A novel pyroptosis-related gene signature exhibits distinct immune cells infiltration landscape in Wilms' tumor.

BACKGROUND: Wilms' tumor (WT) is the most common renal tumor in childhood. Pyroptosis, a type of inflammation-characterized and immune-related programmed cell death, has been extensively studied in multiple tumors. In the current study, we aim to construct a pyroptosis-related gene signature for predicting the prognosis of Wilms' tumor. METHODS: We acquired RNA-seq data from TARGET kidney tumor projects for constructing a gene signature, and snRNA-seq data from GEO database for validating signature-constructing genes. Pyroptosis-related genes (PRGs) were collected from three online databases. We constructed the gene signature by Lasso Cox regression and then established a nomogram. Underlying mechanisms by which gene signature is related to overall survival states of patients were explored by immune cell infiltration analysis, differential expression analysis, and functional enrichment analysis. RESULTS: A pyroptosis-related gene signature was constructed with 14 PRGs, which has a moderate to high predicting capacity with 1-, 3-, and 5-year area under the curve (AUC) values of 0.78, 0.80, and 0.83, respectively. A prognosis-predicting nomogram was established by gender, stage, and risk score. Tumor-infiltrating immune cells were quantified by seven algorithms, and the expression of CD8( +) T cells, B cells, Th2 cells, dendritic cells, and type 2 macrophages are positively or negatively correlated with risk score. Two single nuclear RNA-seq samples of different histology were harnessed for validation. The distribution of signature genes was identified in various cell types. CONCLUSIONS: We have established a pyroptosis-related 14-gene signature in WT. Moreover, the inherent roles of immune cells (CD8( +) T cells, B cells, Th2 cells, dendritic cells, and type 2 macrophages), functions of differentially expressed genes (tissue/organ development and intercellular communication), and status of signaling pathways (proteoglycans in cancer, signaling pathways regulating pluripotent of stem cells, and Wnt signaling pathway) have been elucidated, which might be employed as therapeutic targets in the future.

The value of somatosensory evoked potentials in intraoperative evaluation of indirect decompression effect of oblique lumbar interbody fusion for lumbar spinal stenosis.

PURPOSE: The aim of this study was to explore the relationship between intraoperative somatosensory evoked potential (SEP) amplitude changes and clinical outcomes of OLIF indirect decompression for degenerative lumbar spinal stenosis (DLSS). METHODS: A prospective study was performed on 201 patients who received oblique lumbar interbody fusion (OLIF) in our hospital from July 2017 to May 2021 due to single segmental DLSS. The patients were divided into three groups: group A (mild DLSS), group B (moderate DLSS), and group C (severe DLSS). The P40 amplitude during operation were recorded, and the clinical efficacy was evaluated by JOA score 1 year postoperative. ROC curves for satisfactory efficacy of P40 amplitude improvement rate and CSA improvement rate were established. Pearson correlation was used to analyze the relationship between P40 improvement rate and JOA improvement rate. RESULTS: In group A and group B, the improvement rate of JOA in P40 significantly improved group was significantly greater that in improved group and unimproved group (Pa = 0.009; Pb < 0.000). No significant among-subgroup differences in group C (all P > 0.05). In both groups A and B, there was a significant difference in the improvement rate of P40 amplitude between the satisfactory group and the ineffective group (Pa = 0.013; Pb = 0.001), while in group C, there was no statistical significance (Pc = 0.107). By variable Person correlation analysis, a significant positive correlation was obtained between JOA improvement rate and P40 amplitude improvement rate in groups A and B (r1 = 0.27, P1 = 0.02; r2 = 0.508, P2 = 0.001), no correlation between the two in group C (r3 = 0.243, P3 = 0.056). The area under the ROC for assessing surgical efficacy in terms of CSA improvement rate was 0.813 (95% CI: 0.737-0.889, P < 0.001) and 0.767 (95% CI: 0.677-0.856, P < 0.001) in group A and group B, respectively, with satisfactory efficacy cutoff points of 50.18% and 67.89%. CONCLUSION: For mild and moderate DLSS, the intraoperative P40 amplitude improvement rate can predict the improvement of clinical symptoms after surgery and can be used as a reference index to assess the effect of indirect decompression. For severe DLSS, the P40 amplitude improvement rate has limited significance in guiding indirect decompression, and OLIF indirect decompression is not the right treatment for this type of patients.

Nitric Oxide Synthases in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by severe joint damage and disability. However, the specific mechanism of RA has not been thoroughly clarified over the past decade. Nitric oxide (NO), a kind of gas messenger molecule with many molecular targets, is demonstrated to have significant roles in histopathology and homeostasis. Three nitric oxide synthases (NOS) are related to producing NO and regulating the generation of NO. Based on the latest studies, NOS/NO signaling pathways play a key role in the pathogenesis of RA. Overproduction of NO can induce the generation and release of inflammatory cytokines and act as free radical gas to accumulate and trigger oxidative stress, which can involve in the pathogenesis of RA. Therefore, targeting NOS and its upstream and downstream signaling pathways may be an effective approach to managing RA. This review clearly summarizes the NOS/NO signaling pathway, the pathological changes of RA, the involvement of NOS/NO in RA pathogenesis and the conventional and novel drugs based on NOS/NO signaling pathways that are still in clinical trials and have good therapeutic potential in recent years, with an aim to provide a theoretical basis for further exploration of the role of NOS/NO in the pathogenesis, prevention and treatment of RA.

Roles of autophagy in rheumatoid arthritis.

Autophagy, a vital mechanism restricted in tissues, exerts its cytoprotective role through the degradation mechanism of damaged or aging organelles, harmful protein aggregates and intracellular pathogens, followed by energy furnishment. However, dysfunctional autophagy is associated with the development of autoimmune diseases such as rheumatoid arthritis (RA). In pathological conditions, autophagy may be involved in the maturation, survival and proliferation of various immune and non-immune cells and plays a key role in the pathogenesis of RA. Furthermore, autophagy appears to be involved in the citrullination of T lymphocytes and the presentation of citrullinated peptides, which are presented to T lymphocytes via the major histocompatibility complex, causing immune responses and chronic inflammation, as well as bone and cartilage destruction associated with apoptosis resistance of RA fibroblast-like synoviocyte (RAFLS) and osteoclastogenesis. In this review, we have summarised the roles of autophagy in the pathogenesis of RA including citrullination, immune tolerance break, osteoclastogenesis, RA FLS cell dysplasia, apoptosis resistance, together with the therapeutic potentials of autophagy regulators.

Roles of Nitric Oxide in Brain Ischemia and Reperfusion.

Brain ischemia and reperfusion (I/R) is one of the most severe clinical manifestations of ischemic stroke, placing a significant burden on both individuals and society. The only FDA-approved clinical treatment for ischemic stroke is tissue plasminogen activator (t-PA), which rapidly restores cerebral blood flow but can have severe side effects. The complex pathological process of brain I/R has been well-established in the past few years, including energy metabolism disorders, cellular acidosis, doubling of the synthesis or release of excitotoxic amino acids, intracellular calcium homeostasis, free radical production, and activation of apoptotic genes. Recently, accumulating evidence has shown that NO may be strongly related to brain I/R and involved in complex pathological processes. This review focuses on the role of endogenous NO in pathological processes in brain I/R, including neuronal cell death and blood brain barrier disruption, to explore how NO impacts specific signaling cascades and contributes to brain I/R injury. Moreover, NO can rapidly react with superoxide to produce peroxynitrite, which may also mediate brain I/R injury, which is discussed here. Finally, we reveal several therapeutic approaches strongly associated with NO and discuss their potential as a clinical treatment for ischemic stroke.

Role of Mitochondrial Pathways in Cell Apoptosis during He-Patic Ischemia/Reperfusion Injury.

Hepatic ischemia-reperfusion injury is a major cause of post-operative hepatic dysfunction and liver failure after transplantation. Mitochondrial pathways can be either beneficial or detrimental to hepatic cell apoptosis during hepatic ischemia/reperfusion injury, depending on multiple factors. Hepatic ischemia/reperfusion injury may be induced by opened mitochondrial permeability transition pore, released apoptosis-related proteins, up-regulated B-cell lymphoma-2 gene family proteins, unbalanced mitochondrial dynamics, and endoplasmic reticulum stress, which are integral parts of mitochondrial pathways. In this review, we discuss the role of mitochondrial pathways in apoptosis that account for the most deleterious effect of hepatic ischemia/reperfusion injury.

Amyloidosis in Alzheimer's Disease: Pathogeny, Etiology, and Related Therapeutic Directions.

The amyloid hypothesis of Alzheimer's disease has long been the predominant theory, suggesting that Alzheimer's disease is caused by the accumulation of amyloid beta protein (Aß) in the brain, leading to neuronal toxicity in the central nervous system (CNS). Because of breakthroughs in molecular medicine, the amyloid pathway is thought to be central to the pathophysiology of Alzheimer's disease (AD). Currently, it is believed that altered biochemistry of the Aß cycle remains a central biological feature of AD and is a promising target for treatment. This review provides an overview of the process of amyloid formation, explaining the transition from amyloid precursor protein to amyloid beta protein. Moreover, we also reveal the relationship between autophagy, cerebral blood flow, ACHE, expression of LRP1, and amyloidosis. In addition, we discuss the detailed pathogenesis of amyloidosis, including oxidative damage, tau protein, NFTs, and neuronal damage. Finally, we list some ways to treat AD in terms of decreasing the accumulation of Aß in the brain.

Role of Cholinergic Signaling in Alzheimer's Disease.

Acetylcholine, a neurotransmitter secreted by cholinergic neurons, is involved in signal transduction related to memory and learning ability. Alzheimer's disease (AD), a progressive and commonly diagnosed neurodegenerative disease, is characterized by memory and cognitive decline and behavioral disorders. The pathogenesis of AD is complex and remains unclear, being affected by various factors. The cholinergic hypothesis is the earliest theory about the pathogenesis of AD. Cholinergic atrophy and cognitive decline are accelerated in age-related neurodegenerative diseases such as AD. In addition, abnormal central cholinergic changes can also induce abnormal phosphorylation of ttau protein, nerve cell inflammation, cell apoptosis, and other pathological phenomena, but the exact mechanism of action is still unclear. Due to the complex and unclear pathogenesis, effective methods to prevent and treat AD are unavailable, and research to explore novel therapeutic drugs is various and active in the world. This review summaries the role of cholinergic signaling and the correlation between the cholinergic signaling pathway with other risk factors in AD and provides the latest research about the efficient therapeutic drugs and treatment of AD.

Role of prostaglandins in rheumatoid arthritis.

Rheumatoid arthritis (RA) is an autoimmune disease characterised by systemic and chronic synovitis that lead to joint destruction, pain, and many complications. Treatments only relieve certain symptoms, but do not cure RA completely. Prostaglandins (PGs) are lipid signalling molecules and released in the early phase of RA. Increasing evidences have shown five main contribution of PGs to the different stages and symptoms of RA. First, PGs maintain the autoimmune response and immune-system inflammation by modulating the differentiation, maturation, and cytokine production of immune cells. Second, PGs are beneficial for leukocyte infiltration, synovial hyperplasia, and angiogenesis to promote synovitis. Third, PGs are involved in cartilage degradation and bone resorption. Fourth, PGs are important mediators of joint-pain regulation. Finally, in the late stage of RA inflammation, PGs play a part in joint protection. Those findings suggest that PGs are potential therapy targets for RA. This review highlights recent advances in the RA development caused by PGs, and provides recommendations for future research directions.

The Roles of Nitric Oxide Synthase/Nitric Oxide Pathway in the Pathology of Vascular Dementia and Related Therapeutic Approaches.

Vascular dementia (VaD) is the second most common form of dementia worldwide. It is caused by cerebrovascular disease, and patients often show severe impairments of advanced cognitive abilities. Nitric oxide synthase (NOS) and nitric oxide (NO) play vital roles in the pathogenesis of VaD. The functions of NO are determined by its concentration and bioavailability, which are regulated by NOS activity. The activities of different NOS subtypes in the brain are partitioned. Pathologically, endothelial NOS is inactivated, which causes insufficient NO production and aggravates oxidative stress before inducing cerebrovascular endothelial dysfunction, while neuronal NOS is overactive and can produce excessive NO to cause neurotoxicity. Meanwhile, inflammation stimulates the massive expression of inducible NOS, which also produces excessive NO and then induces neuroinflammation. The vicious circle of these kinds of damage having impacts on each other finally leads to VaD. This review summarizes the roles of the NOS/NO pathway in the pathology of VaD and also proposes some potential therapeutic methods that target this pathway in the hope of inspiring novel ideas for VaD therapeutic approaches.

LTB4-induced anti-apoptosis and infiltration of neutrophils in rheumatoid arthritis.

Rheumatoid arthritis (RA) is the most common autoimmune disease, resulting in synovitis, joint pain and stiffness, even deformity and disability. The interactions between leukotriene B4 (LTB4) and neutrophils in RA progression have not been elucidated in detail. Our review focuses on the correlation of LTB4 and neutrophils in the development of RA especially in terms of infiltration and delayed life span of neutrophils. In this article, the roles of LTB4 in the anti-apoptosis of neutrophils will be detailed, which is achieved by suppressed pro-apoptotic Bax and up-regulated anti-apoptotic Mcl-1, and several key molecules, as well as signalling pathways and factors relevant to the enhancement of LTB4 production and functions. The mechanisms of LTB4-induced anti-apoptosis and infiltration of neutrophils provide more potential targets in the treatment of RA and recent therapeutic strategies are also discussed.

Hepatocyte growth factor plays a dual role in tendon-derived stem cell proliferation, migration, and differentiation.

Heterotopic ossification is common in tendon healing after trauma, but the detailed mechanisms remain unknown. Tendon-derived stem cells (TDSCs) are a type of progenitor cell found in the tendon niche, and their incorrect differentiation after trauma may lead to tendon calcification. The expression of hepatocyte growth factor (HGF) presents drastic fluctuations in serum/tissue after trauma and was found to activate quiescent stellate cells and contribute to wound healing; however, its potential role in TDSCs remains elusive. In this study, TDSCs isolated from rats were cultured in media containing HGF with or without a signaling inhibitor, and the proliferation, migration, and differentiation ability of TDSCs were measured to determine the role and mechanism of HGF in TDSCs. We showed that HGF promotes TDSC proliferation and migration but inhibits TDSC osteogenic differentiation ability. HGF activated-HGF/c-Met, mitogen-activated protein kinase (MAPK)/extracellular signal-regulated protein kinases 1 and 2 (ERK1/2), and phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling, which was positively correlated with TDSCs proliferation and migration but negatively related to TDSC osteogenic differentiation ability. The phosphorylation of Smad1/5/8 was also negatively related to HGF/c-Met, MAPK/ERK1/2, and PI3K/AKT signaling, which demonstrated that the inhibition of osteogenic differentiation was dependent on BMP/Smad1/5/8 signaling. Overall, we showed that HGF could promote TDSCs proliferation and migration and inhibit osteogenic differentiation in vitro, suggesting a potential role for HGF as a cytokine treatment of tendon trauma.

Roles of eNOS in atherosclerosis treatment.

BACKGROUND: Atherosclerosis (AS) is the main pathogeny of coronary heart disease, cerebral infarction and peripheral vascular disease. Endothelial dysfunction is one of the important pathogenesis of AS. As an important endothelium-derived relaxation factor, nitric oxide (NO) plays a role in cardiovascular protection and anti-AS function; but in the pathological state, endothelial nitric oxide synthase (eNOS) disorder causes an abnormal production of NO, which may damage endothelial function and trigger AS. This review summarized the research progresses in the treatment strategies for AS based on correcting the disordered eNOS/ NO signaling pathway. MAIN BODY: According to the topic, select the search terms 'atherosclerosis,' 'nitric oxide,' 'eNOS,' 'treatment,' 'management,' 'medication,' 'maintenance,' 'remission'. Using these terms, a structured literature search via multiple electronic databases was performed for the most recent trial evidence in recent years. We read and analyze these literatures carefully, classified these literatures according to their content, and then summarized and outlined the common main points in these classified literatures. Finally, literature data were organized to discuss these main points logically. We found that both aberrant expression and dysfunction of eNOS are closely related to AS development, and some new treatment strategies aimed at eNOS have been proposed, including upregulation of eNOS expression and inhibition of eNOS uncoupling. The former one is mainly related to inflammatory inhibition and protection of the PKB-eNOS signaling pathway; whereas the latter one is associated with the addition of the L-arginine substrate of eNOS, arginase inhibition, and the supplement of tetrahydrobiopterin, which can elevate no level. CONCLUSIONS: eNOS can be an important target for prevention and treatment of AS, and eNOS drugs may be another potent class of effective therapeutic treatment for AS following traditional lipid-lowering, anti-platelet, vasodilator drugs. But applying these experimental results to clinic treatment still requires further studies and development of biotechnology.

Pain and bone damage in rheumatoid arthritis: role of leukotriene B4.

Rheumatoid arthritis is a chronic autoimmune disease characterised by unbearable joint pain as well as bone and cartilage destruction. Although RA development is greatly controlled, the pain and bone damage failed to be relieved and managed. Leukotriene B4 (LTB4) has been proved to play an essential role in the induction of pain and bone damage. The nerve injury of RA can promote the production of LTB4, which act on their receptors, leading to the increased release of pro-inflammatory cytokines and ROS to reduce neuron viability and pain threshold. Moreover, LTB4-BLT1 activation can also increase intracellular calcium concentration and neuron excitability as well as NF-κB pathway activation, which further promote the production of MMP-9 and CXC3R-1. The mutual promotion between LTB4 and neutrophil accumulation accelerates the release of TNF-α and IL-ß, which enhance both peripheral and central nerve system sensitisation. LTB4 also involve in TrpV1 channel activation and modulation of P2X3 receptor activation. All above mechanisms contribute to the development of RA pain. IL-23, cPLA2 and PI3K increase the production of CD11b+Gr1high myeloid subtype and calcium concentration, which promote the production of LTB4 and further accelerate IL-17 and TNF activation as well as calcium influx to conduce to osteoclastogenesis, resulting in aggregated bone damage. Our review is the first to conclude the signalling pathways and associated molecules in LTB4-induced pain and bone damage.

Effects of immunotherapy on mortality in neonates with suspected or proven sepsis: a systematic review and network meta-analysis.

BACKGROUND: To investigate the efficacies of different immunotherapies in neonates with suspected or proven sepsis. METHODS: We searched the Cochrane Library, EMBASE, MEDLINE, EBSCOhost, and Web of Science for studies published before May 2019 that investigated different immunotherapies in neonates with suspected or proven sepsis. Comparisons were among immunotherapies and between immunotherapy and placebo. The review was registered in the PROSPERO CRD database. RESULTS: All-cause mortality was not significantly different between patients who received the immunoglobulin (IgG), IgM-enriched immunoglobulin (IgGAM), granulocyte-colony stimulating factor (G-CSF) or granulocyte-macrophage colony stimulating factor (GM-CSF) immunotherapies and those who received placebo. The RRs of the immunotherapies were 0.80 (95% CI: 0.57 to 1.1), 0.45 (95% CI: 0.17 to 1.0), 0.93 (95% CI: 0.64 to 1.2) and 0.67 (95% CI: 0.39 to 1.1), respectively. Compared with placebo, none of the interventions showed statistically significant differences in the duration of hospital stay. The MDs of the immunotherapies were - 2.7 (95% CI: - 8.4 to 3.5), - 0.18 (95% CI: - 7.3 to 7.7), - 1.7 (95% CI: - 7.3 to 3.9) and - 7.2 (95% CI: - 28 to 13), respectively. CONCLUSIONS: No significant differences in all-cause mortality or the duration of hospital stay were found in neonates with suspected or proven sepsis treated with the four types of immunotherapies and those treated with placebo.

Elevated nitric oxide levels associated with hepatic cell apoptosis during liver injury.

Hepatic injury is a major event in liver surgery such as liver transplantation and it always leads to hepatic cell apoptosis. Nitric oxide (NO) is a key signaling regulation molecule. Many researchers have shown that increased NO level can influence liver cell apoptosis by promoting or inhibiting the relative signaling pathways that are involved in the caspase family, Bax/Bcl-2, mitochondria, oxidative stress, death receptors, and mitogen-activated protein kinases. Elucidating the relationships between NO and hepatic cell apoptosis is necessary for ameliorating prognosis of liver surgery. This article reviews the newest research progress in the relationships between higher NO levels and hepatic cell apoptosis in liver injury.

Tumor necrosis factor-α and transforming growth factor-ß1 facilitate differentiation and proliferation of tendon-derived stem cells in vitro.

OBJECTIVES: To investigate the effects of tumor necrosis factor-α (TNF-α) and transforming growth factor-ß1 (TGF-ß1) on the proliferation and differentiation of tendon-derived stem cells (TDSC). RESULTS: TNF-α inhibits the proliferation and tenogenic/osteogenic differentiation of TDSC but, after simultaneous or sequential treatment with TGF-ß1 and TNF-α, the expression of tenogenic/osteogenic-related marker and proliferation of TDSC was significantly increased. During these processes, Smad2/3 and Smad1/5/8 were highly phosphorylated, meaning that the TGF-ß and BMP signaling pathways were highly activated. Further study revealed that the expression of Inhibitor-Smad appeared to be negatively correlated to the proliferation and differentiation of TDSC. CONCLUSIONS: Combining the use of TNF-α and TGF-ß1 could improve the proliferation and differentiation of TDSC in vitro, and the expression of I-Smad is negatively correlated with TDSC proliferation and differentiation.

Combined effects of engineered tendon matrix and GDF-6 on bone marrow mesenchymal stem cell-based tendon regeneration.

OBJECTIVES: To examine whether an engineered tendon matrix (ETM) environment and growth and differentiation factor-6 (GDF-6) have synergistic effects on the tenogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and the quality of tendon repair. RESULTS: ETM and GDF-6 promote tenogenic differentiation of BMSCs in vitro. Implantation of GDF-6-incorporated ETM containing BMSCs into a tendon injury model significantly improved the histological and mechanical properties of the repaired tendon. CONCLUSIONS: GDF-6-incorporated ETM containing BMSCs represents a promising strategy for tendon injury repair.

Combined effect of ligament stem cells and umbilical-cord-blood-derived CD34+ cells on ligament healing.

Transplantation of ligament-tissue-derived stem cells has become a promising approach in the repair of injured ligament. Neovascularization plays an important role in ligament healing and remodeling. Recently, human umbilical-cord-blood-derived CD34+ cells have been reported to contribute to neoangiogenesis. Therefore, we performed a series of experiments to test our hypothesis that the combination of medial collateral ligament stem cells (MCL-SCs) and umbilical-cord-blood-derived CD34+ cells has synergistic effects on tendon healing. MCL-SCs and umbilical-cord-blood-derived CD34+ cells were isolated and cultured. Rat MCL injury was treated by MCL-SCs and/or CD34+ cells. Response to the cell therapy was assessed by gross observation, histological evaluation and biomechanical testing at 2 and 4 weeks after each treatment. Although each cell therapy group induced macroscopic and morphological recovery in healing MCLs, the combined use of MCL-SCs/CD34+ cells led to further improvement in healing quality. Capillary density was significantly higher in the CD34+ cell transplantation groups than in the other groups at week 2. Biomechanical testing demonstrated that the failure load of the healing ligament was greatest in the combination therapy group. The combination of MCL-SCs and CD34+ cells as a cell therapeutic thus enhances healing and restores biomechanical function toward normal after MCL injury. The findings obtained in our study suggest that the combination of MCL-SCs and CD34+ cells transplantation represents a promising strategy for ligament injury.

[Relationship between anogenital distance and cryptorchidism in human newborns].

OBJECTIVE: To explore the relation of the anogenital distance (AGD) with cryptorchidism in male newborns. METHODS: This study included 350 male infants delivered in two community hospitals between September 2013 and September 2014. Within 24 hours after birth, a pediatric surgeon measured the AGD of the neonates and determined whether they had cryptorchidism. According to the testicular position, we divided the undescended testes into three types: upper scrotal, inguinal, and non-palpable. RESULTS: Totally 39 cases of cryptorchidism were found in the 350 newborns. The AGD of the cryptorchidism infants was significantly shorter than that of the normal neonates ([2.01 ± 0.22] vs [2.35 ± 0.19] cm, P < 0.01), and statistically significant differences remained even when preterm and low birth-weight infants were excluded ([2.32 ± 0.14] vs [2.06 ± 0.19] cm; (2.37 ± 0.17) cm vs (2.12 ± 0.12) cm, all P < 0.01). The newborns with higher-position cryptorchidism had a shorter AGD, though with no significant difference (F = 0.434, P > 0.05). No significant differences were observed in the AGD between unilateral and bilateral cryptorchidism ([1.96 ± 0.13] vs [2.02 ± 0.17] cm, P > 0.05). CONCLUSION: Shorter AGD is associated with a higher incidence of cryptorchidism in male newborns. AGD could serve as a potential biomarker for disruption of androgen action during the male programming window period.