Targeting histone demethylases JMJD3 and UTX: selenium as a potential therapeutic agent for cervical cancer.

BACKGROUND: The intriguing connection between selenium and cancer resembles a captivating puzzle that keeps researchers engaged and curious. While selenium has shown promise in reducing cancer risks through supplementation, its interaction with epigenetics in cervical cancer remains a fascinating yet largely unexplored realm. Unraveling the intricacies of selenium's role and its interaction with epigenetic factors could unlock valuable insights in the battle against this complex disease. RESULT: Selenium has shown remarkable inhibitory effects on cervical cancer cells in various ways. In in vitro studies, it effectively inhibits the proliferation, migration, and invasion of cervical cancer cells, while promoting apoptosis. Selenium also demonstrates significant inhibitory effects on human cervical cancer-derived organoids. Furthermore, in an in vivo study, the administration of selenium dioxide solution effectively suppresses the growth of cervical cancer tumors in mice. One of the mechanisms behind selenium's inhibitory effects is its ability to inhibit histone demethylases, specifically JMJD3 and UTX. This inhibition is observed both in vitro and in vivo. Notably, when JMJD3 and UTX are inhibited with GSK-J4, similar biological effects are observed in both in vitro and in vivo models, effectively inhibiting organoid models derived from cervical cancer patients. Inhibiting JMJD3 and UTX also induces G2/M phase arrest, promotes cellular apoptosis, and reverses epithelial-mesenchymal transition (EMT). ChIP-qPCR analysis confirms that JMJD3 and UTX inhibition increases the recruitment of a specific histone modification, H3K27me3, to the transcription start sites (TSS) of target genes in cervical cancer cells (HeLa and SiHa cells). Furthermore, the expressions of JMJD3 and UTX are found to be significantly higher in cervical cancer tissues compared to adjacent normal cervical tissues, suggesting their potential as therapeutic targets. CONCLUSIONS: Our study highlights the significant inhibitory effects of selenium on the growth, migration, and invasion of cervical cancer cells, promoting apoptosis and displaying promising potential as a therapeutic agent. We identified the histone demethylases JMJD3 and UTX as specific targets of selenium, and their inhibition replicates the observed effects on cancer cell behavior. These findings suggest that JMJD3 and UTX could be valuable targets for selenium-based treatments of cervical cancer.

Group membership modulates empathic neural responses to pain in deaf individuals.

Empathy deficiencies are prevalent among deaf individuals. It has yet to be determined whether they exhibit an ingroup bias in empathic responses. This study employed explicit and implicit empathy tasks (i.e. attention-to-pain-cue [A-P] task and attention-to-nonpain-cue [A-N] task) to explore the temporal dynamics of neural activities when deaf individuals were processing painful/nonpainful stimuli from both ingroup models (deaf people) and outgroup models (hearing people), which aims to not only assist deaf individuals in gaining a deeper understanding of their intergroup empathy traits but also to aid in the advancement of inclusive education. In the A-P task, we found that (i) ingroup priming accelerated the response speed to painful/nonpainful pictures; (ii) the N2 amplitude of painful pictures was significantly more negative than that of nonpainful pictures in outgroup priming trials, whereas the N2 amplitude difference between painful and nonpainful pictures was not significant in ingroup priming trials. For N1 amplitude of the A-N task, we have similar findings. However, this pattern was reversed for P3/late positive component amplitude of the A-P task. These results suggest that the deaf individuals had difficulty in judging whether hearing individuals were in pain. However, their group identification and affective responses could shape the relatively early stage of pain empathy.

Assessment of 3.0 Tesla magnetic resonance imaging in Madelung's deformity: findings and implications.

OBJECTIVE: The aim of the study was to investigate the 3.0 Tesla magnetic resonance imaging (MRI) features of Madelung's deformity. MATERIALS AND METHODS: The wrist MRI scans of 19 patients clinically diagnosed with Madelung's deformity and 20 patients without deformity were consecutively selected from Beijing Jishuitan Hospital between April 2019 and December 2022 for observation, in the case group and control group, respectively. Multiple linear regression was used to analyze the factors affecting tilting angle and width of central disc (CD, also termed as triangular fibrocartilage, the main component of triangular fibrocartilage complex), while the chi-square test was used to compare the occurrences of CD (radial) attachment displacement, VL, and RTL. p < 0.05 indicated statistical significance. RESULTS: Madelung's deformity significantly contributed to the tilting and thickening of the CD. In the case group, the tilting angle and thickness of CD were (51.46 ± 1.33)° and (0.23 ± 0.01) cm, respectively, which was statistically significant (p < 0.05); the radial attachment of the CD significantly shifted away from the distal articular surface level (χ2 = 39.00, p < 0.001), with a mean displacement of (0.97 ± 0.38) cm. Furthermore, the cases demonstrated abnormally developed Vickers ligament (χ2 = 35.19, p < 0.001) and radiotriquetral ligament (χ2 = 25.66, p < 0.001). CONCLUSION: MRI provides a notable advantage in diagnosing Madelung's deformity. Compared with the control group, patients with Madelung's deformity exhibited tilting and thickening of the CD. Additionally, the radial attachment of the CD was significantly shifted proximally with abnormal development of Vickers and radiotriquetral ligaments.

A case of colonic muco-submucosal elongated polyp (CMSEP) misdiagnosed as a inverted colonic diverticulum (ICD).

CMSEP is a large intestine polyp with a long and broad stalk and a "worm-like" appearance which is covered by normal mucosa. The submucosal layer consists of edematous and fibrotic interstitium, adipose tissue, dilated blood vessels, and lymphatic follicles[1]. Endoscopic magnification of the mucosal surface showed a uniform honeycomb pattern of regular blood vessels, with soft and deformable "folds" and "gyrus" at the top. The exact pathogenesis of CMSEP is still unclear.

Endoscopic observation of a rare duodenal tumor

A 30-year-old young previously healthy man presented to our hospital with middle and upper abdominal discomfort. Abdominal computerized tomography (CT) showed no significant abnormalities. White light endoscopy showed the local mucosa in the descending part of the duodenum had granuloid uplift, some of which were fused into pieces with red color, and some other areas showed fading tone. Magnifying endoscopy with indigo-carmine staining and narrow-band imaging showed a finger-like, loose villous structure with irregular microvessels on the surface. Pathological examination of biopsy specimens showed that lymphocytes were diffused and dispersed in the mucosa with relatively simple morphology, no lymphoid follicles were observed, and local compression was obvious. Immunohistochemical staining revealed a lymphoid population highly positive for CD20 and CD10. These results were consistent with duodenal-type follicular lymphoma (D-FL). (AU)

Visuospatial ability and attention as risk factors for suicidal ideation in middle-aged and elderly schizophrenia patients: a cross-sectional study.

BACKGROUND: Schizophrenia patients have a high risk of suicide, and their cognition function is impaired with increasing age. The association between neurocognitive and suicidality in schizophrenia patients are heterogeneous. We aimed to explore the relationship between neurocognitive function and suicidal ideation in schizophrenia patients across age groups. METHODS: A total of 587 patients with schizophrenia were enrolled in this study. The schizophrenia patients were divided into young group (aged 18-44) and middle-aged and elderly group (aged 45-70). The schizophrenia patients were divided into suicidal ideation group and non-suicidal ideation group according to the evaluation results of the Beck Scale for Suicide Ideation. Insomnia symptoms were measured by the Insomnia Severity Index (ISI). Psychotic symptoms were measured by the Positive and Negative Syndrome Scale (PANSS), and cognitive function was measured by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). RESULTS: There was a negative correlation between the age and attention scores of RBANS (P = 0.018). The young schizophrenia patients had higher risk of suicidality than middle-aged and elderly schizophrenia patients (P = 0.001). In the logistic regression analysis, the scores of ISI and positive symptoms scores of PANSS were associated with suicidal ideation among young schizophrenia patients (All P < 0.05). Age, BMI, the scores of ISI, general symptoms scores of PANSS, visuospatial scores of RBANS and attention scores of RBANS were associated with suicidal ideation in middle-aged and elderly schizophrenia patients (All P < 0.05). CONCLUSIONS: High visuospatial scores of RBANS and attention scores of RBANS were risk factors for suicidal ideation in middle-aged and elderly schizophrenia patients.

Hemorrhagic fever with renal syndrome and reversible splenial lesion syndrome.

Hemorrhagic fever with renal syndrome (HFRS) and reversible splenial lesion syndrome are both considered uncommon conditions relatively rare. Fever, hemorrhage, and acute kidney injury are the prevailing symptoms frequently observed in cases of HFRS. We describe a case of a middle-aged man who had been hospitalized with fever and acute neurological symptoms. His main symptom was recurrent dizziness. Cranial computed tomography (CT) did not reveal any obvious lesions, such as encephalorrhagia or infarctions. The splenium of corpus callosum showed hyperintensity on brain magnetic resonance imaging (MRI), which is in line with the characteristic radiographic observations of reversible splenial lesion syndrome (RESLES). Further analyses revealed that the patient's platelet counts had decreased to 7×109/L while hemorrhagic fever antibodies were positive. Eventually, the patient was diagnosed with HFRS and exhibited clinical improvements after active treatment.

Solid food dysphagia caused by aortic arch malformation compressing esophagus.

A 66-year-old woman presented to our hospital with a long history of solid food dysphagia. Gastroscopy revealed that esophagus was distorted and slightly narrow in the middle section. High-resolution esophageal manometry testing was used to assess the esophageal motor function. We tried to insert the manometric catheter into the patient's stomach, but found that when the patient swallowed, the picture presented an up-down symmetry phenomenon, and the esophageal peristalsis lost its normal slope. Therefore, we believed that the manometer catheter folded back cephalad at her upper esophagus, demonstrating a strange appearance of a curly manometry catheter. Subsequently, a barium esophagram was performed and revealed that there was a stenosis in the middle of the esophagus, and the narrowest of which was about 2cm in diameter. We reviewed the computed tomography and found the aortic arch of the patient was compressing on her esophagus, causing local lumen stenosis.

Prevalence and molecular characterization of Giardia duodenalis in dairy cattle in Central Inner Mongolia, Northern China.

Giardia duodenalis is a gastrointestinal protozoan ubiquitous in nature. It is a confirmed zoonotic pathogen, and cattle are considered a source of giardiasis outbreaks in humans. This study aimed to evaluate the prevalence and multilocus genotype (MLG) of G. duodenalis in dairy cattle in Central Inner Mongolia. This study was based on the small subunit ribosomal RNA (SSU rRNA), glutamate dehydrogenase (gdh), triosephosphate isomerase (tpi), and beta-giardin (bg) genes of G. duodenalis. DNA extraction, polymerase chain reaction (PCR), and sequence analysis were performed on 505 dairy cattle fecal samples collected in 2021 from six sampling sites and four age groups in Central Inner Mongolia to determine the prevalence and MLG distribution of G. duodenalis. The PCR results of SSU rRNA revealed that the overall prevalence of G. duodenalis was 29.5% (149/505) and that the overall prevalence of the diarrhea and nondiarrhea samples was 31.5% (46/146) and 28.5% (103/359), respectively; the difference was not significant (p > 0.05). SSU rRNA sequence analysis revealed that G. duodenalis assemblage E (91.1%, 133/146) was primarily detected and that assemblage A (8.9%, 13/146) was detected in 13 samples. The G. duodenalis-positive samples were PCR amplified and sequenced for gdh, tpi, and bg, from which 38, 47, and 70 amplified sequences were obtained, respectively. A combination of G. duodenalis assemblages A and E were detected in seven samples. Multilocus genotyping yielded 25 different assemblage E MLGs, which formed six subgroups. To the best of our knowledge, this is the first report regarding G. duodenalis infection in dairy cattle in Inner Mongolia, China. This study revealed that Inner Mongolian cattle pose a risk of giardiasis transmission to humans and that the distribution of local cattle G. duodenalis assemblage E MLGs is diverse. The findings of this study can bridge the knowledge gap in the molecular epidemiological investigation of giardiasis in Central Inner Mongolia.

Prevalence and molecular characterization of Cryptosporidium spp. in dairy cattle in Central Inner Mongolia, Northern China.

BACKGROUND: Cryptosporidium is a gastrointestinal protozoan that widely exists in nature, it is an established zoonotic pathogen. Infected cattle are considered to be associated with cryptosporidiosis outbreaks in humans. In the present study, we aimed to assess the prevalence and species distribution of Cryptosporidium in dairy cattle in Central Inner Mongolia. METHODS: We focused on the small subunit ribosomal RNA gene (SSU rRNA) of Cryptosporidium and 60-kDa glycoprotein gene (gp60) of Cryptosporidium parvum. We collected 505 dairy cattle manure samples from 6 sampling sites in Inner Mongolia in 2021; the samples were divided into 4 groups based on age. DNA extraction, polymerase chain reaction (PCR), sequence analysis, and restriction fragment length polymorphism (RFLP) using SspI and MboII restriction endonucleases were performed. RFLP analysis was performed to determine the prevalence and species distribution of Cryptosporidium. RESULTS: SSU rRNA PCR revealed that the overall prevalence of Cryptosporidium infection was 29.90% (151/505), with a prevalence of 37.67% (55/146) and 26.74% (96/359) in diarrheal and nondiarrheal samples, respectively; these differences were significant. The overall prevalence of Cryptosporidium infection at the 6 sampling sites ranged from 0 to 47.06% and that among the 4 age groups ranged from 18.50 to 43.81%. SSU rRNA sequence analysis and RFLP analysis revealed the presence of 4 Cryptosporidium species, namely, C. bovis (44.37%), C. andersoni (35.10%), C. ryanae (21.85%), and C. parvum (11.92%), along with a mixed infection involving two or three Cryptosporidium species. Cryptosporidium bovis or C. andersoni was the most common cause of infection in the four age groups. The subtype of C. parvum was successfully identified as IIdA via gp60 analysis; all isolates were identified as the subtype IIdA19G1. CONCLUSIONS: To the best of our knowledge, this is the first report of dairy cattle infected with four Cryptosporidium species in Inner Mongolia, China, along with a mixed infection involving two or three Cryptosporidium species, with C. bovis and C. andersoni as the dominant species. Moreover, this is the first study to identify C. parvum subtype IIdA19G1 in cattle in Inner Mongolia. Our study findings provide detailed information on molecular epidemiological investigation of bovine cryptosporidiosis in Inner Mongolia, suggesting that dairy cattle in this region are at risk of transmitting cryptosporidiosis to humans.

Endoscopic Endoscopic observation of a rare duodenal tumor of a rare duodenal tumor.

A 30-year-old young previously healthy man presented to our hospital with middle and upper abdominal discomfort. Abdominal computerized tomography (CT) showed no significant abnormalities. White light endoscopy showed the local mucosa in the descending part of the duodenum had granuloid uplift, some of which were fused into pieces with red color, and some other areas showed fading tone. Magnifying endoscopy with indigo-carmine staining and narrow-band imaging showed a finger-like, loose villous structure with irregular microvessels on the surface. Pathological examination of biopsy specimens showed that lymphocytes were diffused and dispersed in the mucosa with relatively simple morphology, no lymphoid follicles were observed, and local compression was obvious. Immunohistochemical staining revealed a lymphoid population highly positive for CD20 and CD10. These results were consistent with duodenal-type follicular lymphoma (D-FL).

Gastric inverted hyperplastic polyp with heterotopic pancreas: a rare case of submucosal eminence of the antrum.

A 43-year-old female underwent gastroscopy due to abdominal discomfort. Gastroscopy showed a submucosal eminence at the greater curvature of the antrum, with smooth surface mucosa, biopsy pathology suggests inflammation. We scheduled an endoscopic ultrasonography (EUS) for her. EUS revealed that the size of the lesion was about 8.7mm*10.8mm, with hypoechoic changes, which originated in the submucosa. Endoscopic submucosal dissection was performed, and representative photomicrographs of histologic sections were shown. The patient was diagnosed with gastric inverted hyperplastic polyp (GIHP) with heterotopic pancreas (HP).

High-grade intraepithelial neoplasia of the cervical esophagus arising from a tiny ectopic gastric mucosa.

A 77-year-old male underwent gastroscopy in our institution. Conventional endoscopic examination revealed two ectopic gastric mucosas (EGMs) located about 17cm from the incisors. One of the EGMs was about 0.6cm in size and was round with a flat surface and a slight uplift in the center. The boundary of the uplift was clear and the villous structure disappeared. Narrow Band Imaging (NBI) showed irregular microvessels with a fine network pattern at the uplift, and there appeared to be small and punctate crypt opening (CO) in the glandular ducts. Then we performed acetic acid staining and found that the lesion showed dense and small CO clearly, suggesting differentiated gastric cancer. Histopathologic diagnosis of the biopsy specimen from the lesion was high-grade intraepithelial neoplasia.

Clinical efficacy and mechanism of transcutaneous neuromodulation on ineffective esophageal motility in patients with gastroesophageal reflux disease.

BACKGROUND: Esophageal motility disorder is one of the pathogenesis of gastroesophageal reflux disease (GERD). The clinical and functional relationship between the ineffective esophageal motility (IEM) and GERD have been found. PPI is a widely used drug of this diaease, but some patients have poor efficacy. The purpose of this study was to investigate the efficacy and possible mechanism of Transcutaneous Neuromodulation in these patients. METHODS: Fifty-six patients with GERD with IEM were enrolled and randomly divided into two groups, one group was TN ST-36 group, the other group was sham TN group. The GERD questionnaire (GerdQ), quality of life score, MOS item short from health survey (SF-36), Hospital Anxiety and Depression Scale (HADS) were used to assess the severity of symptoms. High-resolution esophageal manometry (HRM) test was performed to assess low esophageal sphincter (LES) pressure and distal contractile integral (DCI). The heart rate variability (HRV) test was performed to assess autonomic nervous function. KEY RESULTS: Compared with sham TN, chronic TN treatment decreased the GERD-Q score (p < 0.001). The anxiety score (p = 0.058) and depression score (p = 0.156) were decreased, but there were no statistical differences. Chronic TN treatment also significantly improved the quality of life of patients, mainly in physical function, physical pain, overall health, vitality, social function, emotional function, and mental health. Acute TN treatment increased the DCI (p < 0.001) and LES pressure (p < 0.001) significantly and decreased the combined percentage of failed and weak peristalsis (p < 0.001). Concurrently, acute TN enhanced vagal activity (p < 0.001). CONCLUSIONS AND INFERENCES: IEM is an important link in the pathogenesis of GERD. Chronic TN treatment can significantly improve the clinical symptoms of patients. Acute TN treatment can significantly increase LES pressure and DCI and reduce the frequency of esophageal lost peristalsis and weak peristalsis. The improvement of esophageal motility in GERD patients with IEM by TN treatment may be related to the regulation of autonomic nervous function.