Quantitative analysis of paravertebral muscle asymmetry and its correlation with spinal deformity in patients with degenerative lumbar scoliosis: a retrospective case-control study.

Background: The degeneration and functional decline of paravertebral muscles (PVMs) are reported to be closely linked to the incidence of degenerative lumbar scoliosis (DLS), a spinal deformity of the mature skeleton. However, the functional role and degeneration of PVMs and their relationship to the development of spinal deformities remain controversial. Therefore, the present study analyzed the morphological changes in the PVMs of patients with DLS, and explored the relationship between PVM degeneration and spinal osseous parameters. Methods: In this retrospective case-control study, we evaluated the PVM parameters of patients with DLS (n=120) and compared them with patients free of DLS (control group, n=120). The cross-sectional area (CSA) and computed tomography (CT) values of the PVM at the lumbar vertebra 1-5 levels were measured. Further, the lumbar scoliosis Cobb, lumbar lordotic, and apical vertebral rotation angles were measured on CT and radiographs in the DLS group, and the relationship between PVM changes and these factors was analyzed. Results: In the control group, the PVM CSA and CT values differed insignificantly between the bilateral sides at all levels (P>0.05). In the DLS group, the CSAs of the multifidus (MF) and erector spinae (ES) were larger on the convex side than the concave side (P>0.05), whereas that of the psoas major (PM) was smaller on the convex side than the concave side (P<0.05). The CT value of the PVM was lower on the convex side at all levels (P<0.05). The CSA and CT values on both sides of the patients were lower in the DLS group than the control group at all levels (P<0.05). Further, the degree of PVM asymmetry at the apical vertebral level was positively correlated with the lumbar scoliosis (P<0.01) and apical vertebral rotation angles (P<0.05), but negatively correlated with the lumbar lordotic angle (P<0.05). Conclusions: Asymmetric degeneration of the PVM was observed bilaterally in DLS patients, and the degeneration was more pronounced on the concave side than the convex side. This asymmetrical degeneration was closely associated with the severity of lumbar scoliosis, vertebral rotation, and loss of lumbar lordosis, and a stronger correlation was observed with the MF and ES than with the PM.

Bioequivalence Study of Atenolol Tablets in Healthy Chinese Subjects Under Fasting and Fed Conditions.

Atenolol, a cardioselective ß1-blocker, exhibits efficacy in treating cardiovascular diseases. We conducted a single-center, randomized, open, single-dose, 2-preparation, 2-cycle, 2-sequence, double-crossover trial with a 7-day washout period to investigate the pharmacokinetics, bioequivalence (BE), and safety of test and reference atenolol tablets (25 mg) in healthy Chinese volunteers. Forty-eight healthy participants were randomized into the fasting and fed arms. After administering a single oral dose of the test or reference formulation (25 mg), plasma atenolol concentrations were measured using liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were obtained from concentration-time profiles. In total, 23 and 24 individuals were included in the fasting and fed arms, respectively. The mean concentration-time profiles for both formulations were similar, and Cmax, AUC0-t, and AUC0-∞ were within the BE range of 80%-125%. Thirteen adverse events (AEs) were observed in 7 participants in the fasting arm; 1 withdrew from the trial early owing to an AE. In the fed arm, 20 AEs were observed in 8 participants, and none withdrew from the trial. All adverse reactions were grade I, with no serious AEs or deaths. Therefore, the 2 tablets are bioequivalent in healthy Chinese individuals under fasting and fed conditions, supporting their further clinical development.

Anxiety and depression in nasopharyngeal carcinoma patients and network analysis to identify central symptoms: A cross-sectional study from a high-incidence area.

PURPOSE: To determine the prevalence of anxiety and depression in patients with nasopharyngeal carcinoma (NPC) and to identify central symptoms and bridge symptoms among psychiatric disorders. METHODS: This cross-sectional study recruited patients with NPC in Guangzhou, China from May 2022, to October 2022. The General Anxiety Disorder-7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9) were used for screening anxiety and depression, respectively. Network analysis was conducted to evaluate the centrality and connectivity of the symptoms of anxiety, depression, quality of life (QoL) and insomnia. RESULTS: A total of 2806 respondents with complete GAD-7 and PHQ-9 scores out of 3828 were enrolled. The incidence of anxiety in the whole population was 26.5% (depression, 28.5%; either anxiety or depression, 34.8%). Anxiety was highest at caner diagnosis (34.2%), while depression reached a peak at late-stage radiotherapy (48.5%). Both moderate and severe anxiety and depression were exacerbated during radiotherapy. Coexisting anxiety and depression occurred in 58.3% of those with either anxiety or depression. The generated network showed that anxiety and depression symptoms were closely connected; insomnia was strongly connected with QoL. "Sad mood", "Lack of energy", and "Trouble relaxing" were the most important items in the network. Insomnia was the most significant bridge item that connected symptom groups. CONCLUSION: Patients with NPC are facing alarming disturbances of psychiatric disorders; tailored strategies should be implemented for high-risk patients. Besides, central symptoms (sad mood, lack of energy, and trouble relaxing) and bridge symptoms (insomnia) may be potential interventional targets in future clinical practice.

Association Between Artificial Intelligence Based Chest Computed Tomography and Clinical/Laboratory Characteristics with Severity and Mortality in COVID-19 Hospitalized Patients.

Background: Some patients with COVID-19 rapidly develop respiratory failure or mortality, underscoring the necessity for early identification of those prone to severe illness. Numerous studies focus on clinical and lab traits, but only few attend to chest computed tomography. The current study seeks to numerically quantify pulmonary lesions using early-phase CT scans calculated through artificial intelligence algorithms in conjunction with clinical and laboratory helps clinicians to early identify the development of severe illness and death in a group of COVID-19 patients. Methods: From December 15, 2022, to January 30, 2023, 191 confirmed COVID-19 patients admitted to Xinhua Hospital Affiliated with Shanghai Jiao Tong University School of Medicine were consecutively enrolled. All patients underwent chest CT scans and serum tests within 48 hours prior to admission. Variables significantly linked to critical illness or mortality in univariate analysis were subjected to multivariate logistic regression models post collinearity assessment. Adjusted odds ratio, 95% confidence intervals, sensitivity, specificity, Youden index, receiver-operator-characteristics (ROC) curves, and area under the curve (AUC) were computed for predicting severity and in-hospital mortality. Results: Multivariate logistic analysis revealed that myoglobin (OR = 1.003, 95% CI 1.001-1.005), APACHE II score (OR = 1.387, 95% CI 1.216-1.583), and the infected CT region percentage (OR = 113.897, 95% CI 4.939-2626.496) independently correlated with in-hospital COVID-19 mortality. Prealbumin stood as an independent safeguarding factor (OR = 0.965, 95% CI 0.947-0.984). Neutrophil counts (OR = 1.529, 95% CI 1.131-2.068), urea nitrogen (OR = 1.587, 95% CI 1.222-2.062), SOFA score(OR = 3.333, 95% CI 1.476-7.522), qSOFA score(OR = 15.197, 95% CI 3.281-70.384), PSI score(OR = 1.053, 95% CI 1.018-1.090), and the infected CT region percentage (OR = 548.221, 95% CI 2.615-114,953.586) independently linked to COVID-19 patient severity.

Peripheral myopic defocus signal affects the efficiency of visual information processing in myopic children.

PURPOSE: Spectacle lenses with peripheral lenslets have shown promise for myopia control by providing peripheral myopic defocus signals. Here, we aimed to investigate the impact of prolonged exposure (>6 months) to peripheral myopic defocus on visual information processing in myopic children. METHODS: The study included 30 myopic children who habitually wore spectacle lenses with highly aspherical lenslets (HAL group) and 34 children who habitually wore single-vision (SV group) spectacles. The quick contrast sensitivity function (qCSF) was used to measure contrast sensitivity (CS) under conditions of no or high noise. Both groups were tested with HAL and SV lenses. The perceptual template model was utilised to fit the contrast sensitivity function (CSF) and determine differences in information processing efficiency through internal additive noise ( N add $$ {N}_{\mathrm{add}} $$ ) and perceptual template gain (ß). RESULTS: The areas under the log CSF in the SV group were significantly higher than for the HAL group in both zero-noise conditions with the SV test lens (p = 0.03) and high-noise conditions with the HAL test lens (p = 0.02). For 2 cycle per degree (cpd) stimuli, ß was significantly higher in the SV group with the HAL test lens than in the HAL group (p = 0.02), while there was a trend towards a significant difference in ß for 6 cpd stimuli (p = 0.07). However, there were no significant differences in N add $$ {N}_{\mathrm{add}} $$ between the two groups, with or without noise interference. CONCLUSION: The reduced CS observed in myopic children wearing HAL lenses for 6 months or more may be due to decreased ß. This suggests that prolonged use of spectacle lenses with peripheral myopic defocus signals may compromise the central visual system's ability to process additional external noise, resulting in decreased efficiency in visual information processing.

Partial response to crizotinib + regorafenib + PD-1 inhibitor in a metastatic BRAF V600EMT colon cancer patient with acquired C-MET amplification and TPM4-ALK fusion: a case report.

Background: Colorectal cancer (CRC) with the Raf murine sarcoma viral oncogene homolog B (BRAF) V600E had a relatively poor prognosis. Anaplastic lymphoma kinase (ALK) fusion and the mesenchymal-to-epithelial transition factor (MET) amplification have been recognized as potentially important therapeutic targets in non-small cell lung cancer (NSCLC). However, both of them are of extremely lower frequencies (<2%) in metastatic CRC, and few studies have mentioned the real application of their inhibitors in CRC treatment. Case Description: A 49-year-old Chinese male was diagnosed with ascending colon adenocarcinoma (cT3N+?M1) with liver metastases. The patient performed next-generation sequencing (NGS) using tissue and circulating tumor DNA (ctDNA), and the results showed a BRAF V600E mutation. He received an initial combination treatment with cetuximab, dabrafenib, and trametinib with a partial response (PR) assessment. We changed the therapy regimen on this patient several times because of the patient's intolerance to the drugs or the inefficacy of the treatment. During this period, we detected the c-MET amplification and tropomyosin 4 (TPM4)-ALK fusion by NGS after triplet targeted therapy (tislelizumab, dabrafenib, and trametinib), thus he was finally treated with programmed cell death protein 1 (PD-1) inhibitor (tislelizumab), MET/ALK inhibitor (crizotinib) plus multikinase inhibitor (regorafenib). Imageological examinations showed that PR was achieved and ctDNA sequencing results indicated a significantly reduced BRAF mutation frequency, MET amplification and TPM4-ALK fusion were undetectable. NGS analysis of peripheral blood showed a recurrence of the MET acquired resistant amplification mutation over 2 months of ongoing treatment. but the patient was assessed as PR and still under treatment of crizotinib, tislelizumab and regorafenib within good physical condition. At the last follow-up on October 2021, the patient died of symptomatic treatment fail for obstructive jaundice. The patient finally achieved 11 months overall survival. Conclusions: This study reported a co-existence of a BRAF V600E mutation, c-MET amplification and TPM4-ALK fusion in a CRC patient. Administration of crizotinib combined with regorafenib and tislelizumab obtained an obvious response. Furthermore, continuous ctDNA detection appears to be a promising technique to monitor tumor burden, which may provide better clinical decision support during the disease course.

BnaABF3 and BnaMYB44 regulate the transcription of zeaxanthin epoxidase genes in carotenoid and abscisic acid biosynthesis.

Zeaxanthin epoxidase (ZEP) is a key enzyme that catalyzes the conversion of zeaxanthin to violaxanthin in the carotenoid and abscisic acid (ABA) biosynthesis pathways. The rapeseed (Brassica napus) genome has 4 ZEP (BnaZEP) copies that are suspected to have undergone subfunctionalization, yet the 4 genes' underlying regulatory mechanisms remain unknown. Here, we genetically confirmed the functional divergence of the gene pairs BnaA09.ZEP/BnaC09.ZEP and BnaA07.ZEP/BnaC07.ZEP, which encode enzymes with tissue-specific roles in carotenoid and ABA biosynthesis in flowers and leaves, respectively. Molecular and transgenic experiments demonstrated that each BnaZEP pair is transcriptionally regulated via ABA-responsive element-binding factor 3 s (BnaABF3s) and BnaMYB44s as common and specific regulators, respectively. BnaABF3s directly bound to the promoters of all 4 BnaZEPs and activated their transcription, with overexpression of individual BnaABF3s inducing BnaZEP expression and ABA accumulation under drought stress. Conversely, loss of BnaABF3s function resulted in lower expression of several genes functioning in carotenoid and ABA metabolism and compromised drought tolerance. BnaMYB44s specifically targeted and repressed the expression of BnaA09.ZEP/BnaC09.ZEP but not BnaA07.ZEP/BnaC07.ZEP. Overexpression of BnaA07.MYB44 resulted in increased carotenoid content and an altered carotenoid profile in petals. Additionally, RNA-seq analysis indicated that BnaMYB44s functions as a repressor in phenylpropanoid and flavonoid biosynthesis. These findings provide clear evidence for the subfunctionalization of duplicated genes and contribute to our understanding of the complex regulatory network involved in carotenoid and ABA biosynthesis in B. napus.

Association between lipoprotein(a) and cardiovascular disease in patients undergoing coronary angiography.

OBJECTIVE: Many previous studies reported the relationship between lipoprotein(a) and cardiovascular disease, but the conclusions were controversial. The aim of our study was to retrospectively investigate the association between lipoprotein(a) and cardiovascular disease in patients undergoing coronary angiography. METHODS: We collected and compared clinical information of patients hospitalized for coronary angiography. Multivariable hierarchical logistic regression was used to evaluate the association between lipoprotein(a) and cardiovascular disease in patients undergoing coronary angiography. RESULTS: There were no significant differences in gender, hypertension, APOA1, smoking, hyperuricemia, obesity, acute myocardial infarction (AMI), cardiac insufficiency, family history of diabetes, or family history of hyperlipidemia among the four groups of lipoprotein(a). Elevated lipoprotein(a) does not increase the risk of hypertriglyceridemia, while elevated lipoprotein(a) increases the risk of high total cholesterol and high low-density lipoprotein cholesterol (LDL-c). Elevated lipoprotein(a) increases the risk of diabetes and premature coronary artery disease (CAD). Elevated lipoprotein(a) increases the incidence of CAD, multivessel lesions, and percutaneous coronary intervention (PCI). Multivariate logistic regression analysis further showed that elevated lipoprotein(a) increases the incidence of high total cholesterol, high LDL­c, diabetes, CAD, premature CAD, multivessel lesions, and PCI. CONCLUSION: The findings indicated that elevated lipoprotein(a) had no obvious relationship with hypertension and obesity. Elevated lipoprotein(a) increases the risk of high total cholesterol, high LDL­c, and premature CAD, and increases the occurrence and severity of coronary heart disease.

Differential Impact of 0.01% and 0.05% Atropine Eyedrops on Ocular Surface in Young Adults.

Purpose: To evaluate the effect of low-concentration (0.01% and 0.05%) atropine eyedrops on ocular surface characteristics in young adults. Methods: Twenty-six myopic students aged 18 to 30 years were randomly assigned to receive either 0.01% or 0.05% atropine once nightly for 14 days, followed by cessation, with a ≥14-day interval between each administration. Assessments were conducted one, two, seven, and 14 days after using atropine with corresponding timepoints after atropine cessation. Tear meniscus height and first and average noninvasive keratograph tear film breakup time (NIKBUT-first, NIKBUT-average) were measured using Keratograph 5M, whereas the objective scatter index (OSI) was measured by OQAS II devices; the ocular surface disease index (OSDI) score was also obtained. Results: The mean OSI peaked after two days of administration of 0.05% atropine (ß = 0.51, P = 0.001), accompanied by significant decreases in NIKBUT-first (ß = -7.73, P < 0.001) and NIKBUT-average (ß = -8.10, P < 0.001); the OSDI peaked after 14 days (ß = 15.41, P < 0.001). The above parameters returned to baseline one week after atropine discontinuation (all P > 0.05). NIKBUT-first and NIKBUT-average reached their lowest points after 14 days of 0.01% atropine administration (NIKBUT-first: ß = -4.46, P = 0.005; NIKBUT-average: ß = -4.42, P = 0.001), but those significant changes were diminished once atropine treatment stopped. Conclusions: Young adult myopes experienced a significant but temporary impact on the ocular surface with 0.05% atropine administration, whereas 0.01% atropine had a minimal effect. Translational Relevance: The investigation of the ocular surface effects of different concentrations of atropine may inform evidence-based clinical decisions regarding myopia control in young adults.

Effect of spectacle lenses with aspherical lenslets on choroidal thickness in myopic children: a 3-year follow-up study.

BACKGROUND: To investigate the impact of wearing spectacle lenses with highly aspherical lenslets (HAL) for 3 years and the impact of switching from single-vision lenses (SVL) to HAL on choroidal thickness (ChT). METHODS: Fifty-one participants who had already worn HAL for 2 years continued wearing them for an additional year (HAL group). Further, 50 and 41 participants who had worn spectacle lenses with slightly aspherical lenslets (SAL) and SVL for 2 years, respectively, switched to wearing HAL for another year (SAL-HAL and SVL-HAL groups). Additionally, 48 new participants aged 10-15 years were enrolled to wear SVL at the third year (new-SVL group). ChT was measured every 6 months throughout the study. RESULTS: Significant differences were observed in the changes in ChT among the four groups at the third year (all P < 0.05 except for the outer nasal region: P = 0.09), with the new-SVL group showing larger reductions compared with the other three groups. However, none of the three HAL-wearing groups showed significant changes in ChT at the third year (all P > 0.05). When comparing the changes in ChT for 3 years among the HAL, SAL-HAL, and SVL-HAL groups, significant differences were found before switching to HAL, but these differences were abolished after all participants switched to HAL. CONCLUSIONS: Compared to those in the SVL group, choroid thinning was significantly inhibited in all the HAL groups. Wearing HAL for 3 years no longer had a choroidal thickening effect but could still inhibit choroidal thinning compared to wearing SVL. TRIAL REGISTRATION: The study was registered at the Chinese Clinical Trial Registry (ChiCTR1800017683), http://www.chictr.org.cn/showproj.aspx?proj=29789 .

Effect of different shapes of steel fibers and palygorskite-nanofibers on performance of ultra-high-performance concrete.

Herein, a practical ultra-high-performance concrete (UHPC) was created by adding two different shapes of steel fibers and curing them at ambient temperature using palygorskite-nanofiber (PN) as the modifier. The compressive strength, flexural strength, water absorption capacity, and porosity were analyzed to determine the effects of the steel fibers and PNs on the UHPC mechanical and physical properties. The steel fibers and PNs were found to improve these properties. The UHPC mechanical properties were outstanding at 1.5% fiber dosage, while physical properties were excellent at 1.0% fiber dosage. The mechanical and physical characteristics of UHPC were preferably at a PN dosage of 0.2% and the fiber dosage of 1.0%. The compressive and flexural strengths of straight-steel-fiber UHPC were 145.57 and 19.67 MPa, respectively, i.e., 42.0 and 109.4% higher than those of the reference specimens (i.e., those without fibers or PNs); the water absorption capacity and porosity decreased by 50.1 and 60.7%, respectively. The compressive and flexural strengths of hooked-end-steel-fiber UHPC were 18.3 and 96.0% higher than those of the reference specimens, respectively, and the water absorption capacity and porosity decreased by 43.2 and 29.8%, respectively. These results could provide vital information for the promotion and practical application of UHPC.

Puerarin enhances TFEB-mediated autophagy and attenuates ROS-induced pyroptosis after ischemic injury of random-pattern skin flaps.

BACKGROUND AND AIM: Necrosis of random-pattern flaps restricts their application in clinical practice. Puerarin has come into focus due to its promising therapeutic effects in ischemic diseases. Here, we employed Puerarin and investigated its role and potential mechanisms in flap survival. EXPERIMENTAL PROCEDURE: The effect of Puerarin on the viability of human umbilical vein endothelial cells (HUVECs) was assessed by CCK-8, EdU staining, migration, and scratch assays. Survival area measurement and laser Doppler blood flow (LDBF) were utilized to assess the viability of ischemic injury flaps. Levels of molecules related to oxidative stress, pyroptosis, autophagy, transcription factor EB (TFEB), and the AMPK-TRPML1-Calcineurin signaling pathway were detected using western blotting, immunofluorescence, dihydroethidium (DHE) staining, RT-qPCR and Elisa. KEY RESULTS: The findings demonstrated that Puerarin enhanced the survivability of ischemic flaps. Autophagy, oxidative stress, and pyroptosis were implicated in the ability of Puerarin in improving flap survival. Increased autophagic flux and augmented tolerance to oxidative stress contribute to Puerarin's suppression of pyroptosis. Additionally, Puerarin modulated the activity of TFEB through the AMPK-TRPML1-Calcineurin signaling pathway, thereby enhancing autophagic flux. CONCLUSIONS AND IMPLICATIONS: Puerarin promoted flap survival from ischemic injury through upregulation of TFEB-mediated autophagy and inhibition of oxidative stress. Our findings offered valuable support for the clinical application of Puerarin in the treatment of ischemic diseases, including random-pattern flaps.

Comprehensive quality evaluation of fermented-steaming Fructus Aurantii based on chemical composition, flavor characteristics, and intestinal microbial community.

Fructus Aurantii (FA) is an edible and medicinal functional food used worldwide that enhances digestion. Since raw FA (RFA) possesses certain side effects for some patients, processed FA (PFA) is commonly used in clinical practice. This study aimed to establish an objective and comprehensive quality evaluation of the PFA that employed the technique of steaming and fermentation. Combined with the volatile and non-volatile components, as well as the regulation of gut microbiota, the differentiation between RFA and PFA was analyzed. The results showed that the PFA considerably reduced the contents of flavonoid glycosides while increasing hesperidin-7-O-glucoside and flavonoid aglycones. The electronic nose and GC-MS (Gas chromatography/mass spectrometry) effectively detected the variation in flavor between RFA and PFA. Correlation analysis revealed that eight volatile components (relative odor activity value [ROAV] ≥ 0.1) played a key role in inducing odor modifications. The original floral and woody notes were subdued due to decreased levels of linalool, sabinene, α-terpineol, and terpinen-4-ol. After processing, more delightful flavors such as lemon and fruity aromas were acquired. Furthermore, gut microbiota analysis indicated a significant increase in beneficial microbial taxa. Particularly, Lactobacillus, Akkermansia, and Blautia exhibited higher abundance following PFA treatment. Conversely, a lower presence of pathogenic bacteria, including Proteobacteria, Flexispira, and Clostridium. This strategy contributes to a comprehensive analysis technique for the quality assessment of FA, providing scientific justifications for processing FA into high-value products with enhanced health benefits. PRACTICAL APPLICATION: This study provided an efficient approach to Fructus Aurantii quality evaluation. The methods of fermentation and steaming showed improved quality and safety.

NSUN2 relies on ALYREF to regulate Nrf2-mediated oxidative stress and alleviate Dox-induced liver injury.

BACKGROUND: Doxorubicin (Dox) is associated with various liver injuries, limiting its clinical utility. This study investigates whether NSUN2 participates in Dox-induced liver injury and the associated molecular mechanism. METHODS: In vivo and in vitro liver cell injury models were constructed based on Dox therapy. The protein levels of NSUN2 and oxidative stress indicators Nrf2, HO-1, and NQO1 were evaluated by Western blot. The RNA binding potential was detected by RNA methylation immunoprecipitation (RIP). Additionally, the effect of NSUN2 on Nrf2 mRNA synthesis and localization was evaluated using an RNA fluorescence probe. RESULTS: NSUN2 was downregulated, and liver tissue suffered significant pathological damage in the Dox group. The levels of ALT and AST significantly increased. NSUN2 interference exacerbated Dox-induced liver cell damage, which was reversed by NSUN2 overexpression. RIP demonstrated that NSUN2 recognized and bound to Nrf2 mRNA. Western blot analysis showed the protein level of Nrf2 in the NSUN2-WT group was significantly higher than that of the control group, whereas there was no significant change in Nrf2 level in the mutant NSUN2 group. Luciferase analysis demonstrated that NSUN2 could recognize and activate the Nrf2 5'UTR region of LO2 cells. In addition, RIP analysis revealed that ALYREF could recognize and bind to Nrf2 mRNA and that ALYREF controls the regulatory effect of NSUN2 on Nrf2. CONCLUSION: NSUN2 regulates Dox-induced liver cell damage by increasing Nrf2 mRNA m5C methylation to inhibit inhibiting antioxidant stress. The regulatory effect of NSUN2 on Nrf2 depends on ALYREF.

Dihydrocapsaicin suppresses the STING-mediated accumulation of ROS and NLRP3 inflammasome and alleviates apoptosis after ischemia-reperfusion injury of perforator skin flap.

Avascular necrosis frequently occurs as a complication following surgery involving the distal perforator flap. Dihydrocapsaicin (DHC) can protect tissue from ischemia-reperfusion (I/R) injury, but its specific role in multizone perforator flaps remains unclear. In this study, the prospective target of DHC in the context of I/R injury was predicted using network pharmacology analysis. Flap viability was determined through survival area analysis, laser Doppler blood flow, angiograms, and histological examination. The expressions of angiogenesis, apoptosis, NLR family pyrin domain containing 3 (NLRP3) inflammasome, oxidative stress, and molecules related to cyclic guanosine monophosphate (GMP)-adenosine monophosphate synthase (cGAS)-interferon gene stimulant (STING) pathway were assessed using western blotting, immunofluorescence, TUNEL staining, and dihydroethidium (DHE) staining. Our finding revealed that DHC promoted the perforator flap survival, which involves the cGAS-STING pathway, oxidative stress, NLRP3 inflammasome, apoptosis, and angiogenesis. DHC induced oxidative stress resistance and suppressed the NLRP3 inflammasome, preventing apoptosis in vascular endothelial cells. Through regulation of STING pathway, DHC controlled oxidative stress in endothelial cells and NLRP3 levels in ischemic flaps. However, activation of the cGAS-STING pathway led to the accumulation of reactive oxygen species (ROS) and NLRP3 inflammasome, thereby diminishing the protective role of DHC. DHC enhanced the survival of multidomain perforator flaps by suppressing the cGAS-STING pathway, oxidative stress, and the formation of NLRP3 inflammasome. These findings unveil a potentially novel mechanism with clinical significance for promoting the survival of multidomain perforator flaps.

Comparison of the effects of different functional exercise sequences on lymphedema in breast cancer: protocol for an exploratory randomised controlled cross-over trial.

INTRODUCTION: Breast cancer-related lymphedema (BCRL) is a common postoperative complication of breast cancer. It develops in a chronic and vicious cycle. Once lymphedema occurs, it cannot be cured and bring serious physiological, psychological, social and economic burden to patients. Upper limb functional exercises are an effective and convenient intervention for managing lymphedema. However, the optimal exercise sequence remains unclear. Therefore, we aim to compare the effects of exercise sequences under the guidance of commonly used exercise sequences and lymphatic flow theory. METHODS: An exploratory randomised controlled cross-over trial will be conducted. 32 patients with BCRL are randomly allocated into two groups (group A and group B). Group A patients will perform functional exercise from wrist joint to shoulder joint, and the exercise direction of group B is opposite to that of group A, that is, from shoulder joint to wrist joint end. Exercise time is once a day, each 20-30 min, for 2 weeks. After 2 weeks of washout period, A and B groups of exchange exercise sequences (exercise frequency and duration unchanged). The primary outcome is upper limb circumference, and secondary outcomes are upper limb function and lymphedema symptoms. ETHICS AND DISSEMINATION: This study protocol is presented in accordance with the Standard Protocol Items: Recommendations for Interventional Trials guidelines. All participants will sign a written informed consent. The research ethics regional committee of Shanghai Seventh People's Hospital has approved the study. Regardless of the outcome of this study, the results will be published in open-access journals to ensure public access. TRIAL REGISTRATION NUMBER: ChiCTR2200066463.

The efficacy of extracted Tanshinone compounds for infantile hemangiomas of the skin: results from a pilot study.

Background: Infantile hemangiomas (IHs) on skin are conventionally treated with beta blockers, pulsed dye laser (PDL), or surgery, either invasive or limited to clinical conditions. Our preclinical studies suggested that Tanshinone, extracted from Salvia miltiorrhiza (Tanshin), had a beneficial effect on IHs. Thus, we conducted a pilot clinical study to evaluate the safety and efficacy of topical Tanshinone compounds on superficial IHs. Methods: The single-armed pilot study included a total of 29 infants diagnosed with IHs. Thrice daily (at an interval of 6-8 hours) topical applications of Tanshinone were used for each patient. The primary response was the skin erythema index assessed by investigators using SkinColorCatch colorimeter instrument (Delfin). The Achauer score and the satisfaction of parents were also evaluated. Results: A total of 29 infants, 22 females (76%) and 7 males (24%), with a median age of 60 days (interquartile range, 45 to 99 days) were included. The position of IHs was distributed in the trunk (44.8%), head (34.5%), and limbs (20.7%). After 6 months of IHs treatment, the decrease in skin erythema index (baseline: 566.79±854.67 vs. after treatment: 467.97±1,118.39, P<0.001) was indicated. A total of 79.31% [23/29] of parents of the participants reported satisfaction on the responses after treatment. No serious side effects were documented. Conclusions: The topical use of Tanshinone compounds might be a potentially effective and noninvasive therapy in treating IHs.

Fine-tuning of thermally induced SCO behaviors of trinuclear cyanido-bridged complexes by regulating the electron donating ability of CCN-terminal fragments.

To achieve fine regulation of FeII SCO behavior, a series of trinuclear cyanido-bridged complexes trans-[CpMen(dppe)MII(CN)]2[Fe1II(abpt)2](OTf)2 (1-4) (1, M = Fe2 and n = 1; 2, M = Fe2 and n = 4; 3, M = Fe2 and n = 5; 4, M = Ru and n = 5; CpMen = alkyl cyclopentadienyl with n = 1, 4, 5; dppe = 1,2-bis-(diphenylphosphino)ethane; abpt = 4-amino-3,5-bis-(pyridin-2-yl)-1,2,4-triazole and OTf = CF3SO3-) were synthesized and fully characterized by using elemental analysis, X-ray crystallography, magnetic measurements, variable-temperature IR spectroscopy and Mössbauer spectroscopy. It is worth mentioning that different from many mononuclear Fe(abpt)2X2 (X = NCS, NCSe, N(CN)2, C(CN)3, (NC)2CC(OCH3)C(CN)2, (NC)2CC(OC2H5)C(CN)2, C16SO3 and Cl) complexes with more than one polymorph, only one polycrystalline form was found in complexes 1-4. Moreover, the thermally induced SCO behaviors of these four complexes are independent of intermolecular π-π interactions. The electron-donating ability of the CCN-terminal fragment of CpMen(dppe)MIICN can be flexibly regulated by changing the methyl number (n) of the cyclopentadiene ligand or metal ion type (MII). These investigations indicate that the electron-donating ability of the CCN-terminal fragment has an influence on the SCO behavior of Fe1II. The spin transition temperature (T1/2) of the complexes decreases with the increase of the electron-donating ability of the fragment CpMen(dppe)MII. This study provides a new strategy to predict and precisely regulate the behaviors of SCO complexes.

Circulating exosome-mediated AMPKα-SIRT1 pathway regulates lipid metabolism disorders in calf hepatocytes.

Subclinical ketosis (SCK) in dairy cows is often misdiagnosed because it lacks clinical signs and detection indicators. However, it is highly prevalent and may transform into clinical ketosis if not treated promptly. Due to the negative energy balance, a large amount of fat is mobilized, producing NEFA that exceeds the upper limit of liver processing, which in turn leads to the disturbance of liver lipid metabolism. The silent information regulator 1 (SIRT1) is closely related to hepatic lipid metabolism disorders. Exosomes as signal transmitters, also play a role in the circulatory system. We hypothesize that the circulating exosome-mediated adenosine 5'-monophosphate (AMP)-activated protein kinase alpha (AMPKα)-SIRT1 pathway regulates lipid metabolism disorders in SCK cows. We extracted the exosomes required for the experiment from the peripheral circulating blood of non-ketotic (NK) and SCK cows. We investigated the effect of circulating exosomes on the expression levels of mRNA and protein of the AMPKα-SIRT1 pathway in non-esterified fatty acid (NEFA)-induced dairy cow primary hepatocytes using in vitro cell experiments. The results showed that circulating exosomes increased the expression levels of Lipolysis-related genes and proteins (AMPKα, SIRT1, and PGC-1α) in hepatocytes treated with 1.2 mM NEFA, and inhibited the expression of lipid synthesis-related genes and protein (SREBP-1C). The regulation of exosomes on lipid metabolism disorders caused by 1.2 mM NEFA treatment showed the same trend as for SIRT1-overexpressing adenovirus. The added exosomes could regulate NEFA-induced lipid metabolism in hepatocytes by mediating the AMPKα-SIRT1 pathway, consistent with the effect of transfected SIRT1 adenovirus.