Comparative analysis of gut microbiota in children with obstructive sleep apnea: assessing the efficacy of 16S rRNA gene sequencing in metabolic function prediction based on weight status.

Background: Analyzing bacterial microbiomes consistently using next-generation sequencing (NGS) is challenging due to the diversity of synthetic platforms for 16S rRNA genes and their analytical pipelines. This study compares the efficacy of full-length (V1-V9 hypervariable regions) and partial-length (V3-V4 hypervariable regions) sequencing of synthetic 16S rRNA genes from human gut microbiomes, with a focus on childhood obesity. Methods: In this observational and comparative study, we explored the differences between these two sequencing methods in taxonomic categorization and weight status prediction among twelve children with obstructive sleep apnea. Results: The full-length NGS method by Pacbio® identified 118 genera and 248 species in the V1-V9 regions, all with a 0% unclassified rate. In contrast, the partial-length NGS method by Illumina® detected 142 genera (with a 39% unclassified rate) and 6 species (with a 99% unclassified rate) in the V3-V4 regions. These approaches showed marked differences in gut microbiome composition and functional predictions. The full-length method distinguished between obese and non-obese children using the Firmicutes/Bacteroidetes ratio, a known obesity marker (p = 0.046), whereas the partial-length method was less conclusive (p = 0.075). Additionally, out of 73 metabolic pathways identified through full-length sequencing, 35 (48%) were associated with level 1 metabolism, compared to 28 of 61 pathways (46%) identified through the partial-length method. The full-length NGS also highlighted complex associations between body mass index z-score, three bacterial species (Bacteroides ovatus, Bifidobacterium pseudocatenulatum, and Streptococcus parasanguinis ATCC 15912), and 17 metabolic pathways. Both sequencing techniques revealed relationships between gut microbiota composition and OSA-related parameters, with full-length sequencing offering more comprehensive insights into associated metabolic pathways than the V3-V4 technique. Conclusion: These findings highlight disparities in NGS-based assessments, emphasizing the value of full-length NGS with amplicon sequence variant analysis for clinical gut microbiome research. They underscore the importance of considering methodological differences in future meta-analyses.

Five new glycosides from the culms of Phyllostachys nigra var. henonis.

Five new glycosides, namely methyl 3-methoxybenzoate-4,5-di-O-ß-D-glucopyranoside (1), (1aS,3aS,3R)-3-(4'-O-ß-D-glucopyranosyl-3'-methoxyphenyl)-5,6-dioxa-bicyclo[3.3.0]octane-1-one (2), quinolin-4(1H)-one-3-O-ß-D-glucopyranoside (3), 3-methoxy-propiophenone 4-O-(6'-ß-D-xylopyranosyl)-ß-D-glucopyranoside (4), methyl 3-methoxybenzoate 4-O-(6'-ß-D-xylopyranosyl)-ß-D-glucopyranoside (5), and one known compound, bambulignan B (6) were isolated from the culms of Phyllostachys nigra var. henonis. Their structures were determined using spectroscopic analysis. All compounds were evaluated for their DPPH radical scavenging activity. Compound 6 exhibited antioxidant activity with IC50 value of 59.5 µM (positive control, L-ascorbic acid, IC50 = 12.4 µM; 2,6-ditertbutyl-4-methyl phenol, IC50 = 11.8 µM).

Sodium tanshinone IIA sulfonate protects vascular relaxation in ApoE-knockout mice by inhibiting the SYK-NLRP3 inflammasome-MMP2/9 pathway.

BACKGROUND: Hyperlipidemia damages vascular wall and serves as a foundation for diseases such as atherosclerosis, hypertension and stiffness. The NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome is implicated in vascular dysfunction associated with hyperlipidemia-induced vascular injury. Sodium tanshinone IIA sulfonate (STS), a well-established cardiovascular protective drug with recognized anti-inflammatory, antioxidant, and vasodilatory properties, is yet to be thoroughly investigated for its impact on vascular relaxant imbalance induced by hyperlipidemia. METHODS: In this study, we treated ApoE-knockout (ApoE-/-) mouse with STS and assessed the activation of the NLRP3 inflammasome, expression of MMP2/9, integrity of elastic fibers, and vascular constriction and relaxation. RESULTS: Our findings reveal that STS intervention effectively preserves elastic fibers, significantly restores aortic relaxation function in ApoE-/- mice, and reduces their excessive constriction. Furthermore, STS inhibits the phosphorylation of spleen tyrosine kinase (SYK), suppresses NLRP3 inflammasome activation, and reduces MMP2/9 expression. CONCLUSIONS: These results demonstrate that STS protects vascular relaxation against hyperlipidemia-induced damage through modulation of the SYK-NLRP3 inflammasome-MMP2/9 pathway. This research provides novel insights into the mechanisms underlying vascular relaxation impairment in a hyperlipidemic environment and uncovers a unique mechanism by which STS preserves vascular relaxation, offering valuable foundational research evidence for its clinical application in promoting vascular health.

Comparing Human-Smartphone Interactions and Actigraphy Measurements for Circadian Rhythm Stability and Adiposity: Algorithm Development and Validation Study.

BACKGROUND: This study aimed to investigate the relationships between adiposity and circadian rhythm and compare the measurement of circadian rhythm using both actigraphy and a smartphone app that tracks human-smartphone interactions. OBJECTIVE: We hypothesized that the app-based measurement may provide more comprehensive information, including light-sensitive melatonin secretion and social rhythm, and have stronger correlations with adiposity indicators. METHODS: We enrolled a total of 78 participants (mean age 41.5, SD 9.9 years; 46/78, 59% women) from both an obesity outpatient clinic and a workplace health promotion program. All participants (n=29 with obesity, n=16 overweight, and n=33 controls) were required to wear a wrist actigraphy device and install the Rhythm app for a minimum of 4 weeks, contributing to a total of 2182 person-days of data collection. The Rhythm app estimates sleep and circadian rhythm indicators by tracking human-smartphone interactions, which correspond to actigraphy. We examined the correlations between adiposity indices and sleep and circadian rhythm indicators, including sleep time, chronotype, and regularity of circadian rhythm, while controlling for physical activity level, age, and gender. RESULTS: Sleep onset and wake time measurements did not differ significantly between the app and actigraphy; however, wake after sleep onset was longer (13.5, SD 19.5 minutes) with the app, resulting in a longer actigraphy-measured total sleep time (TST) of 20.2 (SD 66.7) minutes. The obesity group had a significantly longer TST with both methods. App-measured circadian rhythm indicators were significantly lower than their actigraphy-measured counterparts. The obesity group had significantly lower interdaily stability (IS) than the control group with both methods. The multivariable-adjusted model revealed a negative correlation between BMI and app-measured IS (P=.007). Body fat percentage (BF%) and visceral adipose tissue area (VAT) showed significant correlations with both app-measured IS and actigraphy-measured IS. The app-measured midpoint of sleep showed a positive correlation with both BF% and VAT. Actigraphy-measured TST exhibited a positive correlation with BMI, VAT, and BF%, while no significant correlation was found between app-measured TST and either BMI, VAT, or BF%. CONCLUSIONS: Our findings suggest that IS is strongly correlated with various adiposity indicators. Further exploration of the role of circadian rhythm, particularly measured through human-smartphone interactions, in obesity prevention could be warranted.

Developing Methods for Assessing Mental Activity Using Human-Smartphone Interactions: Comparative Analysis of Activity Levels and Phase Patterns in General Mental Activities, Working Mental Activities, and Physical Activities.

BACKGROUND: Human biological rhythms are commonly assessed through physical activity (PA) measurement, but mental activity may offer a more substantial reflection of human biological rhythms. OBJECTIVE: This study proposes a novel approach based on human-smartphone interaction to compute mental activity, encompassing general mental activity (GMA) and working mental activity (WMA). METHODS: A total of 24 health care professionals participated, wearing wrist actigraphy devices and using the "Staff Hours" app for more than 457 person-days, including 332 workdays and 125 nonworkdays. PA was measured using actigraphy, while GMA and WMA were assessed based on patterns of smartphone interactions. To model WMA, machine learning techniques such as extreme gradient boosting and convolutional neural networks were applied, using human-smartphone interaction patterns and GPS-defined work hours. The data were organized by date and divided into person-days, with an 80:20 split for training and testing data sets to minimize overfitting and maximize model robustness. The study also adopted the M10 metric to quantify daily activity levels by calculating the average acceleration during the 10-hour period of highest activity each day, which facilitated the assessment of the interrelations between PA, GMA, and WMA and sleep indicators. Phase differences, such as those between PA and GMA, were defined using a second-order Butterworth filter and Hilbert transform to extract and calculate circadian rhythms and instantaneous phases. This calculation involved subtracting the phase of the reference signal from that of the target signal and averaging these differences to provide a stable and clear measure of the phase relationship between the signals. Additionally, multilevel modeling explored associations between sleep indicators (total sleep time, midpoint of sleep) and next-day activity levels, accounting for the data's nested structure. RESULTS: Significant differences in activity levels were noted between workdays and nonworkdays, with WMA occurring approximately 1.08 hours earlier than PA during workdays (P<.001). Conversely, GMA was observed to commence about 1.22 hours later than PA (P<.001). Furthermore, a significant negative correlation was identified between the activity level of WMA and the previous night's midpoint of sleep (ß=-0.263, P<.001), indicating that later bedtimes and wake times were linked to reduced activity levels in WMA the following day. However, there was no significant correlation between WMA's activity levels and total sleep time. Similarly, no significant correlations were found between the activity levels of PA and GMA and sleep indicators from the previous night. CONCLUSIONS: This study significantly advances the understanding of human biological rhythms by developing and highlighting GMA and WMA as key indicators, derived from human-smartphone interactions. These findings offer novel insights into how mental activities, alongside PA, are intricately linked to sleep patterns, emphasizing the potential of GMA and WMA in behavioral and health studies.

Discovery and validation of combined biomarkers for the diagnosis of esophageal intraepithelial neoplasia and esophageal squamous cell carcinoma.

Early diagnosis and intervention of esophageal squamous cell carcinoma (ESCC) can improve the prognosis. The purpose of this study was to identify biomarkers for ESCC and esophageal precancerous lesions (intraepithelial neoplasia, IEN). Based on the proteomic and genomic data of esophageal tissue including previously reported data, up-regulated proteins with copy number amplification in esophageal cancer were screened as candidate biomarkers. Five proteins, including KDM2A, RAD9A, ECT2, CYHR1 and TONSL, were confirmed by immunohistochemistry on ESCC and normal esophagus (NE). Then, we investigated the expression of 5 proteins in 236 participants (60 NEs, 93 IENs and 83 ESCCs) which were randomly divided into training set and test set. When distinguishing ESCC from NE, the area under curve (AUC) of the multiprotein model was 0.940 in the training set, while the lowest AUC of a protein was 0.735. In the test set, the results were similar. When distinguishing ESCC from IEN or distinguishing IEN from NE, the diagnostic efficiency of the multi-protein models were also improved compared with that of single protein. Our findings suggest that combined detection of KDM2A, RAD9A, ECT2, CYHR1 and TONSL can be used as potential biomarkers for the early diagnosis of ESCC and precancerous lesion development prediction. SIGNIFICANCE: Candidate biomarkers including KDM2A, RAD9A, ECT2, CYHR1 and TONSL screened by integrating genomic and proteomic data from the esophagus can be used as potential biomarkers for the early diagnosis of esophageal squamous cell carcinoma and precancerous lesion development prediction.

Isolation and identification of three new phenylpropanoids from the culms of phyllostachys nigra var. henonis (mitford) Rendle.

Three new phenylpropanoids, namely (7'R,8'R) guaiacylglycerol 4'-O-ß-D-[6″-O-(4-O-ß-D-glucopyranosyl)-p-hydroxyl-benzoyl]-glucopyranoside (1), (7 R,8R) guaiacylglycerol 8-O-1'-(2',6'-dimethoxy-4'-O-ß-D-glucopyranosyl)-benzene (2), (7'R,8'R) guaiacylglycerol 4'-O-ß-D-[6″-O-3,5-dimethoxy-4-hydroxylbenzoyl]-gluco-pyranoside (3), along with one known phenylpropanoid (4) were isolated from the ethanol extract of Phyllostachys nigra var. henonis fresh culm. The structures of all compounds were determined by analysis of UV, 1D NMR, 2D NMR, HR-ESI-MS and CD data. All compounds were evaluated for their DPPH radical scavenging activity. Compound 2 (IC50 54.9 µM) and 3 (IC50 77.2 µM) exhibited moderate antioxidant activity compared with two positive control compounds L-ascorbic acid (IC50 15.5 µM) and 2,6-ditertbutyl-4-methyl phenol (IC50 19.1 µM).

Asia-Pacific consensus on long-term and sequential therapy for osteoporosis.

Objectives: This study aimed to present the Asia-Pacific consensus on long-term and sequential therapy for osteoporosis, offering evidence-based recommendations for the effective management of this chronic condition. The primary focus is on achieving optimal fracture prevention through a comprehensive, individualized approach. Methods: A panel of experts convened to develop consensus statements by synthesizing the current literature and leveraging clinical expertise. The review encompassed long-term anti-osteoporosis medication goals, first-line treatments for individuals at very high fracture risk, and the strategic integration of anabolic and antiresorptive agents in sequential therapy approaches. Results: The panelists reached a consensus on 12 statements. Key recommendations included advocating for anabolic agents as the first-line treatment for individuals at very high fracture risk and transitioning to antiresorptive agents following the completion of anabolic therapy. Anabolic therapy remains an option for individuals experiencing new fractures or persistent high fracture risk despite antiresorptive treatment. In cases of inadequate response, the consensus recommended considering a switch to more potent medications. The consensus also addressed the management of medication-related complications, proposing alternatives instead of discontinuation of treatment. Conclusions: This consensus provides a comprehensive, cost-effective strategy for fracture prevention with an emphasis on shared decision-making and the incorporation of country-specific case management systems, such as fracture liaison services. It serves as a valuable guide for healthcare professionals in the Asia-Pacific region, contributing to the ongoing evolution of osteoporosis management.

Fully Integrated Multiplexed Wristwatch for Real-Time Monitoring of Electrolyte Ions in Sweat.

Considerable progress has already been made in sweat sensors based on electrochemical methods to realize real-time monitoring of biomarkers. However, realizing long-term monitoring of multiple targets at the atomic level remains extremely challenging, in terms of designing stable solid contact (SC) interfaces and fully integrating multiple modules for large-scale applications of sweat sensors. Herein, a fully integrated wristwatch was designed using mass-manufactured sensor arrays based on hierarchical multilayer-pore cross-linked N-doped porous carbon coated by reduced graphene oxide (NPCs@rGO-950) microspheres with high hydrophobicity as core SC, and highly selective monitoring simultaneously for K+, Na+, and Ca2+ ions in human sweat was achieved, exhibiting near-Nernst responses almost without forming an interfacial water layer. Combined with computed tomography, solid-solid interface potential diffusion simulation results reveal extremely low interface diffusion potential and high interface capacitance (598 µF), ensuring the excellent potential stability, reversibility, repeatability, and selectivity of sensor arrays. The developed highly integrated-multiplexed wristwatch with multiple modules, including SC, sensor array, microfluidic chip, signal transduction, signal processing, and data visualization, achieved reliable real-time monitoring for K+, Na+, and Ca2+ ion concentrations in sweat. Ingenious material design, scalable sensor fabrication, and electrical integration of multimodule wearables lay the foundation for developing reliable sweat-sensing systems for health monitoring.

Pyroptotic macrophages induce disruption of glutamate metabolism in periodontal ligament stem cells contributing to their compromised osteogenic potential.

Macrophage pyroptosis is of key importance to host defence against pathogen infections and may participate in the progression and recovery of periodontitis. However, the role of pyroptotic macrophages in regulating periodontal ligament stem cells (PDLSCs), the main cell source for periodontium renewal, remains unclear. First, we found that macrophage pyroptosis were enriched in gingiva tissues from periodontitis patients compared with those of healthy people through immunofluorescence. Then the effects of pyroptotic macrophages on the PDLSC osteogenic differentiation were investigated in a conditioned medium (CM)-based coculture system in vitro. CM derived from pyroptotic macrophages inhibited the osteogenic differentiation-related gene and protein levels, ALP activity and mineralized nodule formation of PDLSCs. The osteogenic inhibition of CM was alleviated when pyroptosis was inhibited by VX765. Further, untargeted metabolomics showed that glutamate limitation may be the underlying mechanism. However, exogenous glutamate supplementation aggravated the CM-inhibited osteogenic differentiation of PDLSCs. Moreover, CM increased extracellular glutamate and decreased intracellular glutamate levels of PDLSCs, and enhanced the gene and protein expression levels of system xc - (a cystine/glutamate antiporter). After adding cystine to CM-based incubation, the compromised osteogenic potency of PDLSCs was rescued. Our data suggest that macrophage pyroptosis is related to the inflammatory lesions of periodontitis. Either pharmacological inhibition of macrophage pyroptosis or nutritional supplements to PDLSCs, can rescue the compromised osteogenic potency caused by pyroptotic macrophages.

Highly Stable Solid Contact Calcium Ion-Selective Electrodes: Rapid Ion-Electron Transduction Triggered by Lipophilic Anions Participating in Redox Reactions of CunS Nanoflowers.

Solid contact (SC) calcium ion-selective electrodes (Ca2+-ISEs) have been widely applied in the analysis of water quality and body fluids by virtue of the unique advantages of easy operation and rapid response. However, the potential drift during the long-term stability test hinders their further practical applications. Designing novel redox SC layers with large capacitance and high hydrophobicity is a promising approach to stabilize the potential stability, meanwhile, exploring the transduction mechanism is also of great guiding significance for the precise design of SC layer materials. Herein, flower-like copper sulfide (CunS-50) composed of nanosheets is meticulously designed as the redox SC layer by modification with the surfactant (CTAB). The CunS-50-based Ca2+-ISE (CunS-50/Ca2+-ISE) demonstrates a near-Nernstian slope of 28.23 mV/dec for Ca2+ in a wide activity linear range of 10-7 to 10-1 M, with a low detection limit of 3.16 × 10-8 M. CunS-50/Ca2+-ISE possesses an extremely low potential drift of only 1.23 ± 0.13 µV/h in the long-term potential stability test. Notably, X-ray absorption fine-structure (XAFS) spectra and electrochemical experiments are adopted to elucidate the transduction mechanism that the lipophilic anion (TFPB-) participates in the redox reaction of CunS-50 at the solid-solid interface of ion-selective membrane (ISM) and redox inorganic SC layer (CunS-50), thereby promoting the generation of free electrons to accelerate ion-electron transduction. This work provides an in-depth comprehension of the transduction mechanism of the potentiometric response and an effective strategy for designing redox materials of ion-electron transduction triggered by lipophilic anions.

Total Tau Protein Mediates the Association of Ischemic Cerebrovascular Disease with Cognitive Decline.

Background: Patients with transient ischemic attack (TIA) or ischemic stroke demonstrate an increased risk of cognitive dysfunction. Accumulating evidence indicates that ischemic cerebrovascular disease (ICVD) may interact with the amyloid/tau/neurodegeneration (AT[N]) biomarkers to promote dementia. However, the precise pathological mechanisms remain to be fully characterized. Objective: To elucidate the interrelationships among ICVD, ATN biomarkers in cerebrospinal fluid (CSF), and cognition. Methods: A total of 2524 participants were recruited from the CABLE study. ICVD referred to TIA/ischemic stroke. Cognitive performance was assessed by China Modified Mini-Mental State Examination (CM-MMSE) and Montreal Cognitive Assessment-b (MoCA-b). Multivariate linear regression analyses were performed to evaluate the associations of ICVD with CSF ATN biomarkers and cognition. Causal mediation analyses were used to identify whether the association was mediated by ATN biomarkers. Results: ICVD was associated with higher total-tau (t-tau) (p = 2.828×10-2) and poorer cognition (CM-MMSE: p = 1.539×10-5, MoCA-b: p = 4.552×10-6). Additionally, no discernible correlation surfaced between ICVD and amyloid-ß (Aß) 42 (p = 6.910×10-1) or phosphorylated tau (p-tau) (p = 4.324×10-1). The influence of ICVD on cognitive function was partially mediated by CSF t-tau (CM-MMSE: proportion: 2.74%, MoCA-b: proportion: 2.51%). Subgroup analyses revealed the influences of t-tau were especially evident in male (CM-MMSE: proportion: 5.45%, MoCA-b: proportion: 5.38%) and mid-life group (CM-MMSE: proportion: 9.83%, MoCA-b: proportion: 5.31%). Conclusions: These results delineated t-tau as a potential mediator for the influence of ICVD on cognition. Targeting brain ischemia and alleviating neuronal injury induced by ischemia may be a promising approach for preventing cognitive decline.

Global trends in colorectal cancer and metabolic syndrome research: a bibliometric and visualization analysis.

Numerous studies have demonstrated a robust correlation between metabolic syndrome (MetS) and colorectal cancer (CRC). Nonetheless, no systematic analysis or visualization of relevant publications has been conducted via bibliometrics. This research, centred on 616 publications obtainable through the Web of Science Core Collection (WoSCC), employed CiteSpace software and VOSviewer software for correlation analyses of authors, journals, institutions, countries, keywords, and citations. The findings indicate that the Public Library of Science had the highest number of publications, while the United States, China, and South Korea were the most contributory nations. Recent years have seen the mechanisms linking Metabolic Syndrome with Colorectal Cancer, including diet, obesity, insulin resistance, and intestinal flora, remain a burgeoning research area. Furthermore, bariatric surgery appears to be a promising new area of study. This paper presents the initial bibliometric and visualization analysis of research literature concerning CRC and MetS which examines research trends and hotspots.

EVA1A, a novel and promising prognostic biomarker in colorectal cancer.

Purpose: The purpose of this study was to investigate the potential of EVA1A as a prognostic biomarker for Colorectal cancer (CRC). Methods: The study utilized public databases to analyze the difference in Evala mRNA expression between CRC tumor tissues and adjacent normal tissues. Additionallymunohistochemical staining was performed on 90 paired tissue samples to detect EVA1A expression. The relationship between EVA1A and clinicopathological features was examined, and a Kaplan-Meier survival analysis was conducted. Univariate and multivariate Cox analyses were employed to identify prognostic factors affecting the overall survival (OS) of CRC patients. Results: The analysis revealed a significant increase in Evala mRNA expression in CRC tumor cells compared to normal controls from public databases (P< 0.05). Immunohistochemical staining further confirmed a significant upregulation of EVA1A expression in CRC tissues (P< 0.05). High EVA1A expression was associated with age, pathological M stage, total tumor stage, and Carbohydrate antigen CA19-9 (CA19-9). Kaplan-Meier analysis demonstrated a significant association between high EVA1A expression and poor OS. Univariate and multivariate analysis identified EVA1A as an independent risk factor for CRC prognosis. Conclusion: The study suggests that EVA1A is increased in CRC tumor tissues and may serve as a potential biomarker for poor prognosis in CRC.

Citrate Improves Biomimetic Mineralization Induced by Polyelectrolyte-Cation Complexes Using PAsp-Ca&Mg Complexes.

Magnesium ions are highly enriched in early stage of biological mineralization of hard tissues. Paradoxically, hydroxyapatite (HAp) crystallization is inhibited significantly by high concentration of magnesium ions. The mechanism to regulate magnesium-doped biomimetic mineralization of collagen fibrils has never been fully elucidated. Herein, it is revealed that citrate can bioinspire the magnesium-stabilized mineral precursors to generate magnesium-doped biomimetic mineralization as follows: Citrate can enhance the electronegativity of collagen fibrils by its absorption to fibrils via hydrogen bonds. Afterward, electronegative collagen fibrils can attract highly concentrated electropositive polyaspartic acid-Ca&Mg (PAsp-Ca&Mg) complexes followed by phosphate solution via strong electrostatic attraction. Meanwhile, citrate adsorbed in/on fibrils can eliminate mineralization inhibitory effects of magnesium ions by breaking hydration layer surrounding magnesium ions and thus reduce dehydration energy barrier for rapid fulfillment of biomimetic mineralization. The remineralized demineralized dentin with magnesium-doped HAp possesses antibacterial ability, and the mineralization mediums possess excellent biocompatibility via cytotoxicity and oral mucosa irritation tests. This strategy shall shed light on cationic ions-doped biomimetic mineralization with antibacterial ability via modifying collagen fibrils and eliminating mineralization inhibitory effects of some cationic ions, as well as can excite attention to the neglected multiple regulations of small biomolecules, such as citrate, during biomineralization process.

Management of deep sacral and ischial pressure injuries with free-style local perforator flaps: A D+P+DPD model.

BACKGROUND: Previous reports on the treatment of sacral and ischial pressure injuries have not provided clear algorithms for surgical therapies. The objective of this study was to establish a reconstruction algorithm to guide the selection of an ideal free-style perforator flap that can be tailored to the defect in question. METHODS: We used 23 perforator flaps to reconstruct 14 sacral and 8 ischial defects in 22 patients over 5 years. A reconstruction algorithm system was developed based on the anatomical features of the perforator vessels (diameter, D; pulsatility [++∼+++], P) and their position in the skin island (DPD) (ie, D+P+DPD). A perforator-based propeller flap was applied as the first-line choice; if this plan was not feasible, we applied an altered V-Y advancement model or another second-choice technique. RESULTS: All flaps survived, and only 1 patient experienced partial wound dehiscence, which healed by secondary intention. After an average follow-up period of 11.2 months, no patient experienced recurrence or infection. CONCLUSIONS: Free-style perforator flap selection is determined by pressure injury and the desired advantage of a specific approach. The use of free-style perforator-based propeller flaps allows a surgeon to transfer healthy tissue into the defect, shifts the suture line away from the bony prominence, and preserves additional future donor sites. In cases where unexpected variations are encountered, the V-Y advancement model or another technique can be used. The simplified surgical algorithm (D+P+DPD) can provide versatility and reliability, achieve a durable, natural esthetic outcome, and minimize injuries to future donor sites.

ATF4 inhibits TRPV4 function and controls itch perception in rodents and nonhuman primates.

ABSTRACT: Acute and chronic itch are prevalent and incapacitating, yet the neural mechanisms underlying both acute and chronic itch are just starting to be unraveled. Activated transcription factor 4 (ATF4) belongs to the ATF/CREB transcription factor family and primarily participates in the regulation of gene transcription. Our previous study has demonstrated that ATF4 is expressed in sensory neurons. Nevertheless, the role of ATF4 in itch sensation remains poorly understood. Here, we demonstrate that ATF4 plays a significant role in regulating itch sensation. The absence of ATF4 in dorsal root ganglion (DRG) neurons enhances the itch sensitivity of mice. Overexpression of ATF4 in sensory neurons significantly alleviates the acute and chronic pruritus in mice. Furthermore, ATF4 interacts with the transient receptor potential cation channel subfamily V member 4 (TRPV4) and inhibits its function without altering the expression or membrane trafficking of TRPV4 in sensory neurons. In addition, interference with ATF4 increases the itch sensitivity in nonhuman primates and enhances TRPV4 currents in nonhuman primates DRG neurons; ATF4 and TRPV4 also co-expresses in human sensory neurons. Our data demonstrate that ATF4 controls pruritus by regulating TRPV4 signaling through a nontranscriptional mechanism and identifies a potential new strategy for the treatment of pathological pruritus.

Unveiling the Activity and Mechanism Alterations by Pyrene Decoration on a Co(II) Macrocyclic Catalyst for CO2 Reduction.

Mechanistic studies involving characterization of crucial intermediates are desirable for rational optimization of molecular catalysts toward CO2 reduction, while fundamental challenges are associated with such studies. Herein we present the systematic mechanistic investigations on a pyrene-appended CoII macrocyclic catalyst in comparison with its pyrene-free prototype. The comparative results also verify the reasons of the higher catalytic activity of the pyrene-tethered catalyst in noble-metal-free CO2 photoreduction with various photosensitizers, where a remarkable apparent quantum yield of 36±3 % at 425 nm can be obtained for selective CO production. Electrochemical and spectroelectrochemical studies in conjunction with DFT calculations between the two catalysts have characterized the key CO-bound intermediates and revealed their different CO-binding behavior, demonstrating that the pyrene group endows the corresponding CoII catalyst a lower catalytic potential, a higher stability, and a greater ease in CO release, all of which contribute to its better performance.

Efficacy of Electronic Cigarettes vs Varenicline and Nicotine Chewing Gum as an Aid to Stop Smoking: A Randomized Clinical Trial.

Importance: Electronic cigarettes (ECs) are often used by smokers as an aid to stopping smoking, but evidence is limited regarding their efficacy compared with nicotine replacement therapy (NRT), and no evidence is available on how their efficacy compares with that of varenicline. Objective: To evaluate whether ECs are superior to NRT and noninferior to varenicline in helping smokers quit. Design, Setting, and Participants: This was a randomized clinical trial conducted at 7 sites in China and including participants who were smoking at least 10 cigarettes per day and motivated to quit, not using stop-smoking medications or EC, and willing to use any of the study products. Participants were first recruited in May 2021, and data analysis was conducted in December 2022. Interventions: A cartridge-based EC (30 mg/mL nicotine salt for 2 weeks and 50 mg/mL after that), varenicline (0.5 mg, once a day for 3 days; 0.5 mg, twice a day for 4 days; and 1 mg, twice a day, after that), and 2 mg (for smokers of ≤20 cigarettes per day) or 4 mg (>20 cigarettes per day) nicotine chewing gum, all provided for 12 weeks and accompanied by minimal behavioral support (an invitation to join a self-help internet forum). Main Outcomes and Measures: The primary outcome was sustained abstinence from smoking at 6 months as validated by an expired-air carbon monoxide reading (<8 parts per million). Participants lost to follow-up were included as nonabstainers. Results: Of 1068 participants, 357 (33.5%) were female, and the mean (SD) age was 33.9 (3.1) years. A total of 409 (38.3%), 409 (38.3%), and 250 (23.4%) participants were randomized to the EC, varenicline, and NRT arms, respectively. The 6-month biochemically validated abstinence rates were 15.7% (n = 64), 14.2% (n = 58), and 8.8% (n = 22) in the EC, varenicline, and NRT study arms, respectively. The quit rate in the EC arm was noninferior to the varenicline arm (absolute risk reduction, 1.47%; 95% CI, -1.41% to 4.34%) and higher than in the NRT arm (odds ratio, 1.92; 95% CI, 1.15-3.21). Treatment adherence was similar in all study arms during the initial 3 months, but 257 participants (62.8%) in the EC arm were still using ECs at 6 months, with no further use in the 2 other study arms. The most common adverse reactions were throat irritation (32 [7.8%]) and mouth irritation (28 [6.9%]) in the EC arm, nausea (36 [8.8%]) in the varenicline arm, and throat irritation (20 [8.0%]) and mouth irritation (22 [8.8%]) in the NRT arm. No serious adverse events were recorded. Conclusions and Relevance: The results of this randomized clinical trial found that when all treatments were provided with minimal behavior support, the efficacy of EC was noninferior to varenicline and superior to nicotine chewing gum. Trial Registration: Chinese Clinical Trial Registry: ChiCTR2100048156.

Role of antibiotics in Milligan-Morgan hemorrhoidectomy for Grade III to IV Hemorrhoids: A randomized clinical trial.

PURPOSE: This study was mainly to compare the safety and long-term clinical efficacy of using intravenous antibiotics in Milligan Morgan hemorrhoidectomy for Grade III to IV Prolapsing Hemorrhoids. METHODS: This was a parallel group, 3-arm, randomized clinical trial to evaluate the efficacy of intravenous prophylactic antibiotics. A total of 150 consecutive patients undergoing Milligan Morgan hemorrhoidectomy (MMH) in a tertiary hospital for grade III/IV hemorrhoids from January 2020 to August 2022 were enrolled. Patients were randomly assigned to three groups using a computer-generated table. Group A did not receive any prophylactic antibiotic, group B received 2 g I/V Cefoxitin Sodium before the induction of anesthesia, and group C received 2 g I/V Cefoxitin Sodium before the induction of anesthesia and 6 h after operation. RESULTS: There was no significant difference in measured VAS values on the 1st day,3rd day and 7th day after surgery (p> 0.05). Compared with VAS values on the 1st day postoperatively, these values got decreased on the 3rd day and 7th day after surgery (p< 0.05). In addition, there was no significant difference among the first defecation time, wound edema, bleeding, urinary retention after surgery (p> 0.05). There was no significant difference in the outcome comparison between all 3 groups' basal and the 3rd day postoperatively no matter in WBC, NUET% or CRP (p> 0.05). However, compared with basal, the WBC, NUET%,CRP(p< 0.05) of group A and group B on the 3rd day postoperatively got rised, the rate of recurrence of hemorrhoids follow-up for 1 year was 1.4%. CONCLUSIONS: Our results suggest that there is no efficacy on intravenous prophylactic antibiotics in Milligan Morgan hemorrhoidectomy.