Propane-2-sulfonic acid octadec-9-enyl-amide, a novel PPARα/γ dual agonist, attenuates molecular pathological alterations in learning memory in AD mice.

OBJECTIVE: Previous studies have revealed that Propane-2-sulfonic acid octadec-9-enyl-amide(N15) exerts a protective role in the inflammatory response after ischemic stroke and in neuronal damage. However, little is known about N15 in Alzheimer's disease (AD). The aim of this study was to investigate the effects of N15 on AD and explore the underlying molecular mechanism. METHODS: AD mice model was established by lateral ventricular injection with Aß25-35. N15 was daily intraperitoneal administered for 28 days. Morris Water Maze was used to evaluate the neurocognitive function of the mice. The expression of PPARα/γ, brain-derived neurotrophic factor (BDNF), Neurotrophin-3 (NT3), ADAM10, PS1 and BACE1 were measured by qPCR. Aß amyloid in the hippocampus was measured by Congo red assay. Toluidine blue staining was used to detect the neuronal apoptosis. Protein levels of ADAM10, PS1 and BACE1 were determined using immunoblotting. RESULTS: N15 treatment significantly reduced neurocognitive dysfunction, which also significantly activated the expression of PPARα/γ at an optimal dose of 200 mg/kg. Administration of N15 alleviated the formation of Aß amyloid in the hippocampus of AD mice, enhanced the BDNF mRNA expression, decreased the mRNA and protein levels of PS1 and BACE1, upregulated ADAM10 mRNA and protein levels. CONCLUSION: N15 exerts its neuroprotective effects through the activation of PPARα/γ and may be a potential drug for the treatment of AD.

Early-life exercise induces immunometabolic epigenetic modification enhancing anti-inflammatory immunity in middle-aged male mice.

Exercise is usually regarded to have short-term beneficial effects on immune health. Here we show that early-life regular exercise exerts long-term beneficial effects on inflammatory immunity. Swimming training for 3 months in male mice starting from 1-month-old curbs cytokine response and mitigates sepsis when exposed to lipopolysaccharide challenge, even after an 11-month interval of detraining. Metabolomics analysis of serum and liver identifies pipecolic acid, a non-encoded amino acid, as a pivotal metabolite responding to early-life regular exercise. Importantly, pipecolic acid reduces inflammatory cytokines in bone marrow-derived macrophages and alleviates sepsis via inhibiting mTOR complex 1 signaling. Moreover, early-life exercise increases histone 3 lysine 4 trimethylation at the promoter of Crym in the liver, an enzyme responsible for catalyzing pipecolic acid production. Liver-specific knockdown of Crym in adult mice abolishes this early exercise-induced protective effects. Our findings demonstrate that early-life regular exercise enhances anti-inflammatory immunity during middle-aged phase in male mice via epigenetic immunometabolic modulation, in which hepatic pipecolic acid production has a pivotal function.

Empagliflozin in children with glycogen storage disease-associated inflammatory bowel disease: a prospective, single-arm, open-label clinical trial.

Glycogen storage disease type Ib (GSD-Ib) is a rare inborn error of glycogen metabolism caused by mutations in SLC37A4. Patients with GSD-Ib are at high risk of developing inflammatory bowel disease (IBD). We evaluated the efficacy of empagliflozin, a renal sodium‒glucose cotransporter protein 2 (SGLT2) inhibitor, on colonic mucosal healing in patients with GSD-associated IBD. A prospective, single-arm, open-label clinical trial enrolled eight patients with GSD-associated IBD from Guangdong Provincial People's Hospital in China from July 1, 2022 through December 31, 2023. Eight patients were enrolled with a mean age of 10.34 ± 2.61 years. Four male and four female. The endoscopic features included deep and large circular ulcers, inflammatory hyperplasia, obstruction and stenosis. The SES-CD score significantly decreased at week 48 compared with before empagliflozin. Six patients completed 48 weeks of empagliflozin therapy and endoscopy showed significant improvement or healing of mucosal ulcers, inflammatory hyperplasia, stenosis, and obstruction. One patient had severe sweating that required rehydration and developed a urinary tract infection. No serious or life-threatening adverse events. This study suggested that empagliflozin may promote colonic mucosal healing and reduce hyperplasia, stenosis, and obstruction in children with GSD-associated IBD.

Blockade of PI3K/AKT signaling pathway by Astragaloside IV attenuates ulcerative colitis via improving the intestinal epithelial barrier.

BACKGROUND: The specific pathogenesis of UC is still unclear, but it has been clear that defects in intestinal barrier function play an important role in it. There is a temporary lack of specific drugs for clinical treatment. Astragaloside IV (AS-IV) is one of the main active ingredients extracted from Astragalus root and is a common Chinese herbal medicine for the treatment of gastrointestinal diseases. This study aimed to determine whether AS-IV has therapeutic value for DSS or LPS-induced intestinal epithelial barrier dysfunction in vivo and in vitro and its potential molecular mechanisms. METHODS: The intestinal tissues from UC patients and colitis mice were collected, intestinal inflammation was observed by colonoscopy, and mucosal barrier function was measured by immunofluorescence staining. PI3K/AKT signaling pathway activator YS-49 and inhibitor LY-29 were administered to colitic mice to uncover the effect of this pathway on gut mucosal barrier modulation. Then, network pharmacology was used to screen Astragaloside IV (AS-IV), a core active component of the traditional Chinese medicine Astragalus membranaceus. The potential of AS-IV for intestinal barrier function repairment and UC treatment through blockade of the PI3K/AKT pathway was further confirmed by histopathological staining, FITC-dextran, transmission electron microscopy, ELISA, immunofluorescence, qRT-PCR, and western blotting. Finally, 16 S rRNA sequencing was performed to uncover whether AS-IV can ameliorate UC by regulating gut microbiota homeostasis. RESULTS: Mucosal barrier function was significantly damaged in UC patients and murine colitis, and the activated PI3K/AKT signaling pathway was extensively involved. Both in vivo and vitro showed that the AS-IV-treated group significantly relieved inflammation and improved intestinal epithelial permeability by inhibiting the activation of the PI3K/AKT signaling pathway. In addition, microbiome data found that gut microbiota participates in AS-IV-mediated intestinal barrier recovery as well. CONCLUSIONS: Our study highlights that AS-IV exerts a protective effect on the integrality of the mucosal barrier in UC based on the PI3K/AKT pathway, and AS-IV may serve as a novel AKT inhibitor to provide a potential therapy for UC.

Modified endoscopic retrograde appendicitis therapy vs. laparoscopic appendectomy for uncomplicated acute appendicitis in children.

OBJECTIVES: Modified endoscopic retrograde appendicitis therapy (mERAT) has been proposed as an alternative to laparoscopic appendectomy for the treatment of appendicitis. However, data from children in large samples are lacking. The aim of this article is to evaluate the efficacy between mERAT and laparoscopic appendectomy (LA) in children with uncomplicated appendicitis. METHOD: We retrospectively analyzed 594 patients with suspected uncomplicated appendicitis from October 2018 to May 2021. A pool of 294 consecutive patients who met the inclusion criteria were ultimately enrolled in this study (228 and 66 patients in mERAT and LA, respectively). Given the differences in baseline clinical data (gender, age), the regression equation including differences in clinical baseline, grouping factor, and white blood cell count was established to address the influence of potential confounding factors. RESULT: The initial success rate of mERAT management was 96.9%, and the recurrence rate was 6.9% in the mERAT group and 1.7% in the LA group within 1 year, which was no significant difference. But the mERAT group had a lower rate of adverse events. Finally, those results indicated that the treatment modalities, LA or mERAT, had no significant effect on initial success rate (P = 0.99) or recurrence rate (P = 0.17) within 1 year, but a significant effect on the adverse events rate during hospitalization (P = 0.01) in the multivariate regression analysis. CONCLUSION: Among children with uncomplicated appendicitis, an initial mERAT management strategy had a success rate of 96.9%, which was similar to the LA group at 1 year. This follow-up supports the feasibility of mERAT alone as an alternative to surgery for uncomplicated appendicitis.

11-deoxycortisol positively correlates with T cell immune traits in physiological conditions.

BACKGROUND: Endogenous steroid hormones have significant effects on inflammatory and immune processes, but the immunological activities of steroidogenesis precursors remain largely unexplored. METHODS: We conducted a systematic approach to examine the association between steroid hormones profile and immune traits in a cohort of 534 healthy volunteers. Serum concentrations of steroid hormones and their precursors (cortisol, progesterone, testosterone, androstenedione, 11-deoxycortisol and 17-OH progesterone) were determined by liquid chromatography-tandem mass spectrometry. Immune traits were evaluated by quantifying cellular composition of the circulating immune system and ex vivo cytokine responses elicited by major human pathogens and microbial ligands. An independent cohort of 321 individuals was used for validation, followed by in vitro validation experiments. FINDINGS: We observed a positive association between 11-deoxycortisol and lymphoid cellular subsets numbers and function (especially IL-17 response). The association with lymphoid cellularity was validated in an independent validation cohort. In vitro experiments showed that, as compared to androstenedione and 17-OH progesterone, 11-deoxycortisol promoted T cell proliferation and Candida-induced Th17 polarization at physiologically relevant concentrations. Functionally, 11-deoxycortisol-treated T cells displayed a more activated phenotype (PD-L1high CD25high CD62Llow CD127low) in response to CD3/CD28 co-stimulation, and downregulated expression of T-bet nuclear transcription factor. INTERPRETATION: Our findings suggest a positive association between 11-deoxycortisol and T-cell function under physiological conditions. Further investigation is needed to explore the potential mechanisms and clinical implications. FUNDING: Found in acknowledgements.

Single-center experience of transitioning from video-assisted laparoscopic to robotic Heller myotomy with Dor fundoplication for esophageal motility disorders.

BACKGROUND: Video-assisted laparoscopic Heller myotomy (LHM) has become the standard treatment option for achalasia. While robotic surgery offering some specific advantages such as better three-dimensional (3D) stereoscopic vision, hand-eye consistency, and flexibility and stability with the endowrist is expected to be shorter in learning curve than that of LHM for surgeons who are proficient in LHM. The aim of this study was to describe a single surgeon's experience related to the transition from video-assisted laparoscopic to robotic Heller myotomy with Dor fundoplication. METHODS: We conducted a retrospective observational study based on the recorded data of the first 66 Heller myotomy performed with laparoscopic Heller myotomy with Dor fundoplication (LHMD, 26 cases) and with the robotic Heller myotomy with Dor fundoplication (RHMD, 40 cases) by the same surgeon in Department of Thoracic Surgery of The First Affiliated Hospital of Nanchang University in China. The operation time and intraoperative blood loss were analyzed using the cumulative sum (CUSUM) method. Corresponding statistical tests were used to compare outcomes of both serials of cases. RESULTS: The median operation time was shorter in the RHMD group compared to the LHMD group (130 [IQR 123-141] minutes vs. 163 [IQR 153-169]) minutes, p < 0.001). In the RHMD group, one patient (2.5%) experienced mucosal perforation, whereas, in the LHMD group, the incidence of this complication was significantly higher at 19.2% (5 patients) (p = 0.031). Based on cumulative sum analyses, operation time decreased starting with case 20 in the LHMD group and with case 18 in the RHMD group. Intraoperative blood loss tended to decline starting with case 19 in the LHMD group and with case 16 in the RHMD group. CONCLUSIONS: Both RHMD and LHMD are effective surgical procedures for symptom relief of achalasia patients. RHMD demonstrates superior outcomes in terms of operation time and mucosal perforation during surgery compared to LHMD. Proficiency with RHMD can be achieved after approximately 16-18 cases, while that of LHMD can be obtained after around 19-20 cases.

Subcellular compartmentalization in the biosynthesis and engineering of plant natural products.

Plant natural products (PNPs) are specialized metabolites with diverse bioactivities. They are extensively used in the pharmaceutical, cosmeceutical and food industries. PNPs are synthesized in plant cells by enzymes that are distributed in different subcellular compartments with unique microenvironments, such as ions, co-factors and substrates. Plant metabolic engineering is an emerging and promising approach for the sustainable production of PNPs, for which the knowledge of the subcellular compartmentalization of their biosynthesis is instrumental. In this review we describe the state of the art on the role of subcellular compartments in the biosynthesis of major types of PNPs, including terpenoids, phenylpropanoids, alkaloids and glucosinolates, and highlight the efforts to target biosynthetic pathways to subcellular compartments in plants. In addition, we will discuss the challenges and strategies in the field of plant synthetic biology and subcellular engineering. We expect that newly developed methods and tools, together with the knowledge gained from the microbial chassis, will greatly advance plant metabolic engineering.

Data-driven subgroups of newly diagnosed type 2 diabetes and the relationship with cardiovascular diseases at genetic and clinical levels in Chinese adults.

BACKGROUND: To subgroup Chinese patients with newly diagnosed type 2 diabetes (T2D) by K-means cluster analysis on clinical indicators, and to explore whether these subgroups represent different genetic features and calculated cardiovascular risks. METHODS: The K-means clustering analysis was performed on two cohorts (n = 590 and 392), both consisting of Chinese participants with newly diagnosed T2D. To assess genetic risks, multiple polygenic risk scores (PRSs) and mitochondrial DNA copy numbers (mtDNA-CN) were calculated for all participants. Furthermore, Framingham risk scores (FRS) of cardiovascular diseases in two cohorts were also calculated to verify the genetic risks. RESULTS: Four clusters were identified including the mild age-related diabetes (MARD)(35.08%), mild obesity-related diabetes (MOD) (34.41%), severe autoimmune diabetes (SAID) 19.15%, and severe insulin-resistant diabetes (SIRD) 11.36% subgroups in the MARCH (metformin, and acarbose in Chinese patients as the initial hypoglycemic treatment) cohort. There was a significant difference in PRS for cardiovascular diseases (CVD) across four subgroups in the MARCH cohort (p < 0.05). Compared with the SIDD and SIRD subgroups, patients in the MOD subgroup had a relatively lower PRS for CVD (p < 0.05) in the MARCH cohort. Females had a higher PRS compared to males, with no significant difference in FRS across the four clusters. The MOD subgroup had a significantly lower FRS which was consistent with the results of PRS. Similar results of PRS and FRS were also replicated in the CONFIDENCE (comparison of glycemic control and b-cell function among newly diagnosed patients with type 2 diabetes treated with exenatide, insulin or pioglitazone) cohort. CONCLUSION: There are different CVD risks in diabetic subgroups based on clinical and genetic evidence which may promote precision medicine.

Enhancing High-Temperature Energy Storage Performance of PEI-Based Dielectrics by Incorporating ZIF-67 with a Narrow Bandgap.

Polymer dielectrics are crucial for use in electrostatic capacitors, owing to their high voltage resistance, high energy storage density, and ultrahigh reliability. Furthermore, high-temperature-resistant polymer dielectrics are applied in various emerging fields. Herein, poly(ether imide) (PEI)-based polymer dielectrics prepared by adding a low loading of dimethylimidazolium cobalt (ZIF-67) with a narrow bandgaps are investigated. The results show that the composites exhibit considerably increased Young's modulus, suppressed conductivity loss, and improved breakdown strength compared with pure PEI. Consequently, a stable energy storage performance is realized for ZIF-67/PEI composites. Particularly, at 150 °C, 1 wt % ZIF-67/PEI composite affords an excellent energy storage density of 4.59 J/cm3 with a discharge energy efficiency of 80.6%, exhibiting a considerable increase compared with the values obtained for PEI (2.58 J/cm3 with a discharge energy efficiency of 68.8%). The results of this study reveal a feasible pathway to design polymer dielectrics with the potential for use in capacitive applications in harsh environments.

The causal effects of leisure screen time on irritable bowel syndrome risk from a Mendelian randomization study.

Associations between leisure sedentary behavior (especially leisure screen time, LST) and irritable bowel syndrome (IBS) have been reported, but causality is unclear. Here, the two-sample Mendelian randomization was performed to investigate the causal association between LST and IBS. Two recently published genome-wide association studies (GWASs) including a total of 1,190,502 people from Europe were used as our data source. Inverse variance weighting (OR = 1.120, 95% CI 1.029-1.219) and weighted median (OR = 1.112, 95% CI 1.000-1.236) analyses revealed a causal effect between LST and IBS. There was no evidence of pleiotropy in the sensitive analysis (MR-Egger, p = 0.139). After removing potentially confounding single nucleotide polymorphisms (SNPs), similar results were found using inverse variance weighting (OR = 1.131, 95% CI 1.025-1.248) and weighted median (OR = 1.151, 95% CI 1.020-1.299), as well as in the validation analyses using inverse variance weighting (OR = 1.287, 95% CI 0.996-1.662). This study provided support for a possible causal relationship between leisure screen time and IBS.

Bryostatin-1: a promising compound for neurological disorders.

The central nervous system (CNS) is the most complex system in human body, and there is often a lack of effective treatment strategies for the disorders related with CNS. Natural compounds with multiple pharmacological activities may offer better options because they have broad cellular targets and potentially produce synergic and integrative effects. Bryostatin-1 is one of such promising compounds, a macrolide separated from marine invertebrates. Bryostatin-1 has been shown to produce various biological activities through binding with protein kinase C (PKC). In this review, we mainly summarize the pharmacological effects of bryostatin-1 in the treatment of multiple neurological diseases in preclinical studies and clinical trials. Bryostatin-1 is shown to have great therapeutic potential for Alzheimer's disease, multiple sclerosis, fragile X syndrome, stroke, traumatic brain injury, and depression. It exhibits significant rescuing effects on the deficits of spatial learning, cognitive function, memory and other neurological functions caused by diseases, producing good neuroprotective effects. The promising neuropharmacological activities of bryostatin-1 suggest that it is a potential candidate for the treatment of related neurological disorders although there are still some issues needed to be addressed before its application in clinic.

Improvement of straw decomposition and rice growth through co-application of straw-decomposing inoculants and ammonium nitrogen fertilizer.

BACKGROUND: The growth of rice is reduced by the slow decomposition of accumulated straw, which competes with rice for soil nitrogen nutrient. In recent year, straw-decomposing inoculants (SDIs) that can accelerate straw decomposition and ammonium nitrogen (N) fertilizer that can quickly generate available N is increasingly adopted in China. However, it is still unknown whether the N demand of straw decomposition and crop growth can be simultaneously met through the co-application of SDIs and ammonium N fertilizer. RESULTS: In this study, we investigated the effect of the co-application of SDIs and ammonium bicarbonate on decomposition rate of wheat straw, rice growth and rice yield over two consecutive years in rice-wheat rotation system. Compound fertilizer (A0) was used as control. The ratios of ammonium bicarbonate addition were 20% (A2), 30% (A3) and 40% (A4), respectively, without SDIs or with SDIs (IA2, IA3, IA4). Our results revealed that without SDIs, compared with A0, straw decomposition rate, rice growth and yield were improved under A2; However, under A3, rice yield was decreased due to the slow decomposition rate of straw and limited growth of rice during late growth stage. Combining SDIs and N fertilizer increased straw decomposition rate, rice growth rate and yield more than that of N fertilizer alone, especially under IA3. Compared with A0, straw decomposition rate, tiller number, aboveground biomass, leaf area index, root length, and nitrogen use efficiency were significantly increased by 16%, 8%, 27%, 12%, 17%, and 15% under IA3. Consequently, the average rice yield of IA3 was increased to 10,856 kg/ha, which was 13% and 9% higher, respectively, than of A0 and A2. CONCLUSION: Our results indicated that ammonium bicarbonate application alone carried a risk of nutrient deficiency during late growth stage and yield decline. Therefore, the co-application of SDIs and 30% ammonium N fertilizer substitution can be a favorable practice to simultaneously accelerate straw decomposition and increase rice crop growth.

Development and validation of the patient reported outcomes questionnaire of children with asthma in China: A Caregiver's proxy-reported measure.

Background: Research on asthma control levels and quality of life is essential for children with asthma during their growth stage. Therefore, it is necessary to develop a questionnaire that can be used for monitoring and evaluating the disease control effectiveness and quality of life of children with asthma in China and to conduct a preliminary evaluation for its reliability, validity, and discriminative ability. Methods: The questionnaire was created through a literature review and qualitative interviews for a targeted population. Based on the previous work, 30 caregivers of children with asthma and 5 experienced pediatricians reviewed and discussed a collection of items. Then, 72 items were screened and selected to form the draft questionnaire. After three rounds of investigation (with 240, 503, and 360 participants, respectively), the final questionnaire was established according to the evaluation results. The structure of the questionnaire was explored through confirmatory factor analysis. Exploratory factor analysis and variability analysis were applied based on the first two rounds of investigation. Reliability, construct validity, and discriminative ability were evaluated based on the third round of investigation. Results: The questionnaire contains 6 dimensions and 34 items, and the total cumulative variance contribution rate was 54.96%; Cronbach's α coefficient was 0.91; the split-half reliability coefficient was 0.75, and the test-retest reliability coefficient was 0.74. The children's age, gender, residence, asthma attack in the last three months, caregivers' education background, and monthly income per caregiver were correlated with patient-reported outcomes of children with asthma. Conclusion: The questionnaire appeared to have good reliability, construct validity, and discriminative ability in children with asthma in China.

A 1.1 Mb duplication CNV on chromosome 17 contributes to skeletal muscle development in Boer goats.

The Boer goat is one of the top meat breeds in modern animal husbandry and has attracted widespread attention for its unique growth performance. However, the genetic basis of muscle development in the Boer goat remains obscure. In this study, we identified specific structural variants in the Boer goat based on genome-wide selection signals and analyzed the basis of the molecular heredity of related candidate genes in muscle development. A total of 9 959 autosomal copy number variations (CNVs) were identified through selection signal analysis in 127 goat genomes. Specifically, we confirmed that the highest signal CNV (HSV) was a chromosomal arrangement containing an approximately 1.11 Mb (CHIR17: 60062304-61171840 bp) duplicated fragment inserted in reverse orientation and a 5 362 bp deleted region (CHIR17:60145940-60151302 bp) with overlapping genes (e.g., ARHGAP10, NR3C2, EDNRA, PRMT9, and TMEM184C). The homozygous duplicated HSV genotype (+/+) was found in 96% of Boer goats but was not detected in Eurasian goats and was only detected in 4% of indigenous African goats. The expression network of three candidate genes ( ARHGAP10, NR3C2, and EDNRA) regulating dose transcription was constructed by RNA sequencing. Results indicated that these genes were involved in the proliferation and differentiation of skeletal muscle satellite cells (SMSCs) and their overexpression significantly increased the expression of SAA3. The HSV of the Boer goat contributed to superior skeletal muscle growth via the dose effects of overlapping genes.

Active kisspeptin DNA vaccines oral immunization disrupt mRNA hormone receptors expression in ram lambs.

To evaluate the efficacy of oral immunization with active kisspeptin DNA vaccine on the expression of hormone receptor mRNA. For this study, ten 56-day-old Hu breed ram lambs were randomly assigned to the treatment and control groups (n = 5). Treatment Experimental group received C500/pKS-asd and the control group received C500/pVAX-asd (aspartate-ß semialdehyde dehydrogenase orally on days 0, 28, and 56, and blood samples were taken at each immunization interval (14-day) and tissues samples were collected at the end of the experimental period (day 98). The collected samples were stored in the refrigerator at -20 °C and liquid nitrogen, respectively, for laboratory examination. Total RNA was extracted from samples using TRIzol reagent and quantitative real-time polymerase chain reaction (QPCR) was used to quantify the levels of KISS1, G protein-coupled receptor-54 (Kiss1r), and gonadotrophin-releasing hormone (GnRH) mRNA in the hypothalamus. Levels of luteinizing hormone receptor (LHR) and luteinizing hormone beta (LHß) mRNA, and follicle-stimulating hormone receptor (FSHR) and follicle-stimulating hormone beta (FSHß) mRNA in the testes and pituitary were analyzed, respectively. Further, gonadotropin-releasing hormone receptor (GnRHR) mRNA expression level in the pituitary was measured. Moreover, the Kiss1r concentration level in the blood was measured using an indirect ELISA. The concentration of Kiss1r in the blood was lower in the treatment group than in the control group (p < 0.05). The levels of testicular FSHR and LHR mRNA were significantly lower in the treatment group (p < 0.05) when compared to the control group. Furthermore, the treatment group's levels of hypothalamic KISS1, Kiss1r, and GnRH mRNA were significantly lower (p < 0.05) than the controls. LH, FSH, and GnRHR mRNA expression in the pituitary were also significantly lower in the treatment group (p < 0.01 and p < 0.05, respectively). These findings imply that oral immunization with active kisspeptin DNA vaccine suppresses hormone receptor mRNA expression in the ram lambs.

Ultra-slim flexible bronchoscopy-guided topical hemostatic drugs administration for the management of life-threatening refractory pulmonary hemorrhage in a preterm infant: Case report.

Pulmonary hemorrhage (PH) is a rare acute catastrophic event with high mortality among neonates, especially preterm infants. Primary treatments included pulmonary surfactant, high-frequency oscillatory ventilation, epinephrine, coagulopathy management, and intermittent positive pressure ventilation. However, there are still challenges in diagnosing and treating refractory or focal pulmonary hemorrhages. Ultra-slim bronchoscopy has been widely used in the field of critically ill children and is increasingly being done in neonates with critical respiratory disease in recent years. In this study, we report a case with refractory pulmonary hemorrhage in premature infants, which was finally diagnosed as localized hemorrhage in the upper left lobe and cured by ultra-slim bronchoscopy-guided topical hemostatic drug administration. Bronchoscopy is an optional, safe, and practicable technique for early diagnosis and direct injection therapy of neonatal PH in managing life-threatening PH.

Estimating and validating the structure of feeding behavior networks.

PURPOSE: Network analysis has been widely used in psychometrics over the past decade, yet it is unknown that whether this methodology could be applied in the field of child health assessment such as caregivers' feeding behavior and child eating behavior. Our study leveraged network psychometrics method to estimating and examining the network structure of Chinese Preschoolers' Caregivers' Feeding Behavior Scale (CPCFBS), and compared the applicability of network methods in the feeding behavior scale. METHODS: The CPCFBS was previously applied in a sample of 768 preschoolers' caregivers, used to estimate the structure of feeding behavior networks. Network structure was estimated with Gaussian Graphical Model. Dimensionality was detected using Exploratory Graph Analysis (EGA). The network structural consistency was tested using EGA bootstrap. The network structure was compared with the original structure using model fit indices and reliability. RESULTS: A seven-dimensional EGA network was explored after rearranging four items and deleting one item with unstable structural consistency. The absolute fit and relative fit of EGA structure were better than the original structure. The EGA structure had nearly same values of the reliability with the original structure. CONCLUSION: Our study presented a novel perspective for feeding behavior analytical strategies, and demonstrated that network analysis was applicable and superior in exploring the structure of feeding behavior scales. LEVEL OF EVIDENCE: Level V, cross-sectional descriptive study.

SDN: Semantic Decoupling Network for Temporal Language Grounding.

Temporal language grounding (TLG) is one of the most challenging cross-modal video understanding tasks, which aims at retrieving the most relevant video segment from an untrimmed video according to a natural language sentence. The existing methods can be separated into two dominant types: 1) proposal-based and 2) proposal-free methods, where the former conduct contextual interactions and the latter localizes timestamps flexibly. However, the constant-scale candidates in proposal-based methods limit the localization precision and bring extra computational costs. In contrast, the proposal-free methods perform well on high-precision metrics-based on the fine-grained features but suffer from a lack of coarse-grained interactions, which cause degeneration when the video becomes complex. In this article, we propose a novel framework termed semantic decoupling network (SDN) that combines the advantages of proposal-based and proposal-free methods and overcomes their defects. It contains three key components: 1) semantic decoupling module (SDM); 2) context modeling block (CMB); and 3) semantic cross-level aggregation module (SCAM). By capturing the video-text contexts in multilevel semantics, the SDM and CMB effectively utilize the benefits of proposal-based methods. Meanwhile, the SCAM maintains the merit of proposal-free methods in that it localizes timestamps precisely. The experiments on three challenge datasets, i.e., Charades-STA, TACoS, and ActivityNet-Caption, show that our proposed SDN method significantly outperforms recent state-of-the-art methods, especially the proposal-free methods. Extensive analyses, as well as the implementation code of the proposed SDN method, are provided at https://github.com/CFM-MSG/Code_SDN.

Treatment of aggressive T-cell lymphoma/leukemia with anti-CD4 CAR T cells.

T-cell lymphomas are aggressive lymphomas that often resist current therapy options or present with relapsed disease, making the development of more effective treatment regimens clinically important. Previously, we have shown that CD4 CAR can effectively target T-cell malignancies in preclinical studies. As IL-15 has been shown to strengthen the anti-tumor response, we have modified CD4 CAR to secrete an IL-15/IL-15sushi complex. These CD4-IL15/IL15sushi CAR T cells and NK92 cells efficiently eliminated CD4+ leukemic cell lines in co-culture assays. Additionally, CD4-IL15/IL15sushi CAR out-performed CD4 CAR in in vivo models, demonstrating a benefit to IL-15/IL-15sushi inclusion. In a Phase I clinical trial, CD4-IL15/IL15sushi CAR T cells were tested for safety in three patients with different T-cell lymphomas. Infusion of CD4-IL15/IL15sushi CAR T cells was well-tolerated by the patients without significant adverse effects and led to the remission of their lymphomas. Additionally, infusion led to the depletion of CD4+ Treg cells and expansion of CD3+CD8+ T cells and NK cells. These results suggest that CD4-IL15/IL15sushi CAR T cells may be a safe and effective treatment for patients with relapsed or refractory T-cell lymphomas, where new treatment options are needed.