Zinc finger BED-type containing 3 promotes hepatic steatosis by interacting with polypyrimidine tract-binding protein 1.

AIMS/HYPOTHESIS: The relationship between metabolic dysfunction-associated steatotic liver disease (MASLD) and type 2 diabetes mellitus, insulin resistance and the metabolic syndrome is well established. While zinc finger BED-type containing 3 (ZBED3) has been linked to type 2 diabetes mellitus and the metabolic syndrome, its role in MASLD remains unclear. In this study, we aimed to investigate the function of ZBED3 in the context of MASLD. METHODS: Expression levels of ZBED3 were assessed in individuals with MASLD, as well as in cellular and animal models of MASLD. In vitro and in vivo analyses were conducted using a cellular model of MASLD induced by NEFA and an animal model of MASLD induced by a high-fat diet (HFD), respectively, to investigate the role of ZBED3 in MASLD. ZBED3 expression was increased by lentiviral infection or tail-vein injection of adeno-associated virus. RNA-seq and bioinformatics analysis were employed to examine the pathways through which ZBED3 modulates lipid accumulation. Findings from these next-generation transcriptome sequencing studies indicated that ZBED3 controls SREBP1c (also known as SREBF1; a gene involved in fatty acid de novo synthesis); thus, co-immunoprecipitation and LC-MS/MS were utilised to investigate the molecular mechanisms by which ZBED3 regulates the sterol regulatory element binding protein 1c (SREBP1c). RESULTS: In this study, we found that ZBED3 was significantly upregulated in the liver of individuals with MASLD and in MASLD animal models. ZBED3 overexpression promoted NEFA-induced triglyceride accumulation in hepatocytes in vitro. Furthermore, the hepatocyte-specific overexpression of Zbed3 promoted hepatic steatosis. Conversely, the hepatocyte-specific knockout of Zbed3 resulted in resistance of HFD-induced hepatic steatosis. Mechanistically, ZBED3 interacts directly with polypyrimidine tract-binding protein 1 (PTBP1) and affects its binding to the SREBP1c mRNA precursor to regulate SREBP1c mRNA stability and alternative splicing. CONCLUSIONS/INTERPRETATION: This study indicates that ZBED3 promotes hepatic steatosis and serves as a critical regulator of the progression of MASLD. DATA AVAILABILITY: RNA-seq data have been deposited in the NCBI Gene Expression Omnibus ( www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE231875 ). MS proteomics data have been deposited to the ProteomeXchange Consortium via the iProX partner repository ( https://proteomecentral.proteomexchange.org/cgi/GetDataset?ID=PXD041743 ).

The clinical and immunological features of pediatric COVID-19 patients in China.

In December 2019, the corona virus disease 2019 (COVID-19) caused by novel coronavirus (SARS-CoV-2) emerged in Wuhan, China and rapidly spread worldwide. Few information on clinical features and immunological profile of COVID-19 in paediatrics. The clinical features and treatment outcomes of twelve paediatric patients confirmed as COVID-19 were analyzed. The immunological features of children patients was investigated and compared with twenty adult patients. The median age was 14.5-years (range from 0.64 to 17), and six of the patients were male. The average incubation period was 8 days. Clinically, cough (9/12, 75%) and fever (7/12, 58.3%) were the most common symptoms. Four patients (33.3%) had diarrhea during the disease. As to the immune profile, children had higher amount of total T cell, CD8+ T cell and B cell but lower CRP levels than adults (P < 0.05). Ground-glass opacity (GGO) and local patchy shadowing were the typical radiological findings on chest CT scan. All patients received antiviral and symptomatic treatment and the symptom relieved in 3-4 days after admitted to hospital. The paediatric patients showed mild symptom but with longer incubation period. Children infected with SARS-CoV-2 had different immune profile with higher T cell amount and low inflammatory factors level, which might ascribed to the mild clinical symptom. We advise that nucleic acid test or examination of serum IgM/IgG antibodies against SARS-CoV-2 should be taken for children with exposure history regardless of clinical symptom.

Antibody responses to SARS-CoV-2 in patients with COVID-19.

We report acute antibody responses to SARS-CoV-2 in 285 patients with COVID-19. Within 19 days after symptom onset, 100% of patients tested positive for antiviral immunoglobulin-G (IgG). Seroconversion for IgG and IgM occurred simultaneously or sequentially. Both IgG and IgM titers plateaued within 6 days after seroconversion. Serological testing may be helpful for the diagnosis of suspected patients with negative RT-PCR results and for the identification of asymptomatic infections.

Accuracy of endoscopic ultrasound in rectal cancer and its use in transanal endoscopic microsurgery.

Introduction: This study evaluated the accuracy of endoscopic ultrasound (EUS) for preoperative staging of rectal cancer and guiding the treatment of transanal endoscopic microsurgery (TEM) in early rectal cancer.Material and methods: One-hundred-twenty-six patients with rectal cancer were staged preoperatively using EUS and the results were compared with postoperative histopathology results. Radical surgeries, including low anterior resection (LAR), abdominal-perineal resection (APR) and Hartmann surgeries, were performed on patients with advanced rectal cancers, and TEM was performed on patients with stage T1. The Kappa statistic was used to determine agreement between EUS-based staging and pathology staging.Results: The overall accuracies of EUS for T and N stage were 90.8% (Kappa = 0.709) and 76.7% (Kappa = 0.419), respectively. The accuracies of EUS for uT1, uT2, uT3, and uT4 stages were 96.8%, 92.1%, 84.1%, and 88.9%, respectively, and for uN0, uN1, and uN2 stages, they were 71.9%, 64.9%, and 93.0%, respectively. Twelve patients underwent TEM and received confirmed pathology results of early rectal cancer. After postoperative follow-up, there were no local recurrences or distant metastases.Conclusion: EUS is a good and comparable technique for postoperative staging of rectal cancer. Moreover, EUS is used as indicator for preoperative staging and tumor assessment strategy when considering TEM.

Madelung's Disease: Is Insobriety the Chief Cause?

BACKGROUND: Madelung's disease (MD) is a rare disease of unknown etiology that is characterized by massive fatty deposits distributed in a symmetrical pattern mainly in the head, neck, and upper trunk. Here, we sought to explore the pathogeny and treatment of MD. METHODS: We enrolled ten patients who underwent surgical operations and one patient who refused an operation at our hospital between January 2009 and December 2016. We collected their medical histories and the preoperative and postoperative serological indices. The serum chemistry clinical outcomes were compared between the preoperative and postoperative states. RESULTS: The mean alcohol intake of the eleven patients exceeded 450 g daily. Ten patients underwent open excisions, and the other patient refused an operation. No significant differences were observed between the preoperative and postoperative serum chemistry results. No recurrence has yet been observed in any of the ten operated patients. CONCLUSIONS: All of the patients in our study had associated alcoholism. Thus, insobriety might be one of the causes of MD. We believe that open operations may be an effective treatment based on the outcomes of the surgeries. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Rupture of sigmoid colon caused by compressed air.

Compressed air has been generally used since the beginning of the 20(th) century for various applications. However, rupture of the colon caused by compressed air is uncommon. We report a case of pneumatic rupture of the sigmoid colon. The patient was admitted to the emergency room complaining of abdominal pain and distention. His colleague triggered a compressed air nozzle against his anus as a practical joke 2 h previously. On arrival, his pulse rate was 126 beats/min, respiratory rate was 42 breaths/min and blood pressure was 86/54 mmHg. Physical examination revealed peritoneal irritation and the abdomen was markedly distended. Computed tomography of the abdomen showed a large volume of air in the abdominal cavity. Peritoneocentesis was performed to relieve the tension pneumoperitoneum. Emergency laparotomy was done after controlling shock. Laparotomy revealed a 2-cm perforation in the sigmoid colon. The perforation was sutured and temporary ileostomy was performed as well as thorough drainage and irrigation of the abdominopelvic cavity. Reversal of ileostomy was performed successfully after 3 mo. Follow-up was uneventful. We also present a brief literature review.

[Expression of ZBTB8A in gastric cancer and its clinical significance].

OBJECTIVE: To investigate the expression of ZBTB8A (zinc finger and BTB domain containing 8A) in gastric cancer tissues and its clinical significance. METHODS: Level of ZBTB8A mRNA in human normal gastric cell line GES-1, human gastric cancer cell line SGC7901 and MGC803 was detected by real-time PCR. Levels of ZBTB8A mRNA and protein in cancer tissues, adjacent cancer tissues from 104 cases with primary gastric cancer and normal gastric mucosal tissues from 40 cases without malignant gastric diseases were detected by RT-PCR and immunohistochemistry, respectively. Association between ZBTB8A expression and clinicopathology was analyzed. RESULTS: ZBTB8A mRNA expressions in SGC7901, MGC803 and GES-1 cells were 0.00138±0.00015, 0.00158±0.00021, 0.00036±0.000055, respectively, and differences among SGC7901, MGC803 and GES-1 were significant respectively (all P<0.05). ZBTB8A mRNA expression was significantly up-regulated in cancer tissues as compared to adjacent cancer tissues and normal tissues (0.0152±0.0126 vs. 0.0070±0.0061 and 0.0079±0.0036, all P>0.05), while no significant difference was found between adjacent cancer tissues and normal tissues (P>0.05). ZBTB8A expression was significantly associated with invasive depth, lymph node metastasis, tumor stage, and degree of adenocarcinoma differentiation (all P<0.05), but not with age, gender, histological type,gross type (all P>0.05). CONCLUSION: ZBTB8A may be a potential carcinogenic factor in gastric carcinoma, and may also be involved in gastric adenocarcinoma cell differentiation, cancer invasion and metastasis.

[Analysis of the protein expression and gene amplification of HER2 in gastric cancer].

OBJECTIVE: To explore the clinical significance of protein expression and gene amplification of HER2 in gastric cancer. METHODS: Immunohistochemistry (IHC) and chromogenic in situ hybridization (CISH) method were used to detect protein expression and gene amplification of HER2 in 80 specimens of gastric cancer patients. RESULTS: Protein expression of HER2 was negative in 51 cases, (+) in 12 cases, (++) in 12 cases, (+++) in 5 cases, and the positive expression rate was 21.3% (17/80). Seven (8.8%) cases had gene amplification of HER2, including gene critical amplification in 3 (3.8%) cases. The result of IHC was positively correlated with CISH (P<0.05), and the coincidence rate was 85.0% (68/80). HER2 positive expression rate was higher in the gastroesophageal junction carcinoma, poorly differentiated and stage III-IIII gastric cancer (all P<0.05). CONCLUSION: The gastric cancer tissue has high positive rate of protein expression and gene amplification of HER2, which is closely correlated to the development of gastric cancer.