Bisphenols (BPs) are extensively used in food packaging, personal care products, and plastics, making them prevalent in both living and working environments, which has raised significant concern. As endocrine-disrupting chemicals, BPs exert toxic effects on the female reproductive system by binding to estrogen receptors, thereby activating or inhibiting the expression of genes related to reproductive functions, which disrupts the normal function of the endocrine system. This paper reviewed the effects of bisphenol A (BPA), bisphenol S (BPS), and bisphenol F (BPF) on female reproductive function, focusing on three key aspects: the effects on the female reproductive organs, the occurrence of associated reproductive disorders, and the mechanisms of toxicity. Specifically, this review highlighted the effects on ovarian function, uterine morphology and function, and fallopian tube function, as well as their correlation with polycystic ovary syndrome, endometriosis, miscarriage, and eclampsia. Additionally, the toxic mechanisms of BPs exposure were summarized, providing a scientific basis for future research on the impact of BPs on the female reproductive system, as well as for the assessment of potential health risks and the development of preventive measures.

Objective:To construct a VP8-mRNA vaccine using human rotavirus spike protein VP8 domain as the immunogen and analyze its immunogenicity in mice.Methods:The VP8-mRNA sequence was designed, optimized, and synthesized. The VP8 gene of rotavirus G1P[8] type was used to construct the plasmid pUC57-VP8-Kan-SapⅠ, which was then sequenced. The plasmid confirmed by sequencing was subjected to large-scale amplification and extraction, followed by linearization, in vitro transcription, and capping. The purified capped products were encapsulated with lipid nanoparticles using a microfluidic control apparatus. The encapsulated VP8-mRNA vaccine was administered intramuscularly to mice at 10, 15, and 20 μg. Serum samples were collected for antibody detection by ELISA. Cellular immune responses were detected by flow cytometry and ELISPOT. Statistical analysis was performed using one-way or two-way analysis of variance and Tukey-Kramer test. Results:The encapsulated VP8-mRNA vaccine was rounded and spherical, with a particle size of about 100 nm, a polymer dispersion index of 0.088, and an encapsulation rate of 92.3%. Two doses of VP8-mRNA vaccine immunization could induce a good immune response in mice. The level of IgG antibody induced after immunization in the 15 μg group was comparable to that of the 20 μg group, and there was no statistical difference ( P>0.05), but the antibody levels in the two groups were significantly higher than that in the 10 μg group ( P<0.000 1). VP8-mRNA vaccine could induce neutralizing antibodies against rotavirus G1 and G9 types. The highest level of neutralizing antibodies against rotavirus type G1 was observed in the 15 μg group, which was significantly higher than that in the 10 μg group ( P<0.05). All immunization groups exhibited good neutralizing ability against rotavirus G9 type. The results of ELISPOT showed that lymphocytes from mice in each vaccine group were able to secrete IFN-γ when stimulated with VP8 peptide. Flow cytometry showed that the proportions of CD8 + T cell subsets in the vaccine groups were higher than that in the control group. Conclusion:The VP8-mRNA vaccine has good immunogenicity in mice and can induce good humoral and T-cell immune responses.

Objective:To construct a VP8-mRNA vaccine using human rotavirus spike protein VP8 domain as the immunogen and analyze its immunogenicity in mice.Methods:The VP8-mRNA sequence was designed, optimized, and synthesized. The VP8 gene of rotavirus G1P[8] type was used to construct the plasmid pUC57-VP8-Kan-SapⅠ, which was then sequenced. The plasmid confirmed by sequencing was subjected to large-scale amplification and extraction, followed by linearization, in vitro transcription, and capping. The purified capped products were encapsulated with lipid nanoparticles using a microfluidic control apparatus. The encapsulated VP8-mRNA vaccine was administered intramuscularly to mice at 10, 15, and 20 μg. Serum samples were collected for antibody detection by ELISA. Cellular immune responses were detected by flow cytometry and ELISPOT. Statistical analysis was performed using one-way or two-way analysis of variance and Tukey-Kramer test. Results:The encapsulated VP8-mRNA vaccine was rounded and spherical, with a particle size of about 100 nm, a polymer dispersion index of 0.088, and an encapsulation rate of 92.3%. Two doses of VP8-mRNA vaccine immunization could induce a good immune response in mice. The level of IgG antibody induced after immunization in the 15 μg group was comparable to that of the 20 μg group, and there was no statistical difference ( P>0.05), but the antibody levels in the two groups were significantly higher than that in the 10 μg group ( P<0.000 1). VP8-mRNA vaccine could induce neutralizing antibodies against rotavirus G1 and G9 types. The highest level of neutralizing antibodies against rotavirus type G1 was observed in the 15 μg group, which was significantly higher than that in the 10 μg group ( P<0.05). All immunization groups exhibited good neutralizing ability against rotavirus G9 type. The results of ELISPOT showed that lymphocytes from mice in each vaccine group were able to secrete IFN-γ when stimulated with VP8 peptide. Flow cytometry showed that the proportions of CD8 + T cell subsets in the vaccine groups were higher than that in the control group. Conclusion:The VP8-mRNA vaccine has good immunogenicity in mice and can induce good humoral and T-cell immune responses.

Objective:To investigate the value of three-dimensional (3D) T 1WI structural images using different acceleration methods including parallel acquisition technique, joint compressed sensing (uCS) technique, and artificial intelligence-assisted compressed sensing (ACS) technique for brain region segmentation. Methods:In this cross-sectional study, fifty patients (female: n=25, age range: 13 to 87 years old) at Corning Hospital of Ningbo University from July to September 2023 were prospectively and consecutively collected. All the subjects underwent brain MRI. Six groups of 3D T 1WI structural images were obtained using different acceleration technique and parameters, including 3D T 1WI without acceleration factor (3D-T 1WI group), 3D T 1WI with parallel acquisition technique with acceleration factor 3 (3D-T 1WI-PI-3 group), 3D T 1WI with uCS technique with acceleration factor 4.5 and 6.9 (3D-T 1WI-uCS-4.5 group, 3D-T 1WI-uCS-6.9 group), 3D T 1WI by ACS technique with acceleration factors of 3 and 5 (3D-T 1WI-ACS-3 group, 3D-T 1WI-ACS-5 group). T 2WI fluid-attenuated inversion recovery (FLAIR) images were also acquired. Subjective scores (cerebral grey matter and white matter clarity scores, clarity scores of cerebral white matter degeneration lesions in relation to the surrounding white matter, and Gibbs artifact scores) and objective metrics [signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), cerebrospinal fluid signal homogeneity, peak signal-to-noise ratio (PSNR), structural similarity index (SSIM), and natural image quality evaluator (NIQE)] were used to evaluate image quality in different groups. Totally 109 brain regions were segmented and volumes were measured using the uAI Research Portal image analysis tool. Kappa or intraclass correlation coefficient ( ICC) was used to evaluate the agreement of subjective and objective evaluation indexes between the 3D-T 1WI-PI-3 group, 3D-T 1WI-uCS-4.5 group, 3D-T 1WI-uCS-6.9 group, 3D-T 1WI-ACS-3 group, 3D-T 1WI-ACS-5 group, and 3D-T 1WI group. Kappa or ICC value>0.70 was considered as good agreement. Results:The acquisition time for the 3D-T 1WI group, 3D-T 1WI-PI-3 group, 3D-T 1WI-uCS-4.5 group, 3D-T 1WI-uCS-6.9 group, 3D-T 1WI-ACS-3 group, and 3D-T 1WI-ACS-5 group were 527, 204, 169, 95, 133, 90 s, respectively. Subjective evaluation showed that the 3D-T 1WI-uCS-4.5, 3D-T 1WI-ACS-3, and 3D-T 1WI-ACS-5 groups had excellent agreement with the 3D-T 1WI group in terms of the distribution of cases of cerebral grey matter and white matter clarity scores, respectively (all Kappa value=1.000); The distribution of cases of clarity score of cerebral white matter lesions and surrounding white matter in the 3D-T 1WI-PI-3 group, 3D-T 1WI-uCS-4.5 group, and 3D-T 1WI-ACS-3 group were in good agreement with that of the 3D-T 1WI group ( Kappa values of 0.775, 0.701, and 0.777, respectively); the distribution of the number of cases of the Gibbs artifact score of the 3D-T 1WI-uCS-4.5, 3D-T 1WI-ACS-3, and 3D-T 1WI-ACS-5 groups was in good agreement with the 3D-T 1WI group (all Kappa value=1.000). Objective evaluation showed the CNR of the images in the 3D-T 1WI-PI-3, 3D-T 1WI-uCS-4.5, and 3D-T 1WI-uCS-6.9 groups were in good agreement with those of the 3D-T 1WI group ( ICC of 0.720, 0.759, and 0.752, respectively); PSNR and SSIM were in good agreement among the 3D-T 1WI-PI-3 group, 3D-T 1WI-uCS-4.5 group, 3D-T 1WI-uCS-6.9 group, 3D-T 1WI-ACS-3 group, and 3D-T 1WI-ACS-5 group (PSNR: ICC=0.854; SSIM: ICC=0.851). NIQE of 3D-T 1WI-PI-3 group, 3D-T 1WI-uCS-4.5 group, and 3D-T 1WI-ACS-3 group images were in good agreement with the 3D-T 1WI group ( ICC value of 0.866, 0.727, 0.753, respectively). The ICC values of the volume of each segmented brain region among the 3D-T 1WI-PI-3, 3D-T 1WI-uCS-4.5, 3D-T 1WI-uCS-6.9, 3D-T 1WI-ACS-3, 3D-T 1WI-ACS-5 group and the 3D-T 1WI group images showed decreased in order (all ICC≥0.62). Conclusions:The uCS and ACS techniques used in 3D-T 1WI show high agreement with 3D-T 1WI in terms of brain segmentation. The application of these accelerating techniques can significantly shorten the acquisition time with obtaining images with good image quality, displaying great value.

Objective To evaluate the differences in chemical composition and pharmacological effects between Angelica-Astragalus medicine pair decoction(DGD)and traditional decotion,and to provide a reference for the rational clinical application of Danggui Buxue decoction.Methods With the two comparison methods of unified and non-uniform raw material source batches,we set up different sample groups,established characteristic maps by HPLC,and evaluated the chemical components based on the similarity of characteristic maps,component types,index component content,common peak area,and other factors.The efficacy of the drug was evaluated in the hemorrhagic blood deficiency model mice.Results ①The similarity of the feature map between the DGD and TD was high(similarity was greater than 0.87).②The number of chromatographic peaks was inconsistent.Traditional decoction from self-purchased decoction pieces,or traditional decoction-Factory A decoction pieces had a total of 12 chromatographic peaks each.The DGD of Factory A had a total of 15 chromatographic peaks.There were 10 chromatographic peaks in the DGD of Factory B.③The contents of ferulic acid and calycosin 7-O-glucoside(CG)in DGD of Factory A were higher than those in traditional decoction(P<0.05,n=3).There was no significant difference between DGD and TD ferulic acid content in Factory B,but the content of CG was lower than that in traditional decoction(P<0.05).④The total area of common peaks in DGD was different from that in TD.The relative total ratios of the contents of the components in the self-purchased traditional decoction pieces,the traditional decoction pieces of Factory A,the formula granules of Factory A,and the formula granules of Factory B were 1.00,0.96,2.14,0.60,respectively.⑤Both DGD and traditional decoction could significantly promote the recovery of hemoglobin and red blood cells in hemorrhagic anemia model mice(P<0.01);Compared with the model control group,there was a significantly difference(P<0.05)except for the DGD group of Plant B.There was no significant difference between DGD and TD of Plant A,but there was a very significant difference between DGD and TD of Plant B(P<0.01).Conclusion Whether the raw material source batch is consistent or not,DGD and TD have certain differences in chemical composition.In terms of pharmacological effect,DGD,prepared from a unified batch of decoction pieces,has similar efficacy to traditional decoction in alleviating hemorrhagic anemia.There are certain differences in the pharmacological effects between DGD prepared from different batches of decoction pieces and traditional decoctions.The differences caused by the different preparation processes of the same source batch of prepared slices were compared,and the quality differences of the formula granules from different manufacturers were caused by the different source batches of prepared slices and different preparation processes,indicating the necessity and urgency of the country to formulate a unified quality standard for formula granules and related process specifications.

Objective:To investigate the clinical significances of evaluation indexes of right heart function injury in patients with BCR-ABL-negative myroproliferative neoplasms (MPN).Methods:The clinical data of 208 patients with BCR-ABL-negative MPN diagnosed in the Second People's Hospital of Lianyungang and Jiangsu Province Hospital from January 2015 to August 2021 were retrospectively analyzed, including 63 cases of primary myelopathic fibrosis (PMF), 39 cases of polycytosis vera (PV) and 106 cases of essential thrombocythemia (ET). The clinical characteristics of patients and the examination results of hematological related indicators were compared among the three groups. The examination results of indexes of right heart function injury were analyzed, including echocardiography, brain natriuretic peptide, soluble growth stimulation expression gene-2 (sST-2), lactate dehydrogenase (LDH), D-dimer, ferritin, β 2-microglobulin, peripheral blood WT1 gene, CD34 + cell count, etc. Results:Of the 208 patients, 109 were male and 99 were female; the median age was 62 years old (23 years old, 89 years old). The differences in levels of hemoglobin, platelet count, D-dimer, LDH and ferritin among PMF, PV and ET patients were statistically significant (all P < 0.05). Color echocardiography was performed in 87 patients, including 26 cases of PMF, 19 cases of PV and 42 cases of ET. Pulmonary artery pressure increased in 69 cases (79.3%), left atrial diameter increased in 76 cases (87.3%), and diameter increased during right ventricular diastolic period in 59 cases (67.8%). There were significant differences in pulmonary artery pressure, left atrial diameter and diameter during right ventricular diastolic period among PMF, PV and ET patients (all P < 0.05). Pearson correlation analysis showed that pulmonary artery pressure was positively correlated with ferritin, LDH, sST-2 and age ( r values were 0.796, 0.768, 0.915 and 0.734, all P<0.05), while it was negatively correlated with platelet count ( r = -2.330, P = 0.034). Conclusions:For BCR-ABL-negative MPN patients, the increase of pulmonary artery pressure, ferritin and LDH and the decreased platelet count and hemoglobin may increase the probability of right heart function impairment. For BCR-ABL-negative MPN patients with the higher levels of ferritin, LDH, sST-2, age, and the lower level of platelet count, the pulmonary artery pressure may be higher.

Alzheimer's disease (AD) is associated with the impairment of white matter (WM) tracts. The current study aimed to verify the utility of WM as the neuroimaging marker of AD with multisite diffusion tensor imaging datasets [321 patients with AD, 265 patients with mild cognitive impairment (MCI), 279 normal controls (NC)], a unified pipeline, and independent site cross-validation. Automated fiber quantification was used to extract diffusion profiles along tracts. Random-effects meta-analyses showed a reproducible degeneration pattern in which fractional anisotropy significantly decreased in the AD and MCI groups compared with NC. Machine learning models using tract-based features showed good generalizability among independent site cross-validation. The diffusion metrics of the altered regions and the AD probability predicted by the models were highly correlated with cognitive ability in the AD and MCI groups. We highlighted the reproducibility and generalizability of the degeneration pattern of WM tracts in AD.
Humans ; White Matter/diagnostic imaging* ; Diffusion Tensor Imaging/methods* ; Alzheimer Disease/complications* ; Reproducibility of Results ; Cognition ; Cognitive Dysfunction/complications* ; Brain/diagnostic imaging*

Objective:To investigate the changes of related indicators of right heart hypofunction in patients with primary myelofibrosis (PMF).Methods:The clinical data of 55 PMF patients in the Second People's Hospital of Lianyungang in Jiangsu Province and Jiangsu Province Hospital from January 2015 to August 2019 were retrospectively analyzed. The differences in right heart function-related echocardiographic indexes and biochemical indexes between pre-fibrosis/early stage fibrosis patients and obvious stage fibrosis patients were compared. Single factor linear regression method was used to analyze the correlations of pulmonary artery pressure with biochemical indexes.Results:The hemoglobin level [119 g/L (47-224 g/L) vs. 78 g/L (33-182 g/L)] and platelet count [233×10 12/L (5×10 12/L-984×10 12/L) vs. 117×10 12/L (7×10 12/L-731×10 12/L)] of patients in the pre-fibrosis/early stage fibrosis group were higher than those in the obvious stage fibrosis group, and the differences were statistically significant (both P<0.05). Among 22 patients with complete results of cardiac ultrasound, 90.9% (20/22) patients had increased pulmonary artery pressure, 72.7% (16/22) patients had increased left atrial diameter, and 90.9% (20/22) patients had increased right ventricular diastolic diameter. There were no patients with abnormal ejection fraction. The pulmonary artery pressure [48 mmHg (46-90 mmHg) vs. 33 mmHg (20-50 mmHg) (1 mmHg = 0.133 kPa)], left ventricular diastolic diameter [46 mm (36-50 mm) vs. 47 mm (43-53 mm)] and fractional shortening rate [38.1% (36.0%-38.9%) vs. 35.4% (32.7%-37.8%)] of patients in the pre-fibrosis/early stage fibrosis group were higher than those in the obvious stage fibrosis group, and the differences were statistically significant (all P < 0.05). The pulmonary artery pressure of patients had positive correlations with age ( r = 0.590), serum ferritin (SF) ( r = 0.608), lactate dehydrogenase (LDH) ( r = 0.711) and soluble growth-stimulating expression gene 2 (ST-2) ( r = 0.580)(all P<0.05), and had negative correlation with platelet count ( r = -0.596, P = 0.003). Conclusion:PMF patients are prone to right heart hypofunction, the pulmonary artery pressure is higher in older patients and patients with high SF, LDH and ST-2 levels and low platelet count.

Objective:To observe any effect of intermittent theta burst stimulation (iTBS) of the cerebellum on swallowing dysfunction after cerebellar infarction, and to explore its mechanism.Methods:Sixty-two cerebellar stroke survivors with dysphagia were randomly divided into an observation group and a control group, each of 29. In addition to the routine swallowing rehabilitation training, the observation group was treated with iTBS, while the control group was given sham iTBS. The incubation and amplitude of the bilateral suprahyoid muscle motor evoked potential (MEP) were recorded before and after 4 weeks of treatment. The exponential approximate entropy (ApEn) of different brain regions was compared between the two groups during reflex and autonomous swallowing. Swallowing function was evaluated using the penetration-aspiration scale (PAS).Results:MEP incubation in the bilateral suprahyoid muscles had decreased significantly after 4 weeks of treatment in the observation group, and the MEP amplitude in the bilateral suprahyoid muscles of the two groups had increased significantly. The average improvement in the amplitude and incubation in the observation group was significantly greater than in the control group. The average ApEn at C3, C4, P3, P4, T5 and T6 had increased significantly in both groups during both reflex and spontaneous swallowing, with the improvement in the observation group significantly greater. Swallowing function had improved significantly in both groups, but the average PAS grade of the observation group was again significantly better.Conclusions:iTBS can improve the swallowing function of dysphagic cerebellar stroke survivors. This may be due to iTBS improving the excitability of the cerebral cortex and improving motor control of the swallowing muscles.

Objective:To improve the cognition of T-cell large granular lymphocytic leukemia (T-LGLL) combined with pure red cell aplasia (PRCA).Methods:The clinical characteristics, peripheral blood and bone marrow laboratory indicators of 14 newly diagnosed patients with T-LGLL combined with PRCA who were admitted to the Second People's Hospital of Lianyungang Affiliated to Bengbu Medical College and the People's Hospital of Jiangsu Province from August 2010 to October 2019 were retrospectively analyzed.Results:Among the 14 patients, there were 7 males and 7 females, with a median age of 58.5 years (33-75 years). At the first visit, the median white blood cell count was 5.02×10 9/L [(1.45-8.49)×10 9/L], the median absolute value of neutrophils was 1.35×10 9/L [(0.43-7.16)×10 9/L], the median lymphocyte ratio was 0.49 (0.13-0.77), the median hemoglobin was 58 g/L (42-106 g/L), the median red blood cell count was 2.01×10 12/L [(0.99-3.20)×10 12/L], the median reticulocyte count percentage was 0.52 (0.14-3.02), the median platelet was 96×10 9/L [(38-281)×10 9/L], the median large granular lymphocytes accounted for 71% (32%-81%) of lymphocytes. Bone marrow aspiration showed that the median large granular lymphocytes accounted for 0.16 (0.08-0.41) of nuclear cells, and the median serum β 2 microglobulin was 4.85 mg/L (2.81-7.22 mg/L). Two patients had ASXL1 and TET2 mutations, and one of them had STAT3, EP300 and FAM46C mutations. Six patients were T cell receptor (TCR) β and γ-positive, 1 patient were TCRβ-positive, 4 patients were TCRγ-positive, 1 patient was TCRδ-positive, 1 patient was TCRβ, γ and δ-positive, and 1 patient was all negative. Eight cases received cyclosporine therapy, 6 cases were effective; 6 cases received methotrexate combined with hormone therapy, 3 cases were effective. The initial induction therapy was effective in 9 cases, 5 patients who failed in the initial treatment received salvage treatment, and 2 cases were effective. Conclusions:The laboratory characteristics of patients with T-LGLL combined with PRCA are similar to those of simple T-LGLL, anemia is a prominent manifestation accompanied by neutropenia or thrombocytopenia. The large granular lymphocytes are easily seen in peripheral blood and bone marrow, and T monoclonal rearrangement of lymphocytes is an important feature, and the patients respond well to immunosuppressive therapy.