Clinical Analysis of 76 Cases of Second Branchial Cleft Fistula.

Objective: To provide the experience of diagnosis and treatment of second branchial cleft fistula in children. Methods: The clinical data of 76 children with second branchial cleft fistulas admitted to Beijing Children's Hospital affiliated with Capital Medical University from January 2016 to December 2020 were retrospectively analyzed. All patients underwent cervical ultrasonography and resection of the second branchial cleft fistula, and their clinical manifestations, surgical methods, complications, recurrence condition, and lesion appearance of the patients were analyzed. Results: Among the 76 cases, the lesions of 43 cases were on the right side, 20 were on the left side, and 13 were bilateral, for a total of 89 lesions. There were 49 type I lesions, 28 type II lesions, 8 type III lesions, and 4 type IV lesions. Type I and type II cases underwent complete excision of the fistula through a small incision in the neck; 2 cases of type III branchial cleft fistulas were treated with trapezoidal incision; 2 cases of type III branchial cleft fistulas underwent single transverse incisions; single small incision-assisted endoscopic resection was adopted in 4 cases of type III and 4 cases of type IV branchial cleft fistulas. During the follow-up period of 6 to 60 months, only 3 cases developed postoperative infection, the others had no postoperative complications, and no cases had recurrence during postoperative follow-up. Conclusion: The incision of the second branchial fistula should be selected according to imaging examination to achieve removal of the fistula while maintaining esthetics.

Safety of Continuing Aspirin Use in Patients With Coronary Heart Disease Who Undergo Thyroid Surgery During the Perioperative Period.

Objective: To investigate the safety of continuing aspirin use in patients with coronary heart disease undergoing thyroid surgery during the perioperative period. Methods: Forty-four patients with coronary heart disease who underwent thyroid surgery in our department from July 2019 to June 2023 were selected as the observation group, and the observation group continued to use aspirin during the perioperative period. Forty-four patients who underwent the same surgery during the same period without coronary heart disease and without anticoagulant or antiplatelet therapy were selected as control group 1. Another 44 patients with coronary heart disease who underwent the same surgery from August 2015 to June 2019 and used low molecular weight heparin bridging during the perioperative period were selected as control group 2. Clinical data from the 3 groups of patients were collected for retrospective analysis. Results: The age and proportion of male patients in the observation group and control group 2 were higher than those in control group 1, and the total hospital stay in control group 2 was longer than in the observation group and control group 1, with statistically significant differences (all P < .05). There were no statistically significant differences in surgical time, intraoperative blood loss, postoperative drainage volume, duration of drainage tube retention, postoperative hospital stay, and perioperative hemoglobin, platelet, and international normalized ratio between the 3 groups of patients (all P > .05). All patients in the 3 groups successfully completed surgery without serious complications or death during the perioperative period. Conclusion: Continuing to use aspirin in patients with coronary heart disease who undergo thyroid surgery during the perioperative period can safely complete surgery without increasing the risk of intraoperative and postoperative bleeding.

NLRP3 Inflammasome Activation During Acute Negative Pressure Injury in the Middle Ear of Mice.

HYPOTHESIS: The present study was conducted to explore the role of the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome in mouse otic barotrauma models. BACKGROUND: Previous studies suggest that the NLRP3 inflammasome plays an important role in the pathogenesis of middle ear disease. However, whether middle ear negative pressure injury underlies NLRP3 inflammasome activation remains unclear. METHODS: Wild-type and Nlrp3 -/- mice were randomly assigned to control and pressure injury groups, respectively. Pressure loading was performed using a pressure cabin with the pressure level set to 20 kPa higher than that of the ambient atmosphere. This was achieved in approximately 15 seconds and maintained for 10 minutes. Hematoxylin and eosin staining was performed to detect morphological changes of the middle ear mucosa, tissue IL-1ß was measured via an enzyme-linked immunosorbent assay, and cleaved caspase-1 was detected by Western blot. RESULTS: We found that the maturation of caspase-1 and IL-1ß production in the middle ear significantly increased after otic barotrauma. In Nlrp3 -/- mice, inflammasome activation is downregulated and mucosal hyperplasia is reduced compared with those of wild-type mice during recovery. CONCLUSION: The NLRP3 inflammasome likely plays an important role in the pathogenesis of otic barotrauma. Controlling activation of the NLRP3 inflammasome may promote middle ear recovery after negative pressure injury.

[Long-term auditory monitoring in children with Alport syndrome based on different degrees of renal injury].

Objective:To investigate long-term auditory changes and characteristics of Alport syndrome（AS） patients with different degrees of renal injury. Methods:Retrospectively analyzing clinical data of patients diagnosed AS from January 2007 to September 2022, including renal pathology, genetic detection and hearing examination. A long-term follow-up focusing on hearing and renal function was conducted. Results:This study included 70 AS patients, of which 33（25 males, 8 females, aged 3.4-27.8 years） were followed up, resulting in a loss rate of 52.9%.The follow-up period ranged from 1.1to 15.8 years, with 16 patients followed-up for over 10 years. During the follow-up, 10 patients presenting with hearing abnormalities at the time of diagnosis of AS had progressive hearing loss, and 3 patients with new hearing abnormalities were followed up, which appeared at 5-6 years of disease course. All of which were sensorineural deafness. While only 3 patients with hearing abnormalities among 13 patients received hearing aid intervention. Of these patients,7 developed end-stage renal disease（ESRD）, predominantly males （6/7）. The rate of long-term hearing loss was significantly different between ESRD group and non-ESRD group（P=0.013）. There was no correlation between the progression of renal disease and long-term hearing level（P>0.05）. kidney biopsies from 28 patients revealed varying degrees of podocyte lesion and uneven thickness of basement membrane. The severity of podocyte lesion was correlated with the rate of long-term hearing loss（P=0.048）, and there was no correlation with the severity of hearing loss（P>0.05）. Among 11 cases, theCOL4A5mutationwas most common （8 out of 11）, but there was no significant correlation between the mutation type and hearing phenotype（P>0.05）. Conclusion:AS patients exhibit progressive hearing loss with significant heterogeneity over the long-term.. THearing loss is more likely to occur 5-6 years into the disease course. Hearing abnormalities are closely related to renal disease status, kidney tissue pathology, and gene mutations, emphasizing the need for vigilant long-term hearing follow-up and early intervention.

Pediatric spindle cell/sclerosing rhabdomyosarcoma with FUS-TFCP2 fusion: a case report and literature review.

Background: FUS-TFCP2 gene fusion is a recently identified and highly distinct molecular subtype of spindle cell/sclerosing rhabdomyosarcoma (RMS), with fewer than 40 cases being reported to date. Due to its low incidence, clinical studies on this subtype are limited. Here, we report a new case of this rare entity to describe and summarize its unique clinical characteristics and treatment process, aiming to emphasize the importance of molecular testing for spindle cell/sclerosing RMS and increase the understanding of this subtype. By summarizing and comparing with previous reports on RMS with the EWSR1/FUS-TFCP2 fusion mutation, we hope to make some new hints for its management. Case Description: In this report, we describe a rare case of spindle cell/sclerosing RMS in a 13-year-old boy, who had a massive destructive lesion involving the mandible. Next-generation sequencing of tumor tissue revealing a FUS-TFCP2 fusion. The tumor was extremely aggressive and showed resistance to polychemotherapy, after 4 cycles of multi drug combined chemotherapy, the primary tumor still continued to grow, and suspicious chest metastasis occurred. Even after aggressive total resection of the primary tumor and postoperative chemotherapy, systemic metastasis to the vertebra and chest could not be prevented yet, ultimately with a fatal outcome within 6 months. We additionally summarize 37 cases of RMS with the EWSR1/FUS-TFCP2 fusion mutation reported in the literature. This subtype was found to be almost exclusively primary in bone and histologically showed a common origin of epithelium and muscle. The high aggressiveness made the conventional standard chemoradiotherapy ineffective. Because most tumors of this subtype express ALK protein, ALK inhibitors seem to be a new target for its therapy. Conclusions: Spindle cell/sclerosing RMS with FUS-TFCP2 fusion has its unique clinical characteristics and progression. It shows a marked skeletal predilection and an aggressive clinical course, typically resistant to traditional standard treatments for RMS. Therefore, molecular detection is crucial in managing this subtype. Once the diagnosis is clear, a more aggressive treatment plan is needed. In addition, almost all cases were found to have a positive expression of ALK. So ALK inhibitors can be a choice of targeted therapy.

Research progress of Paris polyphylla in the treatment of digestive tract cancers.

Cancer has become one of the most important causes of human death. In particular, the 5 year survival rate of patients with digestive tract cancer is low. Although chemotherapy drugs have a certain efficacy, they are highly toxic and prone to chemotherapy resistance. With the advancement of antitumor research, many natural drugs have gradually entered basic clinical research. They have low toxicity, few adverse reactions, and play an important synergistic role in the combined targeted therapy of radiotherapy and chemotherapy. A large number of studies have shown that the active components of Paris polyphylla (PPA), a common natural medicinal plant, can play an antitumor role in a variety of digestive tract cancers. In this paper, the main components of PPA such as polyphyllin, C21 steroids, sterols, and flavonoids, amongst others, are introduced, and the mechanisms of action and research progress of PPA and its active components in the treatment of various digestive tract cancers are reviewed and summarized. The main components of PPA have been thoroughly explored to provide more detailed references and innovative ideas for the further development and utilization of similar natural antitumor drugs.

Pediatric obstructive sleep apnea diagnosis: leveraging machine learning with linear discriminant analysis.

Objective: The objective of this study was to investigate the effectiveness of a machine learning algorithm in diagnosing OSA in children based on clinical features that can be obtained in nonnocturnal and nonmedical environments. Patients and methods: This study was conducted at Beijing Children's Hospital from April 2018 to October 2019. The participants in this study were 2464 children aged 3-18 suspected of having OSA who underwent clinical data collection and polysomnography(PSG). Participants' data were randomly divided into a training set and a testing set at a ratio of 8:2. The elastic net algorithm was used for feature selection to simplify the model. Stratified 10-fold cross-validation was repeated five times to ensure the robustness of the results. Results: Feature selection using Elastic Net resulted in 47 features for AHI ≥5 and 31 features for AHI ≥10 being retained. The machine learning model using these selected features achieved an average AUC of 0.73 for AHI ≥5 and 0.78 for AHI ≥10 when tested externally, outperforming models based on PSG questionnaire features. Linear Discriminant Analysis using the selected features identified OSA with a sensitivity of 44% and specificity of 90%, providing a feasible clinical alternative to PSG for stratifying OSA severity. Conclusions: This study shows that a machine learning model based on children's clinical features effectively identifies OSA in children. Establishing a machine learning screening model based on the clinical features of the target population may be a feasible clinical alternative to nocturnal OSA sleep diagnosis.

Characteristics of ADHD Symptoms and EEG Theta/Beta Ratio in Children With Sleep Disordered Breathing.

Objectives. This study aimed to explore parent-reported symptoms of attention deficit-hyperactivity disorder (ADHD) and sleep electroencephalogram (EEG) theta/beta ratio (TBR) characteristics in children with sleep disordered breathing (SDB). Methods. The parents of children (aged 6-11 years) with SDB (n = 103) and healthy controls (n = 28) completed the SNAP-IV questionnaire, and children underwent overnight polysomnography. Children with SDB were grouped according to obstructive apnea/hypopnea index: primary snoring, mild, and moderate-severe obstructive sleep apnea (OSA) groups. The TBR in non-rapid eye movement (NREM) periods in three sleep cycles was analyzed. Results. Children with SDB showed worse ADHD symptoms compared with the healthy control. There was no intergroup difference in TBR. The time-related decline in TBR observed in the control, primary snoring and mild OSA groups, which was not observed in the moderate-severe OSA group. Overnight transcutaneous oxygen saturation was negatively associated with the hyperactivity/impulsivity score of ADHD symptom. The global TBR during the NREM period in the first sleep cycle was positively correlated with inattention score. Conclusion. Children with SDB showed more ADHD inattention symptoms than the healthy control. Although we found no difference in TBR among groups, we found significant main effect for NREM period. There existed a relationship between hypoxia, TBR, and scores of ADHD symptoms. Hence, it was speculated that TBR can reflect the nocturnal electrophysiological manifestations in children with SDB, which may be related to daytime ADHD symptoms.

Treatment of nasolabial fold rhabdomyosarcoma in children: A single-institution experience.

OBJECTIVES: To summarize the clinical characteristics and prognosis of children with nasolabial fold rhabdomyosarcoma (RMS). METHODS: Retrospective review of children treated for nasolabial fold RMS from January 2014 to September 2019. RESULTS: Of 21 patients with nasolabial fold RMS, 90.48% were alveolar subtype, in which PAX3/7-FOXO1 fusion positive accounted for 87.5%. Ten patients (47.62%) had nodals invasion. Almost all patients received comprehensive treatment (chemotherapy [100%], radiation therapy [100%], and surgery [95.24%]). The median follow-up time was 34.3 months. The 3-year overall survival (OS) and event-free survival (EFS) was 67.7% ± 14.1% and 42.1% ± 13.5%, respectively. Four patients had regional lymph node relapse (NR), all in the ipsilateral submandibular lymph node region. CONCLUSION: Majority of the patients with RMS in the nasolabial fold area were alveolar subtype and had positive PAX3/7-FOXO1 gene fusion. In addition, the nasolabial fold RMS had a high probability of regional lymph node metastasis in the submandibular area. To maintain the facial aesthetics and functions, the surgical area for nasolabial fold RMS is often very conservative and restricted. This could be one of the contributors for the poor prognosis of nasolabial fold RMS beside its worse pathological subtype and gene fusion.

Animal study: Basic mechanism of vocal cord paralysis caused by button battery ingestion in children.

PURPOSE: Vocal cord paralysis has been reported as a common complication of button battery (BB) ingestion, and there is a need to confirm the mechanism of vocal cord paralysis for the development of a standardized treatment. METHODS: A new CR2032 BB and artificial saliva were placed in a fresh pig esophagus with the recurrent laryngeal nerve (RLN); the negative electrode faced the nerve in the experimental group, while the positive electrode faced the nerve in the control group. The pH values of the intra- and extraesophageal walls were measured simultaneously. Pathological examination was performed after the esophagus and nerves were damaged. RESULTS: After BB ingestion, the pH near the intraesophageal negative electrode increased rapidly, reaching 11.5 at 30 min and over 14 at 6 h, while the extraesophageal pH did not change at 1 h and began to accelerate after 2 h, reaching 10 at 6 h. After 6 h of exposure, the pathological section showed that the structure of the mucosa, submucosa, and muscle layer were destroyed; chromatin in the nucleus faded, and part of the nerve bundle in the adventitia had liquefaction necrosis. CONCLUSION: The basic mechanism of vocal cord paralysis caused by BB ingestion is that the OH- generated by the electrolytic reaction of the negative electrode penetrates the esophageal wall and corrodes the RLN, which may be the cause of vocal cord paralysis caused by BB ingestion without esophageal perforation.

LncRNA ZNF674-AS1 drives cell growth and inhibits cisplatin-induced pyroptosis via up-regulating CA9 in neuroblastoma.

Neuroblastoma (NB) is a challenging pediatric extracranial solid tumor characterized by a poor prognosis and resistance to chemotherapy. Identifying targets to enhance chemotherapy sensitivity in NB is of utmost importance. Increasing evidence implicates long noncoding RNAs (lncRNAs) play important roles in cancer, but their functional roles remain largely unexplored. Here, we analyzed our RNA sequencing data and identified the upregulated lncRNA ZNF674-AS1 in chemotherapy non-responsive NB patients. Elevated ZNF674-AS1 expression is associated with poor prognosis and high-risk NB. Importantly, targeting ZNF674-AS1 expression in NB cells suppressed tumor growth in vivo. Further functional studies have revealed that ZNF674-AS1 constrains cisplatin sensitivity by suppressing pyroptosis and promoting cell proliferation. Moreover, ZNF674-AS1 primarily relies on CA9 to fulfill its functions on cisplatin resistance. High CA9 levels were associated with high-risk NB and predicted poor patient outcomes. Mechanistically, ZNF674-AS1 directly interacted with the RNA binding protein IGF2BP3 to enhance the stability of CA9 mRNA by binding with CA9 transcript, leading to elevated CA9 expression. As a novel regulator of CA9, IGF2BP3 positively upregulated CA9 expression. Together, these results expand our understanding of the cancer-associated function of lncRNAs, highlighting the ZNF674-AS1/IGF2BP3/CA9 axis as a constituting regulatory mode in NB tumor growth and cisplatin resistance. These insights reveal the pivotal role of ZNF674-AS1 inhibition in recovering cisplatin sensitivity, thus providing potential therapeutic targets for NB treatment.

ZnO-Au@ZIF-8 core-shell nanorod arrays for ppb-level NO2 detection.

ZnO-Au@ZIF-8 core-shell heterostructures were prepared by ZIF-8 encapsulation of sacrificial ZnO-Au nanorods. Because of the catalytic activity of the Au nanoparticles and the sieving effects of the ZIF-8, the ZnO-Au@ZIF-8 heterostructures showed an outstanding response of 1.8 to 5 ppb NO2, and exhibited higher selectivity, stability, anti-humidity and fast response and recovery properties. The combination of the gas-selective catalytic activity of noble metals with the MOF filter used in this work can be easily extended to synthesize other types of MOS@MOF sensors, opening a new avenue for the detection of hazardous gases.

Impaired declarative memory consolidation in children with REM sleep-related obstructive sleep apnea.

STUDY OBJECTIVES: We explored whether declarative memory consolidation is impaired in children with rapid eye movement sleep-related obstructive sleep apnea (REM-OSA) and investigated the correlation between memory consolidation and sleep-related respiratory parameters. METHODS: Participants were children with habitual snoring aged 6-14 years and control children. Participants underwent polysomnography and declarative memory testing. Participants with snoring were categorized as primary snoring (PS), non-rapid eye movement sleep-related obstructive sleep apnea (NREM-OSA), stage-independent (SI)-OSA, and REM-OSA according to obstructive apnea-hypopnea index (OAHI), OAHI in REM sleep (OAHIREM), and OAHI in NREM sleep (OAHINREM). Declarative memory consolidation level was assessed by recall and recognition rates. RESULTS: There were 34 controls and 228 children with sleep-disordered breathing: 73 PS, 48 NREM-OSA, 59 SI-OSA, and 48 REM-OSA. Total arousal index was lower in the REM-OSA group than in the NREM-OSA group. In all groups, retest scores were higher than immediate test scores. Recall consolidation in PS, SI-OSA, and REM-OSA groups was lower than for controls and lower in REM-OSA than in NREM-OSA. There were no correlations between recall consolidation or recognition consolidation and OAHI, OAHINREM, oxygen desaturation index in REM sleep, total arousal index, or REM sleep percent. Recognition consolidation was negatively correlated with OAHIREM. CONCLUSIONS: Memory consolidation is impaired in children with REM-OSA compared with NREM-OSA and controls. There was no significant correlation between memory consolidation and OAHI, and recognition consolidation was negatively correlated with OAHIREM. It is important to pay attention to the OSA subtype in children. CITATION: Tang Y, Yang C, Wang C, Wu Y, Xu Z, Ni X. Impaired declarative memory consolidation in children with REM sleep-related obstructive sleep apnea. J Clin Sleep Med. 2024;20(3):417-425.

A Case of Nasopharyngeal Pleomorphic Lipoma.

We describe the presentation and treatment of the first reported case of a nasopharyngeal pleomorphic lipoma. The mass was successfully treated with a combined endoscopic trans-oral surgical excision approach by using low temperature-controlled plasma technology, resulting in optimal patient outcomes. Laryngoscope, 2023.

Safety and efficacy of microwave ablation for symptomatic benign thyroid nodules in children.

OBJECTIVE: To evaluate the efficacy and safety of microwave ablation (MWA) for the treatment of symptomatic benign thyroid nodules in children. METHODS: A retrospective study of MWA for the treatment of 34 symptomatic benign thyroid nodules in 25 children was conducted. Volume reduction ratio (VRR), technique efficacy, symptom score, cosmetic score, and thyroid function were used to evaluate the efficacy of the technique. The associated complications and side effects were recorded. RESULTS: The participants were followed for at least 6 months (median 12 months, range 6-48 months). After MWA treatment, the volumes of the targeted nodules decreased gradually (median volume 5.86 mL before MWA and 0.34 mL at the final follow-up assessment), the VRR achieved was up to 85.03% at the final follow-up assessment, and the technical efficacy at this time was 91.2%. The subjective and objective nodule-related symptoms were also ameliorated. The circulating hormone concentrations reflecting thyroid function remained within their normal ranges in all the participants after one month of follow-up. The procedure had no major complications. CONCLUSIONS: MWA seems to be an effective and safe technique for the treatment of symptomatic benign thyroid nodules in pediatric patients. CLINICAL RELEVANCE STATEMENT: Microwave ablation is a safe and effective method to treat symptomatic benign thyroid nodules in pediatric patients. This treatment may be selected if the patient or parents are not suitable or refuse to undergo surgery. KEY POINTS: • Microwave ablation is effective in reducing the volume of benign thyroid nodules and ameliorating nodule-related symptoms in pediatric patients. • Microwave ablation is a safe method in children, with low complications. • Microwave ablation does not affect the circulating thyroid hormone concentrations of children.

Dexmedetomidine attenuates the neuroinflammation and cognitive dysfunction in aged mice by targeting the SNHG14/miR­340/NF­κB axis.

Neuroinflammation plays a key role in the pathogenesis of postoperative cognitive dysfunction (POCD). Results of our previous study demonstrated that dexmedetomidine (Dex) attenuates neuroinflammation in BV2 cells treated with lipopolysaccharide (LPS) by targeting the microRNA (miR)-340/NF-κB axis. However, the molecular mechanisms by which Dex improves POCD remain unclear. In the present study, the association between long non-coding (lnc)RNA small nucleolar RNA host gene 14 (SNHG14) and miR-340 in BV2 microglial cells was determined using a dual-luciferase reporter assay. In addition, SNHG14, miR-340 and NF-κB expression levels were measured in LPS-treated BV-2 cells and hippocampal tissues of mice with POCD, and an enzyme-linked immunosorbent assay was used to determine the levels of proinflammatory mediators. Results of the present study demonstrated that SNHG14 exhibited potential as a target of miR-340. In addition, SNHG14 knockdown increased the levels of miR-340 and reduced the levels of NF-κB in LPS-treated BV2 cells. In addition, Dex treatment significantly reduced the levels of SNHG14 and NF-κB, and elevated the levels of miR-340 in the hippocampus of aged mice with POCD. Moreover, Dex treatment notably decreased the expression levels of TNF-α, IL-1ß, IL-2, IL-6, IL-8 and IL-12 in the hippocampus of aged mice with POCD by upregulating miR-340. The spatial memory impairments in aged mice with POCD were also notably increased following Dex treatment via upregulation of miR-340. Collectively, results of the present study demonstrated that Dex may protect microglia from LPS-induced neuroinflammation in vitro and attenuate hippocampal neuroinflammation in aged mice with POCD in vivo via the SNHG14/miR-340/NF-κB axis. The present study may provide further insights into the mechanisms underlying Dex in the treatment of POCD.

Adipose-derived stem cells repair radiation-induced chronic lung injury via inhibiting TGF-ß1/Smad 3 signaling pathway.

To investigate the effect of adipose-derived stem cells (ASCs) transplantation on radiation-induced lung injury (RILI), Sprague-Dawley rats were divided into phosphate-buffered saline (PBS) group, ASCs group, Radiation + PBS group, and Radiation + ASCs group. Radiation + PBS and Radiation + ASCs groups received single dose of 30 Gy X-ray radiation to the right chest. The Radiation + PBS group received 1 mL PBS suspension and Radiation + ASCs group received 1 mL PBS suspension containing 1 × 107 CM-Dil-labeled ASCs. The right lung tissue was collected on Days 30, 90, and 180 after radiation. Hematoxylin-eosin and Masson staining were performed to observe the pathological changes and collagen fiber content in the lung tissue. Immunohistochemistry (IHC) and western blot (WB) were used to detect levels of fibrotic markers collagen I (Collal), fibronectin (FN), as well as transforming growth factor-ß1 (TGF-ß1), p-Smad 3, and Smad 3. Compared with the non-radiation groups, the radiation groups showed lymphocyte infiltration on Day 30 after irradiation and thickened incomplete alveolar walls, collagen deposition, and fibroplasia on Days 90 and 180. ASCs relieved these changes on Day 180 (Masson staining, P = 0.0022). Compared with Radiation + PBS group, on Day 180 after irradiation, the Radiation + ASCs group showed that ASCs could significantly decrease the expressions of fibrosis markers Collal (IHC: P = 0.0022; WB: P = 0.0087) and FN (IHC: P = 0.0152; WB: P = 0.026) and inhibit the expressions of TGF-ß1 (IHC: P = 0.026; WB: P = 0.0152) and p-Smad 3 (IHC: P = 0.0043; WB: P = 0.0087) in radiation-induced injured lung tissue. These indicated that ASCs could relieve RILI by inhibiting TGF-ß1/Smad 3 signaling pathway.

Analysis of the gut microbiota in children with gastroesophageal reflux disease using metagenomics and metabolomics.

Background: There is no direct evidence of gut microbiota disturbance in children with gastroesophageal reflux disease (GERD). This study aimed to provide direct evidence and a comprehensive understanding of gut microbiota disturbance in children with GERD through combined metagenomic and metabolomic analysis. Methods: 30 children with GERD and 30 healthy controls (HCs) were continuously enrolled, and the demographic and clinical characteristics of the subjects were collected. First, 16S rRNA sequencing was used to evaluate differences in the gut microbiota between children with GERD and HC group, and 10 children with GERD and 10 children in the HC group were selected for metagenomic analysis. Nontargeted metabolomic analysis was performed using liquid chromatography/mass spectrometry (LC/MS), and metagenomic and metabolomic data were analyzed together. Results: There were significant differences in the gut microbiota diversity and composition between children with GERD and HCs. The dominant bacteria in children with GERD were Proteobacteria and Bacteroidota. At the species level, the top three core bacterial groups were Bacteroides stercoris, Bacteroides vulgatus and Alistipes putredinis. The main differential pathways were identified to be related to energy, amino acid, vitamin, carbohydrate and lipid metabolism. LC/MS detected 288 different metabolites in the positive and negative ion modes between children with GERD and HCs, which were mainly involved in arachidonic acid (AA), tyrosine, glutathione and caffeine metabolism. Conclusion: This study provides new evidence of the pathogenesis of GERD. There are significant differences in the gut microbiota, metabolites and metabolic pathways between HCs and children with GERD, and the differences in metabolites are related to specific changes in bacterial abundance. In the future, GERD may be treated by targeting specific bacteria related to AA metabolism.

Construction and functional verification of size-reduced plasmids based on TMP resistance gene dfrB10.

IMPORTANCE: Plasmid size is one of the factors affecting transfection efficacy in most of the molecular genetic research studies. One effective approach for reducing plasmid size is to replace relatively large, conventional antibiotic resistance genes with the short-size dfrB10 gene. The successful construct of a series of dfrB10-based tool plasmids and their functional validation, via comparison with original plasmids, suggest that dfrB10 is a potent drug resistance selection marker. The antibiotic trimethoprim offers convenient usage comparable to that of ampicillin or kanamycin. Additionally, fluorescence analysis has demonstrated the compatibility of TMP with protein expression in various host cells. Based on these findings, TMP-dfrB10 could be an alternative choice for future use in molecular genetic research studies that require miniature plasmids to achieve optimal results.

Nlrp3 Deficiency Alleviates Lipopolysaccharide-Induced Acute Kidney Injury via Suppressing Renal Inflammation and Ferroptosis in Mice.

The nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome is a vital component of many inflammatory responses. Here, we intended to investigate the involvement of NLRP3 in lipopolysaccharide (LPS)-induced sepsis-associated acute kidney injury (S-AKI) and explore its mechanisms. For the first time, we validated elevated NLRP3 expression in the renal tissues of S-AKI patients by immunohistochemistry analysis. Through LPS injection in both wild-type and Nlrp3-/- mice, a S-AKI model was developed. It was found that LPS-induced kidney injury, including an abnormal morphology in a histological examination, abnormal renal function in a laboratory examination, and an increase in the expression of AKI biomarkers, was dramatically reversed in Nlrp3-deficient mice. Nlrp3 deletion alleviated renal inflammation, as evidenced by the suppression of the expression of pro-inflammatory cytokines and chemokines. A combinative analysis of RNA sequencing and the FerrDb V2 database showed that Nlrp3 knockout regulated multiple metabolism pathways and ferroptosis in LPS-induced S-AKI. Further qPCR coupled with Prussian blue staining demonstrated that Nlrp3 knockout inhibited murine renal ferroptosis, indicating a novel mechanism involving S-AKI pathogenesis by NLRP3. Altogether, the aforementioned findings suggest that Nlrp3 deficiency alleviates LPS-induced S-AKI by reducing renal inflammation and ferroptosis. Our data highlight that NLRP3 is a potential therapeutic target for S-AKI.