Development of the first officially licensed live attenuated duck hepatitis A virus type 3 vaccine strain HB80 in China and its protective efficacy against DHAV-3 infection in ducks.

Duck hepatitis A virus type 3 (DHAV-3) is an infectious virus that is highly fatal to ducklings and causes significant economic losses in the duck industry worldwide. Biosecurity and vaccination are required to control the pathogen. In the present study, we attenuated a lowly pathogenic DHAV-3 clinical isolate, named as HB, by serial passaging in duck embryos, and followed by several adaptive proliferations in specific-pathogen-free (SPF) chicken embryos. The virulence of DHAV-3 at different passages was assessed by infecting 3-day-old ducklings. We found that the HB strain lost pathogenicity to ducklings from the 55th passage onwards. The 80th passage strain (HB80), which achieved good growth capacity in duck embryos with a viral titer of 108.17 50% egg lethal dose per milliliter (ELD50/mL), was selected as a live attenuated vaccine candidate. The HB80 strain did not induce clinical symptoms or pathological lesions in 3-day-old ducklings and showed no virulence reversion after 5 rounds of in vivo back-passage. The minimum effective dose of HB80 was determined to be 104.5 ELD50 by hypodermic inoculation of the neck. Importantly, a single dose of HB80 elicited good immune responses and provided complete protection against challenge with the lethal DHAV-3 strain. Compared with the genomic sequence of the parental HB strain, HB80 had 7 amino acid substitutions, two of them are in the hypervariable region of the VP1 and polymerase-encoding 3D regions, which may play a role in virulence attenuation. Our data suggest that the attenuated HB80 strain is a promising vaccine candidate for the prevention of DHAV-3 infections in China. HB80 has been registered as a New Veterinary Drug Registration Certificate by the Chinese Ministry of Agriculture and Rural Affairs (MARA), and is the first live attenuated DHAV-3 vaccine strain to be officially licensed in China.

TMB Signature-Related RCAN2 Promotes Apoptosis by Upregulating EHF/DR5 Pathway in Hepatocellular Carcinoma.

BACKGROUND: The tumour mutation burden (TMB) is a valuable indicator of the accumulation of somatic mutations, and is thought to be associated with the biological behaviour and prognosis of tumours. However, the related genetic mechanism for these association is still unclear. The aim of the present study was to identify the key gene(s) associated with TMB in hepatocellular carcinoma (HCC) and to investigate its biological functions, downstream transcription factors, and mechanism of action. METHODS: Patients in The Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC) database were classified according to TMB signature-related genes. Key genes related to the TMB signature and tumour prognosis were identified. Immunohistochemistry and Quantitative Real-Time Polymerase Chain Reaction (qPCR) were then used to assess gene expression in clinical HCC tissues and HCC cells. Cells with altered gene expression were evaluated for the effect on cell proliferation and apoptosis, both in vitro and in vivo. Three independent databases and cell sequencing data were used to identify the mechanisms involved and the downstream transcription factors. The mechanism was also studied by altering the expression of downstream transcription factors in vitro. RESULT: The integrated cluster (IC) 2 group, characterized by 99 TMB signature-related genes, showed a significant different TMB score compared to the IC1 group (p < 0.001), as well as more favourable tumour prognosis (p = 0.031). We identified five key prognostic genes that were differentially expressed between IC2 and IC1 and were associated with overall survival. The expression of one of these key prognostic genes, RCAN2, was negatively correlated with TMB in 18 out of 33 tumour types examined. A high level of RCAN2 was correlated with better overall survival in HCC (p = 0.0009). Overexpression of RCAN2 enhanced apoptosis in vitro and in vivo, whereas knockdown of RCAN2 attenuated apoptosis. The mechanism by which RCAN2 promotes apoptosis may involve upregulation of the expression of ETS homologous factor (EHF) and of death receptor 5 (DR5). CONCLUSIONS: Downregulation of RCAN2 expression was found to correlate with elevated TMB in multiple cancer types. RCAN2 was also found to be a biomarker of HCC prognosis, and to promote the apoptosis of HCC cells through the EHF/DR5 pathway. These findings provide a new perspective on systemic treatment for advanced HCC with a high TMB.

Novel insights into necrozoospermia from a single-center study: reference ranges, possible etiology, and impact on male fertility.

ABSTRACT: Necrozoospermia is a poorly documented condition with a low incidence, and its definition and clinical significance are unclear. Herein, we provide a reference range for necrozoospermia and discuss its possible etiology and impact on male fertility and assisted reproductive outcomes. We extracted relevant information from 650 Chinese male partners of infertile couples and statistically analyzed sperm vitality. Necrozoospermia was present in 3.4% (22/650) of our study population, and the lower cut-off value for sperm vitality was 75.3%. We compared two methods for assessing sperm vitality (eosin-nigrosin head staining and hypo-osmotic swelling test [HOST]), for which the percentage in the eosin-nigrosin group (mean ± standard deviation [s.d.]: 77.5% ± 10.5%) was significantly higher than that in the HOST group (mean ± s.d.: 58.1% ± 6.7% [5-10 min after incubation] and 55.6% ± 8.2% [25-30 min after incubation]; both P < 0.001). The incidence of necrozoospermia increased with age (odds ratio [OR] = 1.116, 95% confidence interval [CI]: 1.048-1.189, P = 0.001), while the percentage of normal sperm morphology and DNA fragmentation index (DFI) were significantly associated with necrozoospermia, with ORs of 0.691 (95% CI: 0.511-0.935, P = 0.017) and 1.281 (95% CI: 1.180-1.390, P < 0.001), respectively. In the following 6 months, we recruited 166 patients in the nonnecrozoospermia group and 87 patients in the necrozoospermia group to compare intracytoplasmic sperm injection (ICSI) and pregnancy outcomes between the two groups. The necrozoospermia group had a significantly lower normal fertilization rate (74.7% vs 78.2%, P = 0.041; OR = 0.822; 95% CI: 0.682-0.992) than that in the nonnecrozoospermia group. This study presents substantial information on necrozoospermia to establish comprehensive and applicable reference values for sperm vitality for spontaneous conception and artificially assisted reproductive management.

Advancing treatment strategies for posterior malleolar malunion: The ankle dislocation method.

BACKGROUND: This study aimed to assess the radiological and clinical outcomes of treatment using the ankle dislocation method for posterior malleolar malunion. METHOD: Thirty-one patients with posterior malleolar malunion who underwent treatment using the ankle dislocation method from May 2015 to October 2021 were retrospectively analyzed. Key outcome measures were radiographic parameters (articular step-off, tibiofibular clear space, fibular length, tibial lateral surface angle, and ankle osteoarthritis), clinical scores (American Orthopaedic Foot and Ankle Society ankle-hindfoot scale and Visual Analogue Scale), and patient satisfaction rate. RESULT: Preoperative computed tomography revealed that Bartoní cek types 3 and 4 accounted for 64.5 % (n = 20) of total cases. Most posterior malleolar malunions were accompanied by depressed intercalary fragments (61.2 % [n = 19]). At the final follow-up, radiographic parameters and clinical scores showed significant improvements postoperatively (P < 0.05), with a high patient satisfaction rate of 77.4 %. Subgroup analysis revealed that the posterior malleolar fracture morphology significantly affected postoperative pain, particularly in more complex fractures (P < 0.001). CONCLUSION: The ankle dislocation method effectively exposes the distal tibial articular surface and facilitates the anatomical restoration of joint congruity under direct vision. This approach substantially improves the clinical and imaging outcomes in patients with complex posterior malleolar malunion. LEVELS OF EVIDENCE: Level IV, retrospective case series.

Temporal changes in biomarkers of neutrophil extracellular traps and NET-promoting autoantibodies following adenovirus-vectored, mRNA, and recombinant protein COVID-19 vaccination.

Neutrophil extracellular traps (NETs) play a role in innate pathogen defense and also trigger B-cell response by providing antigens. NETs have been linked to vaccine-induced thrombotic thrombocytopenia. We postulated a potential link between NET biomarkers, NET-promoting autoantibodies, and adverse events (AEs) after COVID-19 vaccine boosters. Healthy donors (HDs) who received ChAdOx1-S (A), mRNA-1273 (M), or recombinant protein (MVC-COV1901) vaccines at the National Taiwan University Hospital between 2021 and 2022 were recruited. We measured serial NET-associated biomarkers, citrullinated-histone3 (citH3), and myeloperoxidase (MPO)-DNA. Serum citH3 and MPO-DNA were significantly or numerically higher in HDs who reported AEs (n = 100, booster Day 0/Day 30, p = 0.01/p = 0.03 and p = 0.30/p = 0.35, respectively). We also observed a positive correlation between rash occurrence in online diaries and elevated citH3. A linear mixed model also revealed significantly higher citH3 levels in mRNA-1273/ChAdOx1-S recipients than MVC-COV1901 recipients. Significant positive correlations were observed between the ratios of anti-heparin platelet factor 4 and citH3 levels on Booster Day 0 and naïve and between the ratios of anti-NET IgM and citH3 on Booster Day 30/Day 0 in the AA-M and MM-M group, respectively. The increased levels of citH3/MPO-DNA accompanied by NET-promoting autoantibodies suggest a potential connection between mRNA-1273/ChAdOx1-S vaccines and cardiovascular complications. These findings provide insights for risk assessments of future vaccines.

Rab4A-directed endosome traffic shapes pro-inflammatory mitochondrial metabolism in T cells via mitophagy, CD98 expression, and kynurenine-sensitive mTOR activation.

Activation of the mechanistic target of rapamycin (mTOR) is a key metabolic checkpoint of pro-inflammatory T-cell development that contributes to the pathogenesis of autoimmune diseases, such as systemic lupus erythematosus (SLE), however, the underlying mechanisms remain poorly understood. Here, we identify a functional role for Rab4A-directed endosome traffic in CD98 receptor recycling, mTOR activation, and accumulation of mitochondria that connect metabolic pathways with immune cell lineage development and lupus pathogenesis. Based on integrated analyses of gene expression, receptor traffic, and stable isotope tracing of metabolic pathways, constitutively active Rab4AQ72L exerts cell type-specific control over metabolic networks, dominantly impacting CD98-dependent kynurenine production, mTOR activation, mitochondrial electron transport and flux through the tricarboxylic acid cycle and thus expands CD4+ and CD3+CD4-CD8- double-negative T cells over CD8+ T cells, enhancing B cell activation, plasma cell development, antinuclear and antiphospholipid autoantibody production, and glomerulonephritis in lupus-prone mice. Rab4A deletion in T cells and pharmacological mTOR blockade restrain CD98 expression, mitochondrial metabolism and lineage skewing and attenuate glomerulonephritis. This study identifies Rab4A-directed endosome traffic as a multilevel regulator of T cell lineage specification during lupus pathogenesis.

Association of Thallium with Diabetes Risk among Patients with Hearing Loss: Result from NHANES 2013 to 2018.

To evaluate the correlation between thallium and diabetes risk among participants with hearing loss. This retrospective cohort study extracted related data such as demographic characteristics, lifestyle factors, and laboratory findings from the National Health and Nutrition Examination Survey (NHANES) database (2013-2018). Logistic regression analysis and interaction analysis were adopted to analyze the correlation between thallium and diabetes risk among patients with hearing loss. Then, the restricted cubic spline was employed to assess the nonlinear relationship between thallium and diabetes risk. The receiver operating characteristic curve and decision curve analysis were used to assess the predictive values of 3 multivariate models with or without thallium for diabetes risk. The Delong test was adopted to assess the significant change of the area under the curves (AUCs) upon thallium addition. A total of 425 participants with hearing loss were enrolled in the study: without diabetes group (n = 316) and diabetes group (n = 109). Patients with hearing loss in the diabetes group had significantly lower thallium (P < .05). The thallium was an independent predictor for diabetes risk after adjusting various covariates (P < .05). The restricted cubic spline (RCS) result showed that there was a linear correlation between thallium and diabetes risk (P nonlinear > .05). Finally, the receiver operating characteristic and decision curve analysis results revealed that adding thallium to the models slightly increased the performance in predicting diabetes risk but without significance in AUC change. Thallium was an independent predictor of diabetes risk among patients with hearing loss. The addition of thallium might help improve the predictive ability of models for risk reclassification. However, the conclusions should be verified in our cohort in the future due to the limitations inherent in the NHANES database.

Endoscopic treatment of extreme esophageal stenosis complicated with esophagotracheal fistula: A case report.

BACKGROUND: At present, there is no unified and effective treatment for extreme corrosive esophageal stenosis (CES) with esophagotracheal fistula (ETF). This case had extreme and severe esophageal stenosis (ES) and ETF after ingesting an enzyme-based chemical detergent, resulting in a serious pulmonary infection and severe malnutrition. Upper gastrointestinal imaging showed that he had an ETF, and endoscopy showed that he had extreme and severe esophageal stricture. This case was complex and difficult to treat. According to the domestic and foreign literature, there is no universal treatment that is low-risk. CASE SUMMARY: A patient came to our hospital with extreme ES, an ETF, and severe malnutrition complicated with pulmonary tuberculosis 1 mo after the consumption of an enzyme-based detergent. The ES was serious, and the endoscope was unable to pass through the esophagus. We treated him by endoscopic incision method (EIM), esophageal stent placement (ESP), and endoscopic balloon dilation (EBD) by using the bronchoscope and gastroscope. This treatment not only closed the ETF, but also expanded the esophagus, with minimal trauma, greatly reducing the pain of the patient. According to the literature, there are no similar reported cases. CONCLUSION: We report, for the first time, a patient with extreme CES complicated with ETF, where the endoscope could not be passed through his esophagus but he could be examined by bronchoscopy and treated by EIM, ESP, and EBD.

Phase to intensity modulation and fading compensation using a single ring resonator for radio-over-fiber links.

In this study, we present a simulation-based analysis of radio-over-fiber (ROF) transmission links incorporating both phase modulation (PM) and a single ring resonator (RR) as the modulation transformer (MT). This configuration offers cost-effectiveness, enhanced operational stability, facile reconfiguration, and heightened robustness. The optimization of the RR involves a comprehensive adjustment of the power coupler coupling coefficient (k) and the roundtrip optical phase shift (φ) to attain superior characteristics in terms of power output, bandwidth, dispersion, and nonlinearity, individually. The simulation encompasses the transmission of diverse data formats, including QPSK, 16QAM, and 16QAM-based OFDM, modulated by the PM-RR system. The results reveal a 0.25 dB improvement in nonlinearity tolerance, increased power, and superior fading mitigation compared to the conventional intensity modulation (IM) approach. Furthermore, through careful tuning of the phase response, the Q factor of the PM-RR system exhibits an enhancement exceeding 40% over a 100 km fiber length when compared to the Mach-Zehnder modulator (MZM) system.

Development of a Silicone Rubber Mold with an Innovative Waterfall Cooling Channel.

A conformal cooling channel (CCC) follows the mold core or cavity profile to carry out uniform cooling in the cooling stage. However, the significant pressure drop along the cooling channels is a distinct disadvantage of the CCC. In this study, an innovative waterfall cooling channel (WCC) was proposed and implemented. The WCC cools the injected products via surface contact, replacing the conventional line contact to cool the injected products. The WCC was optimized using numerical simulation software. Silicone rubber molds with two kinds of cooling channels were designed and implemented. The cooling time of the molded part was evaluated using a low-pressure wax injection molding machine. The experimental results of the cooling time of the molded part were compared with the simulation results from numerical simulation software. The results showed that the optimal mesh element count was about 1,550,000 with a mesh size of 1 mm. The simulation software predicted the filling time of the water cup injection-molded product to be approximately 2.008 s. The cooling efficiency for a silicone rubber mold with a WCC is better than that of the silicone rubber mold with a CCC since the core and cavity cooling efficiency is close to 50%. The pressure drop of the WCC is smaller than that of the CCC, which reduces the pressure drop by about 56%. Taking a water cup with a mouth diameter of 70 mm, a height of 60 mm, and a thickness of 2 mm as an example, the experimental results confirmed that the use of the WCC can save the cooling time of the product by about 265 s compared with the CCC. This shows how a WCC can increase cooling efficiency by approximately 17.47%.

DNA methylation-activated full-length EMX1 facilitates metastasis through EMX1-EGFR-ERK axis in hepatocellular carcinoma.

Altered DNA methylation is a crucial epigenetic event in hepatocellular carcinoma (HCC) development and progression. Through methylation-transcriptomic analysis, we identified a set of sixty potential DNA methylation-based epidriver genes. In this set of genes, we focused on the hypermethylation of EMX1, which is frequently observed in hepatobiliary tumors. Despite of its frequent occurrence, the function of EMX1 remains largely unknown. By utilizing bisulfite-next-generation sequencing, we have detected EMX1 DNA hypermethylation on the gene body, which is positively correlated with EMX1 mRNA expression. Further analysis revealed that EMX1 mRNA terminal exon splicing in HCC generated two protein isoforms: EMX1 full length (EMX1-FL) and alternative terminal exon splicing isoform (EMX1-X1). Cellular functional assays demonstrated that gain-of-function EMX1-FL, but not EMX1-X1, induced HCC cells migration and invasion while silencing EMX1-FL inhibited HCC cells motility. This result was further validated by in vivo tumor metastasis models. Mechanistically, EMX1-FL bound to EGFR promoter, promoting EGFR transcription and activating EGFR-ERK signaling to trigger tumor metastasis. Therefore, EGFR may be a potential therapeutic target for EMX1-high expression HCC. Our work illuminated the crucial role of gene body hypermethylation-activated EMX1-FL in promoting tumorigenesis and metastasis in HCC. These findings pave the way for targeting the EMX1-EGFR axis in HCC tumorigenicity and metastasis.

[Etiology composition and prognosis of pediatric chronic critical illness in a pediatric intensive care unit]. / å„¿ç«¥é‡ç—‡ç›‘æŠ¤å®¤å„¿ç«¥æ ¢æ€§å±é‡ç—‡çš„ç— å› ç»„æˆåŠé¢„åŽåˆ†æž.

OBJECTIVES: To explore the etiology composition and outcomes of pediatric chronic critical illness (PCCI) in the pediatric intensive care unit (PICU). METHODS: The children who were hospitalized in the PICU of Dongguan Children's Hospital Affiliated to Guangdong Medical University and met the diagnostic criteria for PCCI from January 2017 to December 2022 were included in the study. The etiology of the children was classified based on their medical records and discharge diagnoses. Relevant clinical data during hospitalization were collected and analyzed. RESULTS: Among the 3 955 hospitalized children in the PICU from January 2017 to December 2022, 321 cases (8.12%) met the diagnostic criteria for PCCI. Among the 321 cases, the most common etiology was infection (71.3%, 229 cases), followed by unintentional injury (12.8%, 41 cases), postoperation (5.9%, 19 cases), tumors/immune system diseases (5.0%, 16 cases), and genetic and chromosomal diseases (5.0%, 16 cases). Among the 321 cases, 249 cases (77.6%) were discharged after improvement, 37 cases (11.5%) were discharged at the request of the family, and 35 cases (10.9%) died in the hospital. Among the deaths, infection accounted for 74% (26/35), unintentional injury accounted for 17% (6/35), tumors/immune system diseases accounted for 6% (2/35), and genetic and chromosomal diseases accounted for 3% (1/35). From 2017 to 2022, the proportion of PCCI in PICU diseases showed an increasing trend year by year (P<0.05). Among the 321 children with PCCI, there were 148 infants and young children (46.1%), 57 preschool children (17.8%), 54 school-aged children (16.8%), and 62 adolescents (19.3%), with the highest proportion in the infant and young children group (P<0.05). The in-hospital mortality rates of the four age groups were 14.9% (22/148), 8.8% (5/57), 5.6% (3/54), and 8.1% (5/62), respectively. The infant and young children group had the highest mortality rate, but there was no statistically significant difference among the four groups (P>0.05). CONCLUSIONS: The proportion of PCCI in PICU diseases is increasing, and the main causes are infection and unintentional injury. The most common cause of death in children with PCCI is infection. The PCCI patient population is mainly infants and young children, and the in-hospital mortality rate of infant and young children with PCCI is relatively high.

Scheme to eliminate the time shift of code edges based on the optimal transmission point of a DP-MZM.

To eliminate the time shift of code edges on a single-sideband (SSB) modulation signal transmission in a radio-over-fiber (RoF) system, a new, to the best of our knowledge, SSB modulation scheme based on an optimal transmission point for a double-parallel Mach-Zehnder modulator (DP-MZM) is proposed. The scheme is based on DP-MZM to realize the separation of the carrier and the +1st-order sideband at the optimal transmission point, and the baseband signal modulates the 2.5 Gb/s data signal to the +1st-order sideband of the SSB signal; then, the carrier and the +1st-order sideband are transmitted with a carrier-to-sideband ratio of 0 dB. Theoretical analysis shows that compared to the traditional SSB-modulated optical millimeter-wave signal generation scheme this scheme completely solves the problem of the time shift of code edges caused by dispersion. The simulation results show that the improved SSB modulation scheme has a Q factor of 23.362, the minimum bit error rate is 4.207×10-127 at 73.453 km, and the eye diagram is still very clear. Under the premise of meeting the basic requirements of communications, the maximum communications distance can reach 135 km, which is 270% of the transmission distance of a traditional SSB modulation model. Thus, the system performance has been greatly improved.

Efficacy and outcome of extensive intraoperative peritoneal lavage plus surgery vs surgery alone with advanced gastric cancer patients.

BACKGROUND: Gastric cancer (GC) is one of the most common malignant tumors. After resection, one of the major problems is its peritoneal dissemination and recurrence. Some free cancer cells may still exist after resection. In addition, the surgery itself may lead to the dissemination of tumor cells. Therefore, it is necessary to remove residual tumor cells. Recently, some researchers found that extensive intraoperative peritoneal lavage (EIPL) plus intraperitoneal chemotherapy can improve the prognosis of patients and eradicate peritoneal free cancer for GC patients. However, few studies explored the safety and long-term outcome of EIPL after curative gastrectomy. AIM: To evaluate the efficacy and long-term outcome of advanced GC patients treated with EIPL. METHODS: According to the inclusion and exclusion criteria, a total of 150 patients with advanced GC were enrolled in this study. The patients were randomly allocated to two groups. All patients received laparotomy. For the non-EIPL group, peritoneal lavage was washed using no more than 3 L of warm saline. In the EIPL group, patients received 10 L or more of saline (1 L at a time) before the closure of the abdomen. The surviving rate analysis was compared by the Kaplan-Meier method. The prognostic factors were carried out using the Cox appropriate hazard pattern. RESULTS: The basic information in the EIPL group and the non-EIPL group had no significant difference. The median follow-up time was 30 mo (range: 0-45 mo). The 1- and 3-year overall survival (OS) rates were 71.0% and 26.5%, respectively. The symptoms of ileus and abdominal abscess appeared more frequently in the non-EIPL group (P < 0.05). For the OS of patients, the EIPL, Borrmann classification, tumor size, N stage, T stage and vascular invasion were significant indicators. Then multivariate analysis revealed that EIPL, tumor size, vascular invasion, N stage and T stage were independent prognostic factors. The prognosis of the EIPL group was better than the non-EIPL group (P < 0.001). The 3-year survival rate of the EIPL group (38.4%) was higher than the non-EIPL group (21.7%). For the recurrence-free survival (RFS) of patients, the risk factor of RFS included EIPL, N stage, vascular invasion, type of surgery, tumor location, Borrmann classification, and tumor size. EIPL and tumor size were independent risk factors. The RFS curve of the EIPL group was better than the non-EIPL group (P = 0.004), and the recurrence rate of the EIPL group (24.7%) was lower than the non-EIPL group (46.4%). The overall recurrence rate and peritoneum recurrence rate in the EIPL group was lower than the non-EIPL group (P < 0.05). CONCLUSION: EIPL can reduce the possibility of perioperative complications including ileus and abdominal abscess. In addition, the overall survival curve and RFS curve were better in the EIPL group.

A review on natural based deep eutectic solvents (NADESs): fundamentals and potential applications in removing heavy metals from soil.

Natural based deep eutectic solvent (NADES) is a promising green solvent to replace the conventional soil washing solvent due to the environmental benign properties such as low toxicity, high biodegradability, high polarity or hydrophilicity, and low cost of fabrication process. The application of NADES is intensively studied in the extraction of organic compounds or natural products from vegetations or organic matters. Conversely, the use of the solvent in removing heavy metals from soil is severely lacking. This review focuses on the potential application of NADES as a soil washing agent to remove heavy metal contaminants. Hydrophilicity is an important feature of a NADES to be used as a soil washing solvent. In this context, choline chloride is often used as hydrogen bond acceptor (HBA) whereby choline chloride based NADESs showed excellent performance in the extraction of various solutes in the past studies. The nature of NADES along with its chemistry, preparation and designing methods as well as potential applications were comprehensively reviewed. Subsequently, related studies on choline chloride-based NADES in heavy metal polluted soil remediation were also reviewed. Potential applications in removing other soil contaminants as well as the limitations of NADES were discussed based on the current advancements of soil washing and future research directions were also proposed.

Polyethylene glycol crosslinked decellularized single liver lobe scaffolds with vascular endothelial growth factor promotes angiogenesis in vivo.

BACKGROUND: Improving the mechanical properties and angiogenesis of acellular scaffolds before transplantation is an important challenge facing the development of acellular liver grafts. The present study aimed to evaluate the cytotoxicity and angiogenesis of polyethylene glycol (PEG) crosslinked decellularized single liver lobe scaffolds (DLSs), and establish its suitability as a graft for long-term liver tissue engineering. METHODS: Using mercaptoacrylate produced by the Michael addition reaction, DLSs were first modified using N-succinimidyl S-acetylthioacetate (SATA), followed by cross-linking with PEG as well as vascular endothelial growth factor (VEGF). The optimal concentration of agents and time of the individual steps were identified in this procedure through biomechanical testing and morphological analysis. Subsequently, human umbilical vein endothelial cells (HUVECs) were seeded on the PEG crosslinked scaffolds to detect the proliferation and viability of cells. The scaffolds were then transplanted into the subcutaneous tissue of Sprague-Dawley rats to evaluate angiogenesis. In addition, the average number of blood vessels was evaluated in the grafts with or without PEG at days 7, 14, and 21 after implantation. RESULTS: The PEG crosslinked DLS maintained their three-dimensional structure and were more translucent after decellularization than native DLS, which presented a denser and more porous network structure. The results for Young's modulus proved that the mechanical properties of 0.5 PEG crosslinked DLS were the best and close to that of native livers. The PEG-VEGF-DLS could better promote cell proliferation and differentiation of HUVECs compared with the groups without PEG cross-linking. Importantly, the average density of blood vessels was higher in the PEG-VEGF-DLS than that in other groups at days 7, 14, and 21 after implantation in vivo. CONCLUSIONS: The PEG crosslinked DLS with VEGF could improve the biomechanical properties of native DLS, and most importantly, their lack of cytotoxicity provides a new route to promote the proliferation of cells in vitro and angiogenesis in vivo in liver tissue engineering.

A Microfluidic Platform with an Embedded Miniaturized Electrochemical Sensor for On-Chip Plasma Extraction Followed by In Situ High-Sensitivity C-Reactive Protein (hs-CRP) Detection.

Blood testing is a clinical diagnostic tool to evaluate physiological conditions, the immune system response, or the presence of infection from whole blood samples. Although conventional blood testing can provide rich biological information, it usually requires complicated and tedious whole blood processing steps operated by benchtop instruments and well-experienced technicians, limiting its usage in point-of-care (POC) settings. To address the above problems, we propose a microfluidic platform for on-chip plasma extraction directly from whole blood and in situ biomarker detection. Herein, we chose C-reactive protein (CRP) as the target biomarker, which can be used to predict fatal cardiovascular disease (CVD) events such as heart attacks and strokes. To achieve a rapid, undiluted, and high-purity on-chip plasma extraction, we combined two whole blood processing methods: (1) anti-D immunoglobulin-assisted sedimentation, and (2) membrane filtration. To perform in situ CRP detection, we fabricated a three-dimensional (3D) microchannel with an embedded electrochemical (EC) sensor, which has a modular design to attach the blood collector and buffer reservoir with standard Luer connectors. As a proof of concept, we first confirmed that the dual plasma extraction design achieved the same purity level as the standard centrifugation method with smaller sample (100 µL of plasma extracted from 400 µL of whole blood) and time (7 min) requirements. Next, we validated the functionalization protocol of the EC sensor, followed by evaluating the detection of CRP spiked in plasma and whole blood. Our microfluidic platform performed on-chip plasma extraction directly from whole blood and in situ CRP detection at a 0.1-10 µg/mL concentration range, covering the CVD risk evaluation level of the high-sensitivity CRP (hs-CRP) test. Based on the above features, we believe that this platform constitutes a flexible way to integrate the processing of complex samples with accurate biomarker detection in a sample-to-answer POC platform, which can be applied in CVD risk monitoring under critical clinical situations.

Novel management indications for conservative treatment of chylous ascites after gastric cancer surgery.

BACKGROUND: Chylous ascites (CA) presents a challenge as a relatively common postoperative complication in gastric cancer (GC). Primary conservative therapy involved total parenteral nutrition, continuous low-pressure drainage, somatostatin, and a low-fat diet. Drainage tube (DT) clamping has been presented as a potential alternative conservative treatment for GC patients with CA. AIM: To propose novel conservative treatment strategies for CA following GC surgery. METHODS: The data of patients with CA after GC surgery performed at the Fudan University Shanghai Cancer Center between 2006 and 2021 were evaluated retrospectively. RESULTS: 53 patients underwent surgery for GC and exhibited postoperative CA during the study period. Postoperative hospitalization and time of DT removal showed a significant positive association (R 2 = 0.979, P < 0.001). We further observed that delayed DT removal significantly extended the total and postoperative hospitalization, antibiotic usage duration, and hospitalization cost (postoperative hospitalization: 25.8 d vs 15.5 d, P < 0.001; total hospitalization: 33.2 d vs 24.7 d, P < 0.01; antibiotic usage duration: 10.8 d vs 6.2 d, P < 0.01; hospitalization cost: ¥9.2 × 104 vs ¥6.5 × 104, P < 0.01). Multivariate analysis demonstrated that postoperative infection and antibiotic usage were independent factors for delayed DT removal. Furthermore, DT removal times were shorter in seven patients who underwent DT clamping (clamped DT vs normal group, 11.8 d vs 13.6 d, P = 0.047; clamped DT vs delayed group, 13.6 d vs 27.4 d, P < 0.001). In addition, our results indicated that removal of the DT may be possible after three consecutive days of drainage volumes less than 300 mL in GC patients with CA. CONCLUSION: Infection and antibiotic usage were vital independent factors that influenced delayed DT removal in patients with CA. Appropriate standards for DT removal can significantly reduce the duration of hospitalization. Furthermore, DT clamping might be a recommended option for conservative treatment of postoperative CA.

High-Resolution Histopathological Image Classification Model Based on Fused Heterogeneous Networks with Self-Supervised Feature Representation.

Applying machine learning technology to automatic image analysis and auxiliary diagnosis of whole slide image (WSI) may help to improve the efficiency, objectivity, and consistency of pathological diagnosis. Due to its extremely high resolution, it is still a great challenge to directly process WSI through deep neural networks. In this paper, we propose a novel model for the task of classification of WSIs. The model is composed of two parts. The first part is a self-supervised encoding network with a UNet-like architecture. Each patch from a WSI is encoded as a compressed latent representation. These features are placed according to their corresponding patch's original location in WSI, forming a feature cube. The second part is a classification network fused by 4 famous network blocks with heterogeneous architectures, with feature cube as input. Our model effectively expresses the feature and preserves location information of each patch. The fused network integrates heterogeneous features generated by different networks which yields robust classification results. The model is evaluated on two public datasets with comparison to baseline models. The evaluation results show the effectiveness of the proposed model.

[Effect of sequential sedation and analgesia in preventing delirium and withdrawal symptoms in children after ventilator weaning]. / åºè´¯é•‡ç—›é•‡é™å¯¹é¢„é˜²è¡Œæœºæ¢°é€šæ°”æ²»ç–—æ‚£å„¿æ’¤æœºåŽè°µå¦„åŠæ’¤è¯ååº”çš„æ•ˆæžœç ”ç©¶.

OBJECTIVES: To investigate the effect of sequential sedative and analgesic drugs in preventing delirium and withdrawal symptoms in children after ventilator weaning. METHODS: A retrospective analysis was performed on 61 children who were admitted and received mechanical ventilation support for ≥5 days in the Pediatric Intensive Care Unit of Dongguan Children's Hospital Affiliated to Guangdong Medical University from December 2019 to September 2021. The children were divided into a control group (30 children with no maintenance of analgesic and sedative drugs after ventilator weaning) and an observation group (31 children with sequential sedative and analgesic drugs maintained for 48 hours after ventilator weaning). The two groups were compared in terms of the Sophia Observation Withdrawal Symptoms Scale (SOS) score, the Pediatric Delirium Scale (PD) score, the Richmond Agitation-Sedation Scale (RASS) score, and the incidence rates of delirium or withdrawal symptoms at 24 and 72 hours after ventilator weaning. RESULTS: There was no significant difference in the incidence rate of delirium at 24 hours and 72 hours after ventilator weaning between the two groups (P>0.05). Compared with the control group, the observation group had significantly lower incidence rate of withdrawal symptoms and scores of SOS, PD, and RASS scales at 24 hours and 72 hours after ventilator weaning (P<0.01). CONCLUSIONS: Sequential sedation and analgesia after ventilator weaning can reduce the incidence of withdrawal symptoms within 72 hours after ventilator weaning, but it cannot reduce the incidence rate of delirium.