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

AIM:To observe the clinical effect of ranibizumab combined with 577nm micropulse laser in the treatment of severe diabetic macular edema(DME). METHODS:There were 52 eyes of 52 patients diagnosed with severe DME who admitted to the People's Hospital of Guangxi Zhuang Autonomous Region from June 2016 to September 2019. The patients were randomly divided into the observation group(26 patients with 26 eyes, treated with ranibizumab combined with 577nm micropulse laser)and the control group(26 patients with 26 eyes, treated with ranibizumab alone). Patients in both groups received intravitreal injection of ranibizumab with “3+PRN” regimen. Followed up at 9mo after treatment to observe the central macular thickness(CMT), the best corrected visual acuity(BCVA)and the times of intravitreal injection of ranibizumab in the two groups.RESULTS:Compared with before treatment, the CMT and BCVA of the two groups were significantly improved at each time point after treatment(all P<0.001), but there was no difference between the two groups(P>0.05). During the follow-up period, the times of vitreous injection of ranibizumabin the observation group was significantly less than that in the control group(5.88±1.24 times vs 7.12±1.24 times, P=0.001). CONCLUSION:Both ranibizumab combined with 577nm micropulse laser and ranibizumab alone are effective in reducing edema and improving vision in patients with severe DME, but the combination therapy reduces the times of injection.

OBJECTIVE: To study insulin sensitivity and the serum level of adiponectin in infants with intrauterine growth retardation (IUGR) and the effect of breastfeeding on the insulin sensitivity through a follow-up study. METHODS: A total of 106 full-term IUGR infants who were hospitalized from October 2014 to October 2018 were enrolled as the IUGR group, and 90 full-term appropriate for gestational age (AGA) infants who were born during the same period of time were enrolled as the AGA group. Birth weight and body length were recorded. Serum levels of fasting blood glucose (FBG), triglyceride (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), insulin, and adiponectin were measured on day 7 after birth. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. According to the feeding pattern, the IUGR group was further divided into a breastfeeding group with 37 infants and a formula feeding group with 42 infants. The above serum indices and growth indices were also measured at the age of 3 and 6 months. RESULTS: Compared with the AGA group, the IUGR group had significantly increased levels in serum insulin and HOMA-IR and a significantly decreased level of adiponectin (P<0.05). There were no significant differences between the breastfeeding and formula feeding groups in growth indices and serum levels of FBG, TG, LDL, and HDL on day 7 after birth and at the ages of 3 and 6 months (P>0.05). In the breastfeeding group, serum insulin and HOMA-IR decreased and adiponectin level increased over the time of breastfeeding (P<0.05). CONCLUSIONS Insulin sensitivity decreases in the early stage after birth in IUGR infants, and breastfeeding can improve insulin sensitivity.
Adiponectin ; Fetal Growth Retardation ; Follow-Up Studies ; Humans ; Infant ; Infant, Newborn ; Insulin ; Insulin Resistance

To explore the way of prenatal echocardiography in the diagnosis of fetal double aortic arch . Methods T he data of fetuses diagnosed as double aortic arch in 6 prenatal centers in Hunan in echocardiograms performed at 20－36 weeks of gestation from 2013 to 2018 were reviewed . T he characteristics of echocardiographic with double aortic arch , and the associated malformations were observed ,the clinical outcome were analyzed . Results T he main echocardiographic features of the double aortic arch were three‐vessel‐tracheal view s ,which showed a bifurcation of the ascending aorta and a ring consisted of aortic right and left arch . From this retrospective analysis , 29 double aortic arches were identified ,which 8 cases ( 28% ) combined with cardiac defect and extracardiac abnormalities , 1 case with 22q11 deletion . Among them ,5 cases were confirmed by autopsy ,24 cases were diagnosed by computed tomography angiography ( 8 cases were confirmed by operation ) . Conclusions Systematic prenatal echocardiography in the diagnosis of fetal double aortic arch has significant clinical value in the cliagnose of double aortic arch ,w hether it is associated with other malformations and is important for assessing fetal prognosis .

OBJECTIVETo evaluate the value of blood lactic acid (BLA) as a predictor for the severity and prognosis of neonatal shock.

METHODSA total of 326 neonates with shock were enrolled and divided into three groups based on the severity, namely mild group (n=147), moderate group (n=105), and severe group (n=74). BLA level was measured during and early after (about 6 hours later) fluid resuscitation, and lactate clearance rate (LCR) was calculated. The receiver operating characteristic (ROC) curve was applied to evaluate the predictive value of BLA in neonatal shock.

RESULTSBLA level was high in all subjects prior to treatment, and was highest in the severe group and lowest in the mild group (P<0.01). BLA level was significantly higher among patients with septic shock than among those with hypovolemic, cardiogenic, and asphyxiating shock (P<0.05). BLA level was significantly reduced in patients in recovery after treatment (P<0.05). Mortality was significantly lower in patients with BLA level ≤4 mmol/L or LCR ≥10% than in those with BLA level >4 mmol/L or LCR <10% (P<0.01). BLA at 11.15 mmol/L had 100% sensitivity and 96.8% specificity in predicting severe shock. BLA at 10.65 mmol/L had 88.9% sensitivity and 74.1% specificity in predicting the prognosis (survival or dead) of newborns with shock.

CONCLUSIONSIn neonates with shock, arterial BLA level increases as the disease severity increases and is associated with prognosis, so it is a useful predictor of the severity and prognosis of neonatal shock.

OBJECTIVETo explore the effect of intrauterine growth retardation (IUGR) on insulin sensitivity in neonates and the relationship between insulin sensitivity and plasma adiponectin level.

METHODSEighty-two term neonates with IUGR and 90 term neonates born appropriate for gestational age (AGA) were enrolled. Weight, height, head circumference and abdomen circumference of the neonates were measured within 24 hours after birth. Fasting serum glucose (FG), triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), plasma insulin and adiponectin were detected in two groups on the 7th day after birth. Homeostasis model assessment for insulin resistance (HOMA-IR) index and insulin sensitivity index (ISI) were calculated.

RESULTSThere were no significant differences in the levels of FG, TG, HDL and LDL between the IUGR and AGA groups (P>0.05). The plasma insulin level in the IUGR group was higher than that in the AGA group, but the plasma adiponectin level was lower than that in the AGA group (P<0.05). HOMA-IR index in the IUGR group was higher than that in the AGA group, but ISI was lower than that in the AGA group (P<0.05). Both Pearson correlation analysis and multiple linear regression analysis showed HOMA-IR index was negatively correlated with plasma adiponectin level and birth weight (P<0.05).

CONCLUSIONSThe neonates with IUGR display a higher plasma insulin level and decreased insulin sensitivity. The decreased plasma adiponectin level may be associated with the decreased insulin sensitivity.

OBJECTIVETo investigate the influence of thrombelastography index changes on its sensitivity and specificity for diagnosis of disseminated intravascular coagulation (DIC) in children.

METHODSA total of 149 children with DIC in our hospital from June 2013 to June 2016 were selected in DIC group, while 106 cases of non-DIC, including healthy children and children with diseases easily confused with DIC, were selected as non-DIC(control) group. The thrombelastography, D-dimer, coagulation functions including prothrombintime (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB) and fibin degradation product (FDP), congental coagulation disorders and platelet count were detected in DIC and non-DIC groups; the statistics of data was performed and the sensitivity and specificity of thromelastraphy indexes such as R time, α angle MA value and A value were evaluated; the relationship of DIC with indexes was analyzed. Moreover, the result difference of thromelastography and routine coagulation function test was compared at diagnosis of DIC.

RESULTSAccording to statistical analysis of clinical data in 2 groups, the average R time in non-DIC group was significantly less than that in DIC group (P<0.05); the average α angle in non-DIC group was larger than that in DIC group (P<0.05), both the MA and A values in the non-DIC group were significantly higher than those in DIC group (P<0.05). The specificity of routine coagulation function test for diagnosis of DIC was as follow: PT-27.2%, APTT-42.2%, international normalized ratio(INR)-47.9%, FIB-44.4%, FDP-42.7% and D-dimer-68.3%, which were significantly lower than that of R time,α angle and MA value for diagnosis of DIC (85.1%, 74.1% and 73%). The α angle and MA value of healthy children were greater than those of children with severe liver disease(P<0.05). while the average R time of healthy children was less than that of children with severe liver disease(P<0.05), but the difference of A value between them did not statistically significant (P>0.05) . The average R time of healthy children was less than that of children with congenital coagulation disorders (P<0.05). but there was no significant differences in α angle MA and Avalues between them.

CONCLUSIONAs compared with routine coagulation function test, the thrombelastography shows more high specificity for diagnosis of DIC, and can more precisely diagnose the DIC; moreover, the thrombelastography combined with roatime coagulation function test can more early find and diagnose the DIC in children, therefore it can improve the survival rate of children with DIC.

OBJECTIVETo explore the effect of Caspase 1 inhibitor Ac-YVAD-CMK on acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation(allo-HSCT) and its mechanism.

METHODSExperiments were divided randomly into 3 groups: allogeneic hematopoietic stem cell transplantation combined with splenic cell infusion group (TS group, n=12), allogeneic hematopoietic stem cell transplantation combined with splenic cell infusion plus injection of low dose Caspase 1 inhibitor group (TS+low dose of C group, n=16) and plus high dose Caspase1 inhibitor (TS+high dose of C group, n=19). The body weight of mice in each group was dynamically detected, and the clinical manifestation of GVHD and score of aGVHD were determined, and the chimerism rate of mice was detected after transplantation for 14 days. Th1, Th2 and Th17 cells in peripheral blood were examined by flow cytometry. Peripheral proinflammatory cytokines IL-1β, IFN-γ, IL-1α and IL-18 were examined by enzyme-linked immunosorbent assay(ELISA). The tissues sections of GVHD target organs (liver, lung, colon and skin) were stained with HE for histopathologic examination and histopathologic score.

RESULTSAc-YVAD-CMK could alleviate murine aGVHD and pathological injury, decreare the incidence and severity of aGVHD in recipient mice. The detection of Th cell subsets in peripheral blood by flow cytometry showed that compared with TS group, the Th1 cell ratio in TS+low dose of C and TS+high dose of C groups was significantly reduced (P<0.05), while the Th2 and Th17 cell ratio was significantly enhanced (P<0.05) in TS+low dose of high dose of C groups. The detection of peripheral inflamematory cytokines by ELISA demonstrated that the inflammatory cytokines including IL-1β,IFN-γ,IL-18 and IL-1α were reduced significantly (P<0.05).

CONCLUSIONAc-YVAD-CMK can improve aGVHD by inhibiting Caspase 1 and reducing the release of some inflammatory cytokines, thereby alleviated the aGVHD pathological damage.

OBJECTIVETo identify the biomarkers of renal cell cancer (RCC) through urine metabolic analysis.

METHODSUrine samples of 27 RCC patients, 26 patients with other urinary cancers and 26 healthy volunteers were examined with gas chromatography-mass spectrometry (GC-MS). SIMCA-P+12.0.1.0 software was used for principal component analysis (PCA) and orthogonal partial least-squares discriminant analysis (OPLS-DA) to screen for the differential metabolites.

RESULTSPCA (R2X=0.846, Q2=0.575) and OPLS-DA (R2X=0.736, R2Y=0.974, Q2Y=0.897) model were established for the RCC patients and control subjects. Fourteen metabolites were selected as the characteristic metabolites, including pentanoic acid, malonic acid, glutaric acid, adipic acid, amino quinoline, quinoline, indole acetic acid, and tryptophan, whose levels in the urine were significantly higher in the RCC patients than in the normal subjects (P<0.01); the RCC patients showed significantly higher urine contents of pentanoic acid, phenylalanine, and 6-methoxy-nitro quinoline than those with other urinary tumors (P<0.01).

CONCLUSIONThe urine metabolites identified based on GC-MS analysis can distinguish RCC patients from patients with other urinary cancers and healthy subjects, suggesting their potential as diagnostic markers for RCC.

Biomarkers ; urine ; Carcinoma, Renal Cell ; urine ; Discriminant Analysis ; Gas Chromatography-Mass Spectrometry ; Humans ; Least-Squares Analysis ; Metabolome ; Metabolomics ; Principal Component Analysis ; Software

Objective To identify the biomarkers of renal cell cancer (RCC) through urine metabolic analysis. Methods Urine samples of 27 RCC patients, 26 patients with other urinary cancers and 26 healthy volunteers were examined with gas chromatography-mass spectrometry (GC-MS). SIMCA-P+12.0.1.0 software was used for principal component analysis (PCA) and orthogonal partial least-squares discriminant analysis (OPLS-DA) to screen for the differential metabolites. Results PCA (R2X=0.846, Q2=0.575) and OPLS-DA (R2X=0.736, R2Y=0.974, Q2Y=0.897) model were established for the RCC patients and control subjects. Fourteen metabolites were selected as the characteristic metabolites, including pentanoic acid, malonic acid, glutaric acid, adipic acid, amino quinoline, quinoline, indole acetic acid, and tryptophan, whose levels in the urine were significantly higher in the RCC patients than in the normal subjects (P<0.01); the RCC patients showed significantly higher urine contents of pentanoic acid, phenylalanine, and 6-methoxy-nitro quinoline than those with other urinary tumors (P<0.01). Conclusion The urine metabolites identified based on GC-MS analysis can distinguish RCC patients from patients with other urinary cancers and healthy subjects, suggesting their potential as diagnostic markers for RCC.