSIONRituximab and dexamethasone combined with cyclophosphamide can improve the outcomes of patients with relapsed and refractory immune thrombocytopenia patients and they were well tolerated, its mechanism may be related with the balance between T cell sunsets and Treg cells.

Antibodies, Monoclonal, Murine-Derived ; B-Lymphocytes, Regulatory ; cytology ; Cyclophosphamide ; therapeutic use ; Dexamethasone ; therapeutic use ; Enzyme-Linked Immunosorbent Assay ; Humans ; Interferon-gamma ; blood ; Interleukin-4 ; blood ; Platelet Count ; Prospective Studies ; Purpura, Thrombocytopenic, Idiopathic ; drug therapy ; Remission Induction ; Rituximab ; therapeutic use ; T-Lymphocytes, Regulatory ; cytology ; Th17 Cells ; cytology

OBJECTIVE: To explore the regulatory effect of TRIP13 on the proliferation and apoptosis of B-cell lymphoma cells and its possible molecular mechanism by knocking down/overexpressing TRIP13 on the cell lines Granta-519 and JVM-2. METHODS: Lentiviral transfection technology was used to construct Granta-519 and JVM-2 cells with knocked down or overexpressed TRIP13 and their control cells. The efficiency of transfection was determined by fluorescence microscopy. The efficiency of knockdown and overexpression was evaluated by real-time quantitative PCR and Western blot. The proliferation was detected by CCK-8 assay. The apoptosis was detected by the Annexin V-APC single staining. The cell cycle was detected by the PI staining. The expression levels of P53, MDM4, and BCL-2 were evaluated by Western blot. RESULTS: After TRIP13 was knocked down, the proliferation ability of Granta-519 and JVM-2 cells was significantly reduced, and the apoptosis rate significantly increased. After TRIP13 was overexpressed, the proliferation ability of Granta-519 and JVM-2 cells was significantly enhanced, and the apoptosis was significantly reduced. After TRIP13 was knocked down, Granta-519 cells had obvious G CONCLUSION TRIP13 promotes the proliferation of B-cell lymphoma cells, inhibits their apoptosis, and affects their proliferation and apoptosis by participating in the regulation of the cell cycle. TRIP13 promotes the expression of BCL-2 proteins and inhibits the expression of MDM4 protein in B-cell lymphoma cells.
ATPases Associated with Diverse Cellular Activities/metabolism* ; Apoptosis ; Cell Cycle Proteins ; Cell Proliferation ; Humans ; Lymphoma, B-Cell ; Proto-Oncogene Proteins

Objective: To estimate the incidence and mortality of esophageal cancer in 2016 and their changing trend during 2010-2016 according to the cancer registration data in Henan province. Methods: The data quality including completeness, validity, and reliability of local registries which submitted the cancer registration data of 2016 were assessed according to the criteria of Guideline on Cancer Registration in China and IARC/IACR. Esophageal cancer cases (ICD10: C15) were extracted from the database, and the incidence and mortality stratified by gender, age, and areas (urban/rural) were calculated, the incidence and mortality of provincial cancer were estimated combined with provincial population data. China's 2000 census population and Segi's population were used to calculate the age-standardized rate. Joinpoint model was used to estimate the changing trend of age standardized incidence and mortality along with the calendar year. Results: Approximately 40.10 thousand new esophageal cancer cases were diagnosed in Henan in 2016, accounting for 13.46% of all new cancer cases, and it ranked the third among cancer of all sites. The crude incidence of esophageal cancer was 37.21/100 000 with an age-standardized incidence rate by China standard population (ASIRC) of 26.74/100 000 and an age-standardized incidence rate by world standard population (ASIRW) of 27.12/100 000. The incidence of esophageal cancer in males was higher than that in females, with the ASIRC of 34.53/100 000 and 19.19/100 000, respectively. It was higher in rural areas than that in urban areas, with the ASIRC of 28.13/100 000 and 20.90/100 000, respectively. About 29.30 thousand deaths of esophageal cancer in Henan in 2016, accounting for 15.61% of all cancer deaths in Henan, which ranked the third among cancer of all sites. The crude mortality rate was 27.14/100 000 with an age-standardized mortality rate by China standard population (ASMRC) of 18.74/100 000 and an age-standardized mortality rate by world standard population (ASMRW) of 18.78/100 000. The mortality in males was higher than that in females, with the ASMRC of 24.78/100 000 and 13.12/100 000, respectively. It was also higher in rural areas than that in urban areas, with the ASMRC of 19.48/100 000 and 15.73/100 000, respectively. The ASIRC and ASMRC were declining with annual percent change (APC) of 3.12% (APC=-3.12%; 95%CI: -5.30%, -0.90%; P=0.015) and 2.47% (APC=-2.47%; 95%CI: -4.70%, -0.20%; P=0.039) during 2010-2016. However, the significant declining trend was only observed in rural areas in Henan, and the changing trend was same between males and females. Conclusions: The incidence and mortality of esophageal cancer are declining since 2010, however, the disease burden remains large in Henan. Therefore, comprehensive prevention and control efforts should be strengthened according to its epidemic characteristics and risk factors.
China/epidemiology* ; Esophageal Neoplasms/epidemiology* ; Female ; Humans ; Incidence ; Male ; Registries ; Reproducibility of Results ; Rural Population ; Urban Population

Objective　Studies are rarely reported on the factors influencing prognosis of surgically resected lung adenocarcinoma with a micropapillary pattern (LAC-MPP). This study aimed to explore the clinicopathological characteristics and risk factors of surgically resected LAC-MPP. Methods　We retrospectively analyzed 384 cases of LAC treated in Henan Cancer Hospital between June 2015 and December 2017, which were classified into an MPP group (n = 82) and a non-MPP control group (n = 302) according to the results of postoperative pathology. We determined the expression of the fusion protein anaplastic lymphoma kinase (ALK), analyzed its association with the clinicopathological features of LAC-MPP, and explored the risk factors of postoperative MPP. Results　Compared with the non-MPP group, the LAC-MPP patients showed a significantly higher expression of ALK (0.03% vs 12.20%, P < 0.05), rate of bronchial invasion (30.80% vs 48.78%, P < 0.05) and vascular tumor thrombus (0.99% vs 25.61%, P < 0.05), but a lower mutation rate of the epidermal growth factor receptor (EGFR) (64.24% vs 51.22%, P < 0.05). Multivariate logistic regression analysis revealed that the expression of ALK, vascular tumor thrombus, and age were significantly associated with the risk of postoperative MPP. Conclusion　There is a high incidence rate of ALK expression in LAC-MPP patients after operation, which may provide some new ideas for the clinical treatment of the disease. Special attention should be paid to the expression of the ALK fusion protein and vascular tumor thrombus, and age in patients with LAC-MPP after operation.

OBJECTIVE: To study the effect of PX-12 on apoptosis of multiple myeloma (MM) cell line induced by bortezomib. METHODS: MM cell line H929 cells were divided into PX-12 group, bortezomib group, combination group, and control group. 5.0 μmol/L PX-12, 20 nmol/L bortezomib, combination of the two drugs, and DMSO were given to the above mentioned group, respectively. After culture for 24, 48, and 72 hours, the changes of cell viability were observed, the MM cell activity was detected by MTT method, and the cell cycle distribution and apoptosis of each group was detected by flow cytometry. The intracellular ROS level was measured by H RESULTS: MTT assay showed that after culture for 72 hours, the activity of H929 cells in PX-12 group (P<0.05) and bortezomib group (P<0.01) was significantly lower than that in the control group, while that in the combination group was decreased most significantly (P<0.01). After culture for 48 hours, cells in G1 phase in PX-12 group was decreased to 40%, while cells in S phase and G CONCLUSION PX-12 can increase the apoptosis of MM cell line H929 induced by bortezomib, which may be caused by increasing of ROS level.
Apoptosis ; Bortezomib/pharmacology* ; Cell Line, Tumor ; Cell Proliferation ; Humans ; Multiple Myeloma

B-cell acute lymphoblastic leukemia (B-ALL) is a common malignant tumor in hematopoietic system. Although the remission rate of the patients with adult B-ALL is similar to those with childhood B-ALL, the rate of long-term disease-free survival (DFS) rate is significantly lower, once recurrence, the remission rate of routine chemotherapy is low and the prognosis is so poor. Based on the expression of tumor cell surface antigens(such as CD19, CD20 and CD22), the specific monoclonal antibodies, bispecific antibodies and chimeric antigen receptor T cells (CAR-T), and other targeted immunotherapy can greatly improve the efficacy of B-ALL patients, especially for patients with relapse and refractory. In this review, the progress of immunotherapy against B-ALL cell surface antigen is summarized briefly.
Adult ; Antigens, CD19 ; Antigens, Surface ; B-Lymphocytes ; Burkitt Lymphoma ; Child ; Humans ; Immunotherapy, Adoptive ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy* ; Receptors, Antigen, T-Cell