Search

Epithelial mesenchymal transition (EMT) is a critical process implicated in the pathogenesis of retinal fibrosis and the exacerbation of diabetic retinopathy (DR) within retinal pigment epithelium (RPE) cells. Apigenin (AP), a potential dietary supplement for managing diabetes and its associated complications, has demonstrated inhibitory effects on EMT in various diseases. However, the specific impact and underlying mechanisms of AP on EMT in RPE cells remain poorly understood. In this study, we have successfully validated the inhibitory effects of AP on high glucose-induced EMT in ARPE-19 cells and diabetic db/db mice. Notably, our findings have identified CBP/p300 as a potential therapeutic target for EMT in RPE cells and have further substantiated that AP effectively downregulates the expression of EMT-related genes by attenuating the activity of CBP/p300, consequently reducing histone acetylation alterations within the promoter region of these genes. Taken together, our results provide novel evidence supporting the inhibitory effect of AP on EMT in RPE cells, and highlight the potential of specifically targeting CBP/p300 as a strategy for inhibiting retinal fibrosis in the context of DR., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The impact of prenatal exposure to a mixture of heavy metals on birth weight in newborns has been a topic of ongoing interest. In this study, 258 mothers and infants from the New Hampshire Birth Cohort Study (NHBCS) were selected as the study subjects, and the concentrations of seven heavy metals in the placenta, including Aluminum (Al), Cobalt (Co), Chromium (Cr), Nickel (Ni), Plumbum (Pb), Selenium (Se) and Arsenic (As) were collected. And the birth weight of newborns, the relevant covariates of mothers and newborns were collected. Three analytical methods, Weighted Quantile Sum (WQS) regression, Quantile g-computation (QGC) and Bayesian kernel machine regression (BKMR) were employed. After adjusting for maternal gestational age, pre-pregnancy BMI, smoking status, education level, parity, gestational age and newborn gender, the combined three methods showed that the total effect of mixed exposure of seven heavy metals on birth weight was negative. Specifically, the WQS analysis revealed that Se had the greatest impact on birth weight, followed by Al. The QGC results showed that the heavy metal associated with the reduction of birth weight was mainly Se and Al in female and male infants, respectively. The BKMR analysis demonstrated a negative combined effect of the seven heavy metals on birth weight in both male and female infants, with Se having the highest posterior inclusion probabilities (PIPs) for female infants (0.45), and Al having the highest PIPs for male infants (0.64) after stratification by gender. In summary, mixed exposure to heavy metals during pregnancy was associated with a decrease in newborn birth weight. Furthermore, there are gender effects with Se and Al associated with decreased birth weight in female and male infants, respectively. These findings provide a theoretical basis for the development of public health policies aimed at preventing adverse pregnancy outcomes and improving the health of newborns.

Background: This study aims to assess the efficacy and safety of Qingpeng ointment (QPO), a Tibetan medicine for alleviating symptoms in individuals with acute gouty arthritis (AGA)., Methods: This study was a randomized, double-blind, placebo-controlled trial that involved individuals with AGA whose joint pain, as measured on a visual analog scale (VAS) from 0 to 10, was equal to or greater than 3. The participants were randomly assigned to either the QPO or the placebo group and received their respective treatments twice daily for seven consecutive days. In case of intolerable pain, the participants were allowed to use diclofenac sodium sustained-release tablets as a rescue medicine. The primary outcomes measured were joint pain and swelling, while the secondary outcomes included joint mobility, redness, serum uric acid levels, C-reactive protein levels, and the amount of remaining rescue medicine. Any adverse events that occurred during the trial were also recorded., Results: A total of 203 cases were divided into two groups, with balanced baselines: 102 in the QPO group and 101 in the placebo group. For joint pain, differences between the groups were notable in the VAS scores [1.75 (0, 3.00) versus 2.00 (1.00, 3.50); P = 0.038], changes in VAS [5.00 (3.00, 6.00) versus 4.00 (2.00, 6.00); P = 0.036], and disappearance rate [26.47% compared to 15.84%; P = 0.046] after treatment. Concerning joint swelling, significant between-group differences were observed in the VAS scores [1.00 (0, 2.30) versus 2.00 (0.70, 3.00); P = 0.032] and disappearance rate [33.33% compared to 21.78%; P = 0.046] at treatment completion. The QPO group exhibited a statistically significant mobility improvement compared to the placebo group (P = 0.004). No significant differences were found in other secondary outcomes. Five patients, four from the QPO group and one from the other, encountered mild adverse events, primarily skin irritation. All of these cases were resolved after dosage reduction or discontinuation of the medication., Conclusions: Compared to the placebo, QPO exhibits positive effects on AGA by alleviating pain, reducing swelling, and enhancing joint mobility, without causing significant adverse effects., Trial Registration: ISRCTN34355813. Registered on 25/01/2021., (© 2024. The Author(s).)

Objective: To compare the differences in clinical symptoms and the time required for diagnosis of benign paroxysmal positional vertigo (BPPV) between older patients and young and middle-aged patients in the structured inquiry of dizziness history. Methods: The medical records of 6 807 patients diagnosed with BPPV from the Vertigo Database of Vertigo Clinical Diagnosis, Treatment, and Research Center of Beijing Tiantan Hospital, Capital Medical University, between January 2019 and October 2021 were retrospectively analyzed. The data included basic demographic information, clinical symptoms in a structured medical history questionnaire, and the time interval from the appearance of BPPV symptoms to diagnosis consultation. The patients were divided into the young and middle-aged group (<65 years old) and the older group (≥65 years old). The differences in clinical symptoms and consultation time were compared between these two groups. Categorical variables were represented by numbers (%), and compared using Chi-squared tests or Fisher's exact probability test for analysis; whereas, continuous variables conforming to normal distribution were represented by mean±standard deviation. Both data groups were compared and analyzed by Student's t -test. Results: The mean age of the older group was 65-92 (71±5) years, while the mean age of the middle-aged group was 18-64 (49±12) years. The incidence of vertigo (42.5% vs. 49.1%, χ 2 =23.69, P <0.001); vertigo triggered by changes in position of the head or body (52.4% vs. 58.7%, χ 2 =22.31, P <0.001); and autonomic symptoms (10.1% vs. 12.4%, χ 2 =7.09, P =0.008) were lower, but hearing loss (11.8% vs. 7.8%, χ 2 =27.36, P <0.001) and sleep disorders (18.5% vs. 15.2%, χ 2 =11.13, P =0.001) were higher in the older group than in the young and middle-aged group. The time from the appearance of dizziness to diagnosis was commonly longer in the older patient group than the other group (55.0% vs. 38.5%, χ 2 =55.95, P <0.001). Conclusions: Older patients with BPPV have more atypical symptoms and complex concomitant symptoms than young and middle-aged patients. For older patients with dizziness, positional testing is needed to confirm the possibility of BPPV even if the clinical symptoms are atypical.

Comprehensive analyses of multi-omics data may provide insights into interactions between different biological layers concerning distinct clinical features. We integrated data on the gut microbiota, blood parameters and urine metabolites of treatment-naive individuals presenting a wide range of metabolic disease phenotypes to delineate clinically meaningful associations. Trans-omics correlation networks revealed that candidate gut microbial biomarkers and urine metabolite feature were covaried with distinct clinical phenotypes. Integration of the gut microbiome, the urine metabolome and the phenome revealed that variations in one of these three systems correlated with changes in the other two. In a specific note about clinical parameters of liver function, we identified Eubacteriumeligens, Faecalibacteriumprausnitzii and Ruminococcuslactaris to be associated with a healthy liver function, whereas Clostridium bolteae, Tyzzerellanexills, Ruminococcusgnavus, Blautiahansenii, and Atopobiumparvulum were associated with blood biomarkers for liver diseases. Variations in these microbiota features paralleled changes in specific urine metabolites. Network modeling yielded two core clusters including one large gut microbe-urine metabolite close-knit cluster and one triangular cluster composed of a gut microbe-blood-urine network, demonstrating close inter-system crosstalk especially between the gut microbiome and the urine metabolome. Distinct clinical phenotypes are manifested in both the gut microbiome and the urine metabolome, and inter-domain connectivity takes the form of high-dimensional networks. Such networks may further our understanding of complex biological systems, and may provide a basis for identifying biomarkers for diseases. Deciphering the complexity of human physiology and disease requires a holistic and trans-omics approach integrating multi-layer data sets, including the gut microbiome and profiles of biological fluids. By studying the gut microbiome on carotid atherosclerosis, we identified microbial features associated with clinical parameters, and we observed that groups of urine metabolites correlated with groups of clinical parameters. Combining the three data sets, we revealed correlations of entities across the three systems, suggesting that physiological changes are reflected in each of the omics. Our findings provided insights into the interactive network between the gut microbiome, blood clinical parameters and the urine metabolome concerning physiological variations, and showed the promise of trans-omics study for biomarker discovery., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Li, Jie, Feng, Fang, Li, Gao, Xia, Zhong, Tong, Madsen, Zhang, Liu, Xu, Wang, Yang, Xu, Hou, Brix, Kristiansen, Yu, Jia and He.)

Background: To investigate the role of CD138 immunohistochemistry in the diagnosis of chronic endometritis (CE) and the risk factors for assisted conception patients having CE complications., Methods: Ninety-three patients, with normal uterine shape confirmed by examination and who were planning to undergo assisted conception treatments, were selected as research subjects. Endometrial tissue was isolated for routine hematoxylin and eosin (HE) and CD138 immunohistochemical staining. Additionally, the disease histories of patients were collected, and the reproductive prognosis was followed up., Results: ① CE detection rate: The rate of CD138 immunohistochemical staining was greater than that of HE staining (27.96 % vs. 26.89 %, P <0.05); ② Pregnancy rate: the pregnancy rate of CD138-positive patients (7.7 %) was lower than the pregnancy rate of CD138-negative patients (31.3 %) (p = 0.017 < 0.05); ③ The results from univariate analysis showed that a previous history of prolonged menstrual bleeding episodes, an abortion history, and complications of fallopian tube obstruction were associated with CE (P <0.05). The results of logistic regression analysis confirmed that prolonged menstrual bleeding episodes (P = 0.014, OR = 5.394, 95 % CI 1.405-20.699), a previous abortion history (P = 0.029, OR = 3.194, 95 % CI 1.125-9.073), and fallopian tube obstruction (P = 0.028, OR = 3.274, 95 % CI 1.139-9.415) were independent risk factors for positive CD138 results., Conclusions: CD138 immunohistochemistry can improve the CE diagnosis rate. A previous history of prolonged menstrual bleeding episodes, an abortion history, and a history of fallopian tube obstruction are risk factors for chronic endometritis, and a CD138 immunohistochemical examination should be advised among them.

Results of this study showed that the bacterial composition in vagina (V) greatly differed from intrauterine microbiome (I). Microbiomes were present in all intrauterine samples of healthy women (Group H (I)) and patients with endometrial polyps (EP) (including Group EP (I) and Group EP/chronic endometritis (CE) (I)). Indeed, the intrauterine bacteria population in Group EP/CE (I) were more diverse than those in Groups EP (I) and H (I). The result also confirmed the bacterial composition differences between vagina and uterus as well as the intrauterine microbiome alteration in the patients, compared to the healthy. Although bacteria of Proteobacteria, Firmicutes and Actinobacteria, dominated the intrauterine microbiome in all samples, however, proportions of Firmicutes from Group EP/CE (I) and Group EP (I) were much higher than that from Group H (I), in contrast, the proportions of Proteobacteria were far lower than the healthy. At the genus level, compared to Group H (I), it is found that proportions of Lactobacillus, Gardnerella, Bifidobacterium, Streptococcus, and Alteromonas were significantly higher, and that of Pseudomonas were significantly lower in Group EP/CE (I) or Group EP (I). In addition, lower proportions of Enterobacter and Sphingomonas and a higher proportion of Prevotella were also observed in Group EP/CE (I). In conclusion, uterine microbiomes between patients with EP and the healthy are significantly different and all the potentially important variation of uterine microbes may cause EP, but not definitively related to CE. Further experiments should be performed to test these relationships to endometritis occurrence.

High-temperature alloy coatings that can resist oxidation are urgently needed as nuclear cladding materials to mitigate the danger of hydrogen explosions during meltdown. Here we apply a combination of computationally guided materials synthesis, high-throughput structural characterization and data analysis tools to investigate the feasibility of coatings from the Fe–Cr–Al alloy system. Composition-spread samples were synthesized to cover the region of the phase diagram previous bulk studies have identified as forming protective oxides. The metallurgical and oxide phase evolution were studied via in situ synchrotron glancing incidence x-ray diffraction at temperatures up to 690 K. A composition region with an Al concentration greater than 3.08 at%, and between 20.0 at% and 32.9 at% Cr showed the least overall oxide growth. Subsequently, a series of samples were deposited on stubs and their oxidation behavior at 1373 K was observed. The continued presence of a passivating oxide was confirmed in this region over a period of 6 h.

Objective: To understand the features of magnetic resonance imaging (MRI) findings and the results of clinical follow-up study in 8 infants and children with hand-foot-and-mouth disease (HFMD) complicated with acute flaccid paralysis (AFP) who were admitted to Beijing Ditan Hospital during the outbreak of HFMD in 2008., Methods: The clinical characteristics of the 8 HFMD cases were investigated, and MRI findings were analyzed. The recovery of their impairment in limbs was followed up for three months., Results: All the 8 cases showed poliomyelitis-like syndrome. MRI of spinal cord showed unilateral or bilateral hyperintense lesions which chiefly occurred in the anterior horn regions of the spinal cord (C(2)-C(7) or T(12)-L(1)) on T(1)/T(2)-weighted images. Lesions of spinal cord chiefly occurred in T(12)-L(1). Most of the cases showed mild paralysis, which occurred in more than half of cases in single lower extremity. The patients who had acute paralysis of single lower extremity recovered faster than those with paralysis of four limbs., Conclusions: In HFMD with AFP cases, MRI of spinal cord showed unilateral or bilateral lesions in the anterior horn regions of the spinal cord (C(2)-C(7) or T(12)-L(1)) on T(1)/T(2)-weighted images. AFP may be to some degree reversible in HFMD cases. MRI can directly and completely show the range and degree of changes associated with AFP in HFMD cases, thus provide instructive suggestions to its treatment. The acute paralysis of HFMD cases may be benefited from earlier treatment for AFP.

Aim: To explore the difference of somatostatin receptor subtype 2 (SST2R) gene expression in pancreatic cancerous tissue and its adjacent tissue, and the relationship between the change of SST2R gene expression and pancreatic tumor angiogenesis related genes., Methods: The expressions of SST2R, DPC4, p53 and ras genes in cancer tissues of 40 patients with primary pancreatic cancer, and the expression of SST2R gene in its adjacent tissue were determined by immunohistochemiscal LSAB method and EnVision(TM) method. Chi-square test was used to analyze the difference in expression of SST2R in pancreatic cancer tissue and its adjacent tissue, and the correlation of SST2R gene expression with the expression of p53, ras and DPC4 genes., Results: Of the tissue specimens from 40 patients with primary pancreatic cancer, 35 (87.5%) cancer tissues showed a negative expression of SST2R gene, whereas 34 (85%) a positive expression of SST2R gene in its adjacent tissues. Five (12.5%) cancer tissues and its adjacent tissues simultaneously expressed SST2R. The expression of SST2R gene was markedly higher in pancreatic tissues adjacent to cancer than in pancreatic cancer tissues (P<0.05). The expression rates of p53, ras and DPC4 genes were 50%, 60% and 72.5%, respectively. There was a significant negative correlation of SST2R with p53 and ras genes (chi(1)(2)=9.33, chi(2)(2)=15.43, P<0.01), but no significant correlation with DPC4 gene (chi(2)=2.08, P>0.05)., Conclusion: There was a significant difference of SST2R gene expression in pancreatic cancer tissues and its adjacent tissues, which might be one cause for the different therapeutic effects of somatostatin and its analogs on pancreatic cancer patients. There were abnormal expressions of SST2R, DPC4, p53 and ras genes in pancreatic carcinogenesis, and moreover, the loss or decrease of SST2R gene expression was significantly negatively correlated with the overexpression of tumor angiogenesis correlated p53 and ras genes, suggesting that SST2R gene together with p53 and ras genes may participate in pancreatic cancerous angiogenesis.

We developed a sandwich ELISA with monoclonal antibodies to monitor filarial antigens in animals and patients after infection and treatment. Levels of antimicrofilarial antibodies and parasite antigens were measured periodically in 40 B. malayi infected jirds. In all animals L3 HC11 antigen was detected earlier than Mf ES34 antigen, while antimicrofilarial antibodies appeared much more slowly. These serologic changes precede the onset of patent infections. After 3 courses of treatment with DEC and M170, the levels of parasite antigen in sera and of Mf in peritoneal cavities were monitored in 23 infected jirds. In 8 jirds Mf became negative, no adult worms were found in 7 jirds and a single degenerating female worm was present in 1 jird. ES34 and HC11 were undetectable in 8/8 and 6/8 necropsy sera. Mf persisted in 11 animals, 9 jirds were necropsied, 8 contained adult worms. Detectable levels of ES34 or HC11 antigen were present in 7/9 and 8/9 from these animals. In sham-treatment, few changes were noted in control animals. Thus, parasitological findings at necropsy are correlated with the results of antigen detection assay. We analyzed serial serum samples from 32 bancroftian microfilaremia collected 1-42 months after DEC therapy. Mf resolved rapidly in all treated individuals. ES34 disappeared faster than HC11, 3 months after treatment. Levels of ES34 and HC11 antigens remained detectable or rising after treatment in 8 and 10 individuals. Four patients' Mf recurred 20-42 months after treatment. These findings show that the remaining or a rise in serum levels of antigen after therapy predicts recurrent microfilaremia in patients and additional treatment is needed.

To evaluate the merit of antigen detection assays as a tool to monitor the efficacy of chemotherapy for lymphatic filariasis, we serially measured antigen levels in sera from jirds infected with Brugia malayi and from humans with bancroftian filariasis. Antigenemia was detected in all animals with parasitologically proven infection and was present in jirds with prepatent or occult filariasis. Antigen levels correlated with worm burdens, and progressively declined in drug-cured animals. Treatment with diethylcarbamazine (DEC) triggered a transient increase in serum levels of filarial antigens bearing the epitope recognized by the monoclonal antibody HC 11. All patients with bancroftian filariasis became amicrofilaremic within one week after DEC treatment. Antigenemia levels slowly declined over a period of several months in all but one treated individual. Forty-two months after treatment, progressively rising antigen levels are present in 10 patients. Six of these remain amicrofilaremic; in the other 4, elevated antigenemia levels preceded or were detected at the same time as recurrent parasitemia. Periodic monitoring of antigenemia levels after treatment of patients with lymphatic filariasis can be used to identify individuals who are likely to develop recurrent microfilaremia before the parasites become detectable in blood samples, thereby allowing timely retreatment.