Novel insights into necrozoospermia from a single-center study:reference ranges,possible etiology,and impact on male fertility

Necrozoospermia is a poorly documented condition with a low incidence,and its definition and clinical significance are unclear.Herein,we provide a reference range for necrozoospermia and discuss its possible etiology and impact on male fertility and assisted reproductive outcomes.We extracted relevant information from 650 Chinese male partners of infertile couples and statistically analyzed sperm vitality.Necrozoospermia was present in 3.4%(22/650)of our study population,and the lower cut-off value for sperm vitality was 75.3%.We compared two methods for assessing sperm vitality(eosin-nigrosin head staining and hypo-osmotic swelling test[HOST]),for which the percentage in the eosin-nigrosin group(mean±standard deviation[s.d.]:77.5%±10.5%)was significantly higher than that in the HOST group(mean±s.d.:58.1%±6.7%[5-10 min after incubation]and 55.6%±8.2%[25-30 min after incubation];both P<0.001).The incidence of necrozoospermia increased with age(odds ratio[OR]=1.116,95%confidence interval[CI]:1.048-1.189,P=0.001),while the percentage of normal sperm morphology and DNA fragmentation index(DFI)were significantly associated with necrozoospermia,with ORs of 0.691(95%CI:0.511-0.935,P=0.017)and 1.281(95%CI:1.180-1.390,P<0.001),respectively.In the following 6 months,we recruited 166 patients in the nonnecrozoospermia group and 87 patients in the necrozoospermia group to compare intracytoplasmic sperm injection(ICSI)and pregnancy outcomes between the two groups.The necrozoospermia group had a significantly lower normal fertilization rate(74.7%vs 78.2%,P=0.041;OR=0.822;95%CI:0.682-0.992)than that in the nonnecrozoospermia group.This study presents substantial information on necrozoospermia to establish comprehensive and applicable reference values for sperm vitality for spontaneous conception and artificially assisted reproductive management.

Serum Gamma-glutamyl Transferase Concentration Within the Reference Range is Related to the Coronary Heart Disease Risk Prediction in Korean Men： Analysis of the Korea National Health and Nutrition Examination Survey （V-1, 2010 and V-2, 2011）

Background：Limited data exist on the association of serum gamma-glutamyl transferase （GGT） level within the reference range with the increased risk of coronary heart disease （CHD） prediction in men.The study examined the association between serum GGT concentration within the reference range and the CHD risk prediction in Korean men.Methods：The study employed data from Korean National Health and Nutrition Examination Survey （V-1,2010 and V-2,2011） where a total of 1301 individuals were analyzed.A 10-year CHD risk prediction was computed using the Framingham Risk Score （FRS） modified by the National Cholesterol Education Program （NCEP） Adult Treatment Panel Ⅲ （ATP Ⅲ）.Results：Positive correlations were established between log-transformed GGT concentration and FRS （r =0.237,P 〈 0.001）.After adjustment of body mass index,the amount of alcohol intake and low-density lipoprotein-cholesterol,the odds ratio （95% confidence interval） for intermediate risk and beyond of 10-year CHD prediction （10-year risk ≥10%） with lowest quartile of participants was 1.21 （0.78-1.87） for second quartiles,1.39 （0.88-2.21） for third quartiles and 2.03 （1.23-3.34） for highest quartiles.Conclusions：Higher serum GGT within its reference range was significantly correlated with a 10-year CHD risk prediction estimation using NCEP ATP Ⅲ in Korean men.

Alanine aminotransferase predicts incident steatotic liver disease of metabolic etiology: Long life to the old biomarker!

Alanine aminotransferase(ALT)serum levels increase because of hepatocellular damage.Metabolic dysfunction-associated fatty liver disease(MAFLD),which identifies steatotic liver disease(SLD)associated with≥2 metabolic abnormalities,has prominent sexual differences.The Metabolic Syndrome defines a cluster comprising abdominal obesity,altered glucose metabolism,dyslipidemia,and hypertension.Male sex,body mass index,glucose,lipids,ferritin,hypertension,and age independently predict ALT levels among blood donors.Over the last few decades,the reference range of ALT levels has been animatedly debated owing to attempts to update sex-specific reference ranges.With this backset,Chen et al have recently published a study which has two main findings.First,>80%of indi-viduals with MAFLD had normal ALT levels.Second,there was a linear increa-sing trend in the association between cumulative excess high-normal ALT levels and the rate of incident MAFLD.This study has biologically credible findings.However,it inaccurately considered sex differences in the MAFLD arena.Therefore,future studies on SLD owing to metabolic dysfunction should adopt locally determined and prospectively validated reference ranges of ALT and carefully consider sex differences in liver enzymes and MAFLD pathobiology.

Z-Score in Fetal Echocardiography–Is there Still Room for New Studies?

Congenital heart disease(CHD)is the most common type of birth defect,representing a significant cause of peri-natal morbidity and mortality.Early diagnosis of such anomalies is crucial for improving outcomes.Current pro-tocols recommend a qualitative assessment of cardiac structures using two-dimensional ultrasound(2DUS)and color Doppler imaging.In cases of suspected abnormalities,quantitative assessments through cardiac structure measurements and reference curves can aid in accurate diagnosis.Similar to centiles widely employed in obste-trics,Z-scores provide more precise quantification of various cardiac structures,particularly at the extremes of the curve.While the development of reference curves and Z-scores has progressed over the past two decades,a lack of standardization in measurements and statistical methodology for their determination is evident.Establishing reference curves requires adherence to specific recommendations to improve their accuracy.The purpose of this study is to provide a narrative review of the major studies that have generated reference values for cardiac struc-tures using 2DUS and Z-scores,to evaluate their methodology,and to provide a summary of the results.

New formula for predicting standard liver volume in Chinese adults

AIM To obtain a reference range of morphological indices and establish a formula to accurately predict standard liver volume(SLV) in Chinese adults.METHODS Computed tomography(CT)-estimated total liver volume(CTLV) was determined in 369 Chinese adults. Age,sex,body weight,body height,body mass index,and body surface area(BSA) were recorded using CT. Total splenic volume,portal venous diameter(PVD),splenic venous diameter(SVD),and portal venous cross-sectional area(PVCSA) were also measured by CT. Stepwise multiple linear regression analysis was performed to evaluate the impact of each parameter on CTLV and to develop a new SLV formula. The accuracy of the new formula was compared with the existing formulas in a validation group.RESULTS The average CTLV was 1205.41 ± 257.53 cm3(range,593.80-2250.10 cm3). The average of PVD,SVD and PVCSA was 9.34 ± 1.51 mm,7.40 ± 1.31 mm and 173.22 ± 48.11 mm2,respectively. The CT-estimated splenic volume of healthy adults varied markedly(range,46.60-2892.30 cm3). Sex,age,body height,body weight,body mass index,and BSA were significantly correlated with CTLV. BSA showed the strongest correlation(r = 0.546,P < 0.001),and was used to establish a new model for calculating SLV: SLV(cm3) = 758.259 × BSA(m2)-124.272(R2 = 0.299,P < 0.001). This formula also predicted CTLV more accurately than the existing formulas,but overestimated CTLV in elderly subjects > 70 years of age,and underestimated liver volume when CTLV was > 1800 cm3.CONCLUSION Our new BSA-based formula is more accurate than other formulas in estimating SLV in Chinese adults.

Decreasing trend in prostate cancer with high serum prostate-specific antigen levels detected at first prostate-specific antigen-based population screening in Japan

To clarify the recent trends in prostate-specific antigen （PSA） distribution in men in Japan, we analyzed the PSA distributions of men undergoing PSA-based population screening. We summarized the annual individual data of PSA-based population screening in Kanazawa, Japan, from 2000 to 2011, and analyzed baseline serum PSA values of the participants at the first population screening. Serum PSA distributions were estimated in all participants and those excluding prostate cancer patients according to age. From 2000 to 2011, 19 620 men participated aged 54-69 years old in this screening program. Mean baseline serum PSA level of all participants at the first screening was 2.64 ng m1-1 in 2000, and gradually decreased to approximately 1.30 ng ml-I in 2006. That of participants excluding prostate cancer patients was 1.46 ng m1-1 in 2000, and there was no remarkable change during the study period. The 95t＂ percentiles in the participants excluding prostate cancer patients detected at the first population screening of men aged 54-59, 60-64, and 65-69 years old were 2.90, 3.60, and 4.50 ng m1-1, respectively. After the commencement of population screening, the proportion of prostate cancer patients with high serum PSA levels decreased. However, there were no changes in serum PSA levels in men without prostate cancer. Age-specific PSA reference level of men without prostate cancer in Japan was similar to that in China and Korea.

Analysis of results related to the percent free prostate specific antigen among men without prostate diseases in Xi'an area

To measure the percent of free prostate specific antigen （fPSA） among men without prostate diseases in Xi＇an area, and to study the relationship of percent fPSA with age and pathological grade, clinical stage of prostate cancer （PCa） with percent fPSA, and to analyze the difference between the data in China and the.overseas data to determine appropriate reference range for Chinese male. Methods： A total of 713 participants were enrolled into the study, with PSA, fPSA in serum measured and the percent fPSA calculated. Out of 713 cases, 679 without prostate diseases were divided into 5 groups by age, and then the relationships of PSA, fPSA and percent fPSA with age were studied, respectively. The relationship of pathological grade and clinical stage with percent fPSA of the 34 participants with PCa was also studied. With the help of the related data of men without prostate disease, the appropriate reference range for Chinese male was established. Results： The increases in PSA or fPSA were correlated with age, while there was no significant correlation between age and percent fPSA. The percent fPSA was also correlated with pathological grade and clinical stage of PCa. The percent fPSA of men without prostate disease in Xi＇an area was significandy lower than that in the related overseas data. The reference range of percent fPSA for Chinese male was≥ 15%. Conclusion： Percent fPSA might be more useful than PSA in the detection of prostate cancer. As the percent fPSA is decreased, the pathological grade is decreased, and the clinical stage is increased, the malignant degree is increased. The reference range of ≥15% is more appropriate for Chinese male.

Reference Intervals of Mitochondrial DNA Copy Number in Peripheral Blood for Chinese Minors and Adults

Background： Mitocbondrial DNA （mtDNA） content measured by different techniques cannot be compared between studies, and age- and tissue-related control values are hardly available. In the present study, we aimed to establish the nonllal reference range of mtDNA copy number in the Chinese population. Methods： Two healthy cohorts of 200 Chinese minors （0.1 18.0 years） and 200 adults （18.0-88.0 years） were recruited. Then, they were further categorized into eight age groups. The absolute mtDNA copy number per cell was measured by a quantitative real-time polymerase chain reaction. We subsequently used this range to evaluate mtDNA content in tbur patients （0.5-4.0 years） with molecularly proven mitochondrial depletion syndromes （MDSs） and 83 cases of mitochondrial disease patients harboring the m.3243A〉G mutation. Results： The reference range ofmtDNA copy number in peripheral blood was 175-602 copies/cell （mean： 325 copies/cell） in minors and 164 500 copies/cell （mean： 287 copies/cell） in adults. There was a decreasing trend in mtDNA copy number in blood with increasing age, especially in 0-2-year-old and 〉50-year-old donors. The mean mtDNA copy number level among the mitochondrial disease patients with m.3243A〉G mutation was significantly higher than that ofhealtby controls. The intDNA content ofPOLG, DGUOK, TK2, and SUCLA2 genes in blood samples from MDS patients was reduced to 25%, 38%, 32%, and 24%, respectively. Conclusions： We primarily establish the refeerence intervals of mtDNA copy number, which might contribute to the clinical diagnosis and monitoring of mitochondrial disease.

Comparison of reference values for immune recovery between event-free patients receiving haploidentical allografts and those receiving human leukocyte antigen-matched sibling donor allografts

To establish optimal reference values for recovered immune cell subsets, we prospectively investigated post-transplant immune reconstitution （IR） in 144 patients who received allogeneic stem ceil transplantation （alio- SCT） and without showing any of the following events： poor graft function, grades II-IV acute graft-versus-host disease （GVHD）, serious chronic GVHD, serious bacterial infection, invasive fungal infection, or relapse or death in the first year after transplantation. IR was rapid in monocytes, intermediate in lymphocytes, CD3~ T cells, CD8~ T cells, and CD19~ B cells, and very slow in CD4~ T cells in the entire patient cohort. Immune recovery was generally faster under HLA-matched sibling donor transplantation than under haploidentical transplantation. Results suggest that patients with an IR comparable to the reference values display superior survival, and the levels of recovery in immune ceils need not reach those in healthy donor in the first year after transplantation. We suggest that data from this recipient cohort should be used as reference values for post-transplant immune ceil counts in patients receiving HSCT.

Distribution of serum prostate-specific antigen in Chinese healthy men： a population-based study

Background The morbidity and mortality of prostate cancer have been increasing rapidly in recent China. There were few studies investigating prostate-specific antigen （PSA） values ranges in the healthy Chinese population. We performed this study to determine the distribution of serum PSA in a large healthy Chinese population.Methods From January 2001 to May 2008, 11 150 healthy Chinese men aged 30-79 years came to our hospital for routine health check-up. All subjects without a previous diagnosis of prostate cancer, a history of prostate surgery, or urogenital tract infection were proposed to undergo systematic serum PSA measurement and digital rectal examination （DRE）. Men with normal DRE and PSA ≤4.0 ng/ml and those PSA ＞4.0 ng/ml or abnormal DRE but without adverse findings on prostate biopsy were included （n=9358）. Age and serum PSA concentration were recorded and correlated through Logistic regression analysis.Results The 95th percentile serum PSA concentration was 1.89 ng/ml for men aged 30 to 39 years, 2.19 ng/ml for men aged 40 to 49 years, 2.88 ng/ml for men aged 50 to 59 years, 4.42 rng/ml for men aged 60 to 69 years, and 6.52 ng/ml for men aged 70 to 79 years. The serum PSA concentration correlated with age （P ＜0.0001） with an annual increase of 0.97% for men in 40 years, 1.58% for men in 50 years, 3.04% for men in 60 years, and 3.99% for men in 70 years.Conclusions The serum PSA level correlates directly with age in Chinese men older than 40 years, not in Chinese men younger than 40 years old. Chinese men have lower PSA level compared with white men above 60 years of age, not in those under 60 years of age.