Seminal plasma S100A8/A9 as a potential biomarker of genital tract inflammation.

ABSTRACT: Infections and inflammatory reactions in the male genital tract are the leading causes of male infertility with a prevalence of 6%-10%, primarily affecting testicular and epididymal function and ultimately compromising sperm quality. However, most infertile patients with genital infection/inflammation are asymptomatic and easily overlooked. Traditional indicators, including white blood cells, elastase, and other components in semen, can reflect inflammation of the genital tract, but there is still a lack of a uniform standard method of detection. Therefore, it is necessary to explore reliable markers in semen that reflect the inflammatory status of the genital tract. Using the experimental autoimmune orchitis (EAO) model to simulate noninfectious chronic orchitis, we successfully collected ejaculated seminal fluid from EAO rats using optimized electrical stimulation devices. Proteomic analysis was performed using isobaric tags for relative and absolute quantification (iTRAQ). Compared to the control group, 55 upregulated and 105 downregulated proteins were identified in seminal plasma samples from the EAO group. In a preliminary screening, the inflammation-related protein S100A8/A9 was upregulated. We further verified that S100A8/A9 was increased in seminal plasma and highly expressed in testicular macrophages of the EAO model. In patients with oligoasthenospermia and genital tract infections, we also found that S100A8/A9 levels were remarkably increased in seminal plasma and testicular macrophages. S100A8/A9 in semen may be a potential biomarker for chronic genital inflammation. Our study provides a new potential biomarker for early diagnosis and further understanding of male infertility caused by genital inflammation.

Cervical elastography in predicting spontaneous preterm birth in singleton pregnancy with a short cervix receiving progesterone treatment at 18 to 24 weeks' gestation.

BACKGROUND: A short cervix in the second trimester is known to increase the risk of preterm birth, which can be reduced with the administration of vaginal progesterone. However, some studies have suggested that a significant number of cases still experience preterm birth despite progesterone treatment. OBJECTIVE: This study was aimed to investigate the potential value of transvaginal cervical elasticity measured by E-Cervix as a predictor for spontaneous preterm birth (sPTB) in singleton pregnancies receiving progesterone treatment for a short cervix (CL ≤ 2.5 cm) diagnosed at 18 to 24 weeks' gestation. STUDY DESIGN: This prospective study was conducted at a single center premature high-risk clinic from January 2020 to July 2022. Singleton pregnancies with a short cervix at 18 to 24 weeks' gestation were enrolled. Cervical elastography using E-Cervix was performed, and maternal and neonatal demographic characteristics, cervical length (CL), elasticity contrast index (ECI), cervical hardness ratio, mean internal os strain (IOS), and mean external os strain (EOS) were compared before and after progesterone treatment in sPTB and term birth groups. Multivariate logistic regression was used to analyze the association between elasticity parameters and spontaneous preterm birth. The screening performance of CL and optimal cervical elasticity parameters in predicting sPTB was evaluated using receiver-operating characteristic (ROC) curve analysis. RESULTS: A total of 228 singleton pregnant women were included in the study, among which 26 (11.4%) had sPTB. There were no significant differences in maternal characteristics and gestational age at enrollment between women with and without sPTB. At the start of progesterone treatment, there were no significant differences in cervical elasticity parameters between the two groups. After two weeks of progesterone treatment, women who had sPTB showed significantly higher levels of ECI, IOS, EOS (p = 0.0108, 0.0001, 0.016), and lower hardness ratio (p = 0.011) compared to those who had a full-term birth. Cervical length did not show significant differences between the two groups, regardless of whether progesterone treatment was administered before or after. Among the post-treatment cervical elasticity parameters, IOS and EOS were associated with a 3.38-fold and 2.29-fold increase in the risk of sPTB before 37 weeks (p = 0.032, 0.047, respectively). The AUROC of the combined model including CL, IOS, and EOS (0.761, 95% CI0.589-0.833) was significantly higher than the AUROC of CL alone (0.618, 95% CI 0.359-0.876). At a fixed false-positive of 13%, the addition of IOS and EOS in the CL model increased sensitivity from 34.6% to 57.6%, PPV from 25.7% to 36.5%, and NPV from 91.1% to 94.1%. CONCLUSION: When assessing the risk of sPTB in singleton pregnancies with a short cervix receiving progesterone therapy, relying solely on cervical length is insufficient. It is crucial to also evaluate cervical stiffness, particularly the strain of the internal and external os, using cervical elastography.

Challenges with the Synthesis of a Macrocyclic Thioether Peptide: From Milligram to Multigram Using Solid Phase Peptide Synthesis (SPPS).

We describe an optimization and scale-up of the 45-membered macrocyclic thioether peptide BMS-986189 utilizing solid-phase peptide synthesis (SPPS). Improvements to linear peptide isolation, macrocyclization, and peptide purification were demonstrated to increase the throughput and purification of material on scale and enabled the synthesis and purification of >60 g of target peptide. Taken together, not only these improvements resulted in a 28-fold yield increase from the original SPPS approach, but also the generality of this newly developed SPPS purification sequence has found application in the synthesis and purification of other macrocyclic thioether peptides.

The combination of deep learning and pseudo-MS image improves the applicability of metabolomics to congenital heart defect prenatal screening.

To investigate the metabolic alterations in maternal individuals with fetal congenital heart disease (FCHD), establish the FCHD diagnostic models, and assess the performance of these models, we recruited two batches of pregnant women. By metabolomics analysis using Ultra High-performance Liquid Chromatography-Mass/Mass (UPLC-MS/MS), a total of 36 significantly altered metabolites (VIP >1.0) were identified between FCHD and non-FCHD groups. Two logistic regression models and four support vector machine (SVM) models exhibited strong performance and clinical utility in the training set (area under the curve (AUC) = 1.00). The convolutional neural network (CNN) model also demonstrated commendable performance and clinical utility (AUC = 0.89 in the training set). Notably, in the validation set, the performance of the CNN model (AUC = 0.66, precision = 0.714) exhibited better robustness than the six models above (AUC≤0.50). In conclusion, the CNN model based on pseudo-MS images holds promise for real-world and clinical applications due to its better repeatability.

The Role of Cells and Cytokines in Male Infertility Induced by Orchitis.

Recent studies on male infertility reveal a growing worry: more infertile men are dealing with inflammation in the testis. Analyzing testicular biopsies from infertile men highlights a significant presence of inflammation. This connection, supported by clinical and pathological evidence, emphasizes that testicular inflammation hampers sperm production, leading to lasting declines in sperm count and quality. However, the exact reasons behind male infertility due to orchitis, a type of testicular inflammation, are still uncertain. Understanding these fundamental aspects of molecular signals and cellular mechanisms in testicular inflammation is crucial. Our review delves into recent literature with a dual objective: elucidating potential mechanisms involving immune cells, non-immune cells, and cytokines that link orchitis to male infertility, while also paving the way for precise interventions and solutions to address the challenges of male infertility.

Childhood maltreatment and association with trajectories of depressive symptoms among older adults: a longitudinal study in China.

OBJECTIVES: Childhood maltreatment has long-lasting effects on mental health. Existing evidence suggests that trajectories of depressive symptoms vary among individuals; however, little is known about how childhood maltreatment shapes these trajectory patterns. Therefore, this study investigated the impacts of childhood maltreatment on eight-year depressive trajectories among Chinese older adults. METHOD: Five waves of longitudinal data from the China Health and Retirement Longitudinal Study were utilized. Growth Mixture Modelling was performed to identify distinct trajectories of depressive symptoms, and multinomial logistic regression was conducted to explore the associations between these trajectories and childhood maltreatment. RESULTS: Four trajectories of depressive symptoms were identified: the 'no symptoms' class (61.83%), the 'increasing symptoms' class (14.49%), the 'decreasing symptoms' class (16.44%), and the 'chronic symptoms' class (7.24%). Older adults who experienced childhood physical abuse were more likely to be in the 'chronic symptoms' class than in the 'no symptoms' class, whereas emotional neglect did not show a significant association with three problematic trajectories. CONCLUSION: This study provides empirical evidence that childhood physical abuse increases the likelihood of developing chronic depressive symptoms in later life. To mitigate this risk, it is crucial to institute comprehensive treatment plans that incorporate trauma-informed care principles, employ evidence-based therapies specifically designed to address the long-term effects of abuse, and prioritize regular screening and assessment of mental health among older adults.

Toxicology, pharmacokinetics, and immunogenicity studies of CCR4-IL2 bispecific immunotoxin in rats and minipigs.

We have developed a diphtheria toxin-based recombinant human CCR4-IL2 bispecific immunotoxin (CCR4-IL2-IT) for targeted therapy of cutaneous T-cell lymphoma (CTCL). CCR4-IL2-IT demonstrated superior efficacy in an immunodeficient mouse CTCL model. Recently, we have compared the in vivo efficacy of CCR4-IL2-IT versus Brentuximab (FDA approved leading drug in CTCL market) in the same immunodeficient mouse CTCL model. The comparison demonstrated that CCR4-IL2-IT was significantly more effective than Brentuximab. In this study, we have performed non-GLP (Good Laboratory Practice) toxicology, pharmacokinetics, immunogenicity studies of CCR4-IL2-IT in both rats and minipigs. CCR4-IL2-IT demonstrated excellent safety profiles in both rats and minipigs. The maximum tolerated dose of CCR4-IL2-IT was determined as 0.4 mg/kg in both rats and minipigs. Complete blood count and chemistry analysis did not show significant difference for all measured parameters between the blood samples of pre-injection versus post-injection from the five-day toxicology studies of CCT4-IL2-IT in both rats and minipigs. Histology analysis did not show difference between the PBS treatment group versus CCR4-IL2-IT treatment group at 50 µg/kg in both rats and minipigs. The half-life of CCR4-IL2-IT was determined as about 45 min in rats and 30 min in minipigs. The antibodies against CCR4-IL2-IT were detected in about two weeks after CCR4-IL2-IT treatment. CCR4-IL2-IT did not induce cytokine release syndrome in a peripheral blood mononuclear cell derived humanized mouse model. The depletion of CCR4+ cell and CD25+ cell (two target cell populations of CCR4-IL2-IT) was observed in minipigs. The excellent safety profile promoted us to further develop CCR4-IL2-IT towards clinical trials.

Validation of hyperthermia as an enhancer of chemotherapeutic efficacy: insights from a bladder cancer organoid model.

OBJECTIVE: This study aimed to evaluate the combined efficacy of hyperthermia and chemotherapy using a bladder cancer organoid model and to explore hyperthermia-related molecular pathways. METHOD: Tumor organoids were generated by embedding RT4 bladder cancer cells into Matrigel. The resulting organoids were treated with pirarubicin or gemcitabine at 37 °C or 42 °C. Proliferation was determined by Ki67 immunofluorescence staining, and apoptosis was assessed using a TdT-mediated dUTP nick end labeling (TUNEL) assay. RNA sequencing was used to identify the differentially expressed genes. RESULTS: Bladder cancer organoids were successfully established and exhibited robust proliferative abilities. Treatment with gemcitabine or pirarubicin under hyperthermic conditions caused pronounced structural damage to the organoids and increased cell death compared to that in the normothermically treated group. Furthermore, Ki67 labeling and TUNEL assays showed that the hyperthermia chemotherapy group showed a significantly reduced proliferation rate and high level of apoptosis. Finally, RNA sequencing revealed the IFN-γ signaling pathway to be associated with hyperthermia. CONCLUSION: Overall, hyperthermia combined with chemotherapy exerted better therapeutic effects than those of normothermic chemotherapy in grade 1-2 non-muscle-invasive bladder cancer, potentially through activation of the IFN-γ-JAK-STAT pathway.

Predictive Model of CK7 Expression in Patients With Clear Cell Renal Cell Carcinoma by Combined Multimodal Ultrasound Diagnostic Techniques: A Retrospective Study.

OBJECTIVE: The aim of the work described here was to develop and validate a predictive model for cytokeratin 7 (CK7) expression in clear cell renal cell carcinoma (ccRCC) patients by combining multimodal ultrasound diagnostic techniques. METHODS: This retrospective study enrolled 157 surgically confirmed ccRCC patients. All patients underwent pre-operative multimodal ultrasound diagnostic examinations, including B-mode ultrasound (US), color Doppler flow imaging (CDFI) and contrast-enhanced ultrasound (CEUS). The patients were randomly divided into a training group (103 cases) and a testing group (54 cases). Univariate and multivariate logistic regression analyses were performed in the training group to identify independent indicators associated with CK7 positivity. These indicators were included in the predictive model. Receiver operating characteristic (ROC) curves and calibration curves were used to evaluate the model's discriminative ability and accuracy. Decision curve analysis (DCA) and nomogram visualization were used to assess the clinical utility of the predictive model. RESULTS: Univariate logistic regression analysis revealed that US and CDFI observations were not correlated with CK7 expression and could not predict it. Multivariate logistic regression analysis identified age (odds ratio [OR] = 0.953, 95% confidence interval [CI]: 0.909-0.999), wash-in pattern (OR = 0.180, 95% CI: 0.063-0.513) and enhancement homogeneity (OR = 11.610, 95% CI: 1.394-96.675) as independent factors related to CK7 positivity in ccRCC. Incorporating these variables into the predictive model resulted in areas under the receiver operating characteristic curve of 0.812 (95% CI: 0.711-0.913) for the training group and 0.792 (95% CI: 0.667-0.924) for the testing group. The calibration curve and DCA revealed that the model had good accuracy and clinical utility of the model. CONCLUSION: The combination of multimodal ultrasound diagnostic techniques in constructing a predictive model for CK7 expression in ccRCC patients has significant predictive value.

Application of contrast-enhanced ultrasound in diagnosis and grading of bladder urothelial carcinoma.

PURPOSE: To explore the application of contrast-enhanced ultrasound (CEUS) for the diagnosis and grading of bladder urothelial carcinoma (BUC). METHODS: The results of a two-dimensional ultrasound, color Doppler ultrasound and CEUS, were analyzed in 173 bladder lesion cases. The ultrasound and surgical pathology results were compared, and their diagnostic efficacy was analyzed. RESULTS: There were statistically significant differences between BUC and benign lesions in terms of color blood flow distribution intensity and CEUS enhancement intensity (both P < 0.05). The area under the time-intensity curve (AUC), rising slope, and peak intensity of BUC were significantly higher than those of benign lesions (all P < 0.05). The H/T (height H / basal width T)value of 0.63 was the critical value for distinguishing high- and low-grade BUC, had a diagnostic sensitivity of 80.0% and a specificity of 60.0%. CONCLUSION: The combination of CEUS and TIC can help improve the diagnostic accuracy of BUC. There is a statistically significant difference between high- and low-grade BUC in contrast enhancement intensity (P < 0.05); The decrease of H/T value indicates the possible increase of the BUC grade.

Effectiveness of Parent-Child Interaction Therapy for Maltreated Families: A Meta-Analysis of Randomized Controlled Trials.

This meta-analysis evaluated the effectiveness of Parent-Child Interaction Therapy (PCIT) for maltreated families and examined potential moderators associated with the intervention. Seven English electronic databases (PubMed, PsycINFO, Web of Science, MEDLINE, Scopus, Cochrane Library, and ProQuest Dissertations and Theses Global) were systematically searched to identify randomized controlled trials (RCTs) published before January 20, 2023. Eleven studies involving 1,069 maltreated or high-risk families were included in the meta-analysis. Our results showed that PCIT significantly reduced child externalizing behaviors, improved parenting skills, and decreased parenting stress and child abuse potential in maltreated families. Additionally, families with confirmed maltreatment history reported larger effect sizes across all outcomes than those at high risk of maltreatment; parenting skills outcomes were more effective in adapted PCIT versions, using per-protocol analysis, and American caregivers, whereas none of the outcomes were related to the number of sessions. These findings provide encouraging evidence for the use of PCIT as an intervention for families with a history of maltreatment, although more high-quality RCTs are required to confirm its effects.

The Impacts of Intimate Partner Violence on Postpartum Depression: An Updated Meta-Analysis.

The associations between intimate partner violence (IPV) and postpartum depression (PPD) have been well established in previous reviews. However, none has explored potential differences between IPV subtypes or exposure times, which could help healthcare providers recognize the adverse impacts of various IPV subtypes and conduct comprehensive IPV screening. This study aimed to estimate the impacts of overall IPV and its subtypes (physical, psychological, and sexual) on PPD using an updated meta-analysis and to examine the potential role of IPV exposure time and regional income levels. Four English databases (Medline, PsycINFO, PubMed, and Web of Science) and two Chinese databases (China National Knowledge Infrastructure [CNKI] and Wanfang Database) were systematically searched. We included 76 studies with 388,966 samples. Random-effects models were used to pool the odds ratios (ORs) across studies. Overall, IPV and its subtypes had statistically significant impacts on PPD (overall: OR = 2.50, physical: OR = 2.31, psychological: OR = 2.22, sexual: OR = 1.75). A higher impact of IPV on PPD was observed in middle- and low-income regions (OR = 3.01) than in high-income regions (OR = 1.92). IPV during pregnancy (OR = 2.73) had a greater impact on PPD than lifetime IPV (OR = 2.24). This study provides updated evidence for the significant impact of IPV and its subtypes and exposure time on PPD. Women at risk of exposure to physical IPV, especially during pregnancy, are in urgent need of support to reduce the risk of PPD.

Associations between contrast-enhanced ultrasound features and WHO/ISUP grade of clear cell renal cell carcinoma: a retrospective study.

BACKGROUND: Clear cell renal cell carcinoma (CCRCC) comprises 70%-80% of RCCs. The World Health Organization/International Society of Urology Pathology (WHO/ISUP) classification is the most important prognostic factor for CCRCC. By evaluating the variations of tumor microvascular density, contrast-enhanced ultrasound (CEUS) can noninvasively predict the WHO/ISUP grade of CCRCC, and provide the appropriate treatment plan before clinical operation. METHODS: In this study, we used CEUS features to analyze 116 CCRCC cases and assess the value of correlation between each indicator and CCRCC WHO/ISUP grading. RESULTS: When compared to high-grade (WHO/ISUP grade III/IV) tumors, low-grade (WHO/ISUP grade I/II) tumors had reduced relative peak intensity (ΔPI) (P = 0.021), relative area under the curve (ΔAUC) (P = 0.019). However, the frequency of incomplete pseudocapsule (P = 0.021) was significantly higher in high-grade tumors. A cut-off value of mean diameter > 5.5 cm, ΔPI > 304 × 10-3, ΔAUC > 350 × 10-3 allowed identification of high-grade tumors with an area under the curve (AUC) of 74.6%, 71.7%, 70.7%, respectively (95% confidence interval). CONCLUSIONS: The features of CEUS are effective for differentiating high-grade tumors from low-grade tumors, thus CEUS can be considered an acceptable method for the preoperative assessment of tumor grade.

Childhood Emotional Neglect and Cognitive Function Among Middle-Aged and Older Adults: Mediating Role of Social Engagement.

Studies have demonstrated that childhood maltreatment and adverse experiences lead to impaired cognitive function. However, relatively few studies have examined the independent effect of childhood emotional neglect on cognitive function in middle-aged and older adults, and the role of social engagement in this relationship. Using a sample from the China Health and Retirement Longitudinal Study, the current study examined the mediating role of social engagement in the association between childhood emotional neglect and cognitive function among middle-aged and older adults. Participants were 32,540 middle-aged and older adults (Mage = 63.45, SD = 8.83). Data were analyzed using a fixed effects model for panel data and bootstrap resampling method. Results showed that participants who experienced emotional neglect had poorer cognitive function (ß = -.068, p < .001). Social engagement mediated 7.55% of the association between emotional neglect and cognitive function (ß = -.004, 95% CI [-0.006, -0.002], p < .05). The results indicated that interventions are required to improve awareness of emotional neglect and facilitate healthy parenting practices. Further research on how to motivate adults who experienced emotional neglect to engage in social activities is necessary.

The efficacy of an evidence-based parenting program in preventing child maltreatment in mainland China.

BACKGROUND: There is limited evidence regarding the effectiveness of online parenting programs for preventing child maltreatment in low- and middle-income countries. Therefore, this study aimed to examine the effectiveness of the online Parenting for Lifelong Health for Young Children (PLH-YC) program in preventing child maltreatment among Chinese families specifically. METHODS: A quasi-experiment was conducted, wherein 274 parents with children aged 2-9 years were assigned to either the online PLH-YC group (n = 135) or a waitlist control group (n = 139). Data were collected at baseline and one week after intervention. A difference-in-differences (DiD) design with propensity score weighting was used to estimate the between-group difference for child maltreatment as well as the associated risk and protective factors. RESULTS: Compared to the parents in the control group, parents in the online PLH-YC intervention reported a significant reduction in the occurrence of corporal punishment (b = -1.21; 95 % CI [-2.37, -0.03]), emotional abuse (b = -3.09; 95 % CI [-5.36, -0.82]), and general maltreatment (b = -4.94; 95 % CI [-8.86, -1.02]) as well as an increased frequency of positive parenting strategies (b = 6.46; 95 % CI [2.21, 10.72]). Additionally, parents with high levels of depressive symptoms were significantly more likely to drop out of the program, and those with lower education levels engaged in fewer sessions. CONCLUSION: The online PLH-YC program can benefit families with young children by reducing the incidence of child maltreatment through improved positive parenting strategies. More randomized controlled trials with long-term follow-ups are required to further verify the accuracy of the results obtained in this study.

Chronic intermittent ethanol exposure-induced m6A modifications around mRNA stop codons of opioid receptor genes.

Chronic alcohol consumption may alter mRNA methylation and expression levels of genes related to addiction and reward in the brain, potentially contributing to alcohol tolerance and dependence. Neuron-like (SH-SY5Y) and non-neuronal (SW620) cells were utilized as models to examine chronic intermittent ethanol (CIE) exposure-induced global m6A RNA methylation changes, as well as m6A mRNA methylation changes around the stop codon of three opioid receptor genes (OPRM1, OPRD1, and OPRK1), which are known to regulate pain, reward, and addiction behaviours. CIE exposure for three weeks significantly increased global RNA methylation levels in both SH-SY5Y (t = 3.98, P = 0.007) and SW620 (t = 2.24, P = 0.067) cells. However, a 3-week CIE exposure resulted in hypomethylation around mRNA stop codon regions of OPRM1 and OPRD1 in both cell lines [OPRM1(SH-SY5Y): t = -5.05, P = 0.0005; OPRM1(SW620): t = -3.19, P = 0.013; OPRD1(SH-SY5Y): t = -13.43, P < 0.00001; OPRD1(SW620): t = -4.00, P = 0.003]. Additionally, mRNA expression levels of OPRM1, OPRD1, and OPRK1 were downregulated (corresponding to mRNA hypomethylation) in both SH-SY5Y and SW620 cells after a 3-week CIE exposure. The present study demonstrated that chronic ethanol exposure altered global RNA methylation levels, as well as mRNA methylation and expression levels of opioid receptor genes in both neuron-like and non-neuronal cells. Our findings suggest a potential epitranscriptomic mechanism by which chronic alcohol consumption remodels the expression of reward-related and alcohol responsive genes in the brain, thus increasing the risk of alcohol use disorder development.Abbreviations: OPRM1: the µ-opioid receptor; OPRD1: the δ-opioid receptor; OPRK1: the κ-opioid receptor; CIE: chronic intermittent ethanol exposure; CIE+WD: chronic intermittent ethanol exposure followed by a 24-hr withdrawal; SH-SY5Y: human neuroblastoma cell Line; SW620: human colon carcinoma cell line; RT-qPCR: reverse transcription followed by quantitative polymerase reaction; MazF-RT-qPCR: MazF digestion followed by RT-qPCR.

Transcriptome analysis of meiotic and post-meiotic spermatogenic cells reveals the potential hub genes of aging on the decline of male fertility.

Genetic and epigenetic changes in sperm caused by male aging may be essential factors affecting semen parameters, but the effects and specific molecular mechanisms of aging on male reproduction have not been fully clarified. In this study, to explore the effect of aging on male fertility and seek the potential molecular etiology, we performed high-throughput RNA-sequencing in isolated spermatogenic cells, including pachytene spermatocytes (marked by the completion of chromosome synapsis) and round spermatids (produced by the separation of sister chromatids) from the elderly and the young men. Functional enrichment analysis of differentially expressed genes (DEGs) in round spermatids between the elderly and young showed that they were significantly enriched in gamete generation, spindle assembly, and cilium movement involved in cell motility. In addition, the expression levels of DEGs in round spermatids (post-meiotic cells) were found to be more susceptible to age. Furthermore, ten genes (AURKA, CCNB1, CDC20, CCNB2, KIF2C, KIAA0101, NR5A1, PLK1, PTTG1, RAD51AP1) were identified to be the hub genes involved in the regulation of sperm quality in the elderly through Protein-Protein Interaction (PPI) network construction and measuring semantic among GO terms and gene products. Our data provide aging-related molecular alterations in meiotic and post-meiotic spermatogenic cells, and the information gained from this study may explain the abnormal aging-related male fertility decline.

Does Child Maltreatment Reduce or Increase Empathy? A Systematic Review and Meta-analysis.

Arguments about the associations between child maltreatment and empathy remain controversial. This systematic review and meta-analysis aim to estimate the direction and magnitude of the relationships between child abuse and neglect and empathy. Four English databases (Web of Science, PsycInfo, PubMed, and Cochrane Library), three Chinese databases (China National Knowledge Infrastructure, Wanfang, and Weipu), and grey literature were systematically searched. We extracted data related to the associations between child maltreatment and empathy and pooled them using random effects models. A total of 24 eligible studies involving 22,580 participants and 176 estimates were included in the analyses. Overall, child maltreatment was significantly related to reduced empathy (r_ = -0.15, 95% CI [-0.17, -0.13]). Specifically, the rank-order mean effect size of subtypes of maltreatment on empathy is: emotional neglect (r_ = -0.18, 95% CI [-0.25, -0.12]) > physical neglect (r_ = -0.16, 95% CI [-0.23, -0.09]) > emotional abuse (r_ = -0.15, 95% CI [-0.21, -0.10]) > physical abuse (r_ = -0.12, 95% CI [-0.17, -0.07]) > sexual abuse (r_ = -0.07, 95% CI [-0.14, -0.01]). Furthermore, the meta-regression results suggested that the aggregated associations between child maltreatment and empathy were not inflated by publication bias, but they were moderated by the age of respondents, sample size, publication language, empathy measurement, and maltreatment type. The results indicate that general maltreatment and its subtypes are associated with reduced empathy. Parent training and empathy enhancement programs should be designed to help children with a history of childhood maltreatment, respectively, from an early stage.