There is a complex biological mechanism in the phosphatidylinositol-3-kinase(PI3K)/protein kinase B(PKB/Akt)/mammalian target of rapamycin(mTOR)signaling pathway,which plays a key role in the development and development of lymphoma.In this review,the relevant literature of PI3K inhibitor research in the past five years summarized and analyzed,and found that the research and development,application,efficacy,and adverse reactions of PI3K inhibitors are the current research hotspots,and the positive results of PI3K inhibitors in clinical trials and basic research have strongly demonstrated the potential of PI3K inhibitors in personalized treatment of lymphoma.In order to maximize the clinical benefits,a variety of strategies need to be explored,including novel drugs with better selectivity and safety,and related combination therapies.

There is a complex biological mechanism in the phosphatidylinositol-3-kinase(PI3K)/protein kinase B(PKB/Akt)/mammalian target of rapamycin(mTOR)signaling pathway,which plays a key role in the development and development of lymphoma.In this review,the relevant literature of PI3K inhibitor research in the past five years summarized and analyzed,and found that the research and development,application,efficacy,and adverse reactions of PI3K inhibitors are the current research hotspots,and the positive results of PI3K inhibitors in clinical trials and basic research have strongly demonstrated the potential of PI3K inhibitors in personalized treatment of lymphoma.In order to maximize the clinical benefits,a variety of strategies need to be explored,including novel drugs with better selectivity and safety,and related combination therapies.

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

Inductively coupled plasma mass spectrometry (ICP-MS) was applied to determine the concentrations of lead (Pb), cadmium (Cd) and arsenic (As) in Lindera aggregata (Sims) Kosterm. The physiologically based extraction test (PBET) digestion in vitro/Caco-2 cell model was established to investigate the bioaccessible contents of Pb, Cd and As in decoction of Lindera aggregata (Sims) Kosterm. The target-organ toxicity dose modification of HI method (TTD) was used to evaluate the cumulative risk caused by the combined exposure of the total levels of Pb, Cd and As in Lindera aggregata (Sims) Kosterm. and the bioaccessible contents in the decoction. The results showed that the total contents of Pb, Cd and As in 4 batches of samples were in the range of 2.901-3.872, 1.299-1.800 and 0.062-0.216 mg·kg^-1, respectively. After transportation by Cacco-2 cells, the bioaccessible contents of Pb, Cd, and As in the decoction were in the range of 0.045-0.080, 0.070-0.112 and 0.004-0.018 mg·kg^-1. The results of risk assessment showed that calculated by the total amounts of heavy metals in the Lindera aggregata (Sims) Kosterm., for the end points of nervous system, the cumulative risks of co-exposure of heavy metals in 3 batches of samples were of concern. After decoction and transportation by Caco-2 cells, for the end points of cardiovascular system, blood, nervous system, kidney and testis, the TTD modification of HI values of all batches of samples were less than 1, and the health risks were acceptable. The study provided methodology basis for a more objective assessment of the health risks of heavy metals and harmful elements in traditional Chinese medicine and for a more scientific limit standard of heavy metals and harmful elements.

BACKGROUND: Prenatal evaluation of fetal lung maturity (FLM) is a challenge, and an effective non-invasive method for prenatal assessment of FLM is needed. The study aimed to establish a normal fetal lung gestational age (GA) grading model based on deep learning (DL) algorithms, validate the effectiveness of the model, and explore the potential value of DL algorithms in assessing FLM. METHODS: A total of 7013 ultrasound images obtained from 1023 normal pregnancies between 20 and 41 + 6 weeks were analyzed in this study. There were no pregnancy-related complications that affected fetal lung development, and all infants were born without neonatal respiratory diseases. The images were divided into three classes based on the gestational week: class I: 20 to 29 + 6 weeks, class II: 30 to 36 + 6 weeks, and class III: 37 to 41 + 6 weeks. There were 3323, 2142, and 1548 images in each class, respectively. First, we performed a pre-processing algorithm to remove irrelevant information from each image. Then, a convolutional neural network was designed to identify different categories of fetal lung ultrasound images. Finally, we used ten-fold cross-validation to validate the performance of our model. This new machine learning algorithm automatically extracted and classified lung ultrasound image information related to GA. This was used to establish a grading model. The performance of the grading model was assessed using accuracy, sensitivity, specificity, and receiver operating characteristic curves. RESULTS: A normal fetal lung GA grading model was established and validated. The sensitivity of each class in the independent test set was 91.7%, 69.8%, and 86.4%, respectively. The specificity of each class in the independent test set was 76.8%, 90.0%, and 83.1%, respectively. The total accuracy was 83.8%. The area under the curve (AUC) of each class was 0.982, 0.907, and 0.960, respectively. The micro-average AUC was 0.957, and the macro-average AUC was 0.949. CONCLUSIONS The normal fetal lung GA grading model could accurately identify ultrasound images of the fetal lung at different GAs, which can be used to identify cases of abnormal lung development due to gestational diseases and evaluate lung maturity after antenatal corticosteroid therapy. The results indicate that DL algorithms can be used as a non-invasive method to predict FLM.
Algorithms ; Deep Learning ; Female ; Gestational Age ; Humans ; Infant ; Infant, Newborn ; Lung/diagnostic imaging* ; Neural Networks, Computer ; Pregnancy

Objective To investigate the relationship between serum angiotensin converting enzyme (ACE) and angiotensinogen (AGT) and gestational hypertension syndrome (HDCP) and the risk factors of HDCP. Methods A total of 135 pregnant hypertensive patients (HDCP group) and 100 normal pregnant women as control check (CK) group were selected. Serum ACE and AGT levels were measured by ELISA, and correlation analysis was performed. The age and gestational age of the two groups, pre-pregnancy body mass index (BMI), parity, number of births, family history of hypertension, family history, education, and other general information, single factor analysis of risk factors for maternal HDCP, single factor regression analysis Statistically significant factors were all used for multivariate logistic regression analysis. Results The serum ACE level in the HDCP group (90.49±47.65) μg/L was significantly higher than that in the CK group (58.72±27.58) μg/L, P<0.05, the difference was statistically significant. The serum AGT level in the HDCP group was (64.57±19.71) μg/L was higher than CK group (58.22±18.64) μg/L, P>0.05, the difference was not statistically significant; single factor analysis showed; age, BMI, hypertension, family history of diabetes, ACE level was maternal (P<0.05), while gestational age, parity, number of births, and education were no significant differences in risk factors for HDCP (P>0.05). Multivariate analysis showed: age, BMI, history of hypertension and ACE. It was a risk factor for pregnancy-induced hypertension. Conclusion ACE levels are associated with HDCP. AGT levels are not associated with HDCP. Patients with a high age, high BMI, and hypertension history have an increased risk of gestational hypertension syndrome.

Applying poly(ADP-ribose) polymerase inhibitors (PARPi) to the treatment of cancers with homologous recombination deficiency (HRDness) has been a great advance in the field of molecular therapeutics. However, in the clinic patients lacking the specific mutations or developing reverse mutations in the process of PARPi treatment may not benefit from PARPi monotherapy. Therefore, targeting homologous recombination (HR) repair with molecularly targeted agents is becoming an attractive research focus and is raising the concept of "chemical HRDness". HR repair is an evolutionarily conserved and extensively regulated process that employs sister chromatids as the template to repair DNA double-strand breaks with high fidelity. In addition to directly targeting HR components, modulation of regulatory pathways controlling HR repair is effective in achieving the "HRDness" phenotype; this includes modulation of the cell cycle checkpoint regulatory pathway, the phosphatidylinositol 3-kinase (PI3K) signaling pathway, the chromatin remodeling pathway, etc. Targeting HR repair can not only result in "synthetic lethality" when combined with PARPi, but also sensitizes cancers to traditional radio/chemotherapy and novel immunotherapy. In this review we describe the HR repair pathway and its regulatory pathways, summarize the preclinical and clinical outcomes of targeting HR repair, discuss the remaining problems in this field and provide a prospective on its application in tumor therapy.

Objective To investigate the relationship between angiotensin converting enzyme (ACE) and angiotensinogen (AGT) gene expression, gene polymorphism and pregnancy-induced hypertension in Qinghai. Methods A total of 210 pregnant hypertensive patients (HDCP group) and 220 normal pregnant women (CK group) were enrolled. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to detect AGT M235T and ACE I/ D gene polymorphism. Results The proportions of ACE gene DD, ID, and Ⅱ in CK group were 28. 15%, 47. 73%, and 24. 09%, respectively. The HDCP group was 33. 81%, 51. 90%, and 14. 29%, respectively (P < 0. 05). The frequency distribution of ACE I/ D polymorphic alleles I and D was different between HDCP group and CK group(P<0. 05). D allele frequency was higher in HDCP group than in CK group (

OBJECTIVE: To investigate the efficacy and safety of decitabine combined with half-course pre-excitation for the treatment of elderly patients with acute myeloid leukemia (AML). METHODS: 44 cases of newly diagnosed elderly AML admitted in our hospital from January 2016 to December 2017 were selected for the retrospective analysis. The patients were randomly divided into 2 groups: pre-excitation therapy group as control and combined therapy group. The 22 patients in pre-excitation therapy group reccived the routine complete course pre-excitation treatment, 22 patients in combined therapy group received the desitabine combined the half course pre-excitation treatment. The therapentic efficacy and adverse reactions during treatment were compared between 2 groups. All patients were followed-up and the survival rate at 6,12 and 24 months was compared between 2 groups. RESULTS: The remission rate(RR) in the combined therapy group was 72.73%, and that in the control group was 50.00%, with significant statistically difference (P<0.05). The median survival time in combined therapy group (17.82±4.19 months) and control group (12.43±3.71 months) was statistically significant (P<0.05). The rate of adverse reactions of digestive tract in combined therapy group was 40.91%, which was higher than that in control group (18.18%), and the difference of two groups was statistically significant (P<0.05). The incidence of adverse reactions in blood system and bone marrow suppression in combined therapy group was 9.09% and 68.18%, which were lower than those in control group (27.27% and 95.45%), with statistically significant differences (P<0.05). There was no statistically significant difference in the incidence of liver dysfunction, cardiac insufficiency and hair loss between the two groups (P>0.05). The incidence of pulmonary infection, intestinal infection and other complications in combined therapy group was 13.64%, which was lower than that in control group 31.82%, and the difference of two groups was statistically significant (P<0.05). No serious complications such as arteriovenous thrombosis occurred in either group, and no patients died during chemotherapy. CONCLUSION Combination of disitamine and half-course prestimulation treatmentis is a safe and effective and elderly patients with AML shown a good tolerance.
Aged ; Antineoplastic Combined Chemotherapy Protocols ; Azacitidine ; Decitabine ; therapeutic use ; Humans ; Leukemia, Myeloid, Acute ; drug therapy ; Retrospective Studies ; Treatment Outcome

OBJECTIVE: To investigate the predictive effect of platelet activation index expression before and after adenosine bisphosphate activation on bleeding risk in patients with primary immune thrombocytopenia (ITP). METHODS: Eighty-nine patients with ITP admitted in our hospital from January 2017 to October 2018 were selected and inrolled in ITP group, the bleeding scoreing and grading were performed by using the ITP-BAT for ITP patients, then 89 ITP patients were divided into 4 subgroups: nothing bleeding symptom group, mild bleeding symprom group, mode rate bleeding symptom group and severe bleeding symptom group according to bleeding scores and grades obtained from ITP-BAT detection. At the same time, 22 persons underwent the health physical examination were selected and enrolled in control group. The adenosine diphosphate (ADP) was used as activator for all patients and controls. The flow cytonetry was used to analyze the expression of platelet membranc glyco protein (GPⅠb, GPⅡb /Ⅲ a) and P-selectin before and after ADP activation, the multiple linear person's correlation analysis was used to analyze the correlation of bleeding degree of ITP patients before and after ADP acbivation with the expression levels of GPⅠb, GPⅡb/Ⅲa and P-selectin. RESULTS: After the ADP activation, the expression level of GPⅠb significantly decreased, while the expression levels of GPⅠb, GPⅡb/Ⅲ a and P-selectin significantly increased in control group, nothing bleeding symptom group and mild bleeding symptom group; but the expression level of GPⅠb significantly increased, while the expression level of GPⅡb/Ⅲ a significantly decreased in moderate and severe bleeding symptom group, the both differences were statistically significant (P＜0.05). however, the expression level of P-selectin in moderate and severe bleeding symptom groups before and after ADP activation was not statistivally significant (P＞0.05). Before ADP activation, the expression level of GPⅠb in ITP subgroups was lower than that in control group, the expression level of GPⅡb/Ⅲ a in ITP subgroups was higher than that in control group, the expression level of P-selectin in moderate and severe bleeding symptom groups was higher than that in control group (P＜0.05). After ADP activation, the expression levels of GPⅠb and P-selectin in ITP subgroups both were lower than those in control group, the expression level of GPⅡb/Ⅲa in ITP subgroups was higher than that in control group (P＜0.05). The comparison among ITP subgroups showed that before ADP activation, the expression level of GPⅠb in moderate and severe bleeding symptom groups was lower than that in nothing bleeding symotom and mild bleeding symptom groups, while the expression levels of GPⅡb/Ⅲa and P-selectin were higher than those in nothing bleeding symptom and mild bleeding symptom groups (P＜0.05), however, after ADP activation, the expression level of GPⅠb in moderate and severe bleeding symptom groups was higher than that in nothing bleeding symptom and mild bleeding symptom groups, while the expression levels of GPⅡb/Ⅲ a and P-selection in moderate and severe bleeding symptom groups were lower than those in nothing and mild bleeding symptom groups (P＜0.05). The correlation analysis showed that before ADP activation, the expression levels of GPⅠb and GPⅡb/Ⅲa positivdy correlated with the bleeding risk (r=0.483, 0.504), and the P-selectin not correlated with the bleeding risk (r=0.000); however, after ADP activation, the expression level of GPⅠb and GPⅡb/Ⅲ a negatively correlated with the bleeding risk (r=-0.627, -0.406, -0.108). CONCLUSION The expression level of platelet activation indicators before and after ADP activation is of certain value for prevention of bleeding risk in ITP patients and can be used as a reference indicator for the treatment and efficacy evaluation.
Adenosine ; Blood Platelets ; Humans ; P-Selectin ; Platelet Activation ; Platelet Count ; Purpura, Thrombocytopenic, Idiopathic