Clinical characteristics and molecular genetic analysis of ten cases of ornithine carbamoyltransferase deficiency in southeastern China.

BACKGROUND: This study aimed to investigate the clinical and molecular genetic characteristics of ten children with ornithine carbamoyltransferase deficiency (OTCD) in southeastern China, as well as the correlation between the genotype and phenotype of OTCD. METHODS: A retrospective analysis was performed on the clinical manifestations, laboratory testing, and genetic test findings of ten children with OTCD admitted between August 2015 and October 2021 at Quanzhou Maternity and Children's Hospital of Fujian Province in China. RESULTS: Five boys presented with early-onset symptoms, including poor appetite, drowsiness, groaning, seizures, and liver failure. In contrast, five patients (one boy and four girls) had late-onset gastrointestinal symptoms as the primary clinical manifestation, all presenting with hepatic impairment, and four with hepatic failure.Nine distinct variants of the OTC gene were identified, including two novel mutations: c.1033del(p.Y345Tfs*50) and c.167T > A(p.M56K). Of seven patients who died, five had early-onset disease despite active treatment. Three patients survived, and two of them underwent liver transplantation. CONCLUSIONS: The clinical manifestations of OTCD lack specificity. However, elevated blood ammonia levels serve as a crucial diagnostic clue for OTCD. Genetic testing aids in more accurate diagnosis and prognosis assessment by clinicians. In addition, we identified two novel pathogenic variants and expand the mutational spectrum of the gene OTC, which may contribute to a better understanding of the clinical and genetic characteristics of OTCD patients.

Clinical application of flexible fiberoptic bronchoscopy in neonatal respiratory diseases.

BACKGROUND: Respiratory disease is a predominantly observed problem in neonates. Moreover, the application of flexible bronchoscopy in newborns is gradually increasing. This study aimed to investigate the value of bronchoscopy in neonates respiratory abnormalities and evaluate the safety of bronchoscopy application. METHODS: Clinical data and outcomes of 56 neonates who underwent flexible bronchoscopy were retrospectively analyzed. Correlations among indications for bronchoscopy, findings, and clinical diseases were assessed. RESULTS: A total of 56 neonates had a minimum weight of 1200 g at the time of bronchoscopy, while the minimum gestational age at birth was 26 + 1 weeks. A total of 22 cases (39.3%) had two or more clinical indications; the five most common indications were respiratory distress in 24 (42.9%), stridor in 22 (39.3%), pulmonary atelectasis in 10 (17.6%), feeding difficulty in 10 (17.6%), and difficult weaning from mechanical ventilation in 6 (10.7%) cases. A total of 13 types of abnormalities were detected in the respiratory tract. The most common abnormalities were laryngomalacia in 29 (59.2%), tracheobroncomalacia in 8 (16.3%), and vocal cord paralysis in 6 (12.2%) cases. Bronchoalveolar lavage was performed in 39 cases. Eight cases were diagnosed by bronchoscopy and then treated with surgery in the Thoracic Surgery/Otolaryngology Department; all of them were cured and discharged from the hospital after surgery. No serious complications, such as pneumothorax or shock, occurred in any of the children, of whom none died. CONCLUSIONS: Flexible bronchoscopy could play an important role in diagnosing and identifying respiratory disorders in neonates and be safely used with few serious complications.

Discussion on the mechanism of Tiaoqi Xiaowei decoction in the treatment of chronic atrophic gastritis based on network pharmacology and molecular docking: An observational study.

To explore the mechanism of Tiaoqi Xiaowei decoction in the treatment of chronic atrophic gastritis by network pharmacology and molecular docking. The main active components and targets of Tiaoqi Xiaowei decoction were obtained from TCMSP database. The databases of Disgenet, GeneCards, and OMIM were used to obtain chronic atrophic gastritis-related targets. The component-target-disease network was constructed by Cytoscape 3.7.1 software, and the protein-protein interaction network was constructed by String database. The core targets were screened by CytoNCA plug-in. Gene ontology analysis and Kyoto Encyclopedia of Genes and Genome pathway enrichment analysis were performed using the Metascape database. The core components and targets were subjected to molecular docking verification using AutoDock Tools 1.5.6 software, and the binding score was obtained. A total of 48 active components were identified, involving 82 action targets. Core active components such as quercetin, beta-sitosterol, kaempferol, luteolin, and naringenin, and core targets such as AKT1, TP53, VEGFA, TNF, IL6, and PTGS2 were obtained. A total of 188 signaling pathways were screened out, including cancer pathway, PI3K-Akt, IL-17, and TNF signaling pathway. Molecular docking results showed that the key components of Tiaoqi Xiaowei decoction had a favorable binding affinity with key targets. Tiaoqi Xiaowei decoction acts on multiple targets such as AKT1, TP53, VEGFA, TNF, IL6, PTGS2, and synergistically treats chronic atrophic gastritis by regulating inflammatory responses and tumor-related signaling pathways.

Bifidobacterium regulates premature infant gut metabolites, reducing serum inflammatory factors: a randomised controlled trial.

BACKGROUND: Analyse the effects of Bifidobacterium BB-12 on intestinal metabolites and serum inflammatory factors in premature infants. METHODS: 71 premature infants at gestational age of ≤32 weeks were randomly divided into the probiotic (n = 36) and control (n = 35) groups. Faecal and blood samples were collected from the two groups of premature infants at the 2nd and 4th week of life for intestinal metabolite detection and assessment of the level of the serum inflammatory markers TLR4, NF- κ B, IL-1ß, and TNF- α. RESULTS: Compared to the control group, the probiotic group contained more amino acids, these elements were enriched on multiple amino acid metabolic pathways, and the probiotic group showed significantly lower levels of the serum inflammatory markers TLR4, NF-κB, IL-1ß, and TNF-α. Finally, the probiotic group showed a lower incidence of feeding intolerance. CONCLUSIONS: The administration of Bifidobacterium BB-12 is associated with increasing the levels of glutamine, glutamic acid, and kynurenine in the gut of premature infants, and associated with reducing the levels of TLR4 and NF-κB in the serum, further decreasing the secretion of the pro-inflammatory factors IL-1ß and TNF-α, and alleviating systemic inflammatory reactions, thereby reducing the incidence of feeding intolerance. IMPACT: 1. The use of Bifidobacterium BB-12 in premature infants can increase the levels of amino acids in the intestine. 2. Increases in Bifidobacterium BB-12 may decrease the serum levels of TLR4, NF-κB, IL-1ß, and TNF-α. 3. Kynurenine may improve the prognosis of preterm infants by reducing inflammation. 4. Bifidobacterium BB-12 may improve the feeding tolerance of premature infants, thus reducing the incidence of feeding intolerance.

Effectiveness and feasibility of continuous renal replacement therapy for acute kidney injury in neonates weighing 3 kg or less: a two-centre, retrospective study.

BACKGROUND: Continuous renal replacement therapy (CRRT) is commonly used for the treatment of acute kidney injury (AKI) in critically ill neonates. This study investigated the effectiveness and feasibility of CRRT for AKI in neonates who weigh ≤3 kg. METHODS: Data from 19 neonates with a weight ≤3 kg and AKI who underwent CRRT at two centres between January 2015 and October 2021 were collected retrospectively. Kidney function, circulatory function, complications and clinical outcomes were recorded. Repeated-measures analyses of variance, t-tests and non-parametric tests were conducted. RESULTS: The median patient age at CRRT initiation was 3 days (IQR: 1-7 days). The median patient weight at CRRT initiation was 2.67 kg (IQR: 2.20-2.85 kg). The median CCRT duration was 46 hours (IQR: 32-72 hours). The serum creatinine and blood urea nitrogen levels decreased significantly, and the mean arterial pressure increased significantly after 12 hours of CRRT and at the end of CRRT. The urinary output was significantly increased at the end of CRRT. 11 patients had thrombocytopaenia, 6 had electrolyte disorders and 3 had blocked tubes. Five patients were discharged, six died after their parents chose to discontinue treatment and eight died after active treatment. Weight at CRRT initiation and urinary output at the end of CRRT were significantly lower among patients who died than among patients who survived. CONCLUSIONS: CRRT is feasible and effective for AKI in neonates who weigh ≤3 kg when accompanied by elaborate supportive care. Lower body weight and persistent oliguria may be correlated with an increased risk of poor clinical outcomes.

Monitoring yellow rust progression during spring critical wheat growth periods using multi-temporal Sentinel-2 imagery.

BACKGROUND: Yellow rust (Puccinia striiformis f. sp. tritici) is a devastating hazard to wheat production, which poses a serious threat to yield and food security in the main wheat-producing areas in eastern China. It is necessary to monitor yellow rust progression during spring critical wheat growth periods to support its prediction by providing timely calibrations for disease prediction models and timely green prevention and control. RESULTS: Three Sentinel-2 images for the disease during the three wheat growth periods (jointing, heading, and filling) were acquired. Spectral, texture, and color features were all extracted for each growth period disease. Then three period-specific feature sets were obtained. Given the differences in field disease epidemic status in the three periods, three period-targeted monitoring models were established to map yellow rust damage progression in spring and track its spatiotemporal change. The models' performance was then validated based on the disease field truth data during the three periods (87 for the jointing period, 183 for the heading period, and 155 for the filling period). The validation results revealed that the representation of the wheat yellow rust damage progression based on our monitoring model group was realistic and credible. The overall accuracy of the healthy and diseased pixel classification monitoring model at the jointing period reached 87.4%, and the coefficient of determination (R2) of the disease index regression monitoring models at the heading and filling periods was 0.77 (heading period) and 0.76 (filling period). The model-group-result-based spatiotemporal change detection of the yellow rust progression across the entire study area revealed that the area proportions conforming to the expected disease spatiotemporal development pattern during the jointing-to-heading period and the heading-to-filling period reached 98.2% and 84.4% respectively. CONCLUSIONS: Our jointing, heading, and filling period-targeted monitoring model group overcomes the limitations of most existing monitoring models only based on single-phase remote sensing information. It performs well in revealing the wheat yellow rust spatiotemporal epidemic in spring, can timely update disease trends to optimize disease management, and provide a basis for disease prediction to timely correct model. © 2024 Society of Chemical Industry.

Overexpression of SmUGGT1 Confers Imidacloprid Resistance to Sitobion miscanthi (Takahashi).

Sitobion miscanthi, the main species of wheat aphids, is one kind of harmful pest. Chemical insecticides are the important agrochemical products to effectively control wheat aphids. However, the broad application has led to serious resistance of pests to several insecticides, and understanding insecticide resistance mechanisms is critical for integrated pest management. In this study, SmUGGT1, a new uridine diphosphate (UDP)-glycosyltransferase (UGT) gene, was cloned and more strongly expressed in the SM-R (the resistant strain to imidacloprid) than in the SM-S (the susceptible strain to imidacloprid). The increased susceptibility to imidacloprid was observed after silencing SmUGGT1, indicating that it can be related to the resistance to imidacloprid. Subsequently, SmUGGT1 regulated post-transcriptionally in the coding sequences (CDs) by miR-81 was verified and involved in the resistance to imidacloprid in S. miscanthi. This finding is crucial in the roles of UGT involved in insecticide resistance management in pests.

Myristic Acid Solid Lipid Nanoparticles Enhance the Oral Bioavailability and Therapeutic Efficacy of Rifaximin against MRSA Pneumonia.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) pneumonia is one of the leading causes of death and an immense financial burden on healthcare systems. Rifaximin (RFX) has good antibacterial activity against MRSA, but its clinical application is limited due to its poor oral absorption. Solid lipid nanoparticles have good biocompatibility, high drug loading, sustained release performance, and the inertia of lipids in gastric acid, which facilitates oral drug delivery. OBJECTIVE: In order to improve the oral bioavailability of rifaximin and expand the clinical application of RFX for MRSA pneumonia, this study developed RFX-loaded myristic acid solid lipid nanoparticles (RFX-SLNs). METHODS: This study first prepared RFX-SLNs through hot melt emulsification and ultrasonic methods and selected the optimal formula of RFX-SLNs through single-factor screening. Afterward, the particle size, zeta potential, and polydispersity index (PDI) of the RFX-SLNs were measured, the morphology of RFX-SLNs was observed by transmission electron microscopy, and the encapsulation efficiency (EE) and drug loading capacity (LC) of RFX-SLNs were detected by high-performance liquid chromatography. Then, the sustained release ability and oral bioavailability of RFX-SLNs were studied through in vitro release and pharmacokinetics. Finally, the therapeutic effect of RFX-SLNs on MRSA pneumonia infection was studied by using a mouse MRSA pneumonia infection model. RESULTS: The optimal formulation of RFX-SLNs was 1% RFX with water (3% PVA) and oil (myristic acid) ratio of 1:19. RFX-SLNs were spherical in shape with a smooth surface and uniform size. The EE and LC of three different batches of RFX-SLNs were 89.35±2.47%, 90.45±3.69%, 88.72±1.18%, and 9.50 ± 0.01%, 10.09±0.01%, and 9.68±0.00%, respectively. In vitro release and pharmacokinetic studies showed that the myristic acid solid lipid nanoparticles showed excellent sustained release as expected and increased the oral bioavailability of RFX by 2.18 times. This indicates that RFX-SLNs can be used for the oral treatment of bacterial infections. Compared to RFX, RFX-SLNs showed good therapeutic effects in a mouse MRSA pneumonia infection model. CONCLUSION: This study indicates that the myristic acid solid lipid nanoparticles might be an effective way to enhance the oral absorption and therapy effects of RFX and other insoluble drugs. This not only opens up avenues for the clinical application of RFX but also provides a way for the development of new dosage forms of water-soluble drugs and the expansion of their clinical application scope.

C188-9 reduces patient-specific primary breast cancer cells proliferation at the low, clinic-relevant concentration.

OBJECTIVES: STAT3 is a transcriptional activator of breast cancer oncogenes, suggesting that it could be a potential therapeutic target for breast cancer. Therefore, this study investigated the potential application of C188-9, a STAT3 signal pathway inhibitor, in the treatment of breast cancer through a novel pre-clinical platform with patient-specific primary cells (PSPCs). METHODS: PSPCs were isolated from breast cancer samples obtained via biopsy or surgery from fifteen patient donors with their full acknowledgements. PSPCs were treated with C188-9 or other chemotherapeutic agents, and then analyzed with cell viability assay. Western blot assay and real-time quantitative PCR were also used to determine the expression and activity of STAT3 signaling pathway of corresponding PSPCs. RESULTS: C188-9 treatment at normal (experimental) concentration had valid inhibition on PSPCs proliferation. Meanwhile, treatment at a low (clinic-relevant) concentration of C188-9 for an extended period reduced cell viability of PSPCs still more than some of other traditional chemotherapy drugs. In addition, C188-9 decreased expression level of pSTAT3 in PSPCs from some, but not all patient samples. The treatment of C188-9 reduced cell viability of the breast cancer samples through inhibiting the STAT3 to C-myc signaling pathway. CONCLUSIONS: In this study, we tested a novel drug C188-9 at a low, clinic-relevant concentration, together with several traditional chemotherapy agents. PSPCs from ten out of fifteen patient donors were sensitive to C188-9, while some of traditional chemotherapy agents failed. This finding suggested that C188-9 could have treatment effects only on those ten PSPC patient donors, indicating the future personalized utilization of PSPCs.

A real-world study on the treatment of extremely preterm infants: a multi-center study in southwest area of Fujian Province in China.

BACKGROUND: Due to regional and cultural differences, the current status of extremely preterm infants(EPIs) treatment across different areas of mainland China remains unclear. This study investigated the survival rate and incidence of major diseases among EPIs in the southwest area of Fujian province. METHOD: This retrospective and multicenter study collected perinatal data from EPIs with gestational ages between 22-27+ 6w and born in the southwest area of Fujian province. The study population was divided into 6 groups based on gestational age at delivery. The primary outcome was the survival status at ordered hospital discharge or correct gestational age of 40 weeks, and the secondary outcome was the incidence of major diseases. The study analyzed the actual survival status of EPIs in the area. RESULT: A total of 2004 preterm infants with gestational ages of 22-27+ 6 weeks were enrolled in this study. Among them, 1535 cases (76.6%) were born in the delivery room but did not survive, 469 cases (23.4%) were transferred to the neonatal department for treatment, 101 cases (5.0%) received partial treatment, and 368 cases (18.4%) received complete treatment. The overall all-cause mortality rate was 84.4% (1691/2004). The survival rate and survival rate without major serious disease for EPIs who received complete treatment were 85.1% (313/368) and 31.5% (116/318), respectively. The survival rates for gestational ages 22-22+ 6w, 23-23+ 6w, 24-24+ 6w, 25-25+ 6w, 26-26+ 6w, and 27-27+ 6w were 0%, 0%, 59.1% (13/22), 83% (39/47), 88.8% (87/98), and 89.7% (174/198), respectively. The survival rates without major serious disease were 0%, 0%, 9.1% (2/22), 19.1% (9/47), 27.6% (27/98), and 40.2% (78/194), respectively. CONCLUSION: The all-cause mortality of EPIs in the southwest area of Fujian Province remains high, with a significant number of infants were given up after birth in the delivery room being the main influencing factor. The survival rate of EPIs who received complete treatment at 25-27 weeks in the NICU was similar to that in developed countries. However, the survival rate without major serious disease was significantly lower compared to high-income countries.

Successful treatment of severe and recurrent hand eczema with infection in human immunodeficiency virus patients: A case report.

Hand eczema is a common allergic disease characterized by a chronic relapsing course with a 15% lifetime prevalence. Human immunodeficiency virus-infected individuals have a higher risk of Staphylococcus aureus infection which is associated with the severity of hand eczema. Incidences of allergic diseases including hand eczema and chronic itch are higher in patients with human immunodeficiency virus. Pruritus is one of the most common symptoms in hand eczema, sometimes intractable pruritus provokes repeated scratching, picking, disfigurement, and can even worsen the lesion. Currently, there is no ideal treatment for hand eczema, the treatment of hand eczema in human immunodeficiency virus patients is even more difficult. Here, we present a case of recurrent and therapy-resistant hand eczema patients combined with Staphylococcus aureus infection, human immunodeficiency virus infection was better improved by being treated with topical ozone therapy.

COLEC10 inhibits the stemness of hepatocellular carcinoma by suppressing the activity of ß-catenin signaling.

BACKGROUND: Liver cancer stem cells (CSCs) contribute to tumor initiation, progression, and recurrence in hepatocellular carcinoma (HCC). The Wnt/ß-catenin pathway plays a crucial role in liver cancer stemness, progression, metastasis, and drug resistance, but no clinically approved drugs have targeted this pathway efficiently so far. We aimed to elucidate the role of COLEC10 in HCC stemness. METHODS: The Cancer Genome Atlas (TCGA) and the Clinical Proteomic Tumor Analysis Consortium (CPTAC) databases were employed to search for the association between COLEC10 expression and HCC stemness. Colony formation, sphere formation, side population, and limiting dilution tumor initiation assays were used to identify the regulatory role of COLEC10 overexpression in the stemness of HCC cell lines. Wnt/ß-catenin reporter assay and immunoprecipitation were performed to explore the underlying mechanism. RESULTS: COLEC10 level was negatively correlated with HCC stemness. Elevated COLEC10 led to decreased expressions of EpCAM and AFP (alpha-fetoprotein), two common markers of liver CSCs. Overexpression of COLEC10 inhibited HCC cells from forming colonies and spheres, and reduced the side population numbers in vitro, as well as the tumorigenic capacity in vivo. Mechanically, we demonstrated that overexpression of COLEC10 suppressed the activity of Wnt/ß-catenin signaling by upregulating Wnt inhibitory factor WIF1 and reducing the level of cytoplasmic ß-catenin. COLEC10 overexpression promoted the interaction of ß-catenin with the component of destruction complex CK1α. In addition, KLHL22 (Kelch Like Family Member 22), a reported E3 ligase adaptor predicted to interact with CK1α, could facilitate COLEC10 monoubiquitination and degradation. CONCLUSION: COLEC10 inhibits HCC stemness by downregulating the Wnt/ß-catenin pathway, which is a promising target for liver CSC therapy.

Utilizing Esophageal Motility Tests in Diagnosing and Evaluating Gastroesophageal Reflux Disease.

Gastroesophageal reflux disease (GERD), a prevalent clinical condition, is often attributed to aberrant esophageal motility, leading to gastric content reflux and associated symptoms or complications. The rising incidence of GERD presents an escalating healthcare challenge. Endoscopic and esophageal reflux monitoring can provide a basis for the diagnosis of patients with gastroesophageal reflux disease, but when the diagnostic basis is at an inconclusive value, some additional supportive evidence will be needed. Advanced technology is the key to improving patient diagnosis, accurate assessment, and the development of effective treatment strategies. High-resolution esophageal manometry (HREM) and endoscopic functional lumen imaging probe (EndoFLIP) represent the forefront of esophageal motility assessment. HREM, an evolution of traditional esophageal manometry, is considered the benchmark for identifying esophageal motility disorders. Its widespread application in esophageal dynamics research highlights its diagnostic significance. Concurrently, EndoFLIP's emerging clinical relevance is evident in diagnosing and guiding the treatment of coexisting esophageal motility issues. This review integrates contemporary research to delineate the contributions of HREM, EndoFLIP, and novel technologies in GERD. It examines their efficacy in facilitating an accurate diagnosis, differentiating similar gastrointestinal disorders, quantifying the extent of reflux, assessing the severity of the disease, forecasting patient responsiveness to proton pump inhibitor therapy, and guiding decisions for surgical interventions. The overarching aim is to deepen the understanding of GERD's underlying mechanisms and advance the formulation of holistic, efficacious treatment approaches.

Analysis of spatiotemporal changes mechanism of cell wall biopolymers and monosaccharide components in kiwifruit during Botryosphaeria dothidea infection.

To further reveal the interaction mechanism between plants and pathogens, this study used confocal Raman microscopy spectroscopy (CRM) combined with chemometrics to visualize the biopolymers distribution of kiwifruit cell walls at different infection stages at the cellular micro level. Simultaneously, the changes in the content of various monosaccharides in fruit were studied at the molecular level using high-performance liquid chromatography (HPLC). There were significant differences in the composition of various nutrient components in the cell wall structure of kiwifruit at different infection times after infection by Botryosphaeria dothidea. PCA could cluster samples with infection time of 0-9 d into different infection stages, and SVM was used to predict the PCA classification results, the accuracy >96 %. Multivariate curve resolution-alternating least squares (MCR-ALS) helped to identify single substance spectra and concentration signals from mixed spectral signals. The pure substance chemical imaging maps of low methylated pectin (LMP), high methylated pectin (HMP), cellulose, hemicellulose, and lignin were obtained by analyzing the resolved concentration data. The imaging results showed that the lignin content in the kiwifruit cell wall increased significantly to resist pathogens infection after the infection of B. dothidea. With the development of infection, B. dothidea decomposed various substances in the host cell walls, allowing them to penetrate the interior of fruit cells. This caused significant changes in the form, structure, and distribution of various chemicals on the fruit cell walls in time and space. HPLC showed that glucose was the main carbon source and energy substance obtained by pathogens from kiwifruit during infection. The contents of galactose and arabinose, which maintained the structure and function of the fruit cell walls, decreased significantly and the cell wall structure was destroyed in the late stage of pathogens infection. This study provided a new perspective on the cellular structure changes caused by pathogenic infection of fruit and the defense response process of fruit and provided effective references for further research on the mechanisms of host-pathogen interactions in fruit infected by pathogens.

High-Frequency Recombination of Human Adenovirus in Children with Acute Respiratory Tract Infections in Beijing, China.

Recombination events in human adenovirus (HAdV) have led to some new highly pathogenic or infectious types. It is vital to monitor recombinant HAdVs, especially in children with acute respiratory tract infections (ARIs). In the retrospective study, HAdV positive specimens were collected from pediatric patients with ARIs during 2015 to 2021, then typed by sequence analysis of the penton base, hexon and fiber gene sequence. For those with inconsistent typing results, a modified method with species-specific primer sets of a fiber gene sequence was developed to distinguish co-infections of different types from recombinant HAdV infections. Then, plaque assays combined with meta-genomic next-generation sequencing (mNGS) were used to reveal the HAdV genomic characteristics. There were 466 cases positive for HAdV DNA (2.89%, 466/16,097) and 350 (75.11%, 350/466) successfully typed with the most prevalent types HAdV-B3 (56.57%, 198/350) and HAdV-B7 (32.00%, 112/350), followed by HAdV-C1 (6.00%, 21/350). Among 35 cases (7.51%, 35/466) with inconsistent typing results, nine cases were confirmed as co-infections by different types of HAdVs, and 26 cases as recombinant HAdVs in six genetic patterns primarily clustered to species C (25 cases) in pattern 1-5, or species D (1 case) in pattern 6. The novel recombinant HAdV of species D was identified with multiple recombinant events among HAdV-D53, HAdV-D64, and HAdV-D8, and officially named as HAdV-D115. High-frequency recombination of HAdVs in six genetic recombination patterns were identified among children with ARIs in Beijing. Specifically, there is a novel Adenovirus D human/CHN/S8130/2023/115[P22H8F8] designed as HAdV D115.

Real-time predictive model of extrauterine growth retardation in preterm infants with gestational age less than 32 weeks.

The aim of this study was to develop a real-time risk prediction model for extrauterine growth retardation (EUGR). A total of 2514 very preterm infants were allocated into a training set and an external validation set. The most appropriate independent variables were screened using univariate analysis and Lasso regression with tenfold cross-validation, while the prediction model was designed using binary multivariate logistic regression. A visualization of the risk variables was created using a nomogram, while the calibration plot and receiver operating characteristic (ROC) curves were used to calibrate the prediction model. Clinical efficacy was assessed using the decision curve analysis (DCA) curves. Eight optimal predictors that namely birth weight, small for gestation age (SGA), hypertensive disease complicating pregnancy (HDCP), gestational diabetes mellitus (GDM), multiple births, cumulative duration of fasting, growth velocity and postnatal corticosteroids were introduced into the logistic regression equation to construct the EUGR prediction model. The area under the ROC curve of the training set and the external verification set was 83.1% and 84.6%, respectively. The calibration curve indicate that the model fits well. The DCA curve shows that the risk threshold for clinical application is 0-95% in both set. Introducing Birth weight, SGA, HDCP, GDM, Multiple births, Cumulative duration of fasting, Growth velocity and Postnatal corticosteroids into the nomogram increased its usefulness for predicting EUGR risk in very preterm infants.

Efficacy and Safety of Oxymatrine in the Treatment of Patients with Erythrodermic Psoriasis.

INTRODUCTION: The management of erythrodermic psoriasis (EP), a rare but severe type of psoriasis, is challenging, especially in patients with concomitant chronic hepatitis B (CHB). We previously demonstrated that oxymatrine treatment alleviated severe plaque psoriasis, but its therapeutic potential in treating EP remains unexplored. This study was to assess the efficacy and safety of oxymatrine for the treatment of EP, with attention to concomitant CHB. METHODS: In this investigator-initiated clinical trial, four consecutive patients with EP, including two (A and B) with concomitant CHB, were treated with intravenous administration of oxymatrine as monotherapy for 8 weeks, and scheduled to be followed up for a minimum of 24 weeks. The primary outcome was at least 75% improvement in the psoriasis area and severity index (PASI 75) at week 32. Secondary outcomes included the body surface area (BSA) score, dermatology life quality index (DLQI)], and safety. RESULTS: Patients A, B, and C achieved PASI 75 at treatment completion and week 32, demonstrating improvements of 77.4%, 97.2%, and 100% in PASI, respectively. Their BSA and DLQI were also improved significantly at week 32 and throughout follow-up of 37, 57, and 105 weeks, respectively. The viral loads in patients A and B with CHB decreased modestly. Patient D discontinued after follow-up for 19 weeks, and the primary outcome could not be analyzed. No adverse events were reported during treatment and follow-up. CONCLUSION: Oxymatrine appears to be efficacious and safe for the treatment of patients with EP, including those with concomitant CHB. TRIAL REGISTRATION: This study was registered at the Chinese Clinical Trial Registry ( www.chictr.org.cn ; Registration number ChiCTR-TRC-14004301).

Risk factors for severe bronchopulmonary dysplasia in a Chinese cohort of very preterm infants.

OBJECTIVES: To examine the risk factors for severe bronchopulmonary dysplasia (BPD) in a cohort of very preterm infants (VPIs) in China, as BPD is common among VPIs and associated with a high mortality rate. METHODS: In this multicenter retrospective study, medical records from infants with BPD born at gestation age (GA) of <32 weeks with birth weight (BW) of <1,500 grams (g) in 7 regions of China were included. The cohort was stratified into different BPD severity groups based on their fraction of inspired oxygen requirement at a modified GA of 36 weeks or post discharge. Risk factors were identified using logistic regression analysis. RESULTS: A significant inverse correlation was revealed between BPD severity and both GA and BW (p<0.001). Independent risk factors for severe BPD (sBPD) were identified as invasive mechanical ventilation (≥7d), multiple blood transfusion (≥3), nosocomial infection (NI), hemodynamically significant patent ductus arteriosus (hsPDA), delayed initiation of enteral nutrition, and longer time to achieve total caloric intake of 110 kcal/kg. Conversely, administration of antenatal steroids was associated with reduced risk of sBPD. CONCLUSION: Our study not only reaffirmed the established risk factors of low GA and BW for sBPD in VPIs, but also identified additional, potentially modifiable risk factors. Further research is warranted to explore whether intervention in these modifiable factors might reduce the risk of sBPD.Clinical Trial Reg. No.: ChiCTR1900023418.

Transcriptome sequencing reveals novel biomarkers and immune cell infiltration in esophageal tumorigenesis.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is one of the most common malignancies worldwide, and its development comprises a multistep process from intraepithelial neoplasia (IN) to carcinoma (CA). However, the critical regulators and underlying molecular mechanisms remain largely unknown. AIM: To explore the genes and infiltrating immune cells in the microenvironment that are associated with the multistage progression of ESCC to facilitate diagnosis and early intervention. METHODS: A mouse model mimicking the multistage development of ESCC was established by providing warter containing 4-nitroquinoline 1-oxide (4NQO) to C57BL/6 mice. Moreover, we established a control group without 4NQO treatment of mice. Then, transcriptome sequencing was performed for esophageal tissues from patients with different pathological statuses, including low-grade IN (LGIN), high-grade IN (HGIN), and CA, and controlled normal tissue (NOR) samples. Differentially expressed genes (DEGs) were identified in the LGIN, HGIN, and CA groups, and the biological functions of the DEGs were analyzed via Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. The CIBERSORT algorithm was used to detect the pattern of immune cell infiltration. Immunohistochemistry (IHC) was also conducted to validate our results. Finally, the Luminex multiplex cytokine analysis was utilized to measure the serum cytokine levels in the mice. RESULTS: Compared with those in the NOR group, a total of 681541, and 840 DEGs were obtained in the LGIN, HGIN, and CA groups, respectively. Using the intersection of the three sets of DEGs, we identified 86 genes as key genes involved in the development of ESCC. Enrichment analysis revealed that these genes were enriched mainly in the keratinization, epidermal cell differentiation, and interleukin (IL)-17 signaling pathways. CIBERSORT analysis revealed that, compared with those in the NOR group, M0 and M1 macrophages in the 4NQO group showed stronger infiltration, which was validated by IHC. Serum cytokine analysis revealed that, compared with those in the NOR group, IL-1ß and IL-6 were upregulated, while IL-10 was downregulated in the LGIN, HGIN, and CA groups. Moreover, the expression of the representative key genes, such as S100a8 and Krt6b, was verified in external human samples, and the results of immunohistochemical staining were consistent with the findings in mice. CONCLUSION: We identified a set of key genes represented by S100a8 and Krt6b and investigated their potential biological functions. In addition, we found that macrophage infiltration and abnormal alterations in the levels of inflammation-associated cytokines, such as IL-1ß, IL-6, and IL-10, in the peripheral blood may be closely associated with the development of ESCC.

Machine-learning-guided Directed Evolution for AAV Capsid Engineering.

Target gene delivery is crucial to gene therapy. Adeno-associated virus (AAV) has emerged as a primary gene therapy vector due to its broad host range, long-term expression, and low pathogenicity. However, AAV vectors have some limitations, such as immunogenicity and insufficient targeting. Designing or modifying capsids is a potential method of improving the efficacy of gene delivery, but hindered by weak biological basis of AAV, complexity of the capsids, and limitations of current screening methods. Artificial intelligence (AI), especially machine learning (ML), has great potential to accelerate and improve the optimization of capsid properties as well as decrease their development time and manufacturing costs. This review introduces the traditional methods of designing AAV capsids and the general steps of building a sequence-function ML model, highlights the applications of ML in the development workflow, and summarizes its advantages and challenges.