CagA-positive Helicobacter pylori may promote and aggravate scrub typhus.

Helicobacter pylori (H. pylori) infection may alter the host's resistance to tsutsugamushi disease pathogens through the Th1 immune response, leading to potential synergistic pathogenic effects. A total of 117 scrub typhus cases at Beihai People's Hospital and affiliated hospitals of Youjiang University for Nationalities and Medical Sciences were studied from January to December 2022, alongside 130 healthy individuals forming the control group. All participants underwent serum H. pylori antibody testing. The prevalence of H. pylori infection was significantly higher among scrub typhus patients (89.7%) compared to healthy individuals (54.6%) (p < 0.05). Moreover, type I H. pylori infection was notably more prevalent in scrub typhus cases (67.5%) compared to healthy individuals (30%) (p < 0.05). Multifactorial analysis demonstrated type I H. pylori infection as an independent risk factor for scrub typhus (adjusted odds ratio: 2.407, 95% confidence interval: 1.249-4.64, p = 0.009). Among scrub typhus patients with multiple organ damage, the prevalence of type I H. pylori infection was significantly higher (50.6%) than type II H. pylori infection (15.4%) (χ2 = 4.735, p = 0.030). These results highlight a higher incidence of H. pylori infection in scrub typhus patients compared to the healthy population. Additionally, type I H. pylori strain emerged as an independent risk factor for scrub typhus development. Moreover, individuals infected with type I H. pylori are more susceptible to multiple organ damage. These findings suggest a potential role of H. pylori carrying the CagA gene in promoting and exacerbating scrub typhus.

[Response of Cadmium in Soil-rice to Different Conditioners Based on Field Trials].

A plot experiment was carried out to assess the applicability of soil conditioners on Cd-polluted acidic paddy fields. The effects of five soil conditioners[Tianxiang 1 Hao (TX1), limestone (Li), silicon fertilizer, Nuodikang (NDK), and calcium magnesium phosphate fertilizer (CaMg-P)] on Cd accumulation and transport between contaminated soil and rice plants and rice yield on the land were analyzed. The results showed that compared with that under the control, other tested methods increased soil pH by 0.41-0.68 units and decreased available Cd content in the soil by 11.2%-39.7%. The difference between Li- and NDK-treated soil available Cd reached a significant level (P < 0.05). ② Compared with that in the blank control, the application of soil conditioner could significantly reduce the total amount of Cd in rice, and the Cd content in roots, other leaves, rachises, chaffs, and brown rice were significantly lower than those in the CK treatment (P < 0.05). The Cd translation factor between various sites was shown as TFroots-other nodes > TFroots-first nodes > TFroots-rachises > TFroots-chaffs ≈ TFroots-flag leaves > TFroots-brown rice. The Cd content of brown rice met the national safety standard (0.2 mg·kg-1), in which the TX1, Li, and CaMg-P treatments showed significant Cd reduction effects, and ω(Cd) was 0.097, 0.094, and 0.134 mg·kg-1, respectively. ③ The application of soil conditioner could increase the yield by 9.9%-35.8%, and the yield of the CaMg-P and TX1 treatments was significantly higher than that of other treatments (P < 0.05). ④ Correlation analysis showed that the Cd content in brown rice was significantly positively correlated with available Cd content in soil, available Fe content in soil, and available phosphorus but negatively correlated with soil pH. In summary, TX1 and CaMg-P are recommended to be applied in farmland lightly polluted by the heavy metal Cd to ensure the safety of agricultural products.

[Characteristics and Planting Safety Assessment of As Content in Dryland Soil and Maize in Guizhou Province].

In order to understand the distribution characteristics of As content in dryland soils and maize seeds in Guizhou province and to evaluate the safety of maize cultivation, 468 natural soil samples, 1260 dryland surface soil samples, and 980 corresponding maize seed samples were systematically collected to determine their As content and basic physicochemical properties. The degree of contamination of the samples was evaluated by using the single-factor contamination index method. The results showed that: ① the range of ω(As) in dryland soil was 0.35-758.53 mg·kg-1, with a geometric mean of 23.28 mg·kg-1. The independent sample T-test showed that the As content of dryland soil in Guizhou province was significantly higher than that of natural soil ω(As) 21.29 mg·kg-1 (P<0.01), indicating the existence of arsenic accumulation effects in dryland soil; compared with the screening value of the "Agricultural Land Soil Pollution Risk Management and Control Standard" (GB 15618-2018), the excess rate of soil samples was 33.81%. ② Corn seed ω(As) ranged from 0.001 to 0.868 mg·kg-1, with a mean value of 0.064 mg·kg-1, and 0.61% of the corn seed samples exceeded the limit value of "Limits of Contaminants in Foods" (GB 2762-2017), with the exceeding points distributed in Bijie City, Qianxinan Prefecture, and Tongren City. ③ When corn seeds were used as feed and grain, maize could be safely grown in dryland soils in Guizhou province. This study showed that the soil As pollution in the dryland of Guizhou province was relatively serious, and overall safe maize cultivation can be achieved; however, the cultivation of maize around the As-related non-ferrous metal mining areas is still of concern.

Comparing the efficacy of thyroglobulin and thyroglobulin/ thyroid-stimulating hormone ratio models in predicting a successful response to radioactive iodine therapy.

BACKGROUND: The thyroglobulin (Tg)/ thyroid-stimulating hormone (TSH) ratio has manifested to be a reliable marker for predicting prognosis in patients with differentiated thyroid carcinoma (DTC). The objective of this study was to compare the efficacy of Tg and Tg/TSH ratio models in predicting a successful response to radioactive iodine therapy. METHODS: One thousand six hundred forty-two DTC patients receiving 131I radiotherapy were finally enrolled in this retrospective study. The patients were divided into a training set (n = 973) and a validation set (n = 669) by the patient consultation time (July 2019). A receiver-operating characteristic curve was constructed for Tg and the Tg/TSH ratio to establish their cutoffs. Then, the variables were screened by univariate logistic regression and incorporated into logistic prediction models by stepwise regression, where Tg/TSH was excluded from model 1 and Tg was excluded from model 2. RESULTS: In 1642 enrolled DTC patients, the first 131I radiotherapy had an excellent response in 855 patients. The cut-offs for Tg level and Tg/TSH ratio were 3.40 ng/ mL [area under the curve (AUC): 0.789] and 36.03 ng/mIU (AUC: 0.788), respectively. In addition, the AUC of the model including Tg was higher than that of the model including Tg/TSH in both the training set (0.837 vs 0.833) and the testing set (0.854 vs 0.836). CONCLUSIONS: Both Tg and Tg/TSH ratios could be considered predictors of the effects of the first 131I ablative therapy. However, the prediction model including Tg performed better than the model including Tg/TSH.

Associations Between Abdominal Obesity Indices and Nonalcoholic Fatty Liver Disease: Chinese Visceral Adiposity Index.

Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver metabolic disease worldwide. Up to 70%-80% of patients with NAFLD were obese, especially abdominal obesity. Many indicators of abdominal obesity have been reported, including waist circumference (WC), visceral obesity index (VAI), lipid accumulation (LAP), and Chinese VAI (CVAI). However, few studies investigated the associations between these indices with NAFLD. This present study aims to explore the associations between abdominal obesity indices with NAFLD. A total of 7,238 participants were involved in the cross-sectional study, and 1,584 participants were included in the longitudinal study from Jidong communities. NAFLD was assessed by abdominal ultrasonography. The trajectory of WC, VAI, LAP, and CVAI during 2013-2016 was identified by a group-based trajectory model. The logistic regression and Cox proportional hazards models analyzed the correlations and causality between abdominal obesity indices with NAFLD. In this study, the prevalence and incidence of NAFLD are approximately 44% and 26%, respectively. In the cross-sectional study, WC, VAI, LAP, and CVAI are associated with NAFLD. After adjustment for potential confounders, the moderate-rising and high-rising groups of CVAI had the highest risk of NAFLD in longitudinal analysis (hazard ratio (HR): 3.903, 95%CI: 2.434-6.259; HR: 5.694 95%CI: 3.098-10.464, respectively). Receiving operating characteristic curves show that CVAI has the best diagnostic value for NAFLD (area under the curve (AUC) = 0.868). CVAI is independently associated with the risk of NAFLD and may also have an important value to the diagnosis of NAFLD.

[Characteristics of Antimony Migration and Transformation and Pollution Evaluation in a Soil-Crop System Around a Tin Mine in Hunan Province].

This study used 193 sets of farmland soil and agricultural product samples collected from around a tin mine in Hunan Province, China, to explore the antimony (Sb) content characteristics and pollution status of soil and agricultural products and to provide a scientific basis for the prevention and control of soil antimony pollution in antimony mining areas and the safe use of farmland. We analyzed the amount of antimony in the soil, basic physical and chemical properties, and antimony content in agricultural products; studied the characteristics of antimony migration and transformation in the soil-agricultural product system; and conducted safety assessments on soil and agricultural products. The results showed that the soil ω(Sb) in the central area of the mine, the southern area of the mine, the central township area, the urban-rural transfer area, and the northern area of the mine reached (2348±2165), (1298±884.1), (311.8±526.5), (302.5±355.9), and (215.6±183.2) mg·kg-1, and the exceeding multiples reached 65.22, 36.06, 8.66, 8.40, and 5.99 times, respectively. The antimony enrichment coefficients of lettuce, scallion, cabbage, water spinach, garlic, and pea seedlings in agricultural products were 0.01-0.1, which indicated good antimony absorption capacity. The antimony enrichment coefficients of loofah, asparagus lettuce, pepper, carrot, bitter gourd, corn, eggplant, cowpea, and celery were less than 0.01, and the antimony absorption capacity was relatively poor. The safety assessment results showed that roots, allium, and garlic vegetables had a high risk of antimony pollution; leafy vegetables and legumes had a higher risk of antimony pollution; and solanaceous vegetables, melons, and fruit vegetables and corn (cereals) had a high risk of antimony pollution. Therefore, it is urgent to take soil antimony pollution control measures in the mining area. At the same time, in order to realize the safe use of agricultural land in the mining area, the farmland far away from the low antimony content of the soil in the central area of the mine should be selected as the planting area, and the agricultural products with weak antimony absorption capacity should be planted first.

Delay of initial radioactive iodine therapy beyond 3 months has no effect on clinical responses and overall survival in patients with thyroid carcinoma: A cohort study and a meta-analysis.

BACKGROUND: More than a third of thyroid carcinoma (TC) patients require treatment with radioactive iodine (RAI), but the timing of initial RAI therapy after thyroidectomy remains controversial. METHODS: We included 1224 differentiated thyroid carcinoma (DTC) patients during 2015-2019, divided them into the early (≤3 months) and the delayed (>3 months) groups based on the interval between surgery and the initial RAI. Clinical outcomes were assessed within 6-8 months of treatment with RAI, including excellent response (ER), indeterminate response (IDR), biochemical incomplete (BIR) and structural incomplete response (SIR). Further transformed them into dichotomous outcomes, we therefore introduced the ordered/binary logistic regression to assess the relation of time interval and quaternary/dichotomous outcomes, respectively. Finally, we conducted a meta-analysis for cohort study to investigate the effect of timing of RAI therapy on the prognosis of TC. RESULTS: Delay RAI therapy beyond 3 months reduced the IR (BIR + SIR) rate in the present cohort study (RR = 0.67, 95% CI: 0.49-91). Following meta-analysis including 38,688 DTC patients confirmed these results (RR = 0.77, 95% CI: 0.66-0.91), further revealed the duration of treatment does not influence OS (pooled RR = 1.05, 95% CI: 0.83-1.33). CONCLUSION: Delayed initial RAI therapy beyond 3 months but no later than 6 months did not impair the prognosis of TC.

Burden of Thyroid Cancer From 1990 to 2019 and Projections of Incidence and Mortality Until 2039 in China: Findings From Global Burden of Disease Study.

Projecting the burden of thyroid cancer (TC) over time provides essential information to effectively plan measures for its management and prevention. This research obtained data from the Global Burden of Disease (GBD) Study from between 1990 and 2019 to model how TC will affect China until 2039 by conducting the Bayesian age-period-cohort analysis. The number of new TC cases in China was 10,030 in 1990, 39,080 in 2019, and is projected to be 47,820 in 2039. This corresponds to 3,320, 7,240, and 4,160 deaths, respectively. Disability-adjusted life years (DALYs) cases increased from 103,490 in 1990 to 187,320 in 2019. The age-standardized rate (ASR) of incidence increased from 1.01 to 2.05 during 1990-2019 and was projected to increase to 3.37 per 100,000 person-years until 2039. The ASR of mortality (ASMR) remained stable during the study period and was projected to have a mild decline from 0.39 to 0.29/100,000 during 2020-2039. Although the ASMR in male patients has maintained increasing at a rate of 2.2% per year over the past 30 years, it is expected to decline at a rate of 1.07% per year in 2019-2039. The most significant increase in crude incidence occurred in people aged 45-65 from 1990 to 2019, however, this will shift into young people aged 10-24 from 2020 to 2039. In addition, the proportion of deaths and DALYs caused by obesity increased from 1990 to 2019 and affected men more than women. In conclusion, a substantial increase in counts of incidence of TC in China is projected over the next two decades, combined with the slightly declining mortality, indicating that rational health policies are needed in the future to cope with the increasing number of TC patients, especially among males and adolescents.

SLC34A2 Up-regulation And SLC4A4 Down-regulation Correlates With Invasion, Metastasis, And The MAPK Signaling Pathway In Papillary Thyroid Carcinomas.

Papillary thyroid carcinoma (PTC) is one of the fastest growing endocrine system malignant carcinomas detected over the past decade. Unfortunately, more than 25% of PTC patients are characterized by their aggressiveness and subsequent metastasis; these characteristics usually indicate poor prognosis. Recently, increasing evidence has suggested that solute carrier (SLC) transporters may play a pivotal role in the initiation, invasion and metastasis of human carcinoma. However, the expression and clinicopathological significance of SLC transporters in patients with PTC remains undetermined. In this study, we aimed to elucidate how the differential expression of SLC transporters affects clinicopathological features, as well as determine the possible regulatory signaling pathways involved. Three differentially expressed SLC transporters were screened from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) database using a bioinformatics approach. The results indicated that high SLC34A2 and low SLC4A4 protein expression exhibited a higher percentage of capsular invasion and extra-thyroid metastasis in patients. Logistic regression analysis showed that high SLC34A2 expression in tumors was identified as an independent risk factor for capsular invasion [odds ratio (OR)=11.400, 95% confidence interval (CI)=1.733-74.995, P=0.011] and extra-thyroid metastasis (OR=4.920, 95%CI=1.234-19.623, P=0.024), while low SLC4A4 expression in tumors was only identified as independent risk factors for extra-thyroid metastasis (OR=8.568, 95%CI =1.186-61.906, P=0.033). Specifically, for tumors with capsular invasion and extra-thyroid metastasis, the protein expression staining of SLC34A2 was markedly enhanced in the cytoplasm of follicular epithelial cells, contrastingly, SLC4A4 expression was notably weakened in the cytomembrane and nucleus. Intriguingly, both high SLC34A2 and low SLC4A4 protein expression were significantly linked to a high urinary iodine concentration in patients with PTC. Mechanistically, compared with adjacent normal thyroids, p-ERK was significantly up-regulated by 17.8% in the invading tumor; p-ERK, p-JNK, and p-P38 were markedly up-regulated by 29.2%, 67.1%, and 38.9% for metastatic tumors, respectively. Importantly, SLC4A4 negatively correlated with p-JNK (r=-0.696, P= 0.004) and p-P38 (r=-0.534, P=0.049). In conclusion, we suggest that up-regulated SLC34A2 (mainly in the cytoplasm) and down-regulated SLC4A4 (mainly in the cytomembrane and nucleus), which might be attributed to excess iodine intake, were closely linked to extra-thyroid metastasis in PTCs. Furthermore, this effect of SLC4A4 may be through the activation of JNK/P38 MAPK signaling pathway. Future in vivo and in vitro gain- or loss-of-function experiments are needed to verify these findings and further elucidate the deeper molecular mechanisms.

Preablative Stimulated Thyroglobulin and Thyroglobulin Reduction Index as Decision-Making Markers for Second Radioactive Iodine Therapy in Patients with Structural Incomplete Response.

PURPOSE: The aim of this study was to evaluate the value of preablative stimulated thyroglobulin (presTg) and thyroglobulin reduction index (TRI) to predict the different responses to second radioactive iodine (RAI) therapy in differentiated thyroid cancer (DTC) patients with structural incomplete response (SIR). PATIENTS AND METHODS: A single-center retrospective study analyzed the different clinical outcomes after second RAI therapy in 206 patients with SIR. PresTg1 and presTg2 were measured before first and second RAI management and TRI was the reduction index of presTg1 and presTg2. Cut-off values of presTg and TRI were obtained using receiver operating characteristic analysis. The univariate logistic regression analysis was performed to confirm these parameters as prognostic factors to predict different responses to second RAI therapy. RESULTS: Only ATA risk stratification, the post-therapy whole-body scanning (Rx-WBS) findings, presTg1, presTg2, TRI, were different in patients with SIR. After second RAI therapy, 28.2% (58/206) of patients with SIR initially were reclassified as excellent response (ER). PresTg1 <6.6 ng/mL, presTg2 <1.2ng/mL, and TRI >74.2% were excellent indications to predict ER from non-ER after second RAI treatment. PresTg1 >14.9 ng/mL, presTg2 >1.8ng/mL and TRI <66.5% were well markers to predict poor outcome (SIR). High risk and distant metastases could still be considered as risk factors. CONCLUSION: DTC patients with SIR could benefit through second RAI treatment. PresTg before each RAI therapy and TRI could be considered as effective decision-making markers for second RAI therapy and as predictive indications for clinical outcomes.

Research trends for papillary thyroid carcinoma from 2010 to 2019: A systematic review and bibliometrics analysis.

BACKGROUND: Thyroid carcinoma comprises the fastest rising incidence of carcinomas over the past decade. Papillary thyroid carcinoma (PTC) is the most predominant type of thyroid carcinoma. This study aimed to assess the research trends in the field of PTC. METHODS: Publications from January 2010 to December 2019 were retrieved from the Web of Science Core Collection database using Thompson Reuters. Searching strategies were determined according to Medical Subject Heading terms. Different kinds of bibliometrics software, such as HistCite and VOSviewer, and online bibliometrics analysis platforms were utilized to evaluate and visualize the results. RESULTS: A total of 8102 publications across 93 countries were identified, with the annual number of publications showing an increasing trend. The United States, China, and South Korea showed their dominant position in PTC publication outputs, H-index, total citations, and international collaborations. Thyroid was the most productive journal. Akira Miyauchi published the most articles, and the most productive institution was Yonsei University. The hotspots keywords proliferation, invasion and metastasis, diagnoses and prognoses, therapeutic resistance, recurrence, and microcarcinomas appeared earlier and were sustained over the last 3 years. CONCLUSIONS: This bibliometric study provides a comprehensive analysis delineating the scientific productivity, collaboration, and research hotspots within the PTC field, which will be very helpful when focusing on the direction of research over the next few years.

A pre-ablative thyroid-stimulating hormone with 30-70 mIU/L achieves better response to initial radioiodine remnant ablation in differentiated thyroid carcinoma patients.

Our aim was to clarify the optimum pre-ablative thyroid-stimulating hormone (TSH) level for initial radioiodine remnant ablation (RRA) in patients with differentiated thyroid carcinoma (DTC). From December 2015 to May 2019, 689 patients undergone RRA at Nuclear Medicine Department, Second Hospital of Shandong University were included in the study. Patients were categorized by their pre-ablative TSH level grouping of < 30, 30-70 and ≥ 70 mIU/L. Response to RRA were evaluated as complete response (including excellent and indeterminate response) and incomplete response (including biochemical and structural incomplete response) after a follow-up of 6-8 months. Multivariable binary logistic regression model was used to explore the optimum pre-ablative TSH level range and independent factors associated with response to RRA. Rates of complete response to RRA were 63.04%, 74.59% and 66.41% in TSH level groups of < 30, 30-70 and ≥ 70 mIU/L, separately. With multivariate analysis, the study found that pre-ablative TSH levels, gender and lymph node dissection were independent predictors of response to RRA. TSH between 30 and 70 mIU/L had a higher rate of complete response compared with TSH < 30 mIU/L, OR 0.451 (95% CI 0.215-0.958, P = 0.036). A pre-ablative TSH level of 30-70 mIU/L was appropriate for patients with DTC to achieve a better response to RRA.

Breakthrough of ZrO2 nanoparticles into fetal brains depends on developmental stage of maternal placental barrier and fetal blood-brain-barrier.

Ingestion of nanoparticles may cause various damages to human body. However, how such ingestion by pregnant mother influences fetal development is not known because, presumably, ingested nanoparticles have to cross multiple biological barriers (such as intestinal and placental) to reach fetus. To answer this crucial question, here we investigated how a relatively biocompatible zirconia nanoparticles (ZrO2 NPs, 16 nm) were translocated to fetal brains in three exposure models of pregnant mice: Model 1, oral exposure of nanoparticles before maternal blood-placental barrier (BPB) was fully developed; Model 2, exposures after BPB was developed, but before fetal blood-brain-barrier (BBB) was fully developed; Model 3, exposures after both maternal BPB and fetal BBB were fully developed. Our experimental results showed that translocation of ZrO2 NPs into fetal brains was 55 % higher in Model 2 and 96 % higher in Model 1 compared with that in Model 3 after nanoparticles (50 mg/kg) were orally exposed to pregnant mice. Therefore, nanoparticles are able to cross multiple biological barriers and nanotoxicity to fetus is highly dependent on stages of pregnancy and fetal development or the maturity of multiple biological barriers. Oral exposures to nanoparticles during pregnancy are dangerous to fetal brain development, especially in early pregnancy.

Association between excessive chronic iodine exposure and the occurrence of papillary thyroid carcinoma.

The aim of the present study was to elucidate the association between excessive chronic iodine exposure and the risk of developing papillary thyroid carcinoma (PTC). The demographic information and pathological characteristics of patients with thyroid nodules were retrieved from medical records at The Second Hospital of Shandong University. A fasting urine specimen was collected, and creatinine and urinary iodine concentration (UIC) were determined. The water iodine data from the domicile districts of these patients were collated from published reports. The results revealed that almost half of the patients with PTC (44.3%) also exhibited a high UIC (≥300 µg/l). Multivariate analysis revealed that the adjusted odds ratio for high UIC was 3.987 (95% CI: 1.355-11.736) and the adjusted area under the receiver operating characteristic curve was 0.776 (95% CI: 0.687-0.864), which was associated with PTC risk in patients with thyroid nodules. Integrated ecological assessment of chronic iodine exposures demonstrated that >80% (81.4%) of the patients with PTC who also exhibited a high UIC were from historically non-iodine-deficient regions, and 66.7% of patients with PTC who resided in historically iodine-excessive regions were characterized by high UICs. Importantly, a high UIC was significantly associated with capsular invasion and extrathyroid metastasis (P<0.05). Moreover, self-matching results indicated that, in patients with PTC, there were no significant differences in UIC grading between the pre- and postoperative specimens. In conclusion, excessive chronic iodine exposure is significantly associated with the risk of PTC, which contributes to increased capsular invasion and extrathyroid metastases. However, further research is required to validate these findings and to elucidate the potential molecular mechanisms involved.

Oral intake of ZrO2 nanoparticles by pregnant mice results in nanoparticles' deposition in fetal brains.

Nanotoxicity to fetal brains after maternal oral exposures during pregnancy is often in question because nanoparticles have to cross multiple biological barriers such as intestinal barrier, maternal blood placental barrier (BPB) and fetal blood brain barrier (BBB). Here, we investigated this seemingly impossible passage for ZrO2 nanoparticles (ZrO2 NPs) from maternal body to fetal brains using a pregnant mouse model. After three oral exposures to pregnant mice at late pregnancy (GD16, 17, 18), ZrO2 NPs were able to accumulate in fetal brains at GD19 via crossing the well-developed maternal BPB and fetal BBB. Moreover, ZrO2 NPs crossed the mature biological barriers with increasing the expression levels of caveolae, clathrin and arf6 proteins as well as decreasing the expression levels of the tight junction proteins claudin-5, occludin and ZO-1 in placenta and fetal brain. From this investigation, we speculated that the main mechanisms for such translocation were receptor-mediated endocytosis transcellular pathway and breakthrough of tight junctions paracellular pathway in mature maternal BPB and fetal BBB. These findings have important implications for other nanoparticles exposures during pregnancy and provide crucial information to safeguard fetal development from contamination of widely used nanoproducts.

Carbon disulfide induced decidualization disorder in the mice uterus at the window of implantation.

Carbon disulfide (CS2) is regarded as a common occupational poison that is widely used in the textile industry in China. Our previous research suggests that CS2 can induce significant implantation disorders in pregnant mice; however, the specific mechanism remains unclear. Uterine conception in mice must undergo decidualization, which is the prerequisite for propitious blastocyst implantation into the endometrium. Therefore, in this study, we established models of pregnant mice to explore the toxic effects of CS2 on decidualization to elucidate the basic mechanism of implantation disorder after CS2 exposure. The uterine tissues were immediately collected according to the predetermined endpoints to measure the expression levels of IGFBP1 and PRL (markers of decidualization differentiation), IL-11 (representing the secretory function of decidual cells), AKT and pAKT by western blotting, RT-PCR, immunohistochemical staining, H&E staining and ELISA. N-carbamoyl glutamic acid (NCG) acted as an agonist of AKT to verify the upstream regulatory mechanism of decidualization disorder by CS2. The results showed that the normal reaction of decidual transformation was obviously disrupted by CS2 upon 3.5 dpc and 4.5 dpc exposure. The blastocyst did not adhere to the epithelium after 3.5 dpc-exposure and did not invade the endometrium after 4.5 dpc-exposure, resulting in its suspension in the uterine cavity, stagnation and eventual loss. The proteins expression levels were decreased by 95.2% for IGFBP1 and 76.2% for PRL at the 4.5 dpc endpoint after 3.5 dpc CS2 exposure compared with the control. Simultaneously, the mRNA and protein expression levels of IL-11 in uterine tissues were significantly reduced by CS2, and consistent decreasing trends over time were observed for IGFBP1 and PRL, compared with the control. Additionally, the ratio of pAKT/AKT protein expression was decreased by 72.2% and 94.8% at 12 h and 18 h after 3.5 dpc exposure and by 53.3% and 74.3% at 6 h and 12 h after 4.5 dpc exposure, respectively, compared with the corresponding controls. Furthermore, NCG could recover the IGFBP1 and PRL protein expression, which was increased by 27.5% and 52.3% at 4.5 dpc and 6.5 dpc, respectively, after 3.5 dpc exposure for IGFBP1 and by 30.3% at 6.5 dpc after 4.5 dpc exposure for PRL, compared with CS2 exposure alone. Collectively, this study suggested that the decidualization disorder caused by CS2 at the window of implantation in pregnant mice, which is triggered by pAKT, contributed to the implantation disorder and eventually led to embryo loss. It is worth noting that our study may provide a new perspective and reference for exploring the toxic mechanism of implantation disorder and even infertility in harmful circumstances.

Carbon Disulfide Induces Embryo Implantation Disorder by Disturbing the Polarization of Macrophages in Mice Uteri.

Carbon disulfide (CS2) induces embryo implantation disorders. Macrophages participate in the process of pregnancy. Therefore, we want to explore the effects of CS2 exposure on polarization and immune function of macrophages in pregnant mice uteri. The exposure times were gestation days 3 (GD3), 4 (GD4), and 5 (GD5), and the observation end points were arranged in a time series after CS2 exposure. The uterine tissues were collected to detect the expression levels of macrophages cytokines (IL-6, IL-12, TGF-ß1, and Vegf-a) and downstream regulatory cytokines of Th1-type (IL-2 and IFN-γ) and Th2-type (IL-10 and IL-4) by flow cytometry, ELISA, and q-PCR. The results showed that, compared with the controls, the ratios of M1/M2 macrophages in the endometrium significantly increased by 96%, 110%, and 177% at the GD4, GD6, and GD7 observation end points after GD3 exposure and increased about 3.88-fold and 2.37-fold at the GD6 and GD7 observation end points after GD4 exposure, respectively. In contrast, the ratio of M1 and M2 macrophages significantly reduced by 53% at the GD5 observation end point after GD3 exposure. Meanwhile, the expression levels of IL-6 were significantly increased about 2.00-fold for mRNA and 1.60-fold for protein at GD4 observation end points after GD3 exposure, and the mRNA levels of IL-12 increased about 3.61-fold at the GD6 observation end points after GD4 exposure. The mRNA levels of TGF-ß1 were significantly decreased by 41%, 25%, and 20% at the GD7 observation end points after exposure at GD3, GD4, and GD5, and the expression levels of Vegf-a mRNA and protein were decreased. Furthermore, the ratio of IL-2/IL4, IL-2/IL-10, IFN-γ/IL-4, and IFN-γ/IL-10 in the uterine tissue was significantly increased at the exposure groups. These findings suggest that the imbalanced polarization of macrophages is the key regulator in the progress of CS2-induced embryo loss.

Carbon disulfide induces embryo loss by perturbing the expression of the mTOR signalling pathway in uterine tissue in mice.

Understanding of the mechanism of embryo loss is critical for successful pregnancy considering an increase in the incidence of infertility. In this study, we focus on the effect of alterations in the expression of the AKT/AMPK/mTOR signalling pathway in mouse uterine tissue after embryo loss induced by harmful environmental exposure to carbon disulfide (CS2). CS2 is a material used in certain production processes, and women are sometimes exposed to it in occupational settings. We created an animal model of gestating mice exposed to CS2 on gestation days 3 (GD3), 4 (GD4), 5 (GD5) and 6 (GD6) with various corresponding endpoints after the exposure. The uterine tissue was collected according to the endpoint time series to detect the expression levels of mTOR, p-mTOR, pAKT, and pAMPK using western blot, RT-PCR, immunohistochemistry staining, and ELISA. Dietary supplementation with N-carbamoyl glutamic acid (NCG) was used to verify the effect of the mTOR signalling pathway on embryo loss caused by CS2. We detected down-regulation of the levels of the mTOR and p-mTOR proteins; the levels of these two proteins were decreased by 49.35% and 51.44% at the GD5 endpoint after GD4 exposure and by 38.55% and 59.51% after GD3 exposure, respectively. The change in the expression level of mTOR mRNA was consistent with the protein expression, and the mRNA level at the GD5 endpoint was decreased by 55.0% after GD4 exposure (P < 0.05). Additionally, protein expression levels of pAKT were decreased by 49.05%, and the levels of pAMPK were increased by 25.51% at the GD5 endpoint after GD4 exposure (P < 0.05). A similar trend was observed for pAKT and pAMPK at the GD4 endpoint after GD3 exposure, at the GD6 endpoint after GD5 exposure, and at the GD7 endpoint after GD6 exposure (P < 0.05). Supplementation with NCG contributed to recovery from the effects of CS2 by increasing the protein expression levels of mTOR and pAKT by 47.54% and 63.79% (P < 0.05), respectively, while the pAMPK protein level was decreased by 37.15% (P < 0.05) at the GD5 endpoint after GD4 exposure. It should be noted that the number of implanted embryos was significantly increased after supplementation with NCG. Our results indicate that down-regulation of mTOR at the time of implantation is regulated by pAKT and pAMPK, that may be an important factor for embryo loss induced by CS2.

Research Trends of Macrophage Polarization: A Bibliometric Analysis.

BACKGROUND: Macrophage polarization is involved in the development of many diseases such as obesity, diabetes, and cancer. This study aimed to understand the trends and hotspots of macrophage polarization research. METHODS: We searched through the Web of Science Core Collection database to obtain original articles in this research domain. CiteSpace, HistCite, and VOSviewer software were used to facilitate the analysis and visualization of scientific productivity and emerging trends. RESULTS: The survey included 3064 articles, and the annual number of publications exhibited an exponential increase. These articles have received a total of 74,801 citations, and the number of annual citations grew from 68 to 18,074 in a decade. Research on macrophage polarization was performed in 76 countries, and the USA ranked first in terms of research output by contributing 1129 (36.8%) articles. The USA also had the highest H-index, total citations, and highly cited article number. PLOS One, Journal of Immunology, and Scientific Reports were the three journals that published the most articles. Interdisciplinary research areas involving macrophage polarization, such as biomaterials, cancer, and diabetes, were identified by journal citation analysis. The top 20 most productive institutions were located mainly in the USA, France, and China, and top authors originated mainly from the USA and Italy. Tumor biology, obesity, and infection were research hotspots and may be promising in the next few years. CONCLUSIONS: This study provides a comprehensive analysis that delineates the scientific productivity, collaboration, and research hotspots of macrophage polarization research.