Effectiveness of fecal DNA syndecan-2 methylation testing for detection of colorectal cancer in a high-risk Chinese population

BACKGROUND Colorectal cancer(CRC)is among the most prevalent and life-threatening malignancies worldwide.Syndecan-2 methylation(mSDC2)testing has emerged as a widely used biomarker for early detection of CRC in stool and serum samples.Cancer(CRC)is among the most prevalent and life-threatening malignancies worldwide.mSDC2 testing has emerged as a widely used biomarker for early detection of CRC in stool and serum samples.AIM To validate the effectiveness of fecal DNA mSDC2 testing in the detection of CRC among a high-risk Chinese population to provide evidence-based data for the development of diagnostic and/or screening guidelines for CRC in China.METHODS A high-risk Chinese cohort consisting of 1130 individuals aged 40-79 years was selected for evaluation via fecal mSDC2 testing.Sensitivity and specificity for CRC,advanced adenoma(AA)and advanced colorectal neoplasia(ACN)were determined.High-risk factors for the incidence of colorectal lesions were determined and a logistic regression model was constructed to reflect the efficacy of the test.RESULTS A total of 1035 high-risk individuals were included in this study according to established criteria.Among them,16 suffered from CRC(1.55%),65 from AA(6.28%)and 189 from non-AAs(18.26%);150 patients were diagnosed with polyps(14.49%).Diagnoses were established based upon colonoscopic and pathological examinations.Sensitivities of the mSDC2 test for CRC and AA were 87.50%and 40.00%,respectively;specificities were 95.61%for other groups.Positive predictive values of the mSDC2 test for CRC,AA and ACN were 16.09%,29.89%and 45.98%,respectively;the negative predictive value for CRC was 99.79%.After adjusting for other high-risk covariates,mSDC2 test positivity was found to be a significant risk factor for the occurrence of ACN(P<0.001).CONCLUSION Our findings confirmed that offering fecal mSDC2 testing and colonoscopy in combination for CRC screening is effective for earlier detection of malignant colorectal lesions in a high-risk Chinese population.

Effects of professional rehabilitation training on the recovery of neurological function in young stroke patients

Young stroke patients have a strong desire to return to the society, but few studies have been conducted on their rehabilitation training items, intensity, and prognosis. We analyzed clinical data of young and middle-aged/older stroke patients hospitalized in the Department of Neurological Rehabilitation, China Rehabilitation Research Center, Capital Medical University, China from February 2014 to May 2015. Results demonstrated that hemorrhagic stroke （59.6%） was the primary stroke type found in the young group, while ischemic stroke （60.0%） was the main type detected in the middle-aged/older group. Compared with older stroke patients, education level and incidence of hyperhomocysteinemia were higher in younger stroke patients, whereas, incidences of hypertension, diabetes, and heart disease were lower. The average length of hospital stay was longer in the young group than in the middle-aged/older group. The main risk factors observed in the young stroke patients were hypertension, drinking, smoking, hyperlipidemia, hyperhomocysteinemia, diabetes, previous history of stroke, and heart disease. The most accepted rehabilitation program consisted of physiotherapy, occupational therapy, speech therapy, acupuncture and moxibustion. Average rehabilitation training time was 2.5 hours/day. Barthel Index and modified Rankin Scale scores were increased at discharge. Six months after discharge, the degree of occupational and economic satisfaction declined, and there were no changes in family life satisfaction. The degrees of other life satisfaction （such as friendship） improved. The degree of disability and functional status improved significantly in young stroke patients after professional rehabilitation, but the number of patients who returned to society within 6 months after stroke was still small.

Single-nucleotide polymorphisms based genetic risk score in the prediction of pancreatic cancer risk

BACKGROUND Disease-related single nucleotide polymorphisms(SNPs)based genetic risk score(GRS)has been proven to provide independent inherited risk other than family history in multiple cancer types.AIM To evaluate the potential of GRS in the prediction of pancreatic cancer risk.METHODS In this case-control study(254 cases and 1200 controls),we aimed to evaluate the association between GRS and pancreatic ductal adenocarcinoma(PDAC)risk in the Chinese population.The GRS was calculated based on the genotype information of 18 PDAC-related SNPs for each study subject(personal genotyping information of the SNPs)and was weighted by external odd ratios(ORs).RESULTS GRS was significantly different in cases and controls(1.96±3.84 in PDACs vs 1.09±0.94 in controls,P<0.0001).Logistic regression revealed GRS to be associated with PDAC risk[OR=1.23,95%confidence interval(CI):1.13-1.34,P<0.0001].GRS remained significantly associated with PDAC(OR=1.36,95%CI:1.06-1.74,P=0.015)after adjusting for age and sex.Further analysis revealed an association of increased risk for PDAC with higher GRS.Compared with low GRS(<1.0),subjects with high GRS(2.0)were 99%more likely to have PDAC(OR:1.99,95%CI:1.30-3.04,P=0.002).Participants with intermediate GRS(1.0-1.9)were 39%more likely to have PDAC(OR:1.39,95%CI:1.03-1.84,P=0.031).A positive trend was observed(P trend=0.0006).CONCLUSION GRS based on PDAC-associated SNPs could provide independent information on PDAC risk and may be used to predict a high risk PDAC population.

Germline mutations in 5’to c.7914 of BRCA2 significantly increase risk of prostate cancer

Dear Editor,Here,we report the association of mutations in the prostate cancer cluster region(PCCR;c.7914 to 3’)and non-PCCR(5’to c.7914)in breast cancer susceptibility gene 2(BRCA2)with prostate cancer(PCa)risk at the population level in Caucasian and Chinese cohorts.

Phi-based risk calculators performed better in the prediction of prostate cancer in the Chinese population

Risk prediction models including the Prostate Health Index(phi)for prostate cancer have been well established and evaluated in the Western population.The aim of this study is to build phi-based risk calculators in a prostate biopsy population and evaluate their performanee in predicting prostate cancer(PCa)and high-grade PCa(Gleason score 27)in the Chinese population.We developed risk calculators based on 635 men who underwent initial prostate biopsy.Then,we validated the performance of prostate-specific antigen(PSA),phi,and the risk calculators in an additional observational cohort of 1045 men.We observed that the phi-based risk calculators(risk calculators 2 and 4)outperformed the PSA-based risk calculator for predicting PCa and high-grade PCa in the training cohort.In the validation study,the area under the receiver operating characteristic curve(AUC)for risk calculators 2 and 4 reached 0.91 and 0.92,respectively,for predicting PCa and high-grade PCa,respectively;the AUC values were better than those for risk calculator 1(PSA-based model with an AUC of 0.81 and 0.82,respectively)(all P<0.001).Such superiority was also observed in the stratified population with PSA ranging from 2.0 ng ml^-1 to 10.0 ng ml^-1.Decision curves confirmed that a considerable proportion of unnecessary biopsies could be avoided while applying phi-based risk calculators.In this study,we showed that,compared to risk calculators without phi,phi-based risk calculators exhibited superior discrimination and calibration for PCa in the Chinese biopsy population.Applying these risk calculators also considerably reduced the number of unnecessary biopsies for PCa.

Prostate Health Index(phi)and its derivatives predict Gleason score upgrading after radical prostatectomy among patients with low-risk prostate cancer

To analyze the performance of the Prostate Health Index(phi)and its derivatives for predicting Gleason score(GS)upgrading between prostate biopsy and radical prostatectomy(RP)in the Chinese population,an observational,prospective RP cohort consisting of 351 patients from two medical centers was established from January 2017 to September 2020.Pathological reclassification was determined by the Gleason Grade Group(GG).The area under the receiver operating characteristic curve(AUC)and logistic regression(LR)models were used to evaluate the predictive performance of predictors.In clinically low-risk patients with biopsy GG≤2,phi(odds ratio[OR]=1.80,95%confidence interval[95%CI]:1.14-2.82,P=0.01)and its derivative phi density(PHID;OR=2.34,95%CI:1.30-4.20,P=0.005)were significantly associated with upgrading to GG≥3 after RP,and the results were confirmed by multivariable analysis.Similar results were observed in patients with biopsy GG of 1 for the prediction of upgrading to RP GG≥2.Compared to the base model(AUC=0.59),addition of the phi or PHID could provide additional predictive value for GS upgrading in low-risk patients(AUC=0.69 and 0.71,respectively,both P<0.05).In conclusion,phi and PHID could predict GS upgrading after RP in clinically low-risk patients.

Association between diacylglycerol kinase kappa variants and hypospadias susceptibility in a Han Chinese population

Previous genome-wide association studies have identified variants in the diacylglycerol kinase kappa （DGKtO gene associated with hypospadias in populations of European descent. However, no variants of DGKKwere confirmed to be associated with hypospadias in a recent Han Chinese study population, likely due to the limited number of single-nucleotide polymorphisms （SNPs） included in the analysis. In this study, we aimed to address the inconsistent results and evaluate the association between DGKK and hypospadias in the Han Chinese population through a more comprehensive analysis of DGKK variants. We conducted association analyses for 17 SNPs in or downstream of DGKKwith hypospadias among 322 cases （58 mild, 113 moderate, 128 severe, and 23 unknown） and 1008 controls. Five SNPs （rs2211122, rs4554617, rs7058226, rs7063116, and rs5915254） in DGKK were significantly associated with hypospadias （P 〈 0.05）, with odds ratios （ORs） of 1.64-1.76. When only mild and moderate cases were compared to controls, 10 SNPs in DGKKwere significant （P〈 0.05）, with ORs of 1.56-2.13. No significant SNP was observed when only severe cases were compared to controls. This study successfully implicated DGKK variants in hypospadias risk among a Han Chinese population, especially for mild/moderate cases. Severe forms of hyposDadias are likely due to other genetic factors.

Effect of Na(Ⅰ)-H2O clusters on self-assembly of sandwich-type U(Ⅵ)-containing silicotungstates and the efficient catalytic activity for the synthesis of substituted phenylsulfonyl-1H-pyrazoles

In this study,a sandwich-type uranium(Ⅵ)-containing silicotungstate KNa11H2(H2O)30[Na(UO2)(SiW9O34)]2·8H2O(1)with new three-dimensional(3D)structure was synthesized and characterized using single-crystal X-ray diffraction,Fourier transform infrared,Raman,solid-state ultraviolet–visible diffuse reflection spectra,thermogravimetric analysis and powder X-ray diffraction.Single crystal analysis revealed that the Na(I)-H2O clusters in 1 showed a two-dimensional structure similar to(4,4)-network and resulted in the formation of a new 3D structure of 1.In addition,it was notable that 1 presented excellent catalytic activity for the synthesis of substituted phenylsulfonyl-1H-pyrazoles via the cyclization reaction of 1,3-diketones with various substituted benzenesulfonyl hydrazides.