High-Throughput Antigen Microarray Identifies Longitudinal Prognostic Autoantibody for Chemoimmunotherapy in Advanced Non-Small Cell Lung Cancer.

Chemoimmunotherapy has evolved as a standard treatment for advanced non-small cell lung cancer (aNSCLC). However, inevitable drug resistance has limited its efficacy, highlighting the urgent need for biomarkers of chemoimmunotherapy. A three-phase strategy to discover, verify, and validate longitudinal predictive autoantibodies (AAbs) for aNSCLC before and after chemoimmunotherapy was employed. A total of 528 plasma samples from 267 aNSCLC patients before and after anti-PD1 immunotherapy were collected, plus 30 independent formalin-fixed paraffin-embedded samples. Candidate AAbs were firstly selected using a HuProt high-density microarray containing 21,000 proteins in the discovery phase, followed by validation using an aNSCLC-focused microarray. Longitudinal predictive AAbs were chosen for ELISA based on responders versus non-responders comparison and progression-free survival (PFS) survival analysis. Prognostic markers were also validated using immunohistochemistry and publicly available immunotherapy datasets. We identified and validated a panel of two AAbs (MAX and DHX29) as pre-treatment biomarkers and another panel of two AAbs (MAX and TAPBP) as on-treatment predictive markers in aNSCLC patients undergoing chemoimmunotherapy. All three AAbs exhibited a positive correlation with early responses and PFS (p < 0.05). The kinetics of MAX AAb showed an increasing trend in responders (p < 0.05) and a tendency to initially increase and then decrease in non-responders (p < 0.05). Importantly, MAX protein and mRNA levels effectively discriminated PFS (p < 0.05) in aNSCLC patients treated with immunotherapy. Our results present a longitudinal analysis of changes in prognostic AAbs in aNSCLC patients undergoing chemoimmunotherapy.

Identification of novel serological autoantibodies in Chinese prostate cancer patients using high-throughput protein arrays.

Autoantibody (AAb) has a prominent role in prostate cancer (PCa), with few studies profiling the AAb landscape in Chinese patients. Therefore, the AAb landscape in Chinese patients was characterized using protein arrays. First, in the discovery phase, Huprot arrays outlined autoimmune profiles against ~ 21,888 proteins from 57 samples. In the verification phase, the PCa-focused arrays detected 25 AAbs selected from the discovery phase within 178 samples. Then, PCa was detected using a backpropagation artificial neural network (BPANN) model. In the validation phase, an enzyme-linked immunosorbent assay (ELISA) was used to validate four AAb biomarkers from 196 samples. Huprot arrays profiled distinct PCa, benign prostate diseases (BPD), and health AAb landscapes. PCa-focused array depicted that IFIT5 and CPOX AAbs could distinguish PCa from health with an area under curve (AUC) of 0.71 and 0.70, respectively. PAH and FCER2 AAbs had AUCs of 0.86 and 0.88 in discriminating PCa from BPD. Particularly, PAH AAb detected patients in the prostate-specific antigen (PSA) gray zone with an AUC of 0.86. Meanwhile, the BPANN model of 4-AAb (IFIT5, PAH, FCER2, CPOX) panel attained AUC of 0.83 among the two cohorts for detecting patients with gray-zone PSA. In the validation cohort, the IFIT5 AAb was upregulated in PCa compared to health (p < 0.001). Compared with BPD, PAH and FCER2 AAbs were significantly elevated in PCa (p = 0.012 and 0.039). We have demonstrated the first extensive profiling of autoantibodies in Chinese PCa patients, identifying novel diagnostic AAb biomarkers, especially for identification of gray-zone-PSA patients.

High-throughput and multi-phases identification of autoantibodies in diagnosing early-stage breast cancer and subtypes.

Autoantibodies (AAbs) targeted tumor-associated antigens (TAAs) have the potential for early detection of breast cancer. Here, 574 early-stage breast cancer (ES-BC) patients containing 4 subtypes (Luminal A, Luminal B, HER2+, TN), 126 benign breast disease (BBD) patients, and 199 normal healthy controls (NHC) were separated into three-phases to discover, verify, and validate AAbs. In discovery phase using high-throughput protein microarray, 37 AAbs with sensitivity of 31.25%-86.25% and specificity over 73% in ES-BC, and 40 AAbs with different positive rates between subtypes were identified as candidates. In verification phase, 18 AAbs were significantly increased compared with the Control (BBD and NHC) in focused array. Ten out of 18 AAbs exhibited a significant difference between subtypes (P < .05). In ELISA validation phase, 5 novel AAbs (anti-KJ901215, -FAM49B, -HYI, -GARS, -CRLF3) exhibited significantly higher levels in ES-BC compared with BBD/NHC (P < .05). The sensitivities of individual AAb and a 5-AAbs panel were 20.41%-28.57% and 38.78%, whereas the specificities were over 90% and 85.94%. Simultaneously, 4 AAbs except anti-GARS differed significantly between TN and non-TN subtype (P < .05). We constructed 3 random forest classifier models based on AAbs to discriminant ES-BC from Control or BBD, and to discern TN subtype, which yielded an area under the curve of 0.870, 0.860, and 0.875, respectively. Biological interaction analysis revealed 4 TAAs, except for KJ901215, that were associated with well known proteins of BC. This study discovered and stepwise validated 5 novel AAbs with the potential to diagnose ES-BC and discern TN subtype, indicating easy-to-detect and minimally invasive diagnostic value of serum AAbs ahead of biopsy for future application.

Variation of Hemoglobin Detection for Lipemic Blood Samples.

BACKGROUND: Blood status is closely related to the hemoglobin test results in clinical laboratory. This paper discusses a case of which hemoglobin test results were not interfered by the "milky" blood status. METHODS: Complete Blood Count with Differential (CBC + Diff) was detected for these two specimens with a Sysmex XN-9000. RESULTS: The results of red cell indices for patient I were as follows: red blood cell count (RBC), 5.10 x 1012/L; hematocrit (HCT), 0.455 L/L; hemoglobin (HGB), 167 g/L; mean corpuscular hemoglobin concentration (MCHC), 367 g/L, and triglycerides (TG), 1.59 mmol/L. There was no "turbidity" warning message. However, there was a "turbidity" warning message for patient II and his red cell indices were RBC, 4.74 x 1012/L; HCT, 0.492 L/L; HGB, 182 g/L; MCHC, 370 g/L, and TG, 12.98 mmol/L. After the plasma exchange, there was no "turbidity" warning message for patient I and his red cell indices were RBC, 4.83 x 1012/L; HCT, 0.444 L/L; HGB, 164 g/L; MCHC, 369 g/L which were consistent with the results before the plasma exchange. For patient II, the "turbidity" warning message disappeared and his results were RBC, 3.87 x 1012/L; HCT, 0.398 L/L; HGB, 135 g/L; MCHC, 339 g/L. CONCLUSIONS: Our case provided an explanation of the normal hemoglobin detection results in the visible lipemic specimen for the first time.

Establishment of the intelligent verification criteria for a routine urinalysis analyzer in a multi-center study.

Background Although laboratory information system (LIS) is widely used nowadays, the results of routine urinalysis still need 100% manual verification. We established intelligent verification criteria to perform the automated verification process and reduce manual labor. Methods A total of 4610 urine specimens were obtained from the patients of three hospitals in Beijing, China. Firstly, 895 specimens were measured to establish the reference intervals of formed-element parameters in UF5000. Secondly, 2803 specimens were analyzed for setting up the intelligent verification criteria (including the microscopic review rules and manual verification rules). Lastly, 912 specimens were used to verify the efficacy and accuracy of the intelligent verification criteria. Phase-contrast microscopes were used for the microscopic review. Results Employing a results level corresponding relationship in specific parameters including hemoglobin (red blood cell [RBC]), leukocyte esterase (white blood cell [WBC]) and protein (cast) between the dry-chemistry analysis and formed-element analysis, as well as instrument flags, we established seven WBC verification rules, eight RBC verification rules and four cast verification rules. Based on the microscopy results, through analyzing the pre-set rules mentioned earlier, we finally determined seven microscopic review rules, nine manual verification rules and three auto-verification rules. The microscopic review rate was 21.98% (616/2803), the false-negative rate was 4.32% (121/2803), the total manual verification rate was 35.71% (1001/2803) and the auto-verification rate was 64.29% (1802/2803). The validation results were consistent. Conclusions The intelligent verification criteria for urinary dry-chemistry and urinary formed-element analysis can improve the efficiency of the results verification process and ensure the reliability of the test results.

Clinicopathological Characteristics, Surgical Treatments, and Survival Outcomes of Patients with Duodenal Gastrointestinal Stromal Tumor.

BACKGROUND: Duodenal gastrointestinal stromal tumors (GISTs) are rare and their clinicopathological features have not been completely described. In this retrospective study, we examined the characteristics and long-term outcomes of patients who underwent surgical treatment for duodenal GISTs. METHODS: We examined patients surgically treated for duodenal GISTs from 1999 to 2016 at the China National Cancer Center. We analyzed patient characteristics, treatments, histological examinations, and survival outcomes. RESULTS: The 52 surgeries performed included 14 pancreaticoduodenectomies (26.9%), 37 limited resections (71.2%), and one palliative bypass procedure (1.9%). No surgery-related death occurred. The complication rate in patients who underwent pancreaticoduodenectomy was slightly higher than that in patients who underwent limited resection. The 5-year overall survival and progression-free survival rates for patients with duodenal adenocarcinoma were 89.1 and 72.9%, respectively. The overall survival and progression-free survival rates were not significantly related to surgical methods. Large tumor size and high mitotic rate were associated with poor overall survival outcomes. However, no independent factor was associated with prognosis, which may be due to the small sample size. CONCLUSION: The prognosis of duodenal gastrointestinal stromal tumors was good. Limited resection seems to be oncologically feasible, with outcomes being less worse than those of pancreaticoduodenectomy.

[Value of urine sediment analyzer in the screening of urinary tract infection in cancer patients].

OBJECTIVE: To evaluate the value of urine sediment analyzer in the screening of clinically suspected urinary tract infection (UTI) in cancer patients. METHODS: The results of bacterial count of 1 053 midstream urine samples by UF-1000i urine sediment analyzer (UF-1000i urine sediment analyzer, UF-1000i) were compared with the results of bacterial culture. Moreover, the results of distinguishing bacterial species by the bacterial scattergram were compared with the results of bacteria culture. At the same time, the sensitivity, specificity, positive predictive value and negative predictive value of UF-1000i analyzer for UTI screening were evaluated. RESULTS: Of all the 1 053 samples, the top three bacteria were E. coli, Enterococci and P. aeruginosa. The top three malignant tumors of UTI were bladder, lung cancer and cervical cancers. The positive rate of UF-1000i analyzer was 20% (211/1 053), and that of bacteria culture was 17.9% (188/1 053). There was statistically no significant difference in the positive rates between the two methods (χ(2)=1.636, P>0.05), and the two methods had a considerable consistency (Kappa=0.756). Compared with the clinical diagnosis, UTI screening by UF-1000i analyzer showed a sensitivity of 79.6% (160/201), specificity of 95.5% (814/852), positive predictive value of 80.8% (160/198) and negative predictive value of 95.2%(814/855). The distribution of cocci and bacilli acquired by the bacterial scattergram was basically in accordance with the results of bacterial culture. CONCLUSIONS: Bacterial count by UF-1000i analyzer plays an important role in early screening of UTI, and the bacterial scattergram may help to distinguish bacterial species, providing reference for the use of antibiotics in early medication.

[Risk factors for Clostridium difficile-associated diarrhea among cancer patients].

OBJECTIVE: The aim of this study was to investigate the prevalence of Clostridium difficile (C. difficile) infection and the risk factors for acquisition of C. difficile-associated diarrhea (CDAD) among cancer patients who received chemotherapy or radiation therapy. METHODS: We analyzed 277 stool samples from cancer patients with diarrhea between Sep 2010 and Dec 2011 in our hospital. Stool C. difficile toxin A/B test, stool culture for C. difficile and routine stool examination were performed. In addition, the risk factors for CDAD were investigated in a set of 41 C. difficile toxin-positive cancer patients and 82 matched C. difficile toxin-negative controls by univariate analysis and multivariate analysis. RESULTS: Out of a total of 277 cancer patients with diarrhea, 41 (14.8%) were C. difficile toxin-positive. Among these 41 cases, 11 (26.8%, 11/41) were C. difficile culture-positive. Univariate analysis showed that antibiotics use (P = 0.853), proton pump inhibitor use (P = 0.718), hypoproteinemia (P = 0.139) and white blood cell count (P = 0.454) did not appear to be associated with acquisition of CDAD in cancer patients. However, receiving chemotherapy (P = 0.023), receiving radiotherapy (P = 0.003), a positive fecal occult blood test result (P = 0.005) and the presence of fecal leukocytes (P = 0.007) showed close association with acquisition of CDAD in cancer patients. Multivariate analysis showed that receiving chemotherapy (OR, 8.308; 95% CI, 1.997-34.572; P = 0.004) and a positive result of fecal occult blood test (OR, 8.475; 95% CI, 1.463-49.109; P = 0.017) were independent risk factors for acquisition of CDAD among cancer patients. CONCLUSIONS: Our results support that receiving chemotherapy and a positive fecal occult blood test result are independent risk factors for acquisition of CDAD among cancer patients. Cancer patients who are at high-risk for CDAD should take stool C. difficile toxin A/B test and stool culture for C. difficile regularly and prevention of CDAD.

Immunogenicity assessment of elder hepatocellular carcinoma patients after inactivated whole-virion SARS-CoV-2 vaccination.

BACKGROUND: Research on immunogenicity after 3rd SARS-CoV-2 vaccine in elder hepatocellular carcinoma (HCC) was limited. This study aimed to investigate the efficacy and influencing factors of inactivated SARS-CoV-2 vaccine in elder HCC. RESEARCH DESIGN AND METHODS: We assessed total antibodies, anti-RBD IgG, and neutralizing antibodies (NAb) toward SARS-CoV-2 wild type (WT) as well as BA.4/5 in 304 uninfected HCC, 147 matched healthy control (HC), and 53 SARS-CoV-2 infected HCC, all aged over 60 years. The levels of antibodies were compared in the period 7-90, 91-180, and >180 days after 2nd or 3rd vaccination, respectively. RESULTS: HCC had lower seropositivity than HC after 2nd dose (total antibodies, 64% vs. 92%, P < 0.0001; anti-RBD IgG, 50% vs. 77%, P < 0.0001). But 3rd dose can efficaciously close the gap (total antibodies, 96% vs. 100%, P = 0.1212; anti-RBD IgG: 87% vs. 87%, P > 0.9999). Booster effect of 3rd dose can persist >180 days in HCC (2nd vs. 3rd: total antibodies, 0.60 vs. 3.20, P < 0.0001; anti-RBD IgG, 13.86 vs. 68.85, P < 0.0001; WT NAb, 11.70 vs. 22.47, P < 0.0001). Vaccinated HCC had more evident humoral responses than unvaccinated ones after infection (total antibodies: 3.85 vs. 3.20, P < 0.0001; anti-RBD IgG: 910.92 vs. 68.85, P < 0.0001; WT NAb: 96.09 vs. 22.47, P < 0.0001; BA.4/5 NAb: 86.53 vs. 5.59, P < 0.0001). CONCLUSIONS: Our findings highlight the booster effect and protective role of 3rd dose. Our results could provide a theoretical foundation for informing decisions regarding SARS-CoV-2 vaccination in elder HCC.

Antibody response to SARS-CoV-2 WT and Omicron BA.4/5 of inactivated COVID-19 vaccine in patients with lung cancer after second and booster immunization.

COVID-19 inactivated vaccine-induced humoral responses in patients with lung cancer (LCs) to SARS-CoV-2 wild-type (WT) strain and variants BA.4/5 after the primary 2-dose and booster vaccination remained unknown. We conducted a cross-sectional study in 260 LCs, 140 healthy controls (HC) and additional 40 LCs with serial samples by detecting total antibodies, IgG anti-RBD and neutralizing antibodies (NAb) toward WT and BA.4/5. SARS-CoV-2-specific antibody responses were augmented by the booster dose of inactivated vaccines in LCs, whereas they were lower than that in HCs. Enhanced humoral responses waned over time after triple injection, notably in NAb against WT and BA.4/5. The NAb against BA.4/5 was much lower than WT. Age ≥ 65 was risk factor for immunization of NAb to WT. Undergoing treatment resulted in a lower antibody response than those without and radiotherapy was a also risk factor for seroconversion of NAb to WT. Lower lymphocyte counts contributed to a lower titer of IgG anti-RBD and NAb against BA.4/5 in LCs than HCs. Specifically, total B cells, CD4+T cells and CD8+T counts were correlated with the humoral response. These results should be taken into consideration for the elderly patients under treatment.

Identification of novel serum autoantibody biomarkers for early esophageal squamous cell carcinoma and high-grade intraepithelial neoplasia detection.

Background: Early diagnosis of esophageal squamous cell carcinoma (ESCC) is critical for effective treatment and optimal prognosis; however, less study on serum biomarkers for the early ESCC detection has been reported. The aim of this study was to identify and evaluate several serum autoantibody biomarkers in early ESCC. Methods: We initially screened candidate tumor-associated autoantibodies (TAAbs) associated with ESCC by serological proteome analysis (SERPA) combined with nanoliter-liquid chromatography combined with quadrupole time of flight tandem mass spectrometry (nano-LC-Q-TOF-MS/MS), and the TAAbs were further subjected to analysis by Enzyme-linked immunosorbent assay (ELISA) in a clinical cohort (386 participants, including 161 patients with ESCC, 49 patients with high-grade intraepithelial neoplasia [HGIN] and 176 healthy controls [HC]). Receiver operating characteristic (ROC) curve was plotted to evaluate the diagnostic performance. Results: The serum levels of CETN2 and POFUT1 autoantibodies which were identified by SERPA were statistically different between ESCC or HGIN patients and HC in ELISA analysis with the area under the curve (AUC) values of 0.709 (95%CI: 0.654-0.764) and 0.741 (95%CI: 0.689-0.793), 0.717 (95%CI: 0.634-0.800) and 0.703 (95%CI: 0.627-0.779) for detection of ESCC and HGIN, respectively. Combining these two markers, the AUCs were 0.781 (95%CI: 0.733-0.829), 0.754 (95%CI: 0.694-0.814) and 0.756 (95%CI: 0.686-0.827) when distinguishing ESCC, early ESCC and HGIN from HC, respectively. Meanwhile, the expression of CETN2 and POFUT1 was found to be correlated with ESCC progression. Conclusions: Our data suggest that CETN2 and POFUT1 autoantibodies have potential diagnostic value for ESCC and HGIN, which may provide novel insights for early ESCC and precancerous lesions detection.

Identification and evaluation of novel serum autoantibody biomarkers for early diagnosis of gastric cancer and precancerous lesion.

PURPOSE: Early diagnosis is crucial for optimal prognosis of gastric cancer (GC). Hereby, we aimed to identify novel serum autoantibody-based biomarkers for precancerous lesion (PL) and early GC. METHODS: We performed serological proteome analysis (SERPA) combined with nanoliter-liquid chromatography combined with quadrupole time of flight tandem mass spectrometry (Nano-LC-Q-TOF-MS/MS) to screen for GC-associated autoantibodies. The identified autoantibodies were analyzed for potential detection value for PL and GC by enzyme-linked immunosorbent assay (ELISA). Receiver operating characteristic (ROC) curves analysis was conducted to evaluate the accuracy of the biomarkers. RESULTS: We identified seven candidates, such as mRNA export factor (RAE1), Nucleophosmin 1 (NPM1), phosphoglycerate kinase 1 (PGK1), and ADP-ribosylation factor 4 (ARF4). Antibodies against all seven proteins were present at higher levels in sera from 242 patients (51 PL, 78 early GC, 113 advanced GC) compared with sera from 122 healthy individuals. RAE1-specific autoantibody discriminated best between patients at different GC stages, with area under the curve (AUC) values of 0.710, 0.745, and 0.804 for PL, early GC, and advanced GC, respectively. Two predictive models composed of gender, RAE1, PGK1, NPM1, and ARF4 autoantibodies (Model 2 for PL) and of age, gender, RAE1, PGK1, and NPM1 autoantibodies (Model 3 for early GC) had improved diagnostic efficiencies, with AUCs of 0.803 and 0.857, sensitivities of 66.7% and 75.6%, and specificities of 78.7% and 87.7%, respectively. CONCLUSION: The identified serum tumor-associated autoantibodies (TAAbs) may have good potential for early detection of GC and PL.

Fetal BM-derived mesenchymal stem cells promote the expansion of human Th17 cells, but inhibit the production of Th1 cells.

Th type 17 (Th17) cells have been identified as a proinflammatory T-cell subset. Here, we investigated the regulation of human Th17 cells by fetal BM-derived mesenchymal stem cells (FBM-MSC). We cocultured FBM-MSC with human PBMC or CD4(+) T cells from healthy donors. FBM-MSC significantly suppressed the proliferation of CD4(+) T cells stimulated by PHA and recombinant IL-2. Significantly higher levels of IL-17 were observed in FBM-MSC cocultured with either PBMC or CD4(+) T cells than that in PBMC cultured alone or CD4(+) T cells cultured alone. Flow cytometry analysis showed that the percentage of Th17 cells in coculture of FBM-MSC and CD4(+) T cells was significantly higher than that in CD4(+) T-cell cultured alone. FBM-MSC did not express IL-17 protein. Consistent with the augmentation of Th17 cells, significantly higher levels of IL-6 and IL-1 were observed in coculture of FBM-MSC and CD4(+) T cells than that in CD4(+) T-cell culture, while the levels of IL-23 were similar between FBM-MSC + PBMC coculture and PBMC alone, or FBM-MSC + CD4(+) T-cell and CD4(+) T-cell alone. The presence of FBM-MSC decreased the percentage of Th1 cells, but minimally affected the expansion of CD4(+)CD25(+) T cells. In conclusion, our data demonstrate for the first time that FBM-MSC promote the expansion of Th17 cells and decrease IFN-gamma-producing Th1 cells. These data suggest that IL-6 and IL-1, instead of IL-23, may be partly involved in the expansion of Th17 cells.

Whole-genome sequencing of prostate cancer reveals novel mutation-driven processes and molecular subgroups.

Prostate cancer (PCa) is the second most frequently diagnosed cancer in men. However, its genetic characteristics in the Chinese population have not been extensively profiled. Here we screened 27 Chinese patients and preformed whole-genome sequencing to dissect their genomic patterns. We found that 18.5% (5/27) tumors harbored non-protein coding mutations on FOXA1. Besides, novel focal amplifications/deletions involving ZBTB7B, SLC4A4, TBX18, CYSLTR2 and EFNA5 were frequently present in tumors. Notably, group specificity of base substitution signature B displayed a strong link to hotspot mutations on SPOP gene. Furthermore, based on six rearrangement signatures, tumors were assigned to five subgroups that revealed different biological mechanisms. Of which, tandem duplicator subgroup harbored all CDK12 mutations, small deletor subgroup owned 75% TP53 changes, and large deletor subgroup had 66.7% SPOP mutations. Taken together, we provide a comprehensive view of genomic patterns which affect the critical cell regulators of PCa in the Chinese population. Our findings may provide valuable insights for designing specific treatments for Chinese patients with PCa.

Diagnostic value of serum glypican-3 alone and in combination with AFP as an aid in the diagnosis of liver cancer.

BACKGROUND: Recently, a series of studies have been published to examine the possible diagnostic and prognostic values of glypican-3 (GPC3) in liver cancer with conflicting results observed. Thus, the present study aimed to assess the values of preoperative serum GPC3 alone and in combination with AFP for the diagnosis of liver cancer. METHODS: An enzyme-linked immunoassay was used to quantify serum GPC3 in hepatocellular carcinoma group (HCC, n = 210), intrahepatic cholangiocarcinoma group (ICC, n = 36), combined hepatocellular cholangiocarcinoma group (cHCC-CC, n = 8), metastatic liver cancer group (MLC, n = 10) and normal controls (NC, n = 134). RESULTS: The area under the curve (AUC) of GPC3 for HCC versus NC was 0.879, with a sensitivity of 79.52% at an optimal cutoff value of 0.0414 ng/mL; when GPC3 was combined with AFP, the AUC and sensitivity were increased to 0.925 and 88.10%, respectively. In addition, 43 of 68 AFP-negative patients had elevated GPC3 levels. Furthermore, the positive rate of GPC3 was significantly higher than the that of AFP for HCC in early stage. CONCLUSIONS: Serum GPC3 was superior to AFP for the diagnosis of early-stage HCC, and may be complementary to AFP for distinguishing HCC from NC.

TPO-independent megakaryocytopoiesis.

Megakaryocytopoiesis is a continuous developmental process of platelet production. In this process, a complex network of hemopoietic growth factors are involved, among which TPO (thrombopoietin) is the most thoroughly investigated regulator of MKs (megakaryocytes). In addition to TPO, other regulators also have non-negligible effects on megakaryocytopoiesis. The majority of their effects are independent of TPO signaling. To date, TPO-independent megakaryocytopoiesis forms a regulatory system that includes four signals and (an) unknown signaling pathway(s). These four pathways are the gp 130 (glycoprotein 130)-dependent signaling pathway, the Notch pathway, NMDA (N-methyl-d-aspartate) receptor-mediated signaling, and the SDF-1 (stromal cell-derived factor-1)/FGF-4 (fibroblast growth factor-4) paradigm. Understanding of the TPO-independent regulatory system is important because the system may offer additional opportunities to understand the developmental process and the mechanisms of disorders characterized by abnormal MK and platelet production, such as thrombocytopenia and thrombocythemia, and to advance the development of therapeutics.

Evaluation of efficacy and safety of minimally invasive segmentectomy in the treatment of lung cancer.

The aim of the study was to investigate the efficacy and safety of minimally invasive segmentectomy in the treatment of lung cancer. A total of 86 lung cancer patients in early stage were selected for the treatment between May, 2010 and December, 2010. The patients were randomly divided into the control (n=43) and observation (n=43) groups. Patients in the control group received conventional thoracotomy as treatment, while thoracoscopic segmentectomy was performed for patients in the observation group. Factors including intraoperative bleeding amount, number of dissected lymph nodes, surgery duration, postoperative intubation time and length of stay (LOS) were compared between the two groups. A visual analogue scale was used for comparison of the postoperative incisional pain experienced by patients in the two groups. The incidence rate of postoperative complications of patients in the two groups was observed. We also assayed variations in the levels of serum inflammatory factors C-reaction protein (CRP), interleukin (IL) -6 and -10 of patients prior to operation and on the 3rd, 5th and 7th days and after operation via ELISA, and on the 7th day after operation, we determined the pulmonary function of patients. During the 5-year follow-up, the recurrence and survival rate of patients in the two groups were observed. In the observation group, the intraoperative bleeding amount of patients was significantly lower than that in the control group, and the surgery duration, postoperative intubation time and LOS were all shorter than those in the control group (P<0.05). By contrast, no significant difference was detected in a comparison of the number of dissected lymph nodes of patients between the two groups (P>0.05). Additionally, in the observation group, patients suffered less pain after operation than those in the control group (P<0.05), and on the 3rd, 5th and 7th days after operation, the levels of CRP, IL-6 and -10 in the observation group were significantly lower than those in the control group (P<0.05). After operation, the incidence rate of complications in the observation group was significantly lower than that in the control group (P<0.05), and the recovery in pulmonary function after operation was superior to that in the control group (P<0.05). In addition, the 5-year survival rate of patients in the observation group was significantly higher than that in the control group, and the recurrence rate was significantly lower than that in the control group (P<0.05). Minimally invasive segmentectomy shows better efficacy in the treatment of lung cancer at early stage than the conventional thoracotomy. In addition to the high safety during surgery, this technique can lower the incidence rate of postoperative complications, protect the pulmonary function, increase the survival rate and decrease the recurrence rate, which shows great value in clinical practice.

First-line chemotherapy regimens for locally advanced and metastatic pancreatic adenocarcinoma: a Bayesian analysis.

BACKGROUND: Systemic chemotherapy is the standard treatment for locally advanced and metastatic pancreatic cancer, but there is no consensus on the optimum regimen. We aimed to compare and rank the locally advanced and metastatic pancreatic adenocarcinoma chemotherapy regimens evaluated in randomized controlled trials (RCTs) in the past 15 years. MATERIALS AND METHODS: PubMed, Embase, Cochrane Collaboration database, and ClinicalTrials.gov were searched for RCTs comparing chemotherapy regimens as first-line treatment for locally advanced and metastatic pancreatic adenocarcinomas. By using Bayesian network meta-analysis, we compared and ranked all included chemotherapy regimens in terms of overall survival, progression-free survival, response rate, and hematological toxicity. RESULTS: The analysis included 68 RCTs, with 14,908 patients and 63 treatment strategies. For overall survival, NSC-631570 (hazard ratio [HR] vs gemcitabine monotherapy 0.44, 95% credible interval: 0.24-0.76) and gemcitabine+NSC-631570 (HR 0.45, 0.24-0.86) were the two top-ranked chemotherapy regimens. For progression-free survival, PEFG (cisplatin + epirubicin + fluorouracil + gemcitabine) ranked first (HR 0.51, 0.34-0.77). PG (gemcitabine + pemetrexed) (odds ratio [OR] 4.68, 2.24-9.64) and FLEC (fluorouracil + leucovorin + epirubicin + carboplatin) (OR 4.52, 1.14-24.00) were ranked the most hematologically toxic, with gastrazole having the least toxicity (OR 0.03, 0.00-0.46). CONCLUSION: The chemotherapy regimens NSC-631570 and gemcitabine+NSC-631570 were ranked the most efficacious for locally advanced and metastatic pancreatic adenocarcinomas in terms of overall survival, which warrants further confirmation in large-scale RCTs.

[Neovascularization potential of mobilized peripheral mononuclear cells from diabetes patients].

OBJECTIVE: To determine whether mobilized peripheral blood mononuclear cells (M-PBMNCs) obtained from patients with diabetes was impaired in therapeutic neovascularization in limb ischemia, and to explore the pathological mechanisms of the impairment. METHODS: Endothelial progenitor cells (EPC) were cultured in EGM-2MV, and then characterized by uptake of 1, 1-dioctadecyl-3, 3, 3, 3-tetramethylindocarbocyanine-labeled acetylated low density lipoprotein (Dil-AcLDL) and binding of ulex europaeus agglutinin (UEA). The number of EPC was compared between M-PBMNCs obtained from diabetic patients and those from normal subjects. M-PBMNCs obtained from diabetic patients, M-PBMNCs obtained from normal controls, or PBS were injected into the ischemic limbs of streptozotocin-induced diabetic nude mice. The limb blood perfusion was detected by laser Doppler blood perfusion imaging between these three groups in the following 1, 3, 7, 14, 21, and 28 days. Ambulatory score and ischemia damage were evaluated in the following 4 weeks. Capillary/fiber ratio was detected by CD31 or BS-1 lectin, and arteriole density was detected by alpha-smooth muscle actin (alpha-SMactin). RESULTS: The number of EPC from diabetic patients were positively correlated with the blood perfusion (R = 0.486, P < 0.05) and capillary density (R = 0.491, P < 0.05), and the EPC number in diabetic patient were negatively correlation with their disease courses (R = - 0.587, P < 0.05). Transplantation of diabetic M-PBMNCs augmented the blood perfusion of ischemia hindlimbs, increased the capillary and arteriole densities, and promoted the collateral vessel formation. However, all the improvements were less significant in the diabetic patients than in the non-diabetic patients (P < 0.05). CONCLUSION: Diabetes decreased the capability of M-PBMNCs to augment neovascularization in ischemia.

Clinicopathological features, surgical treatments, and survival outcomes of patients with small bowel adenocarcinoma.

To date, because of their rarity, the clinicopathological features and surgical outcomes of small bowel adenocarcinomas (SBAs) have been insufficiently explored. We evaluated the clinicopathological features and long-term outcomes of patients who underwent surgery for SBA.This retrospective study (from 1999 to 2016) examined patients with SBA treated surgically at the China National Cancer Center/Cancer Hospital. Clinicopathological features, preoperative evaluation, surgical treatment, and outcome parameters were reviewed and analyzed.Among the 241 patients studied, pancreaticoduodenectomies were performed in 51.0%, partial resection in 24.5%, palliative bypass surgery in 23.7%, and abdominal exploration in 0.8% of the patients. Majority of the patients were diagnosed at an advanced disease stage, and the duodenum was the most common tumor site. Postoperative complications occurred in 44.4% of the patients. Median overall and progression-free survival rates were 22.0 and 13.0 months, respectively. The 5-year overall and progression-free survival rates for patients with duodenal adenocarcinoma were 30.2% and 21.7%, respectively. Duodenal adenocarcinomas, lymph node metastases, distant metastases, poor differentiation, and lymphovascular invasion were associated with poor overall survival outcomes. The 3 factors associated with progression-free survival were the degree of differentiation, lymph node metastases, and distant metastases.Surgery remains the mainstay of treatment for SBA. A poor prognosis could be owing to the site, metastasis, differentiation, and lymphovascular invasion; however, the prognosis may improve through early diagnosis and operation.