CD20highCD138low tumor-infiltrating lymphocytes predominantly related to cytokine‒cytokine receptor interactions are associated with favorable outcomes in neuroblastoma patients.

Recent advances have revealed that the role of the immune system is prominent in the antitumor response. In the present study, it is aimed to provide an expression profile of tumor-infiltrating lymphocytes (TILs), including mature B cells, plasma cells, and their clinical relevance in neuroblastoma. The expression of CD20 and CD138 was analyzed in the Cangelosi786 dataset (n = 769) as a training dataset and in our cohort (n = 120) as a validation cohort. CD20 high expression was positively associated with favorable overall survival (OS) and event-free survival (EFS) (OS: P < 0.001; EFS: P < 0.001) in the training dataset, whereas CD138 high expression was associated with poor OS and EFS (OS: P < 0.001; EFS: P < 0.001) in both the training and validation datasets. Accordingly, a combined pattern of CD20 and CD138 expression was developed, whereby neuroblastoma patients with CD20highCD138low expression had a consistently favorable OS and EFS compared with those with CD20lowCD138high expression in both the training and validation cohorts (P < 0.0001 and P < 0.01, respectively). Examination of potential molecular functions revealed that signaling pathways, including cytokine‒cytokine receptor interactions, chemokine, and the NF-kappa B signaling pathways, were involved. Differentially expressed genes, such as BMP7, IL7R, BIRC3, CCR7, CXCR5, CCL21, and CCL19, predominantly play important roles in predicting the survival of neuroblastoma patients. Our study proposes that a new combination of CD20 and CD138 signatures is associated with neuroblastoma patient survival. The related signaling pathways reflect the close associations among the number of TILs, cytokine abundance and patient outcomes and provide therapeutic insights into neuroblastoma.

Association of diet and lifestyle factors with semen quality in male partners of Chinese couples preparing for pregnancy.

BACKGROUND: Semen quality significantly influences conception, and its preservation is crucial for couples seeking pregnancy. We investigated dietary and lifestyle risk factors impacting semen quality. METHODS: A total of 466 males from the Guangzhou Women and Children's Medical Center's pre-pregnancy consultation clinic were recruited between January 2021 and March 2023 for inclusion. Semen analysis was performed, and diet and lifestyle data were gathered via questionnaire. Logistic regression was utilized to examine the link between diet, lifestyle variables, and semen quality. RESULTS: Smoking worsened progressive sperm motility (38.0% vs. 36.0%, t = 2.262; P = 0.049). Alcohol consumption impaired progressive motility (40.5 ± 17.8% vs. 34.7 ± 16.1%, t = 3.396; P < 0.001) and total motility (56.0% vs. 64.0%; P = 0.001). Using plastic beverage bottles for oil or seasonings lowered sperm concentrations (40.4% vs. 59.0% vs. 65.5%; P = 0.032). A sweet diet correlated with higher total sperm motility (55.0% vs. 60.0%, 62.0% vs. 63.2%; P = 0.017). Higher milk product intake improved sperm concentration (41.6106 vs. 63.7106 vs. 66.1*106; P = 0.021) and motility (54.5% vs. 56.0% vs. 63.0%; P = 0.033). More frequent egg consumption increased semen volume (3.1 mL vs. 3.8 mL vs. 4.0 mL; P = 0.038). Roughage intake enhanced sperm concentration (160.8106 vs. 224.6106; P = 0.027), and adequate sleep improved progressive sperm motility rate (35.4% ± 18.2% vs. 40.2 ± 16.3%, F = 3.747; P = 0.024) and total motility (52.7% vs. 61.5%; P = 0.013). The regression model showed that using plastic containers for condiments was a protective factor for semen volume (OR: 0.12; CI 0.03-0.55; P = 0.006), sperm concentration (OR: 0.001, CI 0.00-0.30; P = 0.012), and count (OR: 0.12, CI 0.03-0.48; P = 0.003). Milk and egg consumption were also protective for semen volume (OR: 0.18, CI 0.06-0.51; P = 0.001 and OR: 0.11, CI 0.03-0.55; P = 0.006, respectively), while sufficient sleep benefitted total sperm motility (OR: 0.47, CI 0.24-0.95; P = 0.034). CONCLUSIONS: Smoking and drinking, type of condiment container, diet preference, sleep duration, and milk, roughage, and egg consumption may reduce semen quality.

Trends and hotspots of acupuncture for allergic rhinitis: A bibliometric analysis from 2002 to 2022.

OBJECTIVE: The study aims to investigate and visualize the hotspots of acupuncture for Allergic rhinitis (AR) over the past two decades and pinpoint future trends in this field. METHOD: We conducted a systematic search of English-language articles or reviews on acupuncture for AR in the Web of Science Core Collection from 2002 to 2022. Using Citespace, VOSviewer, and Bibliometrix, we analyzed and visualized the publications, countries, institutions, authors, journals, and keywords from various angles. RESULT: The study identified 197 documents, 80 journals, 458 keywords, and 928 authors associated with acupuncture for AR. Although article publication fluctuated over the past 20 years, an overall upward trend emerged, with rapid growth during the second decade. China contributed the most to acupuncture research on AR and had the closest collaborations with the United States and Germany. China Medical University was the most prolific institution, and Benno Brinkhaus was the most productive and influential author. The most published journal was Medicine, while the Journal of Allergy and Clinical Immunology was the most frequently cited journal. The highest frequency keywords included acupuncture, allergic rhinitis, and asthma. Randomized controlled trials and alternative & complementary medicine remained significant research hotspots, while rhinoconjunctivitis is expected to be the emerging focus of future investigations. CONCLUSION: acupuncture has experienced robust development for the treatment of allergic rhinitis over the last two decades, with rhinoconjunctivitis and clinical research being the anticipated trends and frontiers of future research.

Association of living environmental and occupational factors with semen quality in chinese men: a cross-sectional study.

Sperm quality can be easily influenced by living environmental and occupational factors. This study aimed to discover potential semen quality related living environmental and occupational factors, expand knowledge of risk factors for semen quality, strengthen men's awareness of protecting their own fertility and assist the clinicians to judge the patient's fertility. 465 men without obese or underweight (18.5 < BMI < 28.5 kg/m2), long-term medical history and history of drug use, were recruited between June 2020 to July 2021, they are in reproductive age (25 < age < 45 years). We have collected their semen analysis results and clinical information. Logistic regression was applied to evaluate the association of semen quality with different factors. We found that living environment close to high voltage line (283.4 × 106/ml vs 219.8 × 106/ml, Cohen d = 0.116, P = 0.030) and substation (309.1 × 106/ml vs 222.4 × 106/ml, Cohen d = 0.085, P = 0.015) will influence sperm count. Experienced decoration in the past 6 months was a significant factor to sperm count (194.2 × 106/ml vs 261.0 × 106/ml, Cohen d = 0.120, P = 0.025). Living close to chemical plant will affect semen PH (7.5 vs 7.2, Cohen d = 0.181, P = 0.001). Domicile close to a power distribution room will affect progressive sperm motility (37.0% vs 34.0%, F = 4.773, Cohen d = 0.033, P = 0.030). Using computers will affect both progressive motility sperm (36.0% vs 28.1%, t = 2.762, Cohen d = 0.033, P = 0.006) and sperm total motility (57.0% vs 41.0%, Cohen d = 0.178, P = 0.009). After adjust for potential confounding factors (age and BMI), our regression model reveals that living close to high voltage line is a risk factor for sperm concentration (Adjusted OR 4.03, 95% CI 1.15-14.18, R2 = 0.048, P = 0.030), living close to Chemical plants is a protective factor for sperm concentration (Adjusted OR 0.15, 95% CI 0.05-0.46, R2 = 0.048, P = 0.001) and total sperm count (Adjusted OR 0.36, 95% CI 0.13-0.99, R2 = 0.026, P = 0.049). Time spends on computer will affect sperm total motility (Adjusted OR 2.29, 95% CI 1.11-4.73, R2 = 0.041, P = 0.025). Sum up, our results suggested that computer using, living and working surroundings (voltage line, substation and chemical plants, transformer room), and housing decoration may association with low semen quality. Suggesting that some easily ignored factors may affect male reproductive ability. Couples trying to become pregnant should try to avoid exposure to associated risk factors. The specific mechanism of risk factors affecting male reproductive ability remains to be elucidated.

Application of real-time PCR-based multicolor melting curve with automatic analysis system in pregestational and prenatal thalassemia diagnoses.

BACKGROUND: To evaluate the value of the real-time PCR-based multicolor melting curve analysis (MMCA) with an automatic analysis system used in a mass thalassemia screening and prenatal diagnosis program. METHODS: A total of 18,912 peripheral blood samples from 9456 couples and 1150 prenatal samples were detected by MMCA assay. All prenatal samples were also tested by a conventional method. Samples with unknown melting peaks, unusual peak height ratios between a wild allele and a mutant allele, or a discordant phenotype-genotype match were further studied by using multiplex ligation-dependent probe amplification (MLPA) or Sanger sequencing. All MMCA results were automatically analyzed and manually checked. The consistency between MMCA assay and conventional methods among prenatal samples was investigated. RESULTS: Except for initiation codon (T > G) (HBB:c.2T > G), all genotypes of thalassemia inside the scope of conventional methods were detected by MMCA assay. Additionally, 27 carriers with 10 rare HBB variants, 13 with α fusion gene, 1 with a rare deletion in α globin gene, and 1 with rare HBA variant were detected by using MMCA assay. CONCLUSION: MMCA can be an alternative approach used in routine thalassemia carrier screening and prenatal diagnosis for its high throughput, sufficient stability, low cost, and easy operation.

Utilization of multiple genetic methods for prenatal diagnosis of rare thalassemia variants.

Background: Thalassemia is the most prevalent monogenic disorder caused by an imbalance between the α- and ß-globin chains as a result of pathogenic variants in the α- or ß-globin genes. Novel or complex structural changes in globin genes are major hurdles for genetic consulting and prenatal diagnosis. Methods: From 2020 to 2022, genetic analysis was performed on 1,316 families suspected of having children with thalassemia major, including 42 pregnant couples suspected of being thalassemia carriers with rare variants. Multiple techniques including multiplex ligation-dependent probe amplification (MLPA), Sanger sequencing, targeted next-generation sequencing, and single-molecule real-time (SMRT) sequencing were used to diagnose rare thalassemia. Results: The rate of prenatal diagnosis for rare thalassemia variants was 3.19% (42/1,316). The most prevalent alleles of α- and ß-thalassemia are Chinese Gγ(Aγδß)0and -- THAI deletion. In addition, ten rare complex genotypes include one Chinese Gγ(Aγδß)0 deletion combined with HBG1-HBG2 fusion, two rare deletions at HBB gene (hg38, Chr11: 5224211-5232470, hg38, Chr11: 5224303-5227790), one complete 7,412 bp fusion gene for anti-Lepore Hong Kong, two complex rearrangements of the α-globin gene cluster, two novel duplications, and two rare large deletions in the α-globin gene cluster. Conclusion: Accurate gene diagnosis for probands with combined molecular biology techniques is the key to prenatal diagnosis of rare thalassemia.

Epigallocatechin-3-gallate Induced HepG2 Cells Apoptosis through ROSmediated AKT /JNK and p53 Signaling Pathway.

BACKGROUND: Hepatocarcinoma is the third leading cause of cancer-related deaths around the world. Recently, some studies have reported that Epigallocatechin-3-gallate (EGCG) may have the anti-cancer potential. However, the affection and putative mechanisms of cytotoxicity induced by EGCG in HepG2 cells remain unknown. Based on the above, the present study evaluated the effect of EGCG on the cytotoxic and anti-cancer mechanisms of HepG2 cells. METHODS: The effect of EGCG on the apoptosis of Hep-G2 cells and its mechanism were studied by cell counting kit-8, mitochondrial membrane potential assay with JC-1, Annexin V-FITC apoptosis detection, cell cycle, and apoptosis analysis, one step TUNEL apoptosis assay, caspase 3 activity assay, caspase 9 activity Assay, Reactive Oxygen Species assay, and Western blot. RESULTS: EGCG-induced HepG2 cell apoptosis was confirmed by accumulation of the sub-G1 cells population, translocation of phosphatidylserine, depletion of mitochondrial membrane potential, DNA fragmentation, caspase-3 activation, caspase-9 activation, and poly (ADP-ribose) polymerase cleavage. Furthermore, EGCG enhanced cytotoxic effects on HepG2 cells and triggered intracellular reactive oxygen species; the signaling pathways of AKT, JNK, and p53 were activated to advance cell apoptosis. CONCLUSION: The results reveal that EGCG may provide useful information on EGCG-induced HepG2 cell apoptosis and be an appropriate candidate for cancer chemotherapy.

The dose-effect relationships of cigarette and alcohol consumption with depressive symptoms: a multiple-center, cross-sectional study in 5965 Chinese middle-aged and elderly men.

BACKGROUND: Although association of depressive symptoms with cigarette or alcohol is well documented, the dose-response relationship between them is rarely studied. This study aims to evaluate dose-response relationships of cigarette and alcohol consumption with depressive symptoms in Chinese middle-aged and elderly men, providing evidence to guide cigarette and alcohol control. METHODS: This multiple-center, cross-sectional study including 5965 Chinese men aged 40-79 years was conducted in 2013-2016 in China. Depressive symptoms were evaluated by Beck Depression Inventory-Short Form. History of cigarette smoking and alcohol drinking were collected with a structured questionnaire. Prevalence of depressive symptoms was compared depending on cigarette and alcohol consumption. Adjusted odds ratios (OR) and 95% confidence interval (CI) were estimated by binary logistic regression. Interpolation analysis was applied to test dose-effect relationships. RESULTS: A parabolic-shaped relationship was observed between cigarette consumption and depressive symptoms. Compared to never smokers, 59.0% (OR = 1.59, 95% CI 1.30-1.94) and 29.0% (OR = 1.29, 95% CI 1.08-1.54) higher odds of depressive symptoms were observed in men smoking < 10 cigarettes/day and 10-20 cigarettes/day, whereas, similar odds of depressive symptoms among men smoking > 20 cigarettes/day (P = 0.092). An inverted J-shaped relationship was observed between alcohol consumption and depressive symptoms. Compared to never drinkers, a tendency of higher prevalence of depressive symptoms (OR = 1.16, 95% CI 0.99-1.36) was observed in men drinking < 140 g/week, and similar prevalence was observed in those drinking 140-280 g/week (P = 0.920), whereas, 29.4% (OR = 0.71, 95% CI 0.57-0.88) lower odds in men drinking > 280 g/week. CONCLUSIONS: Associations of cigarette smoking and alcohol drinking with depressive symptoms differ with consumption in middle-aged and elderly men. Health-care providers should exercise great caution on depressive symptoms in conducting cigarette and alcohol control.

Detection of rare thalassemia mutations using long-read single-molecule real-time sequencing.

Gap- polymerase chain reaction (PCR), reverse dot-blot assay (RDB), real-time PCR based multicolor melting curve analysis (MMCA assay), multiplex ligation-dependent probe amplification (MLPA) and Sanger sequencing are conventional methods to diagnose thalassemia but all of them have limitations. In this study, we applied single-molecule real-time (SMRT) sequencing following multiplex long-range PCR to uncover rare mutations in nine patients and their family members. The patients with different results between Gap-PCR and MMCA assay or with phenotype not matching genotype were included. Using SMRT sequencing, we first identified the carriers with αααanti3.7/HKαα, -α762bpα/αα (chr16:172,648-173,409), ααfusion/αQSα (in a trans configuration), two cases with novel gene rearrangements and another case with a novel 341 bp insertion in α-globin gene cluster, respectively. One carrier with --SEA/αααanti4.2, and two carriers with the coexistence of globin variant and an α-globin gene duplication were also found. Most importantly, we could determine two defects in α-globin gene cluster being a cis or trans configuration in a single test. Our results showed that SMRT has great advantages in detection of α-globin gene triplications, rare deletions and determination of a cis or trans configuration. SMRT is a comprehensive and one-step method for thalassemia screening and diagnosis, especially for detection of rare thalassemia mutations.

Interpregnancy interval and subsequent perinatal risk of congenital heart disease in Guangzhou, Southern China: a retrospective cohort study, 2014-2019.

BACKGROUND: The association between maternal interpregnancy interval (IPI) and congenital heart disease (CHD) in neonates remains inconclusive. This study aimed to examine the effect of maternal IPI on birth risk of CHD. METHODS: Chinese women with two consecutive singleton deliveries in Guangzhou between January 2014 and December 2019 were selected as participants. Information on IPI and CHD was extracted from the Guangzhou Perinatal Health Care and Delivery Registry and the Guangzhou Birth Defects Surveillance Program. We stratified IPI into four categories: <24 months, 24-35 months, 36-59 months, and ≥60 months. A multivariate logistic regression model was used to examine the association between IPI and CHD. Subgroup analysis was also performed to assess whether the associations differed across top three CHD subtypes. RESULTS: For 119,510 women enrolled in this study, the mean ages at two consecutive deliveries were 26.2 ± 3.8 and 28.8 ± 4.0 years, which yielded a median IPI of 51.2 (interquartile range, 32.1-77.2) months. Among them, 828 delivered infants with CHD during their second pregnancy. There was a J-shaped curve relationship between IPI and CHD with the lowest birth prevalence (5.33‰) at 24-35-month interval. Compared to women with an IPI of 24-35 months, those with an IPI ≥60 had an increased risk of delivering infants with CHD (adjusted odds ratio (OR), 1.41; 95% confidence interval (CI), 1.19-1.64). However, for those with an IPI <24 months (adjusted OR, 1.24; 95% CI, 0.97-1.51), IPI was statistically insignificant associated with the risk of delivering infants with CHD (p = .12). There were different patterns of associations for different CHD subtypes. CONCLUSIONS: Longer maternal IPI (≥60 months) was associated with an increased risk of delivering infants with CHD in the Chinese population.

Association between the rs3802201 polymorphism of the lncRNA MIR2052HG gene and the risk of recurrent miscarriage in a Southern Chinese population.

BACKGROUND: Plenty of studies have indicated that some genetic polymorphisms of the breast cancer which associated with its susceptibility may also be related to the susceptibility of abortion. MIR2052HG plays an important role in the onset and progression of breast cancer by maintaining the level of ERα, but to the best of our knowledge, the correlation between risk of recurrent abortion and MIR2052HG rs3802201 C>G polymorphism is still unclear. Therefore, we conducted this case-control study to investigate whether MIR2052HG rs3802201 C>G polymorphism is associated with susceptibility of recurrent miscarriage (RM). METHODS: We recruited 392 healthy controls and 248 patients with RM to process this research, the participants were all from southern China, and genotyping was performed by TaqMan method. RESULTS: Our results showed that there was no evidence indicates the MIR2052HG rs3802201 C>G is related to RM (CG and CC: adjusted OR = 0.970, 95% CI = 0.694-1.355, p = 0.8577; GG and CC: adjusted OR = 0.743, 95% CI = 0.416-1.330, p = 0.3174; dominant model: adjusted OR = 0.925, 95% CI = 0.672-1.272, p = 0.6298; recessive model: adjusted OR = 0.751, 95% CI = 0.430-1.321, p = 0.3233). CONCLUSION: We verified that the MIR2052HG rs3802201 C>G allele might be uncorrelated to the RM risk, but these findings require further validation in multicenter studies with larger sample size and different ethnicities.

Evaluation of intervention strategy of thalassemia for couples of childbearing ages in Centre of Southern China.

BACKGROUND: To describe the free intervention strategy of thalassemia for childbearing couples in Guangzhou. METHODS: Routine hematology examinations were conducted for 137,222 couples. Among them, 37,501 couples who had mean corpuscular volume (MCV) <82 fL or mean corpuscular hemoglobin <27 pg were elected for Hb analysis and the deletions of four common α-thalassemia mutation. Reverse dot blot for common nondeletional α-thalassemia and ß-thalassemia was selectively used. Three thousand twenty-two couples randomly selected were offered all those tests as a control group. Sanger sequencing, multiplex ligation-dependent probe amplification and next-generation sequencing were used for rare thalassemia. High-risk couples were offered prenatal diagnosis at 10-13 weeks' gestation based on informed consent. RESULTS: The carrier rates of α-, ß-, and αß-thalassemia and 뫧 thalassemia/deletional HPFH were 7.7%, 3.02%, 0.5% and 0.059% respectively. Of them, 1.37% were identified as at-risk couples and 345 couples terminated the pregnancy. No severe α- and ß-thalassemia births were observed. In the control group, two ß- thalassemia carriers and one case with -α3.7 /ααQS were misdiagnosed, but all at-risk couples were found, and we could save 1,523,774 ¥ using our strategy. The cut-off points of 73.46 fL and 23.25 pg would be useful to find -α+ /αT thalassemia. CONCLUSION: The intervention strategy was cost-effective and offered reference in population thalassemia screening.

Hb Lepore-Hong Kong: First Report of a Novel δ/ß-Globin Gene Fusion in a Chinese Family.

We describe a new δ/ß fusion gene causing ß-thalassemia (ß-thal) trait and its formation mechanism. The proband was a 39-year-old woman who presented with persistent microcytic microcytosis without iron deficiency. Molecular diagnoses revealed a 뫧 configuration within a 54 bp region between the Cap site (+22) and codon 8, causing a deletion (NG_000007.3: g.63154_70565del). This results in a variant that has been named Hb Lepore-Hong Kong and shows a decreased ß-globin mRNA in carriers compared to that of normal subjects. It is assumed that combination of this variant with ß-thal may cause severe ß-thal syndrome.

Hypomorphic and hypermorphic mouse models of Fsip2 indicate its dosage-dependent roles in sperm tail and acrosome formation.

Loss-of-function mutations in multiple morphological abnormalities of the sperm flagella (MMAF)-associated genes lead to decreased sperm motility and impaired male fertility. As an MMAF gene, the function of fibrous sheath-interacting protein 2 (FSIP2) remains largely unknown. In this work, we identified a homozygous truncating mutation of FSIP2 in an infertile patient. Accordingly, we constructed a knock-in (KI) mouse model with this mutation. In parallel, we established an Fsip2 overexpression (OE) mouse model. Remarkably, KI mice presented with the typical MMAF phenotype, whereas OE mice showed no gross anomaly except for sperm tails with increased length. Single-cell RNA sequencing of the testes uncovered altered expression of genes related to sperm flagellum, acrosomal vesicle and spermatid development. We confirmed the expression of Fsip2 at the acrosome and the physical interaction of this gene with Acrv1, an acrosomal marker. Proteomic analysis of the testes revealed changes in proteins sited at the fibrous sheath, mitochondrial sheath and acrosomal vesicle. We also pinpointed the crucial motifs of Fsip2 that are evolutionarily conserved in species with internal fertilization. Thus, this work reveals the dosage-dependent roles of Fsip2 in sperm tail and acrosome formation.

Bi-allelic mutation in Fsip1 impairs acrosome vesicle formation and attenuates flagellogenesis in mice.

Fibrous sheath interacting protein 1 (Fsip1) is a cytoskeletal structural protein of the sperm flagellar proteome. A few studies have reported that it plays a vital role in the tumorigenesis and cancer progression. However, little is known about the role of Fsip1 in spermatogenesis and mammalian sperm flagellogenesis. Fsip1 protein showed the highest expression in round spermatids, and was translocated from nucleus to the anterior region of the elongating spermatid head. To investigate its role we constructed homozygous Fsip1 null (Fsip1-/-) mice. We found that the homozygous Fsip1-/- mutant mice were infertile, with a low sperm count and impaired motility. Interestingly, a subtle phenotype characterized by abnormal head shape, and flagella deformities was observed in the sperm of Fsip1-/- mutant mice similar to the partial globozoospermia phenotype. Electron microscopy analysis of Fsip1-/- sperm revealed abnormal accumulation of mitochondria, disrupted axoneme and retained cytoplasm. Testicular sections showed increased cytoplasmic vacuoles in the elongated spermatid of Fsip1-/-mice, which indicated an intraflagellar transport (IFT) defect. Using proteomic approaches, we characterized the cellular components and the mechanism underlying this subtle phenotype. Our result indicated that Fsip1-/-downregulates the formation of acrosomal membrane and vesicles proteins, intraflagellar transport particles B, and sperm flagellum components. Our results suggest that Fsip1 is essential for normal spermiogenesis, and plays an essential role in the acrosome biogenesis and flagellogenesis by attenuating intraflagellar transport proteins.

Associations between smoking, sex hormone levels and late-onset hypogonadism in men differ depending on age.

Few studies have investigated whether associations between smoking, sex hormone levels, and symptoms of late-onset hypogonadism (LOH) in men are affected by age. This multi-center, cross-sectional study involving 6,296 men aged 40-79 years was conducted between June 1, 2013 and August 31, 2016 in 6 provinces of China. Total testosterone, free testosterone, and Aging Males' Symptoms scale (AMS) scores were compared depending on smoking status and the number of cigarettes smoked. Total testosterone was higher in smokers than in non-smokers in all except the 70-79 year old subgroup. Free testosterone was higher in smokers than non-smokers for the 40-49 and 50-59 year old subgroups, but not the 60-69 and 70-79 year old subgroups. Total testosterone was positively associated with number of cigarettes consumed in smokers aged 40-49 and 50-59 years. Sexual and somatic AMS scores were higher in current and ex-smokers than in non-smokers in all age subgroups from 40 to 79 years and were negatively associated with cigarette consumption in smokers aged 40-49 years. These results indicate that, as men age, the positive association between smoking and testosterone weakens, while the positive association between smoking and LOH symptoms becomes stronger.

Prevalence of late-onset hypogonadism among middle-aged and elderly males in China: results from a national survey.

This study aimed to propose an operational definition of late-onset hypogonadism (LOH) that incorporates both clinical symptoms and serum testosterone measurements to evaluate the prevalence of LOH in aging males in China. A population-based sample of 6296 men aged 40 years-79 years old was enrolled from six representative provinces in China. Serum total testosterone (TT), sex hormone-binding globulin (SHBG), and luteinizing hormone (LH) were measured and free testosterone (cFT) was calculated. The Aging Males' Symptoms (AMS) scale was used to evaluate the LOH symptoms. Finally, 5078 men were included in this analysis. The TT levels did not decrease with age (P = 0.59), and had no relationship with AMS symptoms (P = 0.87 for AMS total score, P = 0.74 for ≥ 3 sexual symptoms). The cFT levels decreased significantly with age (P < 0.01) and showed a negative association with the presence of ≥ 3 sexual symptoms (P = 0.03). The overall estimated prevalence of LOH was 7.8% (395/5078) if a cFT level <210 pmol l-1 combined with the presence of ≥ 3 sexual symptoms was used as the criterion of LOH. Among them, 26.1% (103/395) and 73.9% (292/395) had primary and secondary hypogonadism, respectively. After adjustment for confounding factors, primary and secondary hypogonadism was positively related to age and comorbidities. Body mass index was an independent risk factor for secondary hypogonadism. The results suggest that the AMS total score is not an appropriate indicator for decreased testosterone, and that the cFT level is more reliable than TT for LOH diagnosis. Secondary hypogonadism is the most common form of LOH.

Decreased testosterone secretion index and free testosterone level with multiple symptoms for late-onset hypogonadism identification: a nationwide multicenter study with 5980 aging males in China.

Late-onset hypogonadism (LOH) is a syndrome in middle-aged and elderly men caused by age-related testosterone deficiency. Age-related change of total testosterone (TT) of Asian males is different from Caucasian population, suggesting difference for LOH identification in Asians. A nationwide cross-sectional study involving six centers in China was conducted. Totally 6296 men aged 40-79 were recruited. After exclusions 5980 men were left for analyses. The serum TT level, was neither decreased with aging nor correlated with most hypogonadal symptoms. Instead, ten hypogonadal symptoms were found to be significantly correlated with free testosterone and testosterone secretion index, thus were chosen to form a concise scale. Further analysis identified a level of free testosterone <210 pmol/L, testosterone secretion index <1.8, and the concise scale score ≧17 could be diagnosed as having significantly aggravated LOH. This study developed an evidence-based criteria for LOH identification in Chinese population and may be adopted in other Asians. It includes the impaired testosterone secretion ability and deficiency of bioavailable testosterone, which should be the main cause in LOH pathogenesis despite normal TT levels, as well as correlated multiple hypogonadal symptoms. Our results may guide the LOH treatment to increase testicular function of testosterone secretion and bioavailable testosterone.

The impact of exogenous testosterone supplementation on spermatogenesis in a rat model of oligoasthenospermia.

Oligoasthenospermia is one of the main causes of infertility in reproductive-age men. This study aimed to explore the feasibility of exogenous testosterone supplemental therapy (TST) for adult male rats with oligoasthenospermia model. The rats (n=40) were randomized equally into 4 groups: control group, model group, low-dose and high-dose groups (n=10, respectively). After establishment of an oligoasthenospermia model that was treated with glucosides of tripterygium wilfordii (GTWs), the low-dose and high-dose groups were treated with 2 testosterone undecanoate (TU) injections at doses of 7.5 mg and 15 mg for 8-week period (4-week intervals). Body weights, serum reproductive hormone levels, sperm measurements in the epididymis, and testis histology were monitored. The TU injections increased serum testosterone levels steadily. The epididymis sperm concentration and motility increased slowly in high dose group at 4-weeks whereas sperm measurements increased significantly in the TST groups at 8 weeks. In addition, exogenous TST increased the intra-testicular testosterone concentration somewhat and alleviated the testicular oxidative stress markers of Malondialdehyde (MDA) and level of GSH-PX (Glutathione Peroxidase) after 8 weeks treatment. The improvement of sperm and testicular function acted mainly by curbing mitochondrial apoptosis in the testis by modulation of Bcl-2, Bax, Caspase-3, and Caspase-9 expression. However, the results of immunohistochemistry and western blotting in the low-dose group were still lower than control values. TST at an appropriate dose within a period of 8 weeks was effective to stimulate spermatogenesis and alleviate inflammation, oxidative stress, and apoptosis through suppression of testis damage in this rat model of oligoasthenospermia.

Hb Westmead (HBA2: c.369C>G): Hematological Characteristics in Heterozygotes with and without α0-Thalassemia.

Hb Westmead (α122(H5)His>Gln) (HBA2: c.369C>G) is a common α-globin variant causing α-thalassemia (α-thal) in Mainland China. In this study, we report the hematological characteristics in Hb Westmead carriers in a Chinese population. There were 546 individuals carrying Hb Westmead based on their molecular diagnosis: 514 Hb Westmead heterozygotes and 32 compound heterozygotes for Hb Westmead and α0-thal. Compared to common deletional α+-thal, Hb Westmead was associated with higher mean corpuscular hemoglobin (Hb) (MCH) values. Compound heterozygotes for Hb Westmead and α0-thal showed significantly higher Hb, mean corpuscular volume (MCV) and MCH values than subjects with deletional Hb H disease. When compared to α0-thal carriers, compound heterozygotes for Hb Westmead and α0-thal showed similar Hb values, but significantly lower MCV and MCH values. Our results indicate that Hb Westmead is a silent nondeletional α+-thal, with a deficiency of α-globin chain milder than deletional α+-thal, and compound heterozygotes for Hb Westmead/α0-thal have a phenotype similar to simple α0-thal.