Platelets are reprogrammed by cancer via a process called education, which favors cancer development. The transcriptional profile of tumor-educated platelets (TEPs) is skewed and therefore practicable for cancer detection. This intercontinental, hospital-based, diagnostic study included 761 treatment-naïve inpatients with histologically confirmed adnexal masses and 167 healthy controls from nine medical centers (China, n = 3; Netherlands, n = 5; Poland, n = 1) between September 2016 and May 2019. The main outcomes were the performance of TEPs and their combination with CA125 in two Chinese (VC1 and VC2) and the European (VC3) validation cohorts collectively and independently. Exploratory outcome was the value of TEPs in public pan-cancer platelet transcriptome datasets. The AUCs for TEPs in the combined validation cohort, VC1, VC2, and VC3 were 0.918 (95% CI 0.889-0.948), 0.923 (0.855-0.990), 0.918 (0.872-0.963), and 0.887 (0.813-0.960), respectively. Combination of TEPs and CA125 demonstrated an AUC of 0.922 (0.889-0.955) in the combined validation cohort; 0.955 (0.912-0.997) in VC1; 0.939 (0.901-0.977) in VC2; 0.917 (0.824-1.000) in VC3. For subgroup analysis, TEPs exhibited an AUC of 0.858, 0.859, and 0.920 to detect early-stage, borderline, non-epithelial diseases and 0.899 to discriminate ovarian cancer from endometriosis. TEPs had robustness, compatibility, and universality for preoperative diagnosis of ovarian cancer since it withstood validations in populations of different ethnicities, heterogeneous histological subtypes, and early-stage ovarian cancer. However, these observations warrant prospective validations in a larger population before clinical utilities.
Humans ; Female ; Blood Platelets/pathology* ; Biomarkers, Tumor/genetics* ; Ovarian Neoplasms/pathology* ; China

OBJECTIVE: To explore the relationship between drug treatment and outcomes in patients with late-onset severe pneumonia (LOSP) after allogeneic stem cell transplantation (allo-SCT). METHODS: We retrospectively analyzed the effects of the initiation time of treatment drugs, especially antiviral drugs and glucocorticoids on the clinical outcomes in 82 patients between January 2016 and August 2021 who developed LOSP after allo-SCT in Peking University People's Hospital. Univariate analysis was performed by Mann-Whitney U test and χ² test, and multivariate analysis was performed by Logistic regression. When multiple groups (n>2) were involved in the χ² test, Bonferroni correction was used for the level of significance test. RESULTS: Of all 82 patients in this study, the median onset time of LOSP was 220 d (93-813 d) after transplantation, and the 60-day survival rate was 58.5% (48/82). The median improvement time of the survival patients was 18 d (7-44 d), while the median death time of the died patients was 22 d (2-53 d). Multivariate analysis showed that the initiation time of antiviral drugs from the onset of LOSP (< 10 d vs. ≥10 d, P=0.012), and the initiation time of glucocorticoids from antiviral drugs (< 10 d vs. ≥10 d, P=0.027) were the factors affecting the final outcome of the patients with LOSP at the end of 60 d. According to the above results, LOSP patients were divided into four subgroups: group A (antiviral drugs < 10 d, glucocorticoids ≥10 d), group B (antiviral drugs < 10 d, glucocorticoids < 10 d), group C (antiviral drugs ≥10 d, glucocorticoids ≥10 d) and group D (antiviral drugs ≥10 d, glucocorticoids < 10 d), the 60-day survival rates were 91.7%, 56.8%, 50.0% and 21.4%, respectively. CONCLUSION Our study demonstrated that in patients who developed LOSP after allo-SCT, the initiation time of antiviral drugs and glucocorticoids were associated with the prognosis of LOSP, and the survival rate was highest in patients who received antiviral drugs early and glucocorticoids later. It suggested that for patients with LOSP of unknown etiology should be highly suspicious of the possibility of a secondary hyperimmune response to viral infection.
Antiviral Agents/therapeutic use* ; Glucocorticoids/therapeutic use* ; Hematopoietic Stem Cell Transplantation/methods* ; Humans ; Pneumonia/etiology* ; Prognosis ; Retrospective Studies ; Transplantation, Homologous/adverse effects*

Astragali Radix(AR)is a clinically used herbal medicine with multiple immunomodulatory activities that can strengthen the activity and cytotoxicity of natural killer(NK)cells.However,owing to the complexity of its composition,the specific active ingredients in AR that act on NK cells are not clear yet.Cell membrane chromatography(CMC)is mainly used to screen the active ingredients in a complex system of herbal medicines.In this study,a new comprehensive two-dimensional(2D)NK-92MI CMC/C18 column/time-of-flight mass spectrometry(TOFMS)system was established to screen for potential NK cell acti-vators.To obtain a higher column efficiency,3-mercaptopropyltrimethoxysilane-modified silica was synthesized to prepare the NK-92MI CMC column.In total,nine components in AR were screened from this system,which could be washed out from the NK-92MI/CMC column after 10 min,and they showed good affinity for NK-92MI/CMC column.Two representative active compounds of AR,isoastragaloside Ⅰ and astragaloside Ⅳ,promoted the killing effect of NK cells on K562 cells in a dose-dependent manner.It can thus suggest that isoastragaloside Ⅰ and astragaloside Ⅳ are the main immunomodulatory compo-nents of AR.This comprehensive 2D NK-92MI CMC analytical system is a practical method for screening immune cell activators from other herbal medicines with immunomodulatory effects.

【Objective】 To analyze the cause of single-ELISA reactive of four blood screening items in 18 blood stations in Henan, so as to provide the basis for improving the quality of blood screening. 【Methods】 The single-ELISA reactive rate of HBsAg, anti-HCV, HIV Ag/Ab and anti-TP of 18 blood station laboratories in Henan throughout 2019 was calculated, and the causes were analyzed according to different ELISA reagent combinations and gray area settings in each laboratory. 【Results】 The overall single-ELISA reactive rates of HBsAg, anti-HCV, HIV Ag/Ab and anti-TP were 1.740(2 154/1 237 789), 0.564‰(698/1 237 789), 1.421‰(1 759/1 237 789) and 1.561‰(1 932/1 237 789), respectively, showing significant differences by detection items (P <0.05). Person correlation analysis showed that the single-ELISA reactive rate was independent of the gray area settings.but dependent on laboratories and reagent combinations. The single-ELISA reactive rate of HBsAg, anti-HCV, HIV Ag/Ab and anti-TP in D laboratory was the highest and higher than that in other labs using the same reagent.The laboratories with high HBsAg single-ELISA reactive rate were mostly those using a combination of imported reagents and domestic reagents, including the top 6 laboratories. The laboratories with high anti-HCV single-ELISA reactive rate were mostly those using certain domestic reagents. No obvious rules was noticed by single-ELISA reactive for anti-HIV. Laboratories with high anti-TP single-ELISA reactive rate were mostly those using combination 4. 【Conclusion】 The HBsAg single-ELISA reactive rate was the highest in the four blood screening items of blood station laboratories in Henan. The single-ELISA reactive rate is related to the laboratory itself and the reagent manufacturer, suggesting that laboratory quality control should be strengthened and proper reagent combination should be selected to reduce the waste of blood.

Objectives: This study aimed to observe the change of arachidonic acid-induced platelet aggregation rate (AA-Ag) and short-term adverse reactions after taking 50 or 100 mg/d aspirin(enteric-coated sustained-release formulation) or 100 mg/d aspirin (enteric-coated aspirin tablet)in the elderly Chinese population (aged 60 years or older). Methods: A total of 1 194 participants aged 60 or older, who should be recommended to take aspirin therapy due to medical reasons, were recruited and randomly assigned into three groups to receive enteric-coated sustained-release aspirin tablet (50 mg, once daily, group A), or 100 mg, once daily (group B) or enteric-coated aspirin tablet 100 mg once daily (group C), respectively. AA-Ag was measured after (14±3)days of aspirin treatment. Adverse events and bleeding events were recorded during the (28±3)days of follow-up. Results: The AA-Ag in group A (n=347), B (n=338) and C (n=332) post 14-day aspirin therapy were 6.65 (4.03,10.84)%, 5.89(3.22,10.03) % and 6.00(3.68,10.09) %, respectively (P>0.05). During the 28 days follow-up, the adverse events rate of group A (n=388), B (n=387) and C (n=385) was 3.87%,3.36%, and 7.95%, and the mild bleeding events rate was 3.09%, 2.33%, and 6.23%, respectively. Adverse events rate and mild bleeding events rate were significantly higher in group C than in group A and B (P<0.05). Conclusions: Compared with 100 mg-dose aspirin, 50 mg-dose aspirin achieves similar anti-platelet aggregation effect in this elderly Chinese population. The short-term adverse events and mild bleeding risk of aspirin with enteric-coated sustained-release formulation were fewer than that of enteric-coated formulation.

PURPOSE: Conditional survival (CS) provides important information on survival for a period of time after diagnosis. Currently, information on CS patterns of patients with nasopharyngeal carcinoma (NPC) is lacking. We aimed to analyze survival rate over time and estimate CS for NPC patients using a national population-based registry. MATERIALS AND METHODS: Patients diagnosed with NPC between 1973 and 2007 with at least 5-year follow-up were identified from the Surveillance Epidemiology End Results registry. Traditional survival rates and crude CS estimateswere calculated using Kaplan-Meier analysis. Risk-adjusted survival curves were plotted from the proportional hazards model using the correct group prognosis method. RESULTS: For 7,713 patients analyzed, adjusted baseline 5-year overall survival improved significantly from 36.0% in patients diagnosed in 1973-1979, 41.7% in 1980-1989, 46.6% in 1990-1999, to 54.7% in 2000-2007 (p < 0.01). CS analysis demonstrated that for every additional year survived, adjusted probability of surviving the next 5 years increased from 66.7% (localized), 54.0% (regional), and 35.3% (distant) at the time of diagnosis, to 83.7% (localized), 75.0% (regional), and 62.2% (distant) for patients who had survived 5 years. Adjusted 5-year CS differed among age, sex, tumor histology, ethnicity, and stage subgroups initially, but converged with time. CONCLUSION: Treatment outcomes of NPC patients have greatly improved over the decades. Increases in CS become more prominent in patients with distant disease than in those with localized or regional disease as patients survive longer. CS provides more dynamic prognostic information for patients who have survived a period of time after diagnosis.
Diagnosis ; Epidemiology* ; Follow-Up Studies ; Humans ; Kaplan-Meier Estimate ; Methods ; Nasopharyngeal Neoplasms ; Prognosis ; Proportional Hazards Models ; SEER Program ; Survival Rate

Objective The pathogenesis of type 2 diabetes mellitus (DM) is complex and its molecular mechanism remains unclear. This study was to explore the effect of metformin on the TLR4/MyD88/NFκB signaling pathway in the skeletal muscle of type 2 DM rats and its anti-inflammation mechanism from the perspective of immune inflammation.Methods Forty SD male rats were equally randomized into four groups, normal diet, type 2 DM model, insulin treatment (DM+INS), and metformin treatment (DM+MET). The DM model was established in the latter three groups by feeding the rats on a diet of high fat and high glucose followed by intraperitoneal injection of STZ at 30 mg/kg at the end of the 8th week. After modeling, the animals of the DM+INS and DM+MET groups were treated by hypodermic injection of insulin at 1 IU/d and intragastrical administration of metformin at 200 mg/（d·kg） respectively for 4 weeks. Then, the Homeostasis Model Assessment-insulin resistance (HOMA-IR) was calculated, the content of serum IL-23 measured by ELISA, the expressions of AMPK, TLR4, MyD88 and NFκB in the skeletal muscle detected by Western blot, and the levels of MyD88 mRNA and TLR4 mRNA determined by RT-PCR.Results HOMA-IR was significantly elevated in the DM model, DM+INS and DM+MET groups as compared with that in the normal diet group (4.55±0.22, 4.32±0.32 and 1.79±0.15 vs 1.56±0.04, P<0.05), lower in the DM+MET than in either the DM model (P<0.05) or the DM+INS group (P<0.05). The content of serum IL-23 was also markedly increased in the DM model, DM+INS and DM+MET groups in comparison with that in the normal diet group (\[2.279±0.472\], \[1.886±0.233\] and \[1.205±0.398\] vs \[0.788±0.193\] μg/L, P<0.05), lower in the DM+MET than in either the DM model (P < 0.05) or the DM+INS group (P<0.05). A positive correlation was found between HOMA-IR and serum IL-23 in both the DM model (r=0.716, P<0.05) and the DM+MET group (r=0.725, P<0.05). The levels of TLR4 mRNA, MyD88 mRNA, TLR4, MyD88, and NFκB were all increased in the DM model, DM+INS and DM+MET groups compared with those in the normal diet group (P<0.05), lower in the DM+INS and DM+MET than in the DM model (P<0.05), and even lower in the DM+MET than in the DM+INS group (P<0.05). The expression of AMPK in the skeletal muscle was remarkably upregulated in the M+MET group as compared with the other three groups (P<0.05).Conclusion Metformin acts against inflammation and improves insulin resistance by activating AMPK, inhibiting the TLR4/MyD88/NFκB signaling pathway in the skeletal muscle and down-regulating the expression of IL-23.

Objective: To observe the effect of poloxamer 188 (P188) on megakaryocyte cultivation and induction from cord blood mononuclear cells in order to obtain more megakaryocyte progenitor cells (MPC). Methods: The cord blood mononuclear cells were isolated and inoculated in cell culture bag or cell culture flask respectively. The WIGGENS shaker and cell culture bags were used to mimick WAVE Bioreactor for three-dimensional (3D) cell culture, and the P188 was added to induction medium, The cells were detected for morphology, surface marker, viability, and number on day 14. Results: In the two-dimensional (2D) culture, CD41(+), CD41(+)/CD61(+), CD61(+) megakaryocytic numbers increased significantly after adding P188 (all P<0.01). And in the 3D culture of adding P188, the cell volume became larger and the nuclear shape was irregular, the cytoplasm appeared magenta granules, and the megakaryocyte cells became more mature. By 3D culture, the expression of CD41/CD61 was (36.30±1.27)% vs (23.95±1.34)%, hence the differentiation for MPC was significantly higher than that in the 2D group (P<0.01). Furthermore, adding P188 in 3D culture resulted in highest differentiation efficiency for MPC [(59.45±1.20)%]. There were no significantly differences in terms of cell viability and cell number among 3D culture containing P188, 2D and 3D culture groups (all P>0.05). Conclusion: 3D culture was beneficial for the differentiation of MPC, but the cell viability was lower than 2D group; However, the satisfied cell growth and better induction efficiency were obtained by adding of P188, which might provide a new method of megakaryocytes production for clinical application.
Bioreactors ; Cell Differentiation ; Cells, Cultured ; Fetal Blood ; Megakaryocytes ; Poloxamer

Recently, integrative pharmacology(IP) has become a pivotal paradigm for the modernization of traditional Chinese medicines(TCM) and combinatorial drugs discovery, which is an interdisciplinary science for establishing the in vitro and in vivo correlation between absorption, distribution, metabolism, and excretion/pharmacokinetic(ADME/PK) profiles of TCM and the molecular networks of disease by the integration of the knowledge of multi-disciplinary and multi-stages. In the present study, an internet-based Computation Platform for IP of TCM(TCM-IP, www.tcmip.cn) is established to promote the development of the emerging discipline. Among them, a big data of TCM is an important resource for TCM-IP including Chinese Medicine Formula Database, Chinese Medical Herbs Database, Chemical Database of Chinese Medicine, Target Database for Disease and Symptoms, et al. Meanwhile, some data mining and bioinformatics approaches are critical technology for TCM-IP including the identification of the TCM constituents, ADME prediction, target prediction for the TCM constituents, network construction and analysis, et al. Furthermore, network beautification and individuation design are employed to meet the consumer's requirement. We firmly believe that TCM-IP is a very useful tool for the identification of active constituents of TCM and their involving potential molecular mechanism for therapeutics, which would wildly applied in quality evaluation, clinical repositioning, scientific discovery based on original thinking, prescription compatibility and new drug of TCM, et al.

Objective To investigate the clinical effect of salmeterol fluticasone propionate combined with montelukast in the treatment of moderate and severe bronchial asthma. Methods 112 patients with moderate and severe bronchial asthma in Taizhou hospital from January 2014 to December 2016 were selected and divided into the control and the study group according to the time of visiting hospital, 56 cases in each group. The control group were given salmeterol fluticasone propionate for treatment, the study group were treated with salmeterol fluticasone propionate combined with montelukast .Keep a record of the asthma control test (ACT), forced expiratory volume (FEV1) percentage expected index changes of pre-treatment and 8 weeks after treatment. Results ACT score and FEV1 percentage expected index changes of two groups there was no significant difference before the treatment. After treatment, ACT score and FEV1 percentage expected index changes of the study group was better than the control group(P<0.05). Conclusion Salmeterol fluticasone propionate combined with montelukast in the treatment can significantly improve the clinical efficacy of patients.