Future COVID-19 Booster Vaccine Refusal in Healthcare Workers after a Massive Breakthrough Infection Wave, a Nationwide Survey-Based Study.

Background: An unprecedented coronavirus disease 2019 (COVID-19) wave occurred in China between December 2022 and January 2023, challenging the efficacy of the primary series of COVID-19 vaccines. The attitudes toward future COVID-19 booster vaccines (CBV) after the massive breakthrough infection among healthcare workers remain unknown. This study aimed to explore the prevalence and determinants of future CBV refusal after the unprecedented COVID-19 wave among healthcare workers. Methods: Between 9 and 19 February 2023, a cross-sectional nationwide online survey was conducted using a self-administered questionnaire vaccine among healthcare workers in China. Sociodemographics, profession, presence of chronic medical conditions, previous COVID-19 infection, attitudes towards future CBV, and reasons for future CBV refusal were collected. We estimated odds ratio [OR] with 95% confidence interval [CI] using a multivariable logistic regression model to explore the factors associated with future CBV refusal. Results: Among the 1618 participants who completed the survey, 1511 respondents with two or more doses of COVID-19 vaccines were analyzed. A total of 648 (41.8%) of respondents were unwilling to receive a future CBV. Multivariable logistic regression analysis revealed the association of CBV refusal with profession (vs. other staff, physician-adjusted OR 1.17, 95%CI 0.79-1.72, nurse-adjusted OR 1.88, 95%CI 1.24-2.85, p = 0.008), history of allergy (adjusted OR 1.72, 95%CI 1.05-2.83, p = 0.032), a lower self-perceived risk of future COVID-19 infection (p < 0.001), and a lower belief in CBV effectiveness (p = 0.014), safety (p < 0.001), and necessities for healthcare workers and the public (p < 0.001, respectively). Conclusions: Our findings highlight that a considerable proportion of healthcare workers were against a future booster dose after an unprecedented COVID-19 wave. Self-perception of future COVID-19 risk, and potential harm or doubtful efficacy of vaccines are the main determinants. Our findings may help public health authorities to establish future COVID-19 vaccination programs.

Psychological stress and coping strategies among frontline healthcare workers supporting patients with coronavirus disease 2019: a retrospective study and literature review.

BACKGROUND: The coronavirus disease 2019 (COVID-19) outbreak might have a psychological impact on frontline healthcare workers. However, the effectiveness of coping strategies was less reported. OBJECTIVES: We aimed to investigate the sources of stress and coping strategies among frontline healthcare workers fighting against COVID-19. We also performed a literature review regarding the effects of coping methods on psychological health in this population. METHODS: We included frontline healthcare workers who completed an online survey using self-made psychological stress questionnaires in a cross-sectional study. We evaluated the association between potential factors and high-stressed status using a logistic regression model. We performed the principal component analysis with varimax rotation for factor analysis. We also performed a systematic review of published randomized controlled studies that reported the effects of coping methods on psychological health in COVID-19 healthcare workers. RESULTS: We included 107 [32 (29-36) years] respondents in the final analysis, with a response rate of 80.5%. A total of 41 (38.3%) respondents were high-stressed. Compared with the low-stressed respondents, those with high-stress were less likely to be male (46.3% versus 72.7%, p = 0.006), nurses (36.6% versus 80.3%, p < 0.001), and more likely to have higher professional titles (p = 0.008). The sources of high-stress in frontline healthcare workers were categorized into 'work factor', 'personal factor', and 'role factor'. A narrative synthesis of the randomized controlled studies revealed that most of the coping methods could improve the psychological stress in healthcare workers during the COVID-19 pandemic. CONCLUSION: Our findings suggest that some frontline healthcare workers experienced psychological stress during the early pandemic. Effective coping strategies are required to help relieve the stress in this population.

Association Between Previous Stroke and Severe COVID-19: A Retrospective Cohort Study and an Overall Review of Meta-Analysis.

Objective: The objective of this study was to investigate the association between previous stroke and the risk of severe coronavirus disease 2019 (COVID-19). Methods: We included 164 (61.8 ± 13.6 years) patients with COVID-19 in a retrospective study. We evaluated the unadjusted and adjusted associations between previous stroke and severe COVID-19, using a Cox regression model. We conducted an overall review of systematic review and meta-analysis to investigate the relationship of previous stroke with the unfavorable COVID-19 outcomes. Results: The rate of severe COVID-19 in patients with previous stroke was 28.37 per 1,000 patient days (95% confidence interval [CI]: 10.65-75.59), compared to 3.94 per 1,000 patient days (95% CI: 2.66-5.82) in those without previous stroke (p < 0.001). Previous stroke was significantly associated with severe COVID-19 using a Cox regression model (unadjusted [hazard ratio, HR]: 6.98, 95% CI: 2.42-20.16, p < 0.001; adjusted HR [per additional 10 years]: 4.62, 95% CI: 1.52-14.04, p = 0.007). An overall review of systematic review and meta-analysis showed that previous stroke was significantly associated with severe COVID-19, mortality, need for intensive care unit admission, use of mechanical ventilation, and an unfavorable composite outcome. Conclusion: Previous stroke seems to influence the course of COVID-19 infection; such patients are at high risk of severe COVID-19 and might benefit from early hospital treatment measures and preventive strategies.

Intravenous thrombolysis prior to endovascular treatment for acute ischemic stroke: a meta-analysis.

OBJECTIVES: Whether intravenous thrombolysis provides additional benefits before direct endovascular treatment (dEVT) in acute ischemic stroke remains unclear. We aimed to compare the functional and safety outcomes of dEVT to endovascular treatment with bridging using intravenous thrombolysis (BT) in acute ischemic stroke. METHODS: This meta-analysis included currently available eligible randomized clinical trials (RCTs) by searching in the PubMed, EMBASE, Cochrane Central Register, and the International Stroke Conference and European Stroke Organisation Conference posted abstracts. RESULTS: The six included RCTs yielded 2334 participants (mean age, 69.8 years [SD, 11.4]; women, 44.3%; 1164 in dEVT group and 1170 in BT group). We found not significantly different 90-day functional outcomes of modified Rankin scale (mRS 0 - 2, odds ratio [OR] 0.93, 95%CI 0.79 - 1.09; mRS 0 - 1, OR 0.99, 95%CI 0.82 - 1.18), mortality (OR 1.08, 95%CI 0.86 - 1.35), and symptomatic intracranial hemorrhage (OR 0.72, 95%CI 0.49 - 1.07) for patients in dEVT and BT group. Patients treated with dEVT were less likely to experience successful recanalization (OR 0.72, 95%CI 0.57 - 0.92, p = 0.009) and any intracranial hemorrhage (OR 0.81, 95%CI 0.68 - 0.97, p = 0.02). There were no significant differences regarding procedural complications between the two groups. CONCLUSION: This meta-analysis showed no significant differences in 90-day functional outcomes or mortality between dEVT and BT, but a lower possibility of successful recanalization and intracranial hemorrhage for dEVT.

Associations and pathways between residential greenness and metabolic syndromes in Fujian Province.

Background: Greenness exposure is beneficial to human health, but its potential mechanisms through which the risk for metabolic syndrome (MetS) could be reduced have been poorly studied. We aimed to estimate the greenness-MetS association in southeast China and investigate the independent and joint mediation effects of physical activity (PA), body mass index (BMI), and air pollutants on the association. Methods: A cross-sectional study was conducted among the 38,288 adults based on the Fujian Behavior and Disease Surveillance (FBDS), established in 2018. MetS was defined as the presence of three or more of the five components: abdominal obesity, elevated triglyceride, reduced high-density lipoprotein cholesterol (HDL-C), high blood pressure, and elevated fasting glucose. The residential greenness exposure was measured as the 3-year mean values of the normalized difference vegetation index (NDVI) and enhanced vegetation index (EVI) within the 250, 500, and 1,000 meters (m) buffer zones around the residential address of each participant. Logistic regression models were used to estimate the greenness-MetS association. The causal mediation analysis was used to estimate the independent and joint mediation effects of PA, BMI, particulate matter with an aerodynamic diameter of 2.5 µm (PM2.5), particulate matter with an aerodynamic diameter ≤ 10 µm (PM10), nitrogen dioxide (NO2), and sulfur dioxide (SO2). Results: Each interquartile range (IQR) increase in greenness was associated with a decrease of 13% (OR = 0.87 [95%CI: 0.83, 0.92] for NDVI500m and OR = 0.87 [95%CI: 0.82, 0.91] for EVI500m) in MetS risk after adjusting for covariates. This association was stronger in those aged < 60 years (e.g., OR = 0.86 [95%CI: 0.81, 0.92] for NDVI500m), males (e.g., OR = 0.73 [95%CI: 0.67, 0.80] for NDVI500m), having an educational level of primary school or above (OR = 0.81 [95%CI: 0.74, 0.89] for NDVI500m), married/cohabitation (OR = 0.86 [95%CI: 0.81, 0.91] for NDVI500m), businessman (OR = 0.82 [95%CI: 0.68, 0.99] for NDVI500m), other laborers (OR = 0.77 [95%CI: 0.68, 0.88] for NDVI500m), and non-smokers (OR = 0.77 [95%CI: 0.70, 0.85] for NDVI500m). The joint effect of all six mediators mediated about 48.1% and 44.6% of the total effect of NDVI500m and EVI500m on the MetS risk, respectively. Among them, BMI showed the strongest independent mediation effect (25.0% for NDVI500m), followed by NO2 and PM10. Conclusion: Exposure to residential greenness was associated with a decreased risk for MetS. PA, BMI, and the four air pollutants jointly interpreted nearly half of the mediation effects on the greenness-MetS association.

Six-month follow-up of functional status in discharged patients with coronavirus disease 2019.

BACKGROUND: The long-term functional outcome of discharged patients with coronavirus disease 2019 (COVID-19) remains unresolved. We aimed to describe a 6-month follow-up of functional status of COVID-19 survivors. METHODS: We reviewed the data of COVID-19 patients who had been consecutively admitted to the Tumor Center of Union Hospital (Wuhan, China) between 15 February and 14 March 2020. We quantified a 6-month functional outcome reflecting symptoms and disability in COVID-19 survivors using a post-COVID-19 functional status scale ranging from 0 to 4 (PCFS). We examined the risk factors for the incomplete functional status defined as a PCFS > 0 at a 6-month follow-up after discharge. RESULTS: We included a total of 95 COVID-19 survivors with a median age of 62 (IQR 53-69) who had a complete functional status (PCFS grade 0) at baseline in this retrospective observational study. At 6-month follow-up, 67 (70.5%) patients had a complete functional outcome (grade 0), 9 (9.5%) had a negligible limited function (grade 1), 12 (12.6%) had a mild limited function (grade 2), 7 (7.4%) had moderate limited function (grade 3). Univariable logistic regression analysis showed a significant association between the onset symptoms of muscle or joint pain and an increased risk of incomplete function (unadjusted OR 4.06, 95% CI 1.33-12.37). This association remained after adjustment for age and admission delay (adjusted OR 3.39, 95% CI 1.06-10.81, p = 0.039). CONCLUSIONS: A small proportion of discharged COVID-19 patients may have an incomplete functional outcome at a 6-month follow-up; intervention strategies are required.

The predictive value of serum level of cystatin C for COVID-19 severity.

To investigate the potential prognostic value of Serum cystatin C (sCys C) in patients with COVID-19 and determine the association of sCys C with severe COVID-19 illness. We performed a retrospective review of medical records of 162 (61.7 ± 13.5 years) patients with COVID-19. We assessed the predictive accuracy of sCys C for COVID-19 severity by the receiver operating characteristic (ROC) curve analysis. The participants were divided into two groups based on the sCys C cut-off value. We evaluated the association between high sCys C level and the development of severe COVID-19 disease, using a COX proportional hazards regression model. The area under the ROC curve was 0.708 (95% CI 0.594-0.822), the cut-off value was 1.245 (mg/L), and the sensitivity and specificity was 79.1% and 60.7%, respectively. A multivariable Cox analysis showed that a higher level of sCys C (adjusted HR 2.78 95% CI 1.25-6.18, p = 0.012) was significantly associated with an increased risk of developing a severe COVID-19 illness. Patients with a higher sCys C level have an increased risk of severe COVID-19 disease. Our findings suggest that early assessing sCys C could help to identify potential severe COVID-19 patients.

The role of microRNAs in regulating cadmium-induced apoptosis by targeting Bcl-2 in IEC-6 cells.

Cadmium (Cd) is one of the most harmful environmental pollutants and has been found to have adverse effects on the gut. However, the toxic effects and potential mechanism of Cd on intestinal epithelial cells (IECs) are poorly understood. This study evaluated the effects of Cd exposure (0, 0.25, 0.5, 1, 2, and 4 µM) on IEC-6 cells in terms of cell viability and apoptosis, as well as apoptosis-associated gene expression. The results indicated that low doses (0.25- 1 µM) of Cd exhibited hormetic effects, while high doses of Cd (2 and 4 µM) reduced cell viability. The apoptotic effect increased in a dose-dependent pattern. Moreover, the mRNA levels of the Bcl-2, Bax and Caspase 3 genes were altered, which was in agreement with their protein expression. Based on sequencing analysis, the expression pattern of the microRNAs (miRNAs) changed significantly in the 2 µM Cd-treated group. QRT-PCR verified that 7 miRNAs, including miR-124-3p and miR-370-3p, were all upregulated with dose-effect relationship. Besides, transfection of miR-124-3p and miR-370-3p mimics /inhibitor and Bcl-2 siRNA into IEC-6 cells verified that these two miRNAs could regulate Cd-induced apoptosis by targeting Bcl-2. Finally, the direct targeting relationship between miR-370-3p and Bcl-2 gene was confirmed by luciferase reporter assay. Overall, the results demonstrated that Cd exposure could induce apoptosis in IEC-6 cells. The potential mechanism may be interference with the regulation of Bcl-2 gene expression by miR-370-3p and miR-124-3p.

Prevalence and outcomes of re-positive nucleic acid tests in discharged COVID-19 patients.

The prevalence and outcomes of patients who had re-activation of coronavirus disease 2019 (COVID-19) after discharge remain poorly understood. We included 126 consecutively confirmed cases of COVID-19 with 2-month follow-up data after discharge in this retrospective study. The upper respiratory specimen using a reverse-transcription polymerase chain reaction test of three patients (71 years [60-76]) were positive within 11-20 days after their discharge, with an event rate of 19.8 (95%CI 2.60-42.1) per 1,000,000 patient-days. Moreover, all re-positive patients were asymptomatic. Our findings suggest that few recovered patients may still be virus carriers even after reaching the discharge criteria.

The effect of vascular risk factor burden on the severity of COVID-19 illness, a retrospective cohort study.

BACKGROUND: Patients with cardiovascular comorbidities are at high risk of poor outcome from COVID-19. However, how the burden (number) of vascular risk factors influences the risk of severe COVID-19 disease remains unresolved. Our aim was to investigate the association of severe COVID-19 illness with vascular risk factor burden. METHODS: We included 164 (61.8 ± 13.6 years) patients with COVID-19 in this retrospective study. We compared the difference in clinical characteristics, laboratory findings and chest computed tomography (CT) findings between patients with severe and non-severe COVID-19 illness. We evaluated the association between the number of vascular risk factors and the development of severe COVID-19 disease, using a Cox regression model. RESULTS: Sixteen (9.8%) patients had no vascular risk factors; 38 (23.2%) had 1; 58 (35.4%) had 2; 34 (20.7%) had 3; and 18 (10.9%) had ≥4 risk factors. Twenty-nine patients (17.7%) experienced severe COVID-19 disease with a median (14 [7-27] days) duration between onset to developing severe COVID-19 disease, an event rate of 4.47 per 1000-patient days (95%CI 3.10-6.43). Kaplan-Meier curves showed a gradual increase in the risk of severe COVID-19 illness (log-rank P < 0.001) stratified by the number of vascular risk factors. After adjustment for age, sex, and comorbidities as potential confounders, vascular risk factor burden remained associated with an increasing risk of severe COVID-19 illness. CONCLUSIONS: Patients with increasing vascular risk factor burden have an increasing risk of severe COVID-19 disease, and this population might benefit from specific COVID-19 prevention (e.g., self-isolation) and early hospital treatment measures.

Association Between Steno-Occlusive Middle Cerebral Artery and Basal Ganglia Perivascular Spaces.

Objectives: Enlarged perivascular spaces in the basal ganglia (BG-EPVS) share common vascular risk factors with atherosclerosis. However, little is known about the relationship between steno-occlusive middle cerebral artery (MCA) and BG-EPVS. In this cross-sectional study, we aimed to test the hypothesis that severe MCA stenosis or occlusion is associated with increased MRI-visible BG-EPVS. Methods: We retrospectively reviewed 112 patients with a steno-occlusive MCA from Fujian Medical University Union Hospital between January 2014 and December 2018. We rated BG-EPVS, white matter hyperintensities (WMH), and lacunes as markers of cerebral small vessel disease (CSVD) on magnetic resonance image (MRI). The severity of steno-occlusive MCA was assessed by computed tomography angiography (CTA) and was classified into moderate (50-69%), severe (70-99%), and occlusion (100%). We evaluated the association of steno-occlusive MCA for >10 BG-EPVS using logistic regression model adjusted for age, gender, hypertension, MR-visible WMH, and lacunes. We also compared the number of BG-EPVS between the affected side and unaffected side in patients with only unilateral steno-occlusive MCA. Results: In multivariable logistic regression analysis, age (OR = 1.07, 95%CI: 1.03-1.13, p = 0.003), hypertension (OR = 2.77, 95%CI: 1.02-7.51, p = 0.046), severe MCA stenosis (OR = 3.65, 95%CI: 1.12-11.87, p = 0.032), or occlusion (OR = 3.67, 95%CI: 1.20-11.27, p = 0.023) were significantly associated with >10 BG-EPVS. The number of BG-EPVS in the affected side was higher than the unaffected side in patients with severe MCA stenosis (12 [9-14] vs. 8 [6-11], p = 0.001) or occlusion (11 [7-14] vs. 8 [5-11], p = 0.028). Conclusions: BG-EPVS were more prevalent in patients with severe MCA atherosclerosis. Our findings suggest a biological link between severe steno-occlusive MCA and increased BG-EPVS. These results need confirmation in prospective studies.

Effectiveness of first-line antiretroviral therapy in HIV/AIDS patients: A 5-year longitudinal evaluation in Fujian Province, Southeast China.

The aim of this study was to evaluate the long-term effectiveness of first-line antiretroviral therapy in HIV/AIDS patients in Southeast China. A total of 450 eligible patients were selected to initiate first-line antiretroviral therapy from February 2005 through August 2009. During the study period from 2009 through 2013, each subject received clinical and laboratory monitoring for effectiveness, safety and toxicity once every 3 months in the first year, and once every 6 months in the following years. The response to first-line antiretroviral therapy was evaluated through body weight gain and immunological and virological outcomes. During the mean follow-up period of 70.86 ± 28.9 months, the overall mortality was 14.2%. The mean body weight and CD4(+) counts increased significantly following antiretroviral therapy as compared to baselines across the follow-up period, and the rate of immunological effectiveness was over 85% in all subjects at 2 to 5 years of treatment. The rate of inhibition of HIV virus was 87.67%, 89.32%, 91.73%, 92.8% and 91.63% across the study period. In addition, significant differences were detected after treatment as compared to baselines, and Pearson correlation analysis revealed a positive correlation between immunological effectiveness and viral inhibition. Forty-eight percent of the subjects changed antiretroviral drugs once, and 16.22% twice, and 31 patients switched from first-line to second-line antiretroviral therapy. Long-term antiretroviral therapy remains effective for treatment of HIV/AIDS, resulting in higher mean body weight, effective viral inhibition and a higher CD4 count. Immunological effectiveness of antiretroviral therapy positively correlates with HIV viral inhibition.

Steps towards preventive HIV treatment in Fujian, China: problems identified via an assessment of initial antiretroviral therapy provision.

BACKGROUND: At the end of 2009, a total of 501 AIDS patients were receiving antiretroviral therapy (ART) in Fujian Province in China, yet there were no assessments to determine treatment efficacy and HIV-1 preventive potency under the current health care delivery system. METHODS: During the period of 2005-2009, we assessed the outcomes of initial ART by following up 381 patients for 12 months in Fujian Province. CD4⁺ T-lymphocyte (CD4) count, plasma viral load (VL), and patient characteristics were analysed. The results were compared between 4 groups divided by the baseline CD4 values at the 25, 50 (median), and 75 percentiles. FINDINGS: Over three-quarters of the subjects reported heterosexual contact as the probable route of transmission. After 12 months of ART, CD4 recovery varied between the 4 groups (P < 0.001), but VL sharply declined regardless of the baseline CD4 count (P = 0.136). Although this VL decline indicates the potency of ART as an HIV-1 prevention tool, the time between positive diagnosis and ART initiation suggests serious delay in both diagnosis and treatment; the medians of periods for the lowest and highest baseline CD4 quartiles were 1.2 and 9.6 months, respectively. CONCLUSION: Current limitations in VL determination make it difficult to assess the efficacy of initial ART, and delays in diagnosis and treatment suggest that subjects contributed to HIV-1 transmission while they were not receiving ART. The current National Free ART scheme does not provide free treatment for sexually transmitted infection (STI), and there is no link between ART and the STI care delivery system. This may interfere with the HIV-1 preventive potency of ART. We highly recommend establishing a collaborating mechanism with STI care, strengthening the VL determination system, and promoting HIV tests and early ART initiation.

Distribution of Two Subgroups of Human T-Lymphotropic Virus Type 1 (HTLV-1) in Endemic Japan.

Endemic areas of human T-lymphotropic virus type 1 (HTLV-1) have been reported in Japan as well as tropical Africa, Central and South America and Melanesia. The existence of two subgroups, i.e., the transcontinental and Japanese subgroups, was reported in Japan. In the present study, we provide data on the ratio of the two subgroups in each endemic area and infection foci and examine the distribution of HTLV-1 in Japan and neighboring areas. A 657 bp fragment of env region of HTLV-1 proviral genome was successfully amplified for 183 HTLV-1 positive DNA samples. The subgroup determination was done by RFLP reactions using endonucleases HpaI and HinfI. The northern part of mainland Kyushu, represented by Hirado and Kumamoto, was monopolized by the Japanese subgroup, while the transcontinental subgroup ranged from 20 to 35% in the Pacific coast areas of Shikoku (Kochi), the Ryukyu Archipelago (Kakeroma and Okinawa) and Taiwan. An interesting finding in the present study is the presence of the transcontinental subgroup in Kochi, suggesting the endemicity of the transcontinental subgroup along the Kuroshio Current.

The nine-repeat DC-SIGNR isoform is associated with increased HIV-RNA loads and HIV sexual transmission.

OBJECTIVES: Determine if different DC-SIGNR genotypes/alleles correlated with HIV susceptibility in the context of the HIV mode of infection, CD4+ T cell counts and blood HIV RNA loads. METHODS: One hundred forty-five HIV infected individuals and 187 uninfected healthy controls were recruited to observe whether DC-SIGNR genotypes/alleles were correlated with HIV susceptibility, CD4+ T cell numbers and HIV-RNA levels. RESULTS: The frequencies of DC-SIGNR genotypes/alleles in HIV-infected patients were similar to those seen in the uninfected population. However, the 9-repeat DCSIGNR allele was more frequently found in patients infected via sexual transmission compared to patients infected via blood transmission/intravenous drug use (p = 0.005). HIV RNA levels in patients with the 9- or 7-repeat DC SIGNR allele were significantly higher than the levels observed in patients with the 5-repeat DC SIGNR allele (p = 0.004, p = 0.004, respectively) and the HIV RNA levels in patients with the 9/7 genotype or with the 7/7 genotype were significantly higher than patients with the 7/5 genotype (p = 0.003, p = 0.029, respectively). There were no significant differences between CD4+ T cells in patients with different DC-SIGNR genotypes/alleles. CONCLUSIONS: No DC-SIGNR genotypes/alleles were associated with reduced HIV susceptibility, however, DC-SIGNR genotypes/alleles with higher repeat numbers were associated with higher HIV-RNA blood levels, that is, the 9-repeat DC-SIGNR allele was significantly associated with increased HIV-RNA levels and HIV sexual transmission.

Comparative studies on the increase of uterine weight and related mechanisms of cadmium and p-nonylphenol.

The research was designed to compare the effect of cadmium and p-nonylphenol on the increase of uterine weight and to study the related mechanisms. It provided basic evidence for us to understand the possible different mechanisms among different EEDs. In this study, both ovaries of 60 Wistar rats (28 days age) were ectomized, and after 21 days recovery, the rats were randomly assigned into six groups and exposed to cadmium (0.12, 1.20mg/kg), NP (100, 200mg/kg), control (sterile PBS), and positive control (17beta-estradiol) per day for 3 days, respectively, then related indexes were detected. The results showed that the increase of uterine weight induced by cadmium was accompanied by the increase of the thickness of luminal epithelium cell and endometrium but the decrease of nuclear/cytoplasm of luminal epithelium cell and endometrium, while the increase of uterine weight induced by p-nonylphenol was accompanied by the increase of the thickness of luminal epithelium cell, endometrium, and myometrium but the decrease of nuclear/cytoplasm of luminal epithelium cell and endometrium. Cadmium could inhibit the positive expression of PCNA while p-nonylphenol prompted it. Exposure to cadmium and NP both could also stimulate phosphorylation of ERK mitogen-activated protein kinases, implying that this signal pathway had an effect on the increase of the uterine weight induced by cadmium and p-nonylphenol. The results indicate that cadmium may induce the increase of uterine weight, which is accompanied with toxic effect on endometrium, while NP's effect of the increase of uterine weight is due to cell proliferation of endometrium, the mechanisms of which are the same as estrogen, but they may both activate ERK signal pathway.