IGF2BP3-NRF2 axis regulates ferroptosis in hepatocellular carcinoma.

Poor sensitivity to sorafenib has been an important constraint on the efficacy of targeted therapy in advanced hepatocellular carcinoma (HCC). Therefore, it is particularly important to explore effective therapeutic targets to improve the sensitivity of HCC cells to sorafenib. Upregulation of IGF2BP3 is strongly associated with tumor invasion, early recurrence and poor prognosis in various human cancers, including HCC, but its roles in the sorafenib treatment of HCC remain unclear. In our study, IGF2BP3 knock-down significantly promoted ferroptosis in HCC cells through the evaluation of the Reactive Oxygen Species (ROS), Fe2+ and malondialdehyde (MDA) levels after sorafenib administration. In addition, NRF2 mRNA was identified as an important target of IGF2BP3 by bioinformatics analysis, RNA binding protein immunoprecipitation (RIP) and RNA pulldown experiments. More importantly, IGF2BP3, as an m6A (N6-Methyladenosine) reader, was shown to promote the stability of NRF2 mRNA by reading its m6A modification. Similar results were obtained from in vivo experiments. In summary, our study uncovered the role of IGF2BP3-NRF2 axis on ferroptosis in HCC, providing significant evidence for new anti-cancer strategies aimed at improving the efficacy of sorafenib.

MicroRNA-199b-5p attenuates TGF-ß1-induced epithelial-mesenchymal transition in hepatocellular carcinoma.

BACKGROUND: Accumulating evidence indicates that N-cadherin is a cell adhesion molecule that has critical roles in tumour progression. However, the role of N-cadherin in hepatocellular carcinoma (HCC) remains controversial. METHODS: This study aims to investigate the expression status of N-cadherin and its molecular mechanisms in HCC. RESULTS: The expression of N-cadherin was markedly overexpressed in HCC tissues and cell lines. We identified that miR-199b-5p binds to the 3'-UTR of N-cadherin mRNA, thus decreasing N-cadherin expression in HCC cells. We also found the downregulation of miR-199b-5p in HCC specimens, which was inversely correlated with N-cadherin upregulation, predicted poor clinical outcomes in HCC patients. Next, we determined that miR-199b-5p overexpression promoted cell aggregation, suppressed cell migration and invasion in HCC cells, and inhibited xenografts tumour metastasis in nude mice. Moreover, we demonstrated that miR-199b-5p attenuated TGF-ß1 induced epithelial-mesenchymal transition (EMT) -associated traits, while its effects could be partially reversed by N-cadherin restoration. Finally, we examined that N-cadherin downregulation or miR-199b-5p overexpression suppressed TGF-ß1-induced Akt phosphorylation, and inhibition of PI3K/Akt pathway blocked TGF-ß1-induced N-cadherin overexpression in HCC cells. CONCLUSIONS: Our data demonstrate that N-Cadherin was markedly overexpressed and miR-199b-5p was significantly downregulated in HCC. MiR-199b-5p exerts inhibitory effects on EMT, and directly targets N-cadherin in HCC, supporting the potential utility of miR-199b-5p as a promising strategy to treat HCC. Also, a positive regulatory loop exists between N-cadherin and Akt signalling represents a novel mechanism of TGF-ß1-mediated EMT in HCC cells.

[Clinical analysis of acute hyperlipidemic pancreatitis during pregnancy and postpartum period].

OBJECTIVE: To describe the characteristics of acute pancreatitis during pregnancy and postpartum. METHODS: From 1994 to 2012, 18 cases of gravida and postpartum women complicated with acute pancreatitis were treated at Peking University Third Hospital and retrospective analysis was performed. RESULTS: The admission rate due to acute pancreatitis was 41.24 per 100 000 admission. The median age was 32.0 (28.0, 34.7) years, with the onset of acute pancreatitis on 35.0 (23.5, 37.0) weeks'gestation. Of all the cases, 13 (72.2%) were interstitial edematous acute pancreatitis, and 5 (27.8%) were necrotizing. Nine (50.0%) were caused by hyperlipidemia, of which 7 (38.9%) were caused by gallstones, and 2 (1.1%) were idiopathic. Stratified by severity, 6 (33.3%) were mild, 7 (38.9%) were moderately severe and 5 (27.8%) were severe, of which 8 were transferred to Intensive Care Unit. Compared with non-hyperlipidemic acute pancreatitis, cases caused by hyperlipidemia were more severe, however, the prognoses of mothers and infants were good. CONCLUSION: The incidence of acute pancreatitis during pregnancy and postpartum was similar to that of the regular population, and mostly caused by gallstones and hyperlipidemia. Although acute hyperlipidemic pancreatitis is more severe, the morbidity and mortality of maternal and perinatal could be decreased by aggressive therapy.

Estimated Pulse Wave Velocity as a Novel Non-Invasive Biomarker for Metabolic Syndrome Among People Living with HIV.

Purpose: This study aims to investigate the relationship between estimated pulse wave velocity (ePWV) and metabolic syndrome (MetS) in people living with HIV (PLWH), proposing a novel and convenient predictor for early detection of MetS in PLWH. Patients and Methods: A total of 485 PLWH were enrolled. These participants were categorized into two groups based on the estimated pulse wave velocity (ePWV) level. Demographic and clinical data were collected to investigate the correlation between ePWV and MetS. Results: The cohort of 485 PLWH was categorized into high-ePWV and low-ePWV groups based on ePWV cutoff value of 10 m/s. We observed significant differences in components of MetS including triglycerides (TG, P < 0.05), HDL cholesterol (HDL-C, P < 0.01), systolic blood pressure (SBP, P < 0.001), diastolic blood pressure (DBP, P < 0.05), and fasting plasma glucose (FPG, P < 0.001) between the two groups. Furthermore, we employed receiver operating characteristic (ROC) curves to demonstrate the effectiveness of ePWV as a predictive indicator for MetS in PLWH (AUC = 0.739, P < 0.001). According to the ROC curve, the optimal cut-off value of ePWV was 7.4 m/s, and its sensitivity and specificity in diagnosing MetS in PLWH were 79.03% and 64.07%, respectively. Although the 7.4 m/s cutoff increased the false positive rate compared to the traditional cutoff, it significantly reduced the rate of missed diagnoses, effectively identifying 79.03% of PLWH with MetS. Conclusion: ePWV is a non-invasive and convenient novel biomarker with predictive capabilities for MetS in PLWH.

Prospective observational study of baloxavir marboxil in adults and adolescents with uncomplicated influenza from China.

Introduction: There are limited data on the efficacy of baloxavir marboxil (baloxavir) versus oseltamivir in Chinese patients with influenza A. Methods: This study is an observational real-world investigation encompassing 246 patients (baloxavir, n = 147; oseltamivir, n = 99) confirmed positive for influenza A. The choice between baloxavir and oseltamivir antiviral treatments was determined collaboratively by the clinician and the patient. A thorough comparative analysis was undertaken between the two groups, examining parameters such as the duration of fever and symptoms, viral load dynamics, lymphocyte changes, and enhancements in health-related quality of life (QoL). Results: No significant differences were observed in demographic data between the two groups. The duration of fever was significantly shorter in the baloxavir group (P < 0.001). However, the duration of symptoms was not significant different (P = 0.167). Multivariable Cox analysis showed the independent factors affecting duration of fever were baloxavir treatment (HR = 2.033, P < 0.001), fever on day 1 (HR = 0.741, P = 0.010) and CRP level (HR = 1.009, P = 0.039). Moreover, sex (HR= 0.660, P = 0.019) and monocyte count (HR = 1.355, P = 0.018) were independent factors affecting the duration of symptoms. No significant difference in change of health-related quality of life (P > 0.05), positive rate of viral antigen on day 3 (P = 0.477) between the two groups. Remarkably, a mutation was observed in one case on the third-day after baloxavir treatment compared with first-day, from cysteine to serine at position 384 of the PA subunit. Conclusion: In the clinical setting, baloxavir demonstrated comparable clinical benefits to oseltamivir, establishing its efficacy as an effective antiviral therapy for Chinese patients with influenza.

Reduced-visit antenatal care model combined with telemedicine for low-risk pregnant women: protocol for a randomised controlled trial.

INTRODUCTION: Antenatal care (ANC) is a critical measure to reduce maternal and perinatal morbidity and mortality. However, there are issues of too many visits and cumbersome procedures of ANC in many maternity hospitals of China. In the past 2 years, reduced-visit ANC models combined with remote monitoring have been recommended and implemented at most hospitals in China during the COVID-19 pandemic. Nevertheless, due to limited evaluations of the cost-effectiveness, policy-makers remain confused on how to appropriately integrate online delivery strategies with routine models to improve ANC quality and efficiency sustainably at scale. This trial aims to evaluate the effectiveness, acceptability and cost of a reduced-visit ANC model combined with telemedicine. METHODS AND ANALYSIS: A single-blind, randomised controlled trial will be conducted among low-risk pregnant women at Peking University Third Hospital in Beijing. 1476 patients (738 in each group) would be required, and they will be randomly assigned in a 1:1 ratio to receive the reduced-visit ANC combined with telemedicine services or the routine ANC. The primary outcome is the composite rate of adverse maternal and perinatal outcomes which will be extracted from the medical records. Secondary outcomes include acceptability of ANC models, which is assessed by satisfaction with ANC, pregnancy-related stress and ANC costs measured from the perspectives of both service providers and demanders. Both intention-to-treat and per-protocol analyses will be performed. Non-inferiority tests will be used to compare the two ANC models for the primary outcome. A cost-effectiveness analysis comparing the two ANC models will be conducted by estimating the incremental cost-effectiveness ratios. ETHICS AND DISSEMINATION: This study was approved by the ethical review committee of the Peking University Third Hospital (Beijing, China). The results of this study will be published in peer-reviewed scientific journals and presented at relevant academic conferences. TRIAL REGISTRATION NUMBER: NCT05290467.

KIAA1522 is a new biomarker of promoting the tumorigenesis and distant metastasis of colorectal carcinoma.

PURPOSE: Our research was absorbed into exploring the expression, clinicopathological value, biological significance and signaling pathway of KIAA1522 in colorectal carcinoma and its distant metastasis. MATERIALS AND METHODS: The expression of KIAA1522 and survival analysis in colorectal carcinoma (CRC) were assessed using GEPIA databases. Then we evaluated the expression of KIAA1522 immunohistochemically in tissue samples of 57 patients with colorectal carcinoma liver metastasis (CRLM). The correlations between the expression of KIAA1522, clinical significance and prognosis of these 57 patients with CRLM were analyzed. The migration and invasion of KIAA1522 were explored by western blotting, CCK-8, colony formation, flow cytometry, wound healing assays and transwell invasion in vitro and tail vein injection models in vivo. Then, transcriptome sequencing and gene set enrichment analysis was performed to identify the signaling pathways involved, while western blotting analysis and immunohistochemistry (IHC) were used to identify the expression of key genes in Notch signaling. RESULTS: KIAA1522 was overexpressed in CRLM tissues and colon cancer cell lines, and the expression of KIAA1522 in metastatic sites was positively correlated with that in primary sites. In addition, the overexpression of KIAA1522 is associated with poor clinicopathological features. Survival analysis showed that the overexpression of KIAA1522 predicted a low overall survival rate in patients with CRLM. Functional studies suggested that KIAA1522 promotes the proliferation, invasion and migration of colon carcinoma in vitro. KIAA1522 could promote distant metastasis of CRC in vivo. Moreover, KIAA1522 upregulated the Notch signaling pathway in colorectal cancer cell lines in vitro and lung metastatic nodes in vivo. CONCLUSION: In conclusion, it is suggested that the upregulation of KIAA1522 might promote the tumorigenicity and metastasis of colorectal carcinoma through Notch signaling pathway. KIAA1522 plays a carcinogenic role in the metastasis of colorectal carcinoma and might serve as a new molecular target for the treatment.

Risk of preeclampsia by gestational weight gain in women with varied prepregnancy BMI: A retrospective cohort study.

Introduction: Despite the important clinical significance, limited data on the joint contribution of prepregnancy body mass index (BMI) and gestational weight gain (GWG) to preeclampsia, the second leading cause of maternal mortality worldwide. This study aimed to estimate the risk of preeclampsia by GWG among women with varied prepregnancy BMI. Methods: We conducted a retrospective cohort study using data of 117 738 singleton pregnant women aged 18-49 years from 150 maternity hospitals in China between 2015 and 2018. GWG was calculated as the measured weight at the time of preeclampsia assessment minus prepregnancy weight; GWG velocity was calculated as the GWG divided by the gestational age at weighing. The non-linear associations of GWG with preeclampsia were examined by restricted cubic spline regression analysis according to prepregnancy BMI. The association of the GWG categories with preeclampsia was further examined by performing robust Poisson regression stratified by the prepregnancy BMI categories. Results: Among participants, 2426 (2.06%) were diagnosed with preeclampsia. Compared to women with normal BMI, those who were overweight and obese had 1.92- fold (95%CI, 1.73-2.14) and 5.06- fold (95%CI, 4.43-5.78) increased risks for preeclampsia, respectively. The association of GWG velocity with preeclampsia was presented as a J-shaped curve with the varied inflexion point (where the rate of preeclampsia was 2%), which was 0.54, 0.38, and 0.25 kg/week in women with normal BMI, overweight, and obesity, respectively; a steep risk rise was observed along with GWG velocity beyond the inflexion points. The overall adjusted relative risk for preeclampsia was calculated among women with the different GWG categories of GWG. Conclusions: The findings highlight that high prepregnancy BMI and exceed GWG contributed to increased risk of preeclampsia with a superimposed effect and underscore the need to optimize the recommendations for GWG for women with different prepregnancy BMI.

Association of Gestational Vitamin E Status With Pre-eclampsia: A Retrospective, Multicenter Cohort Study.

Introduction: Pre-eclampsia is the second leading cause of maternal mortality worldwide. The controversy for the association of vitamin E with pre-eclampsia has raged unabated for two decades. We aimed to determine the association of vitamin E level in the first trimester and the gestational change with pre-eclampsia. Materials and Methods: A retrospective cohort study was conducted among singleton pregnant women aged 15-49 years at 137 hospitals in China. Serum vitamin E concentrations in the first trimester and at pre-eclampsia assessment time were uniformly quantified in a laboratory by high performance liquid chromatography. Logistic regression models with restricted cubic splines were performed to reveal a non-linear association of vitamin E concentrations in the first trimester and the gestational change with pre-eclampsia. Results: We included 73 317 participants (47.8% aged 25-29 years) and 2.28% were diagnosed with pre-eclampsia. Higher risk was observed in those with lower concentration in the first trimester and greater gestational decrease, with a range from 0.81 to 80.60%. A non-linear L-shaped association was observed between vitamin E concentrations in the first trimester and pre-eclampsia, suggesting a threshold at 7.3 mg/L and a ceiling effect: the risk saw a steep rise when the concentrations in the first trimester were < 7.3 mg/L but was relatively flat beyond the inflection point. Sharply increased pre-eclampsia risk was also found in those with gestational vitamin E decrease after accounting for the baseline status in the first trimester. However, gestational vitamin E increase was associated with decreased pre-eclampsia risk when the baseline concentrations were < 7.3 mg/L but did not confer additional benefits when it was above the threshold. Conclusion: We demonstrated alarmingly high pre-eclampsia risk in women with vitamin E concentrations of < 7.3 mg/L in the first trimester and gestational vitamin E decrease. These findings underscore the need to supplement vitamin E among pregnant women with low baseline status.

ST8SIA6-AS1 promotes the development of hepatocellular carcinoma cells through miR-338-3p/NONO Axis.

BACKGROUND: Increasing studies have shown a vital fact that long non-coding RNAs (lncRNAs) play a considerable regulatory role in hepatocellular carcinoma (HCC) progression. However, whether ST8 alpha-N-acetyl-neuraminide alpha-2, 8-sialyltransferase 6 antisense RNA 1 (ST8SIA6-AS1) affects the development of HCC is unclear. METHODS: The target genes in HCC cell lines were quantified via utilzing quantitative real-time polymerase chain reaction (RT-qPCR) analysis and western blot. Effects of ST8SIA6-AS1 on proliferative, apoptosis and migratory ability of HCC cells were proved by a series of function experiments. The cellular distribution of ST8SIA6-AS1 was examined through fluorescent in situ hybridization (FISH) assay and subcellular fractionation experiments. RNA pulldown assay was implemented to explore the target of ST8SIA6-AS1. RNA Binding Protein Immunoprecipitation (RIP) and luciferase reporter assays were performed to identify the specific relationships between miR-338-3p and ST8SIA6-AS1/ non-POU domain containing octamer binding (NONO). RESULTS: The expression of ST8SIA6-AS1 was apparently elevated in HCC cell. Silenced ST8SIA6-AS1 reduced proliferative, migratory and invasive ability of HCC cells. Moreover, ST8SIA6-AS1 targeted miR-338-3p to modulate the expression of NONO in HCC cells. CONCLUSIONS: ST8SIA6-AS1 enhances the progression of HCC via miR-338-3p/NONO axis in vitro.

Migration of hem-o-lock clips and stitches into the duodenum after laparoscopic hepatectomy and cholecystectomy: A case report.

RATIONALE: Migration of endoclips and stitches into the duodenum after laparoscopic hepatectomy is incredibly rare with a poorly understood mechanism. PATIENT CONCERNS: A 56-year-old woman who underwent laparoscopic left hepatectomy and cholecystectomy in August 2016 was admitted to our hospital with nausea and vomiting in December 2017. DIAGNOSES: Abdominal computed tomography (CT) scan showed high density shades in duodenal ampulla. Esophagogastroduodenoscopy showed deformation of the duodenal ampulla into two lumens; hem-o-lock clips and stitches were detected in the upper lumen. Contrast enhanced CT scan revealed gastric cancer with liver metastasis (GCLM). INTERVENTIONS: The hem-o-lock clips and stitches were present in the wall of the duodenum; therefore, no attempt was made to remove them. High quality liquid diet, partial parenteral nutrition, and chemotherapy were administered to the patient. OUTCOMES: In September 2018, the patient died of hepatic failure caused by GCLM. LESSONS: This rare complication of the migration of endoclips and stitches into the duodenum after laparoscopic hepatectomy can cause epigastric pain and duodenal obstruction. The complication could be potentially avoided using absorbable endoclips and stitches or by performing of ultrasonic dissection by a skilled operator.

Pancreatogenic choledocholithiasis in common bile duct stump after Roux-en-Y hepaticojejunostomy: A case report.

RATIONALE: Choledocholithiasis in common bile duct (CBD) stump after Roux-en-Y hepaticojejunostomy (RYHJ) is incredibly rare and its pathophysiology is poorly understood. PATIENT CONCERNS: A 79-year-old woman was admitted to our hospital with upper abdominal pain radiating through to the back in November 2016. DIAGNOSES: Abdominal computed tomography (CT) scan and magnetic resonance cholangiopancreatography (MRCP) revealed filling defects in CBD stump, chronic pancreatitis, and dilatation of CBD stump and main pancreatic duct (MPD). INTERVENTIONS: During the endoscopic retrograde cholangiopancreatography (ERCP), cannulation proceeded easily from MPD to CBD through a variant pancreatic duct, and then white crushed stones extracted from the CBD stump. Elemental analysis and infrared spectrophotometry demonstrated that the main constituent of the calculi was calcium carbonate. OUTCOMES: After a therapeutic ERCP, the patient's symptoms disappeared, and a 9-month follow-up indicated no remaining stones or lithiasis relapse. LESSONS: This type of choledocholithiasis in CBD stump after RYHJ has never been reported before. We nominated it as "pancreatogenic choledocholithiasis," and pancreatobiliary reflux caused by a variant pancreatic duct may be the main cause.

A case of severe preeclampsia diagnosed as post-partum hemolytic uremic syndrome.

Post-partum hemolytic uremic syndrome (PHUS) is a severe thrombotic microangiopathy clinically characterized by hemolytic anemia, renal dysfunction, and low platelets after birth with rapid progression and poor prognosis. Here, we reported a rare case of severe preeclampsia diagnosed as hemolytic uremic syndrome after birth. The patient was diagnosed with PHUS and underwent intermittent plasma exchange with supportive treatment including glucocorticoid injections and transfusion of suspended red blood cells. After these treatments, the patient experienced no apparent remission and chronic renal dysfunction occurred on her. PHUS is a severe emergency with acute onset, rapid progress, and poor prognosis. Early detection, diagnosis, and treatment can significantly improve the prognosis.

A case of aggravation of hemolytic anemia, elevated liver enzymes and low platelet count syndrome after delivery.

BACKGROUND: Hemolytic anemia, elevated liver enzymes and low platelet count (HELLP) syndrome is a severe obstetric complication which usually resolves in most patients after delivery. METHODS: We report a rare case of aggravation of HELLP syndrome after delivery. RESULTS: The patient underwent the treatment for HELLP syndrome, including glucocorticoid therapy. The symptoms of HELLP syndrome reappeared and became more severe than before the termination of pregnancy. The patient also had severe and persistent hypoproteinemia, hyponatremia and hypocalcemia. CONCLUSIONS: HELLP syndrome is an acute and critical obstetric syndrome which can have heterogeneous presentations and variable prognosis. We should be fully aware of the diverse clinical characteristics of this condition.