Clinical and molecular features of 40 Chinese patients with idiopathic hypogonadotropic hypogonadism.

Background: Male idiopathic hypogonadotropic hypogonadism (IHH) is a heterogeneous clinical rare genetic disorder that can be divided into two forms: Kallmann syndrome (KS) and olfactory normal IHH (nIHH). Nearly half of unknown pathogenic genes and related pathogenic mechanisms have yet to be explored. Methods: Clinical data of 40 IHH patients (22 KS and 18 nIHH) were retrospectively recorded. All patients were diagnosed at the Department of Endocrinology of Jinling Hospital, Jiangsu Provincial People's Hospital, and the First Affiliated Hospital of the University of Science and Technology of China from 2014 to 2021. The proband genomic DNA (gDNA) was confirmed by whole exome sequencing (WES) and Sanger sequencing. Results: Ten new genetic mutations related to IHH in four families and eight sporadic unrelated IHH patients were identified. The total positive detection rate of 40 patients was 30% (nIHH 8/18 + KS 4/22), and the FGFR1 mutation rate accounted for 7.5% (3/40). Mutation rates of ANOS1, CHD7, and KISS1R were 5% (2/40), respectively. The mutation rates of SEMA3E, PROKR2, and SOX10 were 2.5% (1/40), respectively. After analysis by SIFT and PolyPhen-2 software, all missense mutation sites, such as SEMA3E (p.P323S), CHD7 (p.W1785C), PROKR2 (p.Y223D and p.R298C), were harmful; all nonsense mutation sites, such as FGFR1 (p.R661X) and KISS1R (p.R331X, p.Y103X), analyzed were pathogenic by Mutation Taster software. The comparison of MEGA5 software showed that all the variants had extremely high homology among different species and were extremely conservative in evolution. Conclusions: The study aims to expand the genotype mutation spectrum of IHH and provide evidence for the follow-up clinical treatment and genetic counseling of the disease.

Low-intensity pulsed ultrasound at ST36 improves the gastric motility by TNF-α/IKKß/NF-κB signaling pathway in diabetic rats.

BACKGROUND AND AIM: Low-intensity pulsed ultrasound (LIPUS) can effectively regulate the central and peripheral nervous system. However, whether LIPUS could act on acupuncture points to modulate the activity of peripheral nervous has rarely been studied. Our study aimed to investigate whether LIPUS at ST36 could improve gastric emptying in diabetic gastroparesis rats. METHODS: Sprague-Dawley male rats were divided into three groups: control group (CON), diabetic gastroparesis group (DM), and diabetic gastroparesis LIPUS treated group (LIPUS). The body weight and blood glucose were recorded every week. Glucose tolerance, gastric emptying rate, and gastric motility were measured before and after treatment. Gastric motility was assessed by ultrasonic examination and Muscle strip experiment. The expression level of c-Kit was assessed by immunohistochemistry staining. Levels of TNF-α, p-NF-κB p-65, NF-κB p-65, and p-IKKß, IKKß were measured by western blot. RESULTS: We reported LIPUS at an intensity of 0.88 W/cm2 exhibited significant differences in functional recovery of gastric delayed emptying in diabetic rats. Through ultrasound gastric motility functional testing and analysis of gastric antral smooth muscle strips indirectly and directly proved the effectiveness of LIPUS for the recovery of gastric delayed emptying. Pathological analysis and western blot indicated that the mechanism by which LIPUS applied to ST36 improved gastric motility may be partially attributed to the inhibition of the TNF-α/IKKß/NF-κB signaling pathway, thereby rescuing the damaged interstitial cells of Cajal network. CONCLUSION: LIPUS at ST36 improved the gastric motility and rescued the damaged networks of interstitial cells of Cajal. LIPUS may have a promising therapeutic potential for diabetic gastroparesis.

Novel insight into the underlying dysregulation mechanisms of immune cell-to-cell communication by analyzing multitissue single-cell atlas of two COVID-19 patients.

How does SARS-CoV-2 cause lung microenvironment disturbance and inflammatory storm is still obscure. We here performed the single-cell transcriptome sequencing from lung, blood, and bone marrow of two dead COVID-19 patients and detected the cellular communication among them. Our results demonstrated that SARS-CoV-2 infection increase the frequency of cellular communication between alveolar type I cells (AT1) or alveolar type II cells (AT2) and myeloid cells triggering immune activation and inflammation microenvironment and then induce the disorder of fibroblasts, club, and ciliated cells, which may cause increased pulmonary fibrosis and mucus accumulation. Further study showed that the increase of T cells in the lungs may be mainly recruited by myeloid cells through ligands/receptors (e.g., ANXA1/FPR1, C5AR1/RPS19, and CCL5/CCR1). Interestingly, we also found that certain ligands/receptors (e.g., ANXA1/FPR1, CD74/COPA, CXCLs/CXCRs, ALOX5/ALOX5AP, CCL5/CCR1) are significantly activated and shared among lungs, blood and bone marrow of COVID-19 patients, implying that the dysregulation of ligands/receptors may lead to immune cell's activation, migration, and the inflammatory storm in different tissues of COVID-19 patients. Collectively, our study revealed a possible mechanism by which the disorder of cell communication caused by SARS-CoV-2 infection results in the lung inflammatory microenvironment and systemic immune responses across tissues in COVID-19 patients.

Continuous In Vitro Culture of Babesia duncani in a Serum-Free Medium.

Human babesiosis is an emerging tick-borne disease, caused by haemoprotozoa genus of Babesia. Cases of transfusion-transmitted and naturally acquired Babesia infection have been reported worldwide in recent years and causing a serious public health problem. Babesia duncani is one of the important pathogens of human babesiosis, which seriously endangers human health. The in vitro culture systems of B. duncani have been previously established, and it requires fetal bovine serum (FBS) to support long-term proliferation. However, there are no studies on serum-free in vitro culture of B. duncani. In this study, we reported that B. duncani achieved long-term serum-free culture in VP-SFM AGTTM (VP-SFM) supplemented with AlbuMaxTM I. The effect of adding different dilutions of AlbuMaxTM I to VP-SFM showed that 2 mg/mL AlbuMaxTM I had the best B. duncani growth curve with a maximum percentage of parasitized erythrocytes (PPE) of over 40%, and it can be used for long-term in vitro culture of B. duncani. However, the commonly used 20% serum-supplemented medium only achieves 20% PPE. Clearly, VP-SFM with 2 mg/mL AlbuMaxTM I (VP-SFMA) is more suitable for the in vitro proliferation of B. duncani. VP-SFM supplemented with CD lipid mixture was also tested, and the results showed it could support the parasite growth at 1:100 dilution with the highest PPE of 40%, which is similar to that of 2 mg/mL AlbuMaxTM I. However, the CD lipid mixture was only able to support the in vitro culture of B. duncani for 8 generations, while VP-SFMA could be used for long-term culture. To test the pathogenicity, the VP-SFMA cultured B. duncani was also subjected to hamster infection. Results showed that the hamster developed dyspnea and chills on day 7 with 30% PPE before treatment, which is similar to the symptoms with un-cultured B. duncani. This study develops a unique and reliable basis for further understanding of the physiological mechanisms, growth characteristics, and pathogenesis of babesiosis, and provides good laboratory material for the development of drugs or vaccines for human babesiosis and possibly other parasitic diseases.

Characteristics of lymphocyte subset alterations in COVID-19 patients with different levels of disease severity.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a respiratory disorder caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which had rapidly spread all over the world and caused public health emergencies in the past two years. Although the diagnosis and treatment for COVID-19 have been well defined, the immune cell characteristics and the key lymphocytes subset alterations in COVID-19 patients have not been thoroughly investigated. METHODS: The levels of immune cells including T cells, B cells, and natural killer (NK) cells in 548 hospitalized COVID-19 patients, and 30 types of lymphocyte subsets in 125 hospitalized COVID-19 patients admitted to Wuhan Huoshenshan Hospital of China were measured using flow cytometry. The relationship between lymphocytes subsets with the cytokine interleukin-6 (IL-6) and the characteristics of lymphocyte subsets in single-cell RNA sequencing (scRNA-seq) data obtained from peripheral blood mononuclear cells (PBMCs) were also analysed in COVID-19 patients. RESULTS: In this study, we found that patients with critical COVID-19 infection exhibited an overall decline in lymphocytes including CD4+ T cells, CD8+ T cells, total T cells, B cells, and NK cells compared to mild and severe patients. However, the number of lymphocyte subsets, such as CD21low CD38low B cells, effector T4 cells, and PD1+ depleted T8 cells, was moderately increased in critical COVID-19 patients compared to mild cases. Notably, except for effector memory T4 cells, plasma blasts and Tregs, the number of all lymphocyte subsets was markedly decreased in COVID-19 patients with IL-6 levels over 30-fold higher than those in healthy cases. Moreover, scRNA-seq data showed obvious differences in the distribution and numbers of lymphocyte subsets between COVID-19 patients and healthy persons, and subsets-specific marker genes of lymphocyte subsets including CD4, CD19, CCR7, and IL7R, were markedly decreased in COVID-19 patients compared with those in healthy cases. CONCLUSION: A comprehensive decrease in immune cell and lymphocyte subsets in critical COVID-19 patients, and peripheral lymphocyte subset alterations showed a clear association with clinical characteristics.

Establishment of a Transient and Stable Transfection System for Babesia duncani Using a Homologous Recombination Strategy.

Genetic modification provides an invaluable molecular tool to dissect the biology and pathogenesis of pathogens. However, no report is available about the genetic modification of Babesia duncani, a pathogen responsible for human babesiosis that is widespread in North America, suggesting the necessity to develop a genetic manipulation method to improve the strategies for studying and understanding the biology of protozoan pathogens. The establishment of a genetic modification method requires promoters, selectable markers, and reporter genes. Here, the double-copy gene elongation factor-1α (ef-1α) and its promoters were amplified by conventional PCR and confirmed by sequencing. We established a transient transfection system by using the ef-1αB promoter and the reporter gene mCherry and achieved stable transfection through homologous recombination to integrate the selection marker hDHFR-eGFP into the parasite genome. The potential of this genetic modification method was tested by knocking out the thioredoxin peroxidase-1 (TPX-1) gene, and under the drug pressure of 5 nM WR99210, 96.3% of the parasites were observed to express green fluorescence protein (eGFP) by flow cytometry at day 7 post-transfection. Additionally, the clone line of the TPX-1 knockout parasite was successfully obtained by the limiting dilution method. This study provided a transfection method for B. duncani, which may facilitate gene function research and vaccine development of B. duncani.

A method comparison of three immunoassays for detection of neutralizing antibodies against SARS-CoV-2 receptor-binding domain in individuals with adenovirus type-5-vectored COVID-19 vaccination.

OBJECTIVE: Detecting neutralizing antibodies targeting receptor-binding domain (RBD) is important for the assessment of humoral protection and vaccine efficacy after vaccination. We compared the performance of three surrogate immunoassays for detection of neutralizing antibodies targeting RBD. METHODS: We analyzed 115 serum samples obtained from individuals with Ad5-vectored COVID-19 vaccination using two competitive enzyme-linked immunosorbent assays (Wantai BioPharm and Synthgene Medical Technology) and one competitive chemiluminescence assay (YHLO Biotech). Performance evaluation and methodology comparison were performed according to the Clinical and Laboratory Standards Institute related guidelines. RESULTS: The precision met the manufacturers' statements. The linear range of the WANTAI was 0.0625-0.545 U/ml and the YHLO was 0.260-242.4 U/ml. The WANTAI's limit of blank (LoB) and limit of detection (LoD) were 0.03 and 0.06 U/ml, respectively. The YHLO's LoB and LoD were 0.048 and 0.211 U/ml, respectively. The correlations of semi-quantitative results of Synthgene with quantitative results of YHLO (ρ = 0.566) and WANTAI (ρ = 0.512) were medium. For YHLO and WANTAI, there was a good agreement (0.62) and a strong correlation (ρ = 0.931). Passing-Bablok analysis and Bland-Altman plot showed a positive bias (112.3%) of the YHLO compared to the WANTAI. The exclusion of samples >50 U/ml did not decrease bias. CONCLUSION: These findings contribute to a deeper understanding of surrogate viral neutralization assays and provide useful data for future comparison studies.

Efficacy and Safety of Tocilizumab Treatment COVID-19 Patients: A Case-Control Study and Meta-Analysis.

INTRODUCTION: As the pandemic progresses, the pathophysiology of COVID-19 is becoming more apparent, and the potential for tocilizumab is increasing. However, the clinical efficacy and safety of tocilizumab in the treatment of COVID-19 patients remain unclear. METHODS: To assess the efficacy and safety of tocilizumab treatment in COVID-19 patients, we performed a retrospective case-control study. The study was conducted, including 95 patients treated with tocilizumab plus standard treatment and matched controls with 95 patients treated with standard treatment therapy by propensity score from February to April 2020. We searched some databases using the search terms for studies published from January 1, 2020, to June 1, 2021. RESULTS: Our case-control study found a lower mortality rate in the tocilizumab treatment group than in the standard treatment group (9.47% versus 16.84%, P = 0.134), but the results were not statistically significant. We also found that the mortality rate in tocilizumab treatment groups was significantly lower than in the standard treatment group in the stratified ICU analysis (OR 0.52, 95% CI 0.44-0.61, P = 0.048 and OR 0.31, 95% CI 0.10-0.99, P = 0.044). We selected 49 studies (including 6568 cases and 11,660 controls) that met the inclusion criteria in the meta-analysis. In the overall analysis, we performed a meta-analysis that showed significantly decreased mortality after patients received tocilizumab (OR 0.81, 95% CI 0.69-0.95, P = 0.008). We also revealed significant associations within some subgroups. The sequential trial analysis showed a true-positive result. No significant associations were observed between tocilizumab and elevated secondary infection risk, discharge, adverse events, and mechanical ventilation in the overall analysis. CONCLUSION: Tocilizumab significantly decreased mortality in COVID-19 patients with no increased discharge, secondary infection risk, adverse events, and mechanical ventilation in a meta-analysis. Our data suggest that clinicians should pay attention to tocilizumab therapy as an effective and safe treatment for COVID-19 patients.

Upregulated IL-6 Indicates a Poor COVID-19 Prognosis: A Call for Tocilizumab and Convalescent Plasma Treatment.

A comprehensive understanding of the dynamic changes in interleukin-6 (IL-6) levels is essential for monitoring and treating patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2). By analyzing the correlations between IL-6 levels and health conditions, underlying diseases, several key laboratory detection indices, and the prognosis of 1,473 patients with the coronavirus disease 2019 (COVID-19), the role of IL-6 during SARS-CoV-2 infection was demonstrated. Our results indicated that IL-6 levels were closely related to age, sex, body temperature, oxygen saturation (SpO2) of blood, and underlying diseases. As a stable indicator, the changes in IL-6 levels could indicate the inflammatory conditions during a viral infection. Two specific treatments, namely, tocilizumab and convalescent plasma therapy (CPT), decreased the level of IL-6 and relieved inflammation. CPT has an important role in the therapy for patients with critical COVID-19. We also found that patients with IL-6 levels, which were 30-fold higher than the normal level, had a poor prognosis compared to patients with lower levels of IL-6.

ZFP57 dictates allelic expression switch of target imprinted genes.

ZFP57 is a master regulator of genomic imprinting. It has both maternal and zygotic functions that are partially redundant in maintaining DNA methylation at some imprinting control regions (ICRs). In this study, we found that DNA methylation was lost at most known ICRs in Zfp57 mutant embryos. Furthermore, loss of ZFP57 caused loss of parent-of-origin-dependent monoallelic expression of the target imprinted genes. The allelic expression switch occurred in the ZFP57 target imprinted genes upon loss of differential DNA methylation at the ICRs in Zfp57 mutant embryos. Specifically, upon loss of ZFP57, the alleles of the imprinted genes located on the same chromosome with the originally methylated ICR switched their expression to mimic their counterparts on the other chromosome with unmethylated ICR. Consistent with our previous study, ZFP57 could regulate the NOTCH signaling pathway in mouse embryos by impacting allelic expression of a few regulators in the NOTCH pathway. In addition, the imprinted Dlk1 gene that has been implicated in the NOTCH pathway was significantly down-regulated in Zfp57 mutant embryos. Our allelic expression switch models apply to the examined target imprinted genes controlled by either maternally or paternally methylated ICRs. Our results support the view that ZFP57 controls imprinted expression of its target imprinted genes primarily through maintaining differential DNA methylation at the ICRs.

Impact of media channels and social interactions on the adoption of straw return by Chinese farmers.

Burning crop straws in open fields presents a major threat to the environment in China. To mitigate this problem, numerous methods have been applied. Straw return provides an environmentally friendly and economically sustainable solution to this problem. However, straw return is not popular among Chinese farmers despite the government support for this practice. In this article, the effect of major information sources-media channels and social interactions-on the adoption of straw return. Specifically the interaction between these two information sources is evaluated using survey data from provinces of Hebei, Hubei and Anhui. The main finding is that receiving information from either source increases the probability that a farmer voluntarily adopts the practice of straw return and that the two information sources reinforce each other in promoting the adoption of straw return.

[Correlation between microRNA-34b/c single nucleotide polymorphism rs4938723 and male infertility].

OBJECTIVE: To investigate the relationship between microRNA-34b/c single nucleotide polymorphism (SNP) rs4938723 and the risk of male infertility. METHODS: This case-control study included 553 males aged 19－40 (29.42 ± 5.09) years with idiopathic infertility, 153 with azoospermia and 400 with oligoasthenospermia, and another 332 normal fertile men aged 19－40 (28.5 4 ± 4.63) years as controls. We collected the clinical data and peripheral blood samples from the subjects, genotyped microRNA-34b/c rs4938723 by Sequenom MassARRAY, and analyzed the relationship between the genotypes of microRNA-34b/c rs4938723 and the risk of male infertility using the logistic regression model. RESULTS: Statistically significant differences were observed between the infertility patients and normal controls in sperm concentration (ï¼»18.71 ± 15.19ï¼½ vs ï¼»79.91 ± 43.96ï¼½ × 106/ml, P < 0.01), the percentage of progressively motile sperm (ï¼»13.27 ± 24.52ï¼½% vs ï¼»42.82 ± 8.86ï¼½%, P < 0.01) and the level of follicle stimulating hormone (ï¼»16.09 ± 17.37ï¼½ vs ï¼»12.20 ± 4.73ï¼½ IU/L, P < 0.01). Compared with the TT genotype, the TC and CC genotypes showed no correlation with male infertility, nor did the genetic locus in the subgroup analysis. CONCLUSIONS: No correlation was found between microRNA-34b/c SNP rs4938723 and male infertility, which, however, needs to be further verified by larger-sized samples.

[Detection of DPY19L2 gene mutation in 2 cases of globozoospermia].

OBJECTIVE: To investigate the mutation of the DPY19L2 gene in patients with globozoospermia. METHODS: We collected the clinical data and peripheral blood from 2 patients with globozoospermia and screened for mutation of the DPY19L2 gene by PCR amplification and DNA sequencing technology. RESULTS: The sperm from the 2 globozoospermia patients were round morphologically under the light microscope, with deeply stained nuclei but no acrosome. Electron microscopy showed the sperm with a large round head but no acrosomal structure, the nuclei enveloped by a single layer of membrane and the cytoplasm dispersed. PCR amplification revealed homozygous deletion of Exon 5, Exon6 and Exon15 in the DPY19L2 gene in both the patients. CONCLUSIONS: This study proved that the homozygous mutation of DPY19L2 could lead to globozoospermia, which has an important significance for researches on the molecular mechanisms and gene diagnosis of the disease as well as for clinicians in genetic counseling and treatment.

The clinical efficacy of acupoint sticking combined with massage to treatment functional dyspepsia: A protocol of systematic review and meta-analysis.

BACKGROUND: The objective of this meta-analysis was to summarize and identify the available evidence from studies to estimate the clinical value of acupoint sticking combined with massage (ASM) in the treatment of functional dyspepsia (FD), and provide clinicians with evidence on which to base their clinical decision making. METHODS: This review will include all studies comparing clinical efficacy of ASM in the treatment of FD. The search strategy will be performed in 10 databases. We will not establish any limitations to language and publication status, published from inception to the August 2020. Two reviewers will screen, select studies, extract data, and assess quality independently. Outcome is alleviation of global dyspeptic symptoms, alleviation of individual dyspeptic symptoms, quality-of-life improvement, and safety. The methodological quality including the risk of bias of the included studies will be evaluated. We will carry out statistical analysis using RevMan 5.3 software. RESULTS: This study will summarize current evidence to assess the efficacy and safety of ASM in the treatment of FD. CONCLUSION: The findings of this study will provide helpful evidence for the clinician, and will promote further studies, as well as studying the value of ASM. REGISTRATION NUMBER: INPLASY2020110072 (DOI number: 10.37766/inplasy2020.11.0072).

Photonics-based simultaneous measurement of distance and velocity using multi-band LFM microwave signals with opposite chirps.

We propose and demonstrate a photonics-based method for simultaneously measuring distance and velocity by adopting multi-band linear-frequency-modulated microwave signals with opposite chirps as transmitted signals. A dual-drive Mach-Zehnder modulator and photodetector (PD) are used to mix transmitted and echo signals. By analyzing the electrical spectra of the electrical signals generated by the PD, distance and the magnitude and direction of velocity can be derived simultaneously, which is significant for real-time radar applications. Proof-of-concept experiments using the proposed approach are also presented. The measured relative errors for distance and velocity are less than 0.005% and 0.59%, respectively.

[Correlation of the single nucleotide polymorphism rs662 of PON1 with the risk of male infertility].

Objective: To investigate the correlation between the single nucleotide polymorphism (SNP) rs662 of the paraoxonase 1 gene (PON1) and the risk of male infertility. METHODS: This case-control study included 403 male idiopathic infertility patients aged 29.00 ± 4.48 years in the case group and 329 normal fertile men aged 28.28 ± 4.08 years as healthy controls. We obtained DNA from the peripheral venous blood of the subjects, genotyped the SNP rs662 of PON1 by Sequenom MassArray, and analyzed the association between different genotypes of PON1 rs662 and male infertility using the logistic regression model. RESULTS: Compared with the normal controls, the infertility patients showed a significantly increased level of follicle-stimulating hormone (FSH) (ï¼»16.30 ± 17.76ï¼½ vs ï¼»4.72 ± 2.51ï¼½ U/L, P < 0.01) but a decreased percentage of progressively motile sperm (PMS) (ï¼»7.40 ± 14.17ï¼½ % vs ï¼»41.93 ± 9.06ï¼½ %, P < 0.01) and sperm concentration (ï¼»2.74 ± 3.64ï¼½ vs ï¼»75.83 ± 63.66ï¼½ ×106/ml, P < 0.01). Statistically significant differences were not found in the other parameters between the two groups of subjects, nor in the correlation of male infertility with the heterozygous genotype GA versus the wild homozygous genotype GG (OR = 0.98, 95% CI: 0.63－1.53, P = 0.923) or the homozygous genotype AA versus the wild homozygous genotype GG (OR = 0.87, 95% CI: 0.56－1.34, P = 0.525). CONCLUSIONS: The SNP rs662 of PON1 was not correlated with male infertility, which, however, needs to be confirmed by further studies with larger samples from a larger area.

[Multiplex fluorescence PCR for detection of Y Chromesome microdeletions].

OBJECTIVE: Detection of azoospermia factor (AZF) microdeletions on the Y chromosome is one of the auxiliary strategies recognized at home and abroad for the examination of male infertility. Traditional PCR gel electrophoresis fails to meet the clinical needs due to its shortcomings. The purpose of this study was to explore the feasibility of multiplex fluorescence PCR in the detection of AZF microdeletions. METHODS: We collected samples of Y chromosomal AZF microdeletions from 238 patients with azoospermia or oligozoospermia and 62 normal males, identified the 14 short tandem repeat (STR) loci in the AZF region of the Y chromosome by multiplex PCR gel electrophoresis and multiplex fluorescence PCR, and analyzed the consistency in the results of the two methods by Kappa test. RESULTS: There was a perfect consistency between multiplex PCR gel electrophoresis and multiplex fluorescence PCR in the detection rate of the STR loci in the 300 samples. Kappa test showed both P and Kappa values to be 1 for the 6 loci in the AZFa, AZFb and AZFc regions of the Y chromosome, with no statistically significant difference between the two methods. CONCLUSIONS: Multiplex fluorescence PCR can save a lot of time, reduce workload and improve laboratory efficiency and therefore is preferable to multiplex PCR gel electrophoresis in detecting Y chromosome microdeletions.

Polymorphisms of protamine genes contribute to male infertility susceptibility in the Chinese Han population.

Protamine (PRM) plays important roles in the packaging of DNA within the sperm nucleus. To investigate the role of PRM1/2 and transition protein 1 (TNP1) polymorphisms in male infertility, 636 infertile men and 442 healthy individuals were recruited into this case-controlled study of the Chinese Han population, using MassARRAY technology to analyze genotypes. Our analysis showed that there were no significant differences between controls and infertile cases among the five single nucleotide polymorphisms identified in PRM1, PRM2 and TNP1 [rs737008 (G/A), rs2301365 (C/A), rs2070923 (C/A), rs1646022 (C/G) and rs62180545 (A/G)]. However, we found that the PRM1 and PRM2 haplotypes GCTGC, TCGCA and TCGCC exhibited significant protective effects against male infertility compared to fertile men, while TCGGA, GCTCC and TCGGC represented significant risk factors for spermatogenesis. Our data showed that rs737008 and rs2301365 in PRM1, and rs1646022 in PRM2, were significantly associated with male infertility and that gene-gene interaction played a role in male infertility. A linkage disequilibrium plot for the five SNPs showed that rs737008 was strongly linked with both rs2301365 and rs2070923. These findings are likely to help improve our understanding of the etiology of male infertility. Further studies should include a larger number of genes and SNPs, particularly growing critical genes; such studies will help us to unravel the effect of individual genetic factors upon male infertility.