Epidemiological features and prognosis for primary gastrointestinal follicular lymphoma.

Primary gastrointestinal follicular lymphoma (PGI-FL) is a rare extra-nodal lymphoma. Its epidemiology and prognosis remain unclear. We performed a retrospective analysis of eligible patients with 1648 PGI-FL and 34 892 nodal FL (N-FL) in the Surveillance, Epidemiology and End Results (SEER) database. The age-adjusted average annual incidence of PGI-FL was 0.111/100000. The median overall survival (OS) for PGI-FL and N-FL patients was 207 and 165 months respectively. The 5-year diffuse large B-cell lymphoma (DLBCL) transformation rates were 2.1% and 2.6% respectively. Age, sex, grade, Ann Arbor stage, primary site and radiation were independent prognostic factors (p < 0.05). Nomograms were constructed to predict 1-, 5- and 10-year OS and disease-specific survival (DSS). The receiver operating characteristic curves and calibration plots showed the established nomograms had robust and accurate performance. Patients were classified into three risk groups according to nomogram score. In conclusion, the incidence of PGI-FL has increased over the past 40 years, and PGI-FL has a better prognosis and a lower DLBCL transformation rate than N-FL. The nomograms were developed and validated as an individualized tool to predict survival. Patients were divided into three risk groups to assist clinicians in identifying high-risk patients and choosing the optimal individualized treatments.

SLF2 Interacts with the SMC5/6 Complex to Direct Hepatitis B Virus Episomal DNA to Promyelocytic Leukemia Bodies for Transcriptional Repression.

Hepatitis B virus (HBV) chronically infects approximately 300 million people worldwide, and permanently repressing transcription of covalently closed circular DNA (cccDNA), the episomal viral DNA reservoir, is an attractive approach toward curing HBV. However, the mechanism underlying cccDNA transcription is only partially understood. In this study, by illuminating cccDNA of wild-type HBV (HBV-WT) and transcriptionally inactive HBV that bears a deficient HBV X gene (HBV-ΔX), we found that the HBV-ΔX cccDNA more frequently colocalizes with promyelocytic leukemia (PML) bodies than that of HBV-WT cccDNA. A small interfering RNA (siRNA) screen targeting 91 PML body-related proteins identified SMC5-SMC6 localization factor 2 (SLF2) as a host restriction factor of cccDNA transcription, and subsequent studies showed that SLF2 mediates HBV cccDNA entrapment in PML bodies by interacting with the SMC5/6 complex. We further showed that the region of SLF2 comprising residues 590 to 710 interacts with and recruits the SMC5/6 complex to PML bodies, and the C-terminal domain of SLF2 containing this region is necessary for repression of cccDNA transcription. Our findings shed new light on cellular mechanisms that inhibit HBV infection and lend further support for targeting the HBx pathway to repress HBV activity. IMPORTANCE Chronic HBV infection remains a major public health problem worldwide. Current antiviral treatments rarely cure the infection, as they cannot clear the viral reservoir, cccDNA, in the nucleus. Therefore, permanently silencing HBV cccDNA transcription represents a promising approach for a cure of HBV infection. Our study provides new insights into the cellular mechanisms that restrict HBV infection, revealing the role of SLF2 in directing HBV cccDNA to PML bodies for transcriptional repression. These findings have important implications for the development of antiviral therapies against HBV.

Nonproductive Hepatitis B Virus Covalently Closed Circular DNA Generates HBx-Related Transcripts from the HBx/Enhancer I Region and Acquires Reactivation by Superinfection in Single Cells.

Hepatitis B virus (HBV) infection remains a public health problem worldwide. Persistent HBV infection relies on active transcription of the covalently closed circular DNA (cccDNA) in hepatocytes, which is less understood at the single-cell level. In this study, we isolated primary human hepatocytes from liver-humanized FRG mice infected with HBV and examined cccDNA transcripts in single cells based on 5' end sequencing. Our 5' transcriptome sequencing (RNA-seq) analysis unambiguously assigns different viral transcripts with overlapping 3' sequences and quantitatively measures viral transcripts for structural genes (3.5 kb, 2.4 kb, and 2.1 kb) and the nonstructural X gene (0.7 kb and related) in single cells. We found that an infected cell either can generate all viral transcripts, signifying active transcription, or presents only transcripts from the X gene and its associated enhancer I domain and no structural gene transcripts. Results from cell infection assays with recombinant HBV show that nonproductive transcription of cccDNA can be activated by incoming virus through superinfection. Moreover, upon HBV infection, cccDNA apparently can be transcribed in the absence of HBx and produces HBx, needed for productive transcription of other viral genes. These results shed new light on cccDNA transcription at the single-cell level and provide insights useful for improving the treatment strategy against chronic HBV infection. IMPORTANCE Hepatitis B virus (HBV) infection can be effectively suppressed but rarely cured by available drugs. Chronic HBV infection is based on persistence of covalently closed circular DNA (cccDNA) and continuous infection and reinfection with HBV in the liver. Understanding transcriptional regulation of cccDNA will help to achieve permanent transcriptional silencing, i.e., functional cure of HBV. In our study, we found that an infected cell either can generate all viral transcripts, signifying active transcription, or presents only transcripts from the X gene and its associated enhancer I domain and no structural gene transcripts. The nonproductive transcription of cccDNA can be activated by incoming virus through superinfection. Upon an infection, cccDNA apparently can be transcribed in the absence of HBx to produce HBx, necessary for subsequent transcription of other HBV genes. Our studies shed new light on the mechanism of HBV infection and may have implications for a functional cure regimen for HBV.

Profiling the clinical characteristics and surgical efficacy of laryngomalacia in children.

OBJECTIVE: To analyze the clinical characteristics of laryngomalacia in Chinese children and explore the surgical efficacy and factors influencing severe laryngomalacia. METHODS: Children (0-18 years) diagnosed with laryngomalacia in our hospital from January 2016 to January 2022 were enrolled in this study. Clinical data of patients, including general conditions, clinical symptoms, grading and classification, medical comorbidities, surgical efficacy, and the risk factors influencing severe laryngomalacia were retrospectively analyzed. RESULTS: A total of 1810 children were enrolled (male:female; 2.02:1), among which most were infants under 1 year (77.18%). Inspiratory laryngeal stridor (69.56%) was the most common symptom. Most patients had mild laryngomalacia (79.28%), with type IV laryngomalacia being the most common classification (52.27%). Congenital heart disease (37.85%) was the most common medical comorbidity. A total of 168 severe laryngomalacia cases were treated via supraglottoplasty with an effective rate of 83.93%. Notably, preterm birth (OR = 3.868, 95% CI 1.340 ~ 11.168), low birth weight (OR = 4.517, 95% CI 1.477 ~ 13.819) and medical comorbidities (OR = 7.219, 95% CI 2.534 ~ 20.564) were independent risk factors for poor prognosis (P < 0.05). CONCLUSION: Laryngomalacia is common among infants under the age of one, and it is mostly characterized by inspiratory laryngeal stridor with various medical comorbidity. Supraglottoplasty is the first treatment choice for severe laryngomalacia cases with high success rates. However, premature delivery, low birth weight, and medical comorbidities significantly affect the efficacy of surgery.

Appearance of fetal intestinal obstruction on fetal MRI.

OBJECTIVE: To retrospectively analyze the imaging findings of fetal intestinal obstruction diagnosed by MRI and compare with postnatal surgery findings. METHODS: MRI data of 3346 pregnant women were retrospectively analyzed; we found 47 cases of suspected fetal small intestinal obstruction. Twenty-nine underwent postnatal surgery. RESULTS: We identified one case of jejunal obstruction secondary to perforation, five annular pancreas, 10 duodenal stenoses, four jejunal stenoses, five jejunal atresias, two ileal atresias, four intestinal volvulus, and four intestinal malrotations. We further found four cases of duodenal stenosis with intestinal malrotation (two cases also showed volvulus). On fetal MRI, annular pancreas and duodenal obstruction manifested as a "double bubble." Jejunal stenosis appeared as a "triple bubble." Jejunal and ileal atresia mainly manifested as proximal dilatation with high signal on T1WI. Intestinal volvulus showed a sausage-like intestinal distortion and mixed signals on T1WI and DWI sequences. Intestinal malrotations were characterized as abnormal duodenal morphology. We missed two malrotations; one jejunal obstruction was misdiagnosed. CONCLUSION: Prenatal MRI can accurately determine the degree of intestinal obstruction and help qualitatively diagnose its possible etiology according to changes in MRI signals in multiple sequences, providing guidance for prenatal counseling.

In Situ Synthesis of Pt/TiO2 Nanosheets on Flexible Ti Mesh for Efficient and Cyclic Phenol Removal.

TiO2 nanostructures that feature a two-dimensional (2D) morphology have attracted extensive attention in environment processing and energy conversion fields owing to their peculiarly large surface area and superior transfer efficiency of photogenerated carriers. In this work, we proposed a hybrid approach including a plasma electrolyte oxidation (PEO) and ion exchange strategy to in situ synthesize TiO2 nanosheets on a flexible Ti mesh substrate, in which the layered Na2Ti2O5 nanosheets were fabricated as a template. The TiO2 nanosheets are crystalline anatase phase and exhibit excellent photocatalytic activity and stability in removing phenol. With the modification of the Pt cocatalyst, the phenol degradation performance has been significantly enhanced. More importantly, the in situ grown TiO2 nanosheets on the flexible Ti mesh provide strong substrate adhesion that enables superior photocatalytic stability for cyclic degradation of phenol. It can be expected that the synthetic strategy proposed in this work can pave a solid way toward the in situ growth of various TiO2-based composite nanophotocatalysts with sufficient active sites and excellent photocatalytic properties, and thus, it will open up more opportunities for environment processing and energy conversion.

Characteristics of a Magnetic Field Sensor with a Concentrating-Conducting Magnetic Flux Structure.

A magnetic field sensor with a new concentrating-conducting magnetic flux structure (CCMFS) is proposed in this paper, using a silicon-on insulator (SOI) Hall element fabricated by complementary metal oxide semiconductor (CMOS) technology as a magnetic sensitive unit. By fixing the CCMFS above the Hall element packaged on a printed circuit board (PCB) based on inner-connect wire bonding technology, a non-magnetized package can subsequently be obtained. To analyze the inner magnetic field vector distribution of the CCMFS, a simulation model was built based on a finite element software, where the CCMFS was processed using Ni-Fe alloys material by a low speed wire-cut electric discharge technology. The test results showed that the measurement of magnetic fields along a sensitive and a non-sensitive axis can be achieved when VDD = 5.0 V at room temperature, with magnetic sensitivities of 122 mV/T and 132 mV/T in a testing range from -30 mT to 30 mT, respectively. This study makes it possible to not only realize the detection of magnetic field, but also to significantly improve the sensitivity of the sensor along a non-sensitive axis.

Prenatal diagnosis of anomalous origin of pulmonary artery.

BACKGROUND: Anomalous origin of the pulmonary arteries is a rare congenital pulmonary vascular malformation that includes unilateral absence of the pulmonary artery (UAPA), anomalous origin of unilateral pulmonary artery (AOPA), and left pulmonary artery sling (LPAS). METHODS: We analyze 15 cases of fetal pulmonary artery abnormalities from 2011 to 2017, detected via prenatal ultrasound at our center. RESULTS: The 15 cases include UAPA (5), AOPA (6), and LPAS (4). Of the UAPA cases, 2 had pulmonary atresia and 3 had pulmonary artery stenosis. In 5 cases, the descending aorta issued collateral vessels to the left lung. Of the AOPA cases, 2 had left pulmonary artery abnormalities originating in the ascending aorta and 4 showed right pulmonary artery abnormalities originating in the ascending aorta. Of the LPAS cases, 2 were type IA, 1 was type IIA, and 1 was type IIB. Two of the LPAS were associated with right lung dysplasia. CONCLUSION: Abnormal origin of the pulmonary artery has a characteristic ultrasonographic appearance. The branch of the pulmonary artery cross section can provide important clues to the diagnosis of abnormal pulmonary artery origin. Pulmonary artery abnormalities are often associated with pulmonary atresia or stenosis.

Mechanistic insights into the contribution of epithelial damage to airway remodeling. Novel therapeutic targets for asthma.

It has been suggested that an inherent airway epithelial repair defect is the root cause of airway remodeling in asthma. However, the relationship between airway epithelial injury and repair, airway remodeling, and airway hyperresponsiveness (AHR) has not been directly examined. We investigated the contribution of epithelial damage and repair to the development of airway remodeling and AHR using a validated naphthalene (NA)-induced murine model of airway injury. In addition, we examined the endogenous versus exogenous role of the epithelial repair peptide trefoil factor 2 (TFF2) in disease pathogenesis. A single dose of NA (200 mg/kg in 10 ml/kg body weight corn oil [CO] vehicle, intraperitoneally) was administered to mice. Control mice were treated with CO (10 ml/kg body weight, intraperitoneally). At 12, 24, 48, and 72 hours after NA or CO injection, AHR and various measures of airway remodeling were examined by invasive plethysmography and morphometric analyses, respectively. TFF2-deficient mice and intranasal treatment were used to examine the role of the epithelial repair peptide. NA treatment induced denudation and apoptosis of airway epithelial cells, goblet cell metaplasia, elevated AHR, and increased levels of endogenous TFF2. Airway epithelial changes peaked at 12 hours after NA treatment, whereas airway remodeling changes were observed from 48 hours. TFF2 was protective against epithelial damage and induced remodeling and was found to mediate organ protection via a platelet-derived growth factor-associated mechanism. Our findings directly demonstrate the contribution of epithelial damage to airway remodeling and AHR and suggest that preventing airway epithelial damage and promoting epithelial repair may have therapeutic implications for asthma treatment.

Secure privacy-preserving biometric authentication scheme for telecare medicine information systems.

Healthcare delivery services via telecare medicine information systems (TMIS) can help patients to obtain their desired telemedicine services conveniently. However, information security and privacy protection are important issues and crucial challenges in healthcare information systems, where only authorized patients and doctors can employ telecare medicine facilities and access electronic medical records. Therefore, a secure authentication scheme is urgently required to achieve the goals of entity authentication, data confidentiality and privacy protection. This paper investigates a new biometric authentication with key agreement scheme, which focuses on patient privacy and medical data confidentiality in TMIS. The new scheme employs hash function, fuzzy extractor, nonce and authenticated Diffie-Hellman key agreement as primitives. It provides patient privacy protection, e.g., hiding identity from being theft and tracked by unauthorized participant, and preserving password and biometric template from being compromised by trustless servers. Moreover, key agreement supports secure transmission by symmetric encryption to protect patient's medical data from being leaked. Finally, the analysis shows that our proposal provides more security and privacy protection for TMIS.

Ultrasound microvascular flow imaging: evaluating fetal mesenteric blood flow and predicting postnatal surgery in meconium peritonitis.

OBJECTIVE: This study explored the characteristics of fetal mesenteric blood flow perfusion across various gestational weeks and evaluated the efficacy of Microvascular Flow (MV-Flow) imaging technology in assessing intestinal wall blood flow in fetuses with meconium peritonitis (MP). METHOD: In this retrospective study, we analyzed 35 fetuses with MP and 160 healthy fetuses. We examined the correlation between the Vascular Index (VI) of mesenteric perfusion and gestational age, conducted an analysis comparing MP operative and non-operative groups, and developed a predictive model for surgical intervention. RESULTS: The VI value demonstrated no significant change with increasing gestational age (correlation coefficient = 0.005, p = 0.946). For healthy fetuses, VI ranged approximately from 34.66% to 67.26% using the automatic ellipse method. The MP operative group exhibited significantly more cesarean deliveries (100% vs. 52.9%, p = 0.003), shorter gestational periods (34.76 ± 2.16 weeks vs. 37.48 ± 1.55 weeks, p < 0.001), lower birth weights (2762.14 ± 452.76 g vs. 3225.88 ± 339.98 g, p = 0.003), more persistent ascites (92.9% vs. 52.9%, p = 0.021), more frequent intestinal wall echo reductions (57.1% vs. 5.9%, p = 0.004), and lower VI (18.57 ± 5.51% vs. 39.41 ± 7.02%, p < 0.001). A predictive model was established: Logit (P)=8.86 - (0.37* VI) + (1.49* ascites), yielding an area under the curve of 0.857, with 78.6% sensitivity and 88.2% specificity. The VI value was significantly associated with the need for postnatal surgery (OR = 0.689, 95% confidence interval: 0.511 - 0.929, p = 0.015). A Receiver Operating Characteristic curve analysis for VI in predicting postnatal surgery showed an area under the curve of 0.971, with an optimal cutoff value of 35%, achieving 91% sensitivity and 94.4% specificity. CONCLUSION: MV-Flow imaging effectively quantified fetal bowel wall blood flow perfusion. There was no significant change in VI across different gestational weeks. Significantly lower VI values in MP fetuses indicated an increased risk of intestinal wall necrosis and the potential need for postnatal surgical intervention.

The role of multimodal ultrasound in diagnosis of fetal bowel dilatation and prediction of adverse neonatal outcomes: A study of 86 cases in a series of 43,562 births.

Objective: To investigate the diagnostic utility of multimodal ultrasound for fetal bowel dilatation (FBD) in different parts of the bowel and to examine its prognostic potential in FBD. Methods: This retrospective study analyzed 86 fetuses with a dilated bowel identified via ultrasound in a 10-month postnatal follow-up. Both two- and three dimensional (2D and 3D, respectively) ultrasound volume imaging were used to characterize dilation across different bowel sections. The optimal intestinal diameter cut-off values for pathological bowel dilatation were determined and a predictive model for neonatal surgery was developed. Results: The 86 cases of dilatation were distributed as follows: duodenal (n = 36); jejunum/ileum (n = 35); and colonic (n = 15). Duodenal dilatations presented the earliest during pregnancy compared to the other 2 groups (24.4 versus [vs.] 29 vs. 33.7 weeks respectively; p < 0.05). Cases with small intestinal dilatation were delivered earlier than those with colonic dilatation (p < 0.05). Infants with duodenal dilatation had the lowest birth weight and the highest rate of multi-system abnormalities (30.6% vs. 5.7% vs. 20%; p < 0.001). More than one-half of the multi-system abnormalities had chromosomal abnormalities (multiple, 54% vs. single, 12.5%; p = 0.015). There were 2 stillbirths, 24 induced labors, 44 postnatal surgeries, and 18 normal cases after birth. In predicting adverse neonatal outcomes of jejunum/ileum dilatation using a cut-off value of 15.5 mm small intestine diameter, sensitivity was 81.5%, specificity was 62.5%, and the area under the receiver operating characteristic curve (AUC) was 0.762 (p < 0.05). For colonic dilatation, using a cut-off value of 21.5 mm colon diameter: sensitivity was 83.3%, specificity was 77.8%, and AUC was 0.861 (p < 0.05). In detecting jejunum/ileum and colonic obstruction, 3D ultrasound demonstrated significantly better diagnostic efficiency than 2D ultrasound (p < 0.05). Using the backward stepwise selection method, a predictive model for neonatal surgery in patients with jejunum/ileum and colonic dilatation was established: logit (P) = -1.58 + (2.32 × polyhydramnios) +(2.0 × ascites) +(1.14 × hyperechogenic bowel). The AUC for the prediction model was 0.874 (p < 0.05), with 76% sensitivity and 94.1% specificity. Conclusions: Duodenal dilatation occurred earlier, with a higher incidence of chromosomal abnormalities and multi-system abnormalities than dilatation of other parts of the bowel. 3D ultrasound played an important role in the detection of jejunum/ileum and colon obstructions. Clinical signs, including polyhydramnios, ascites, and strong echoes in the intestine, can be used to predict neonatal surgery.