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.

Observing Proton-Electron Mixed Conductivity in Graphdiyne.

Mixed conducting materials with both ionic and electronic conductivities have gained prominence in emerging applications. However, exploring material with on-demand ionic and electronic conductivities remains challenging, primarily due to the lack of correlating macroscopic conductivity with atom-scale structure. Here, the correlation of proton-electron conductivity and atom-scale structure in graphdiyne is explored. Precisely adjusting the conjugated diynes and oxygenic functional groups in graphdiyne yields a tunable proton-electron conductivity on the order of 103. In addition, a wet-chemistry lithography technique for uniform preparation of graphdiyne on flexible substrates is provided. Utilizing the proton-electron conductivity and mechanical tolerance of graphdiyne, bimodal flexible devices serving as capacitive switches and resistive sensors are created. As a proof-of-concept, a breath-machine interface for sentence-based communication and self-nursing tasks with an accuracy of 98% is designed. This work represents an important step toward understanding the atom-scale structure-conductivity relationship and extending the applications of mixed conducting materials to assistive technology.

Multiscale Heterogeneities-Based Piezoresistive Interfaces with Ultralow Detection Limitation and Adaptively Switchable Pressure Detectability.

Mechanical compliance and electrical enhancement are crucial for pressure sensors to promote performances when perceiving external stimuli. Here we propose a bioinspired multiscale heterogeneity-based interface to adaptively regulate its structure layout and switch to desirable piezoresistive behaviors with ultralow detection limitation. In such a multiscale heterogeneities system, the micro-/nanoscale spiny Ag-MnO2 heterostructure contributes to an ultralow detection limitation of 0.008 Pa and can perceive minor pressure increments under preloads with high resolution (0.0083%). The macroscale heterogeneous orientation of the cellular backbone enables anisotropic deformation, allowing the sensor to switch to rational sensitivity and working range (e.g., 580 kPa-1 for 0-20 kPa/54 kPa-1 for 60-140 kPa) as required. The sensor's stepwise activation progresses from the micro-/nanoscale heterostructure to the macroscale heterogeneous orientation, which can adaptively match diverse sensing tasks in complex applications scenarios. This multiscale heterogeneous and switchable design holds immense potential in the development of intelligent electromechanical devices, including wearable sensors, soft robotics, and smart actuators.

Hydroclimatic changes on multiple timescales since 7800 y BP in the winter precipitation-dominated Central Asia.

Central Asia (CA) is one of the world's most significant arid regions, which is markedly impacted by global warming. A better understanding of the dynamical processes governing its Holocene climate variability is critical for a better understanding of possible future impacts of climate change in the region. To date, most of the existing CA paleoclimate records are from the summer precipitation-dominated eastern CA (ECA), with few records from the winter precipitation-dominated western CA (WCA). Here, we present a precisely dated (~6‰) and highly resolved (<4-y) record of hydroclimatic variations from the WCA covering the period between 7,774 and 656 y BP. Utilizing multiple proxies (δ18O, δ13C, and Sr/Ca) derived from a stalagmite from the Fergana Valley, Kyrgyzstan, we reveal a long-term drying trend in WCA, which is in contrast with the wetting trend in ECA. We propose that different responses of winter and summer westerly jets to seasonal solar insolation over the past 8,000 y may have resulted in an antiphased precipitation relationship between the WCA and ECA. Our data contain dominant quasiperiodicities of 1,400, 50 to 70, and 20 to 30 y, indicating close connections between the WCA climate and the North Atlantic. We further identified a series of droughts and pluvials on centennial-to-decadal timescales, which may have influenced regional societies and trans-Eurasian culture exchanges during historical and prehistorical times.

Efficacy and safety of moxibustion for ulcerative colitis: protocol for a systematic review and meta-analysis.

INTRODUCTION: Ulcerative colitis (UC) is a global chronic inflammatory bowel disease, and the poor efficacy of currently available pharmacological regimens makes the management of UC a great challenge. Moxibustion has shown great potential in the management of UC. However, its effectiveness and safety are still controversial. The purpose of this study is to synthesise the latest evidence regarding the clinical efficacy and safety of moxibustion for UC. METHODS AND ANALYSIS: The Cochrane Library, PubMed, EMBASE, CNKI, Wanfang, VIP and SinoMed databases will be searched from inception to July 2023, to identify all randomised controlled trials with moxibustion for UC. The primary outcome will be clinical efficacy, as measured by validated scales. The serum inflammatory factor, colonoscopy results, quality of life, recurrence rate and adverse events will be the secondary outcomes. The Cochrane Risk of Bias 2.0 tool will be used to assess the methodological quality of each included trial. All data extraction will be carried out independently by two investigators. RevMan V.5.4 software will be used for data analysis and Cochran's Q statistic and I2 test will be used to assess heterogeneity between studies. In addition, we will perform subgroup analyses, sensitivity analyses and publication bias if the available data are sufficient. The strength of evidence will be graded using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system. ETHICS AND DISSEMINATION: Ethics approval is not required for this review. Our findings will be published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42023425481.

Skin-Inspired Multi-Modal Mechanoreceptors for Dynamic Haptic Exploration.

Active sensing is a fundamental aspect of human and animal interactions with the environment, providing essential information about the hardness, texture, and tackiness of objects. This ability stems from the presence of diverse mechanoreceptors in the skin, capable of detecting a wide range of stimuli and from the sensorimotor control of biological mechanisms. In contrast, existing tactile sensors for robotic applications typically excel in identifying only limited types of information, lacking the versatility of biological mechanoreceptors and the requisite sensing strategies to extract tactile information proactively. Here, inspired by human haptic perception, a skin-inspired artificial 3D mechanoreceptor (SENS) capable of detecting multiple mechanical stimuli is developed to bridge sensing and action in a closed-loop sensorimotor system for dynamic haptic exploration. A tensor-based non-linear theoretical model is established to characterize the 3D deformation (e.g., tensile, compressive, and shear deformation) of SENS, providing guidance for the design and optimization of multimode sensing properties with high fidelity. Based on SENS, a closed-loop robotic system capable of recognizing objects with improved accuracy (≈96%) is further demonstrated. This dynamic haptic exploration approach shows promise for a wide range of applications such as autonomous learning, healthcare, and space and deep-sea exploration.

The features of dome-shape Macula and related complications in high myopia on optical coherence tomography.

PURPOSE: This study used optical coherence tomography scanning and 3D reconstruction of the macular region in high myopia to examine more thoroughly and carefully the differences between high myopia-related macular complications with and without dome-shape macula (DSM) and to determine whether the DSM's fine structure has an effect on them. METHODS: Retrospective analysis of the medical records of 345 eyes with high myopia who underwent an optical coherence tomography (OCT) examination. They were divided into the DSM group (69 eyes) and the group without DSM (276 eyes). Macular complications between the two groups were compared. The height of the DSM and the diameter of the dome base were measured. And then the association between DSM type, protrusion height and macular problems were analyzed. RESULTS: Epiretinal membrane (ERM) and extrafoveal schisis occurred more frequently in the DSM group, but the was no statistically significant difference in the frequency of foveal schisis between the two groups. The majority of eyes in the DSM categorization had a horizontal oval-shaped domain. In the DSM group, there was no evident difference in the percentage of eyes with macular complications in the groups below 150 um and above 150 um. CONCLUSIONS: OCT examination-based fine macular structure analysis reveals that DSM affects various macular problems in distinct ways. DSM could increase the risk of extrafoveal schisis and ERM while decreasing the risk of foveal schisis. The height of the DSM had no obvious impact on the prevalence of macular complications.

Hypersampsonone H attenuates ulcerative colitis via inhibition of PDE4 and regulation of cAMP/PKA/CREB signaling pathway.

BACKGROUND AND OBJECTIVES: Ulcerative colitis (UC) is a recurrent intestinal inflammatory disease which poses a serious threat to the life of patients. However, there are no specific drugs for UC yet. Hypericum sampsonii Hance (HS) is a Chinese herbal medicine traditionally used to treat enteritis and dysentery. Our previous studies have demonstrated that HS holds potential anti-UC effects, and a novel compound named Hypersampsonone H (HS-1) isolated from HS possesses significant anti-inflammatory activity. However, the beneficial effects of HS-1 on UC remain unclear. This study aimed to investigate the therapeutic effects of HS-1 on UC and its potential mechanisms, both in vitro and in vivo. METHODS: The in vitro model was employed using LPS-induced RAW264.7 cells to investigate the anti-inflammatory effects of HS-1 and its possible mechanisms. Furthermore, the therapeutic efficacy and potential mechanisms of HS-1 against dextran sulfate sodium (DSS)-induced acute colitis were assessed through histopathological examination, biochemical analysis, and molecular docking. RESULTS: In vitro, HS-1 significantly reduced LPS-induced inflammatory responses, as indicated by inhibiting NO production, down-regulating the overexpression of COX-2 and iNOS, as well as regulating the imbalanced levels of IL-6, TNF-α, and IL-10. Moreover, HS-1 also inhibited the expression of PDE4, elevated the intracellular cAMP level, and promoted the phosphorylation of CREB, thereby activating the PKA/CREB pathway in RAW264.7 cells. In vivo, HS-1 demonstrated therapeutic capacity against DSS-induced colitis by alleviating the symptoms of colitis mice, regulating the abnormal expression of inflammatory mediators, protecting the integrity of intestinal epithelial barrier, and reducing tissue fibrosis. Consistently, HS-1 was found to decrease the expression of PDE4 isoforms, subsequently activating the cAMP/PKA/CREB signaling pathway. Furthermore, the molecular docking results indicated that HS-1 exhibited a high affinity for PDE4, particularly PDE4D. Further mechanistic validation in vitro demonstrated that HS-1 possessed a synergistic effect on forskolin and an antagonistic effect on H-89 dihydrochloride, thereby exerting anti-inflammatory effects through the cAMP/PKA/CREB signaling pathway. CONCLUSION: We disclose that HS-1 serves as a promising candidate drug for the treatment of UC by virtue of its ability to reduce DSS-induced colitis via the inhibition of PDE4 and the activation of cAMP/PKA/CREB signaling pathway.

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.

Profiling and Bioinformatics Analyses of Hypoxia-Induced Differential Expression of Long Non-coding RNA in Glioblastoma Multiforme Cells.

Hypoxic microenvironments are intricately linked to malignant characteristics of glioblastoma multiforme (GBM). Long non-coding ribonucleic acids (lncRNAs) have been reported to be involved in the progression of GBM and closely associated with hypoxia. Nevertheless, the differential expression profiles as well as functional roles of lncRNAs in GBM cells under hypoxic conditions remain largely obscure. We explored the expression profiles of lncRNAs in hypoxic U87 cells as well as T98G cells using sequencing analysis. The effect of differentially expressed lncRNAs (DElncRNAs) was assessed through bioinformatic analysis. Furthermore, the expression of lncRNAs significantly dysregulated in both U87 and T98G cells was further validated using quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Relevant cell functional experiments were also conducted. We used predicted RNA-binding proteins (RBPs) to construct an interaction network via the interaction prediction module. U87 and T98G cells showed dysregulation of 1115 and 597 lncRNAs, respectively. Gene Ontology (GO) analysis indicated that altered lncRNA expression was associated with nucleotide-excision repair and cell metabolism in GBM cells. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed the association between dysregulated lncRNAs and the Hippo signaling pathway under hypoxia. The dysregulation of six selected lncRNAs (ENST00000371192, uc003tnq.3, ENST00000262952, ENST00000609350, ENST00000610036, and NR_046262) was validated by qRT-PCR. Investigation of lncRNA-microRNA (miRNA)-mRNA networks centered on HIF-1α demonstrated cross-talk between the six validated lncRNAs and 16 related miRNAs. Functional experiments showed the significant inhibition of GBM cell proliferation, invasion, and migration by the knockdown of uc003tnq.3 in vitro. Additionally, uc003tnq.3 was used to construct a comprehensive RBP-transcription factor (TF)-miRNA interaction network. The expression of LncRNAs was dysregulated in GBM cells under hypoxic conditions. The identified six lncRNAs might exert important effect on the development of GBM under hypoxic microenvironment.

Hypericum sampsonii Hance: a review of its botany, traditional uses, phytochemistry, biological activity, and safety.

Ethnopharmacological relevance: Hypericum sampsonii Hance, also known as Yuanbao Cao in Chinese, is a traditional medicinal herb from the Guttiferae family and has been widely used in China to treat various conditions, including dysentery, enteritis, mastitis, scrofula, and contusion. Aim of the review: This review aims to provide a comprehensive overview of the botany, traditional uses, phytochemistry, biological activity and safety of H. sampsonii and to highlight its potential for medical application and drug development. Materials and methods: We searched several databases, i.e., Web of Science, SciFinder, PubMed, CBM, CNKI, Google Scholar, etc., for relevant information on H. sampsonii. Additionally, we also consulted some books on Chinese medicine. Results: To date, 227 secondary metabolites have been isolated from H. sampsonii, including polycyclic polyprenylated acylphloroglucinols (PPAPs), benzophenones, xanthones, flavonoids, naphthodianthrones, anthraquinones and aromatic compounds. These metabolites exhibit various biological activities such as anti-inflammatory, anti-tumor, anti-depressant, anti-oxidant, anti-viral and anti-bacterial effects. PPAPs are considered the main active metabolites with rich biological activities. Despite being known as rich source of PPAPs, the full extent of H. sampsonii biological activities, including their potential as PDE4 inhibitors, remained unclear. Since, previous studies have mainly been based on structural identification of metabolites in H. sampsonii, and efficacy evaluations of these metabolites based on clinical applications of H. sampsonii lack sufficient data. However, current evidence suggest that PPAPs are the most likely material basis for efficacy. From the limited information available so far, there is no evidence of potential safety issues and the safety data are limited. Conclusion: Collectively, this review provides a comprehensive overview of the botany, traditional uses, phytochemistry, pharmacology, and safety of H. sampsonii, a valuable medicinal plant in China with various pharmacological activities. Based on pharmacological studies, H. sampsonii shows potential for treating gastrointestinal and gynecological disorders as well as traumatic injuries, which aligns with traditional medicinal use due to the presence of PPAPs, benzophenones, xanthones, and flavonoids. Therefore, further studies are needed to evaluate the pharmacological effects and elucidate the pharmacological mechanisms. In addition, pharmacological mechanisms and safety evaluation of PPAPs on animal models need to be clarified. Yet, further comprehensive studies are required to elucidate the phytochemical constituents, pharmacological mechanisms, structure-activity relationships, safety evaluation, and quality standards of this plant. Takentogether, this review highlights the potential of H. sampsonii for medical application and drug development.

Neutrophil elastase in dexmedetomidine alleviating sepsis-related renal injury in rats.

BACKGROUND: This research was to investigate the mechanism of neutrophil elastase (NE) in dexmedetomidine (DEX) alleviates sepsis-related renal injury in rats. METHODS: Sixty healthy male SD rats aged 6-7 weeks were randomly assigned to the control group (Sham group (S group)), Model group (M group), Model + DEX group (M + DEX group), and Model + DEX + Elaspol group (M + DEX + Elaspol (sivelestat) group), with 15 rats in each group. The renal morphology and pathological changes of different groups of rats after modeling were observed, and renal tubular injury was scored. Serum samples were collected at 6 h, 12 h, and 24 h after modeling, and the rats were sacrificed. Renal function indicators, including neutrophil gelatinase-associated lipoprotein (NGAL), kidney injury molecule-1 (KIM-1), tumor necrosis factor (TNF-α), interleukin-6 (IL-6), NE, serum creatinine (SCr), and blood urea nitrogen (BUN), were analyzed by enzyme-linked immunosorbent assay at different time periods. The level of NF-кB in renal tissue was detected by immunohistochemistry. RESULTS: It was revealed that the general color of renal tissue in M group was dark red, swollen, and congested, and the renal tubular epithelial cells were significantly enlarged, with obvious vacuolar degeneration and inflammatory cell infiltration. Compared with M group, the color and morphology of renal tissue in M + DEX group and M + DEX + Elaspol group were improved, and the amount of inflammatory cell infiltration was reduced. The renal tubular injury score, SCr level, BUN level, NGAL level, KIM-1 level, TNF-α, IL-6, NE level, and NF-кB level in M group were significant different from S group 12 h after the operation (P < 0.001). The renal tubular injury score, SCr level, BUN level, NGAL level, KIM-1 level, TNF-α, IL-6, NE level, and NF-кB level in M + DEX group were significant different from M group (P < 0.01). The renal tubular injury score, SCr level, BUN level, NGAL level, KIM-1 level, TNF-α, IL-6, NE level, and NF-кB level in M + DEX + Elaspol group were significant different from those in M group at 12 h after the operation (P < 0.001). CONCLUSION: NE plays an active role in the reduction of sepsis-related renal injury in rats by inhibiting the inflammatory response.

Polycyclic polyprenylated acylphloroglucinols from Hypericum sampsonii Hance and their anti-inflammatory activity.

Phytochemical investigation of Hypericum sampsonii Hance resulted in the isolation of thirty-five polycyclic polyprenylated acylphloroglucinols including six new ones (1, 3, 5, and 15-17). Their structures were elucidated by UV, IR, NMR, HRESIMS, and calculated ECD analysis. Some compounds were evaluated for their anti-inflammatory effects in LPS-induced RAW264.7 cells. Compounds 1 and 26 showed significant inhibitory effects on LPS-induced NO production, and markedly suppressed the protein expression of iNOS and COX-2 in LPS-activated RAW264.7 cells.

The SnRK2.3-AREB1-TST1/2 cascade activated by cytosolic glucose regulates sugar accumulation across tonoplasts in apple and tomato.

Soluble sugars are the core components of fruit quality, and the degree of sugar accumulation is largely determined by tonoplast-localized sugar transporters. We previously showed that two classes of tonoplast sugar transporters, MdERDL6 and MdTST1/2, coordinately regulate sugar accumulation in vacuoles. However, the mechanism underlying this coordination remains unknown. Here we discovered that two transcription factors, MdAREB1.1/1.2, regulate MdTST1/2 expression by binding their promoters in apple. The enhanced MdAREB1.1/1.2 expression in MdERDL6-1-overexpression plants resulted in an increase in MdTST1/2 expression and sugar concentration. Further studies established that MdSnRK2.3, whose expression could be regulated by expressing MdERDL6-1, could interact with and phosphorylate MdAREB1.1/1.2, thereby promoting the MdAREB1.1/1.2-mediated transcriptional activation of MdTST1/2. Finally, the orthologous SlAREB1.2 and SlSnRK2.3 exhibited similar functions in tomato fruit as in their apple counterparts. Together, our findings provide insights into the regulatory mechanism of tonoplast sugar transport exerted by SnRK2.3-AREB1-TST1/2 for fruit sugar accumulation.

Rh(II)-Catalyzed Chemoselective Oxy-alkynylation of Acceptor-Acceptor Carbenes: Synthesis of C2-Quaternary Alkyne-Substituted 3(2H)-Furanones.

A Rh(II)-catalyzed oxy-alkynylation of acceptor-acceptor carbenes using EBX reagents was successfully developed. The key alkyne-transfer step is likely to occur through a tandem process involving a ß-addition, an α-elimination, and a 1,2-shift, which was supported by the formation of alkylidene carbene. Various diverse C2-quaternary alkyne-substituted benzofuran-3-ones and 2,2,4,5-tetrasubstituted 3(2H)-furanones can be synthesized smoothly, depending on the choice of diazo compounds and the base additives. Furthermore, this reaction is characterized by mild conditions, high functional group compatibility, and a broad substrate scope.

Myositis Ossificans of the Trapezius Muscle: A Case Report and Literature Review.

Myositis ossificans (MO) is a benign, self-limiting, and nonneoplastic lesion involving the skeletal muscle or soft tissue, rarely occurring in the head and neck. It is relatively rare in clinical practice, and it is difficult to distinguish specific cases from musculoskeletal conditions, which poses unique challenges for clinical diagnosis and treatment. We reported that a 9-year-old boy suffered from local and nontraumatic MO of the trapezius muscle. Given the rarity of this case, the present article detailed the diagnosis and treatment of this rare case and reviewed the relevant literature on MO, focusing on the clinical, pathological, and radiographic characteristics of MO. Notably, these investigations aimed to enhance clinicians' understanding of the disease and improve diagnostic accuracy.

Exogenous application of melatonin to mitigate drought stress-induced oxidative damage in Phoebe sheareri seedlings.

Background: Drought stress is a major prevalent environmental factor impairing growth. Melatonin mitigates the impacts of drought stress on plants. However, melatonin's role in Phoebe sheareri (Hemsl.) Gamble (P. sheareri) is unknown. We aimed to reveal the protective effects of melatonin on P. sheareri seedlings under drought conditions. Methods: Melatonin was sprayed under drought or normal water conditions. The parameters, including growth, physiological factors, and phytohormones of P. sheareri, were examined. Results: Compared to the normal control group, drought stress inhibited the growth of seedlings and significantly reduced the content of carotenoids, SOD, POD, APX, PPO, CAT, GR, and soluble sugars, and increased the contents of MDA, O2 •-, proline, soluble proteins, ABA, and JA-Me in P. sheareri seedlings. However, melatonin treatment significantly reversed the adverse drought-induced responses and promoted the P. sheareri seedling's growth. Moreover, the heatmap and principal component analysis suggested a high similarity in the behavior patterns of the six measured antioxidant enzymes in P. sheareri seedlings. Conclusion: Our study reported for the first time that melatonin has a protective role in P. sheareri seedlings under drought-stress conditions. This role is related to ROS scavenging, activation of antioxidant enzymes, and crosstalk of phytohormones. This study provided a theoretical basis for improving the ability of P. sheareri adapted to arid environments.

Differences in Efficacy and Safety of Sirolimus and Sildenafil in Pediatric Lymphatic Malformations.

OBJECTIVES: To explore the differences in the efficacy and safety of oral sirolimus and sildenafil in the treatment of pediatric intractable lymphatic malformations (LMs). METHODS: From January 2014 to May 2022, we retrospectively enrolled children with intractable LMs treated with oral drugs (sirolimus or sildenafil) and divided the patients into sirolimus and sildenafil groups from Beijing Children's Hospital (BCH). Clinical features, treatment, and follow-up data were collected and analyzed. The indicators were the ratio of reduction in lesion volume pre and posttreatment, the number of patients with improved clinical symptoms, and adverse reactions to the two drugs. RESULTS: Twenty-four children in the sildenafil group and 31 children in the sirolimus group were included in the present study. The effective rate in the sildenafil group was 54.2% (13/24), with a median lesion volume reduction ratio of 0.32 (-0.23, 0.89) and clinical symptoms improved in 19 patients (79.2%). On the contrary, the effective rate in the sirolimus group was 93.5% (29/31), with a median lesion volume reduction ratio of 0.68 (0.34, 0.96), and clinical symptoms improved in 30 patients (96.8%). There were significant differences (p < 0.05) between the two groups. Regarding safety, four patients in the sildenafil group and 23 patients in the sirolimus group with mild adverse reactions were reported. CONCLUSION: Both sildenafil and sirolimus can reduce the volume of LMs and improve clinical symptoms in partial patients with intractable LMs. Sirolimus is more effective than sildenafil and the adverse reactions associated with both drugs are mild and controllable. LEVEL OF EVIDENCE: III Laryngoscope, 133:3192-3199, 2023.

Plio-Pleistocene deep-sea ventilation in the eastern Pacific and potential linkages with Northern Hemisphere glaciation.

Antarctic bottom water (AABW) production is a key factor governing global ocean circulation, and the present disintegration of the Antarctic Ice Sheet slows it. However, its long-term variability has not been well documented. On the basis of high-resolution chemical scanning of a well-dated marine ferromanganese nodule from the eastern Pacific, we derive a record of abyssal ventilation spanning the past 4.7 million years and evaluate its linkage to AABW formation over this period. We find that abyssal ventilation was relatively weak in the early Pliocene and persistently intensified from 3.4 million years ago onward. Seven episodes of markedly reduced ocean ventilation indicative of AABW formation collapse are identified since the late Pliocene, which were accompanied by key stages of Northern Hemisphere glaciation. We suggest that the interpolar climate synchronization within these inferred seven collapse events may have intensified global glaciation by inducing poleward moisture transport in the Northern Hemisphere.