objectives Radiographic examination is currently the most commonly used method for diagnosing developmental dysplasia of the hip (DDH). In recent years, artificial intelligence (AI) has made significant advances in image recognition, segmentation, decision-making, and statistical analysis of a large number of data sets. Our study aim is whether AI model can be accurately measured angles in pelvic radiography of hip. Then evaluation of AI model effectiveness of pelvic radiographs in diagnosis of DDH and BDDH. Methods A total of 1029 patients, comprising 273 men and 757 women (aged 18–84 years, median age: 33 years) who underwent pelvic radiography examination between January 2020 and January 2022 were retrospectively included in this study. The images were randomly allocated into the training set (720 cases), validation set (103 cases), and test set (206 cases). The anatomical key points were marked: L-fhc, L-uar, L-tar, L-lt, R-fhc, R-uar, R-tar, and R-lt. The Sharp, Tönnis, and Center edge (CE) angles were calculated automatically based on the above coordinates and corresponding rules. Hip development situation was compared among measurements obtained by the AI model and those obtained manually by two radiologists. The area under the receiver operating characteristic (ROC) curve was used to evaluate the diagnostic effectiveness of the AI model. Results Manually- and AI model-measured results showed no significant differences in terms of Sharp, Tönnis and Center edge (CE) angles (all P > 0.05). ICCs and correlation coefficient r values were greater than 0.75, indicating that AI model and manual measurements had good repeatability and were positively correlated. AI model measurement results are highly consistent with manual measurement results, with smaller errors. Both AI model and manual measurement results had similar repeatability. The AI model measurement was therefore faster than the radiologists (P < 0.001). AI model measurement had a high diagnostic accuracy, sensitivity and specificity of DDH. AI model has high diagnostic performance for DDH. AI model and manual measurements were basically consistent with clinical diagnosis results (P < 0.05). AI model can be used to evaluate the hip condition by measuring hip sharp, Tönnis and CE angles, which are similar to the clinical diagnosis results and can be used for the auxiliary diagnosis of DDH and BDDH. Conclusion AI model measurement results are highly consistent with manual measurement results. The AI model measurement was far faster than the radiologists. Sharp, Center edge, and Tönnis angles measured using the deep learning based convolutional neural network model can be used to diagnose DDH and BDDH with a high diagnostic performance. AI model can completely replace manual measurement key angles of hip and diagnosing DDH and BDDH, faster and more precise.

Objective:This study aimed to reveal the insomnia burden and relevant influencing factors among informal caregivers (ICs) of hospitalized patients with lung cancer.Methods:A cross-sectional study on ICs of hospitalized patients with lung cancer was conducted from December 31, 2020 to December 31, 2021. ICs' burden was assessed using the Caregiver Reaction Assessment (CRA), Hospital Anxiety and Depression Scale (HADS), and Insomnia Severity Index (ISI). Linear and logistic regression models were used to identify the influencing factors.Results:Among 289 ICs of hospitalized patients with lung cancer, 83 (28.72%), 53 (18.34%), and 14 (4.84%) ICs experienced mild, moderate, and severe insomnia, respectively. The scores concerning self-esteem, lack of family support, financial problems, disturbed schedule, and health problems were 4.32 ± 0.53, 2.24 ± 0.79, 2.84 ± 1.14, 3.63 ± 0.77, and 2.44 ± 0.95, respectively. ICs with higher Activities of Daily Living Scale (ADLS) scores were associated with a lower risk of insomnia, with an odd ratio ( OR) and 95% confidence interval ( CI) of 0.940 (0.898-0.983). Among the ICs, female gender ( OR = 2.597), alcohol consumption ( OR = 3.745), underlying medical conditions ( OR = 11.765), long-term caregiving experience ( OR = 37.037), and higher monthly expenses ( OR = 5.714) were associated with a high risk of insomnia.Conclusion:Of the hospitalized patients with lung cancer, 51.9% experienced insomnia. Patients' ADL, ICs gender, alcohol consumption, underlying medical conditions, caregiving duration, and monthly expenses were influencing factors. Therefore, prompt screening and early intervention for ICs of patients with lung cancer is necessary.

Background: Advanced non-small cell lung cancer (NSCLC) patients with poor performance status (PS) are likely to receive programmed cell death 1 (PD-1) inhibitors, despite limited evidence. The aim of the present study was to report the clinical outcomes and potential prognostic biomarkers in advanced NSCLC patients with poor PS receiving PD-1 inhibitors. Methods: We conducted a retrospective study enrolling 101 advanced NSCLC patients from our hospital. Data of patients with poor PS 2-4 receiving PD-1 inhibitors were retrieved from medical records. Patients were stratified based on dichotomized baseline neutrophil-to-lymphocyte ratio (NLR), change in NLR (Delta NLR; 6 weeks post-treatment NLR minus baseline NLR), and their combination. The receiver-operating characteristic curve was used to assess the best cutoff for NLR. Multivariate Cox analysis was used to evaluate the prognostic value of NLR and Delta NLR for patients' survival. Results: The optimal cutoff for NLR was 4.5. The median follow-up was 25.7 months, baseline NLR >= 4.5, and Delta NLR >= 0, which were independently and significantly associated with shorter overall survival (both P=0.002) and progression-free survival (P=0.004 for NLR and P<0.001 for Delta NLR). Furthermore, simultaneous elevation of the 2 factors was associated with worsened prognosis; patients with both NLR >= 4.5 and Delta NLR >= 0 had significantly increased risk of death [hazards ratio (HR): 10.79, 95% confidence interval (CI): 4.30-27.10] and disease progression (HR: 10.49, 95% CI: 4.39-25.09), compared with both low NLR and Delta NLR patients. Patients with either NLR >= 4.5 or Delta NLR >= 0 showed an intermediate risk for death (HR: 3.12, 95% CI: 1.35-7.21) and progression (HR: 3.45, 95% CI: 1.62-7.36). Conclusions: High baseline NLR and increased post-treatment NLR might aid in the stratification of high progression and death risk groups in advanced NSCLC patients with poor PS receiving PD-1 inhibitors.

Rationale exists for combining immune checkpoint inhibitors and PARP inhibitors (PARPi), and results of clinical trials in ovarian cancer are promising, but data in other cancers are limited. Efficacy and safety of PARPi/anti-PD-1 in advanced solid tumors were retrospectively analyzed. The efficacy measures included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS). This retrospective study included data from 40 patients. The ORR was 27.5% (95% CI, 13.0–42.0%), with a DCR of 85.0% (95% CI, 73.4–96.6%). Except four patients in first-line treatment (three with PR and one with SD), the ORR of ≥second-line treatment, non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) was 22.2%, 23.1% and 28.6%, and the DCR was 83.3%, 84.6% and 71.4%, separately. The median PFS of all patients, ≥second-line treatment, NSCLC and SCLC was 4.6 m, 4.2 m, 4.5 m and 3.7 m. The median OS was 9.4 m, 11.4 m, 12.7 m and 5.4 m, respectively. Multivariable analysis revealed that BRCA1/2 mutation was positively correlated with ORR (P = 0.008), and LDH≥250U/L was negatively correlated with lowered DCR (P = 0.018), while lymphocyte number, ECOG and LDH significantly influenced both PFS and OS. We found that the possible resistant mechanisms were sarcomatous degeneration and secondary mutation, including BRCA2 truncation mutation, A2M, JAK1,T790M, KEAP1 and mTOR mutation. 37.5% patients had ≥grade 3 adverse events. PARPi/anti-PD-1 is an effective and tolerable method for patients with advanced solid tumors, and BRCA1/2 is a potential biomarker.

BackgroundChemotherapy is one of the main approaches to treating malignant neoplasms [1,2].The chemotherapy drugs, cisplatin, and methotrexate can be used to kill the tumor cells that reproduce rapidly, but these also affect the highly proliferative normal cells, such as hematopoietic systems, gastrointestinal and oral mucosal epithelial cells [2][3][4].Oral mucositis (OM) is a common adverse effect of the chemotherapy, it results from direct toxic injury to the mucosal epithelial cells by the chemotherapy drugs.Lesions of the oral mucosa may inhibit liquid and solid food intake of cancer patients, resulting in lack of nutrition, water electrolyte disorders, weakened immunity, serious systemic infection and life-threatening, and it will eventually affect the overall effectiveness of anticancer therapy [5][6][7].Therefore, it is particularly important to take effective preventive measures to prevent and reduce the occurrence of OM.This retrospectively study compared the incidence and severity of OM between a group of 64 patients who started taking Compound Zhuye Shigao Granule (CZSG) one day before chemotherapy (CZSG group) and a group of 85 patients who not taking CZSG (control group).We found that the incidence of OM in CZSG group significantly decreased than that of the control group.CZSG is a new drug self-developed by Dr Junzhang Lu in our hospital, a traditional Chinese medicine (TCM) compound based on the Zhuye gypsum soup, previous animal experiments and clinical studies have demonstrated CZSG has effective prevention and treatment of acute radiation esophagitis and recurrent oral ulcer [8,9].The results of our study showed that CZSG also had a strong prevention and treatment effect on OM induced by chemotherapy, which provided a new clue for OM precaution in patients with malignant tumors.

The efficacies of pembrolizumab and nivolumab have never been directly compared in a real-world study. Therefore, we sought to retrospectively evaluate the objective response rate (ORR) and the progression-free survival (PFS) of patients with recurrent or advanced non-small cell lung cancer (NSCLC) in a real-world setting. This study included patients with recurrent or advanced NSCLC diagnosed between September 1, 2015 and August 31, 2019, who were treated with programmed cell death 1 (PD-1) inhibitors at the Cancer Center of the Chinese People’s Liberation Army. PFS was estimated for each treatment group using Kaplan–Meier curves and log-rank tests. The multivariate analysis of PFS was performed with Cox proportional hazards regression models. A total of 255 patients with advanced or recurrent NSCLC treated with PD-1 inhibitors were identified. The ORR was significantly higher in the pembrolizumab group than in the nivolumab group, while PFS was not significantly different between the two groups. Subgroup analysis showed that the ORR was significantly higher for pembrolizumab than for nivolumab in patients in the first-line therapy subgroup and in those in the combination therapy as first-line therapy subgroup. Survival analysis of patients receiving combination therapy as second- or further-line therapy showed that nivolumab had better efficacy than pembrolizumab. However, the multivariate analysis revealed no significant difference in PFS between patients treated with pembrolizumab and those treated with nivolumab regardless of the subgroup. In our study, no significant difference in PFS was noted between patients treated with pembrolizumab and those treated with nivolumab in various clinical settings. This supports the current practice of choosing either pembrolizumab or nivolumab based on patient preferences.

To investigate the effect of multidisciplinary interventions on pain management in cancer inpatients. Four hundred thirty eight patients with cancer pain, who performed the multidisciplinary intervention were recruited. Before and after intervention, the Brief Pain Inventory (BPI) and the MD Anderson Symptom Inventory (MDASI) score as the primary endpoints and QOL scores as the secondary endpoint were all evaluated. To investigate the factors that led to different responses to multidisciplinary interventions, patients were classified as non-responders or responders. Finally, 92 patients (63 male and 29 female) scheduled for cancer pain management by inter-professional team were studied. After individualized multidisciplinary therapy, both pain and symptom severity was improved, as demonstrated by lowered BPI worst and average pain scores, as well as symptom severity score measured by MDASI (P = .017, P = .003, and P = .011, respectively). The proportion of patients with mild pain increased regarding the BPI worst and average pain at baseline and after treatment (P < .05). The QOL analyses showed multidisciplinary interventions could significantly improve the function and symptom scores (P < .001). More patients in responder group received chemotherapy (58, 70.7%, P = .003), while fewer received mini-invasive therapy (6, 7.32%, P = .011). Multidisciplinary interventions had certain beneficial effect on cancer pain management, especially in patients with moderate or severe pain.

For patients with advanced non-small cell lung cancer (NSCLC), immune checkpoint inhibitors (ICIs) can offer an effective treatment. However, despite their potential benefits, the use of ICIs can lead to inflammation in various organs, including pneumonitis. Interstitial lung disease (ILD), which is a common complication in patients with NSCLC, can increase the risk of pneumonitis. For NSCLC patients with ILD, the safety of ICIs has yet to be established. Durvalumab is a selective, high-affinity, engineered, human IgG1 monoclonal antibody, which showed durable response and manageable side effects in stage III NSCLC patients after definitive chemoradiotherapy. Pneumonitis in patients who received durvalumab was mostly low grade, given the potential applications in NSCLC with ILD. A 77-year-old man was diagnosed with Stage IV lung squamous carcinoma and ILD at our hospital. The PD-L1 expression assessed by VENTANA PD-L1 (SP263) Assay showed about 60% of tumor cells exhibit positive. Because the patient refused chemotherapy, he was given durvalumab at 20 mg/kg every 4 weeks as first-line anti-tumor therapy. After four cycles of therapy, the patient achieved partial remission, and complete remission(CR) had been achieved after 6 cycles of therapy and maintained over two years. No immune-related adverse events were reported. In this case, PD-L1 inhibitors were used to safely treat an NSCLC patient with ILD, which presents the need for further evaluation of their use.

BACKGROUND:Yes-associated protein (YAP) is downstream of the Hippo signaling pathway, which regulates several cellular processes. P53 is a key transcriptional regulator that responds to a variety of cellular stresses and regulates key cellular processes such as DNA repair, cell-cycle progression, angiogenesis, and apoptosis. Overexpression of YAP antagonizes P53 activity and targets its expression. However, the mechanism that underlies the post-transcriptional crosstalk between P53 and YAP has not been well dissected. METHODS:We performed an integrated analysis and found that SIRT1 is a key candidate that connects YAP and P53 by modulating their acetylation. RESULTS:We found that YAP promotes P53 deacetylation, promotes cell survival by inhibiting P53-induced G0/G1 arrest and apoptosis in A549 cells. Conversely, P53 enhances YAP acetylation, and decreases A549 cell survival by strengthening YAP acetylation-induced G0/G1 arrest and apoptosis both in vitro and in vivo. CONCLUSION:Our results demonstrate that SIRT1 is responsible for YAP and P53 deacetylation of specific residues, and reveal for the first time, a new regulatory mechanism of P53 and YAP crosstalk by SIRT1-mediated deacetylation, which may be involved in lung tumorigenesis.

1Department of Oncology, Chinese PLA General Hospital, Beijing 100853, People’s Republic of China; 2Princeton International School of Mathematics and Science, Princeton, NJ 08540, USA; 3Department of Biological Analysis, Explore (Beijing) Biotech Co, Ltd, Beijing 100091, People’s Republic of China; 4Department of Plastic Surgery, Chinese PLA General Hospital, Beijing 100853, People’s Republic of China

Objective: To explore influences of icariin on Stromal-Derived Factor-1 (SDF-1) and CXC Chemokine Receptor 4 (CXCR-4) of rats with acute ischemic stroke and study on its protection function for nerve. Methods: Healthy SD rats were selected, they were divided into the sham operation group (N group), model control group (M group), high and low icariin dosage group (T1 and T2), rats were given normal dieting for 24 h after model build, and intragastric administration, of which, N group and M group were given intragastric NS, rats in low dosage and high dosage group were given 30 mg/kg and 60 mg/kg icariin separately, once one day, last about 14 d, cutting off neck and sudden death. 3 rats were selected from M group, N group, T2 and T1 and given NSS. Rats in each group were given evaluation in 2 h, 1, 7 and 14 d’s after surgery and given PCR measurement according to evaluation results. Results: Neurological impairment in M group after surgery reached to 1 d, then decreased gradually, neurological score of T1 compared with model control group, there were no statistical differences (P>0.05), compared with T2 group, there were statistical differences (P<0.05). According to results of this test, from detection results of gene in M and T2 group we can know, SDF-1 and CXCR-4 gene in T2 group were higher than M group, but there were no statistical differences (P<0.05) in 7 d. Gene in T2 two groups were higher than control group through comparison between SDF-1 and CXCR-4 gene level of two groups in 14 d, the differences of SDF-1 and CXCR-4 had significant (P<0.05), the comparison differences of SDF-1 gene level were extremely significant (P<0.01). Conclusion: Icariin can promote neurological function recovery of rats after ischemia, its mechanism may have relations with icariin up-regulating SDF-1 and CXCR4.

Objective: To observe the characteristics and regularities of the adverse drug reactions (ADRs) induced by everolimus, in order to provide reference for clinical application. Methods: A total of 72 patients in our hospital from June 2013 to June 2014 were included. ADRs induced by everolimus were collected and analyzed in respect of sex, age of the patients, entity, ECOG score, condition of drug use, organs or systems involved in ADRs, clinical manifestations, sequelae and other relavant information. Results:The everolimus was applied in a method of increasing the dose gradually. There were 112 ADRs in 72 patients, among which, the percentage of digestive system accounted for the highest (40.18%), and follwed by respiratory system (23.21%); the grade 1 –2 ADR accounted for 82.14%; the most common grade 3 –4 adverse reactions were cough (3.57%), stomatitis (2.68%), diarrhea (1.79%); 62.50% of ADRs occurred within 2 weeks. In respect of sequelae, 80.56% (58/72) of the patients recovered with supportive care, 4 cases had to reduce the dose and receive speciifc treatment;10 cases improved after drug withdrawal. Conclusion: By increasing the dose of everolimus gradually, the drug was well tolerated. Since ADRs induced by everolimus were slight, all the ADRs were well managed.It is important to enhance follow-up observations of patients to prevent some serious ADRs.

Objective:To observe the efifcacy of aprepitant in the prevention of the acute and delayed nausea and vomiting induced by cisplatin. Methods: A total of 100 cancer patients who received cisplatin (75 mg·m-2) in our hospital from January 1, 2014 to October 1, 2014 were enrolled. The antiemetic regimen for aprepitant group consisted of aprepitant, 5-HT3 receptor antagonist and dexamethasone;regimen for control group was 5-HT3 receptor antagonist and dexamethasone. The primary endpoints were the percentage of patients with a complete response (CR:no nausea and no salvage treatment) during the acute phase (day 1) and the delayed phase (days 2–5). The secondary endpoint was the percentage of patients without severe nausea during the entire study period (5 days) with chemotherapy. Results: There was no statistical differences in CR rates of acute phase between two groups (CR:70%vs 54%, P=0.149). The efifcacy of aprepitant group was better than that of control group in delayed phase (CR:78%vs 46%, P=0.002). The percentages of patients with no severe nausea during the entire study period in aprepitant group and control group were 86%and 62%(P=0.012), respectively. There were not signiifcant differences between two groups in respect of adverse reactions. Conclusion: Due to the good efifcacy and safety, the triple therapy containing aprepitant can be recommended for the prevention of cisplatin-induced nausea and vomiting.

Cervical cancer is a commonly-encountered malignant tumor in women. Cervical screening is particularly important due to early symptoms being deficient in specificity. The main purpose of the study is to assess the application value of cervical thinprep cytologic test (TCT) and human papillomavirus (HPV) detection in screening for cervical cancer and precancerous lesions. In the study, cervical TCT and HPV detection were simultaneously performed on 12,500 patients selected in a gynecological clinic. Three hundred patients with positive results demonstrated by cervical TCT and/or HPV detection underwent cervical tissue biopsy under colposcopy, and pathological results were considered as the gold standard. The results revealed that 200 out of 12,500 patients were abnormal by TCT, in which 30 cases pertained to equivocal atypical squamous cells (ASCUS), 80 cases to low squamous intraepithelial lesion (LSIL), 70 cases to high squamous intraepithelial lesion (HSIL) and 20 cases to squamous cell carcinoma (SCC). With increasing pathological grade of cervical biopsy, however, TCT positive rates did not rise. Two hundred and eighty out of 12,500 patients were detected as positive for HPV infection, in which 50 cases were chronic cervicitis and squamous metaplasia, 70 cases cervical intraepithelial neoplasia (CIN) I, 60 cases CIN II, 70 cases CIN III and 30 cases invasive cervical carcinoma. Two hundred and thirty patients with high-risk HPV infection were detected. With increase in pathological grade, the positive rate of high-risk HPV also rose. The detection rates of HPV detection to CIN III and invasive cervical carcinoma as well as the total detection rate of lesions were significantly higher than that of TCT. Hence, HPV detection is a better method for screening of cervical cancer at present.

Most of cancer patients are suffering from psychological distress which is under-diagnosed and under-treated in China. The purpose of this study is to evaluate the psychometric properties of a new screening instrument for psychological distress in cancer patients based on Chinese culture and personality traits. The scale was created after face-to-face interviews and focus group discussion of 50 medical staff and 30 cancer patients; the analysis of reliability and validity came from 1122 scales completed by cancer patients and non-cancer patients. Data was analyzed for internal consistency reliability, construct validity and discrimination validity in clinical practice. The internal consistency reliability of the scale was 0.906. Principal components factor analysis and structural equation modeling showed that the scale was comprised of four dimensions: depression, anxiety, interpersonal barrier and suspiciousness. The fit indices were chi(2)(149) = 257.594, chi(2)/df = 1.729, GFI = 0.927, NFI = 0.846, NNFI = 0.906, RMSEA = 0.061. These results indicated there were significant differences between cancer patients and non-cancer patients, with respect to the total scores, anxiety scores, interpersonal barrier scores and suspiciousness scores. The psychological distress scale is a new screening instrument for Chinese cancer patients, which is in line with the emphasis of Chinese culture.

OBJECTIVE:To explore the expression and significance of tumor specific growth factor (TSGF), carcinoembryonic antigen (CEA) and alpha fetoprotein (AFP) in cancer tissue and serum of patients with colon cancer. MATERIALS AND METHODS:Radical surgery for colon cancer was performed on 43 patients with laparoscope under conditions of general anesthesia. The Elisa method was used to detect the levels of serum TSGF, CEA and AFP before and after radical operation, and cancer tissue underwent TSGF, CEA and AFP immunohistochemistry staining after laparoscopic surgery. The decreased conditions of serum TSGF, CEA and AFP in patients with colon cancer at different levels of differentiation and clinical stagings were analyzed, and the relationships of expression rates between histological types, colon cancer morphology, lymph node metastasis and TSGF, CEA as well as AFP in cancer tissue were assessed. RESULTS:Compared with before radical surgery, the levels of serum TSGF, CEA and AFP decreased notably in patients after operations (p<0.01). The decreased degree of TSGF and CEA was the largest in patients with poorly differentiated cancer tissue (p<0.01), while that of AFP was noted in patients with moderately differentiated cancer tissue (p<0.01). The decreased degree of TSGF and AFP was the largest in patients at phase Dukes A (p<0.01), while that of CEA in patients at phase Dukes C (p<0.01). There were no significant differences among the positive expression rates of TSGF, CEA and AFP with different histological types and colon cancer morphologies (p>0.05). The positive expression rates of TSGF and CEA in patients with lymph node metastasis were significantly higher than those without lymph node metastasis (p<0.01). CONCLUSIONS:TSGF, CEA and AFP can be used to evaluate the effect of radical operation for colon cancer, and the changed levels of different markers are associated with tumor differentiation, clinical stating and presence or absence of lymph node metastasis.

The multidrug resistance 1 gene (MDR1) is an important candidate gene for influencing breast cancer susceptibility. This study aimed to evaluate the association between MDR1 genetic variants and breast cancer susceptibility. A total of 340 breast cancer patients and 348 cancer-free controls were enrolled in this study. The patients’ general characteristics and related risk factors of breast cancer were collected by questionnaires. The c.4125A>C genetic variant was genotyped through created restriction site polymerase chain reaction method. Our data suggest that there are no significant differences in the allelic and genotypic frequencies between breast cancer patients and cancer-free controls. Moreover, the distribution of breast cancer patients’ risk factors is not different among AA, AC, and CC genotypes. These preliminary results suggest that the c.4125A>C genetic variant is not significantly associated with breast cancer susceptibility.

PURPOSE: Gemcitabine, a third-generation anticancer agent, has been shown to be active in several solid tumors. High-grade hemorrhage (grade ≥ 3) has been reported with this drug, although the overall risk remains unclear. We conducted a meta-analysis of randomized controlled trials evaluating the incidence and risk of high-grade hemorrhage associated with gemcitabine. METHODS: Pubmed was searched for articles published from January 1, 1990 to December 31, 2012. Eligible studies included prospective randomized controlled phase II and III trials evaluating gemcitabine-based vs non-gemcitabine-based therapy in patients with solid tumors. Data on high-grade hemorrhage were extracted. Overall incidence rates, relative risk (RR), and 95% confidence intervals (CI) were calculated employing fixed- or random-effects models depending on the heterogeneity of included trials. RESULTS: A total of 6433 patients from 20 trials were included. Among patients treated with gemcitabine-based chemotherapy, the overall incidence of high-grade hemorrhage was 1.7% (95%CI: 0.9-3.1%), and the RR of high-grade hemorrhage was 2.727 (95%CI: 1.581-4.702, p<0.001). Exploratory subgroup analysis revealed the highest RR of hemorrhage in non-small-cell lung cancer (NSCLC) patients (RR: 3.234; 95%CI, 1.678-6.233; p<0.001), phase II trials (RR 7.053, 95%CI: 1.591-31.27; p = 0.01), trials reported during 2006-2012 (RR: 3.750; 95%CI: 1.735-8.108, p<0.001) and gemcitabine used as single agent (RR 7.48; 95%CI: 0.78-71.92, p = 0.081). CONCLUSION: Gemcitabine is associated with a significant increase risk of high-grade hemorrhage in patients with solid tumors when compared with non-gemcitabine-based therapy.