A xonotlite nanofiber bioactive 3D-printed hydrogel scaffold based on osteo-/angiogenesis and osteoimmune microenvironment remodeling accelerates vascularized bone regeneration.

BACKGROUND: Coordination between osteo-/angiogenesis and the osteoimmune microenvironment is essential for effective bone repair with biomaterials. As a highly personalized and precise biomaterial suitable for repairing complex bone defects in clinical practice, it is essential to endow 3D-printed scaffold the above key capabilities. RESULTS: Herein, by introducing xonotlite nanofiber (Ca6(Si6O17) (OH)2, CS) into the 3D-printed silk fibroin/gelatin basal scaffold, a novel bone repair system named SGC was fabricated. It was noted that the incorporation of CS could greatly enhance the chemical and mechanical properties of the scaffold to match the needs of bone regeneration. Besides, benefiting from the addition of CS, SGC scaffolds could accelerate osteo-/angiogenic differentiation of bone mesenchymal stem cells (BMSCs) and meanwhile reprogram macrophages to establish a favorable osteoimmune microenvironment. In vivo experiments further demonstrated that SGC scaffolds could efficiently stimulate bone repair and create a regeneration-friendly osteoimmune microenvironment. Mechanistically, we discovered that SGC scaffolds may achieve immune reprogramming in macrophages through a decrease in the expression of Smad6 and Smad7, both of which participate in the transforming growth factor-ß (TGF-ß) signaling pathway. CONCLUSION: Overall, this study demonstrated the clinical potential of the SGC scaffold due to its favorable pro-osteo-/angiogenic and osteoimmunomodulatory properties. In addition, it is a promising strategy to develop novel bone repair biomaterials by taking osteoinduction and osteoimmune microenvironment remodeling functions into account.

Quercetin-loaded mesoporous nano-delivery system remodels osteoimmune microenvironment to regenerate alveolar bone in periodontitis via the miR-21a-5p/PDCD4/NF-κB pathway.

BACKGROUND: Impaired osteo-/angiogenesis, excessive inflammation, and imbalance of the osteoimmune homeostasis are involved in the pathogenesis of the alveolar bone defect caused by periodontitis. Unfortunately, there is still a lack of ideal therapeutic strategies for periodontitis that can regenerate the alveolar bone while remodeling the osteoimmune microenvironment. Quercetin, as a monomeric flavonoid, has multiple pharmacological activities, such as pro-regenerative, anti-inflammatory, and immunomodulatory effects. Despite its vast spectrum of pharmacological activities, quercetin's clinical application is limited due to its poor water solubility and low bioavailability. RESULTS: In this study, we fabricated a quercetin-loaded mesoporous bioactive glass (Quercetin/MBG) nano-delivery system with the function of continuously releasing quercetin, which could better promote the bone regeneration and regulate the immune microenvironment in the alveolar bone defect with periodontitis compared to pure MBG treatment. In particular, this nano-delivery system effectively decreased injection frequency of quercetin while yielding favorable therapeutic results. In view of the above excellent therapeutic effects achieved by the sustained release of quercetin, we further investigated its therapeutic mechanisms. Our findings indicated that under the periodontitis microenvironment, the intervention of quercetin could restore the osteo-/angiogenic capacity of periodontal ligament stem cells (PDLSCs), induce immune regulation of macrophages and exert an osteoimmunomodulatory effect. Furthermore, we also found that the above osteoimmunomodulatory effects of quercetin via macrophages could be partially blocked by the overexpression of a key microRNA--miR-21a-5p, which worked through inhibiting the expression of PDCD4 and activating the NF-κB signaling pathway. CONCLUSION: In summary, our study shows that quercetin-loaded mesoporous nano-delivery system has the potential to be a therapeutic approach for reconstructing alveolar bone defects in periodontitis. Furthermore, it also offers a new perspective for treating alveolar bone defects in periodontitis by inhibiting the expression of miR-21a-5p in macrophages and thereby creating a favorable osteoimmune microenvironment.

A prognostic model of idiopathic pulmonary fibrosis constructed based on macrophage and mitochondria-related genes.

BACKGROUND: Studies have shown that mitochondrial function and macrophages may play a role in the development of idiopathic pulmonary fibrosis (IPF). However, the understanding of the interactions and specific mechanisms between mitochondrial function and macrophages in pulmonary fibrosis is still very limited. METHODS: To construct a prognostic model for IPF based on Macrophage- related genes (MaRGs) and Mitochondria-related genes (MitoRGs), differential analysis was performed to achieve differentially expressed genes (DEGs) between IPF and Control groups in the GSE28042 dataset. Then, MitoRGs, MaRGs and DEGs were overlapped to screen out the signature genes. The univariate Cox analysis and the least absolute shrinkage and selection operator (LASSO) algorithm were implemented to achieve key genes. Furthermore, the independent prognostic analysis was employed. The ingenuity pathway analysis (IPA) was employed to further understand the molecular mechanisms of key genes.Next, the immune infiltration analysis was implemented to identify differential immune cells between two risk subgroups. RESULTS: There were 4791 DEGs between IPF and Control groups. Furthermore, 26 signature genes were achieved by the intersection processing. Three key genes including ALDH2, MCL1, and BCL2A1 were achieved, and the risk model based on the key genes was created. In addition, a nomogram for survival forecasting of IPF patients was created based on riskScore, Age, and Gender, and we found that key genes were associated with classical pathways including 'Apoptosis Signaling', 'PI3K/AKT Signaling', and so on. Next, two differential immune cells including Monocytes and CD8 T cells were identified between two risk subgroups. Moreover, we found that MIR29B2CHG and hsa-mir-1-3p could regulate the expression of ALDH2. CONCLUSION: We achieved 3 key genes including ALDH2, MCL1,, and BCL2A1 associated with IPF, providing a new theoretical basis for clinical treatment of IPF.

A Federated Learning and Deep Reinforcement Learning-Based Method with Two Types of Agents for Computation Offload.

With the rise of latency-sensitive and computationally intensive applications in mobile edge computing (MEC) environments, the computation offloading strategy has been widely studied to meet the low-latency demands of these applications. However, the uncertainty of various tasks and the time-varying conditions of wireless networks make it difficult for mobile devices to make efficient decisions. The existing methods also face the problems of long-delay decisions and user data privacy disclosures. In this paper, we present the FDRT, a federated learning and deep reinforcement learning-based method with two types of agents for computation offload, to minimize the system latency. FDRT uses a multi-agent collaborative computation offloading strategy, namely, DRT. DRT divides the offloading decision into whether to compute tasks locally and whether to offload tasks to MEC servers. The designed DDQN agent considers the task information, its own resources, and the network status conditions of mobile devices, and the designed D3QN agent considers these conditions of all MEC servers in the collaborative cloud-side end MEC system; both jointly learn the optimal decision. FDRT also applies federated learning to reduce communication overhead and optimize the model training of DRT by designing a new parameter aggregation method, while protecting user data privacy. The simulation results showed that DRT effectively reduced the average task execution delay by up to 50% compared with several baselines and state-of-the-art offloading strategies. FRDT also accelerates the convergence rate of multi-agent training and reduces the training time of DRT by 61.7%.

Ovulation induction with clomiphene citrate or letrozole following laparoscopy in infertile women with minimal to mild endometriosis: a prospective randomised controlled trial.

We conducted a prospective randomised controlled trial to explore the efficacy of clomiphene citrate (CC) and Letrozole (LTZ) for improving fecundity in infertile women with minimal to mild endometriosis after operative laparoscopy. We found that the ovulation rate of LTZ (88.7%) and CC (84.5%) were significantly higher than that of Control (70.5%) (p < .001). However, there was no significant difference in cumulative clinical pregnancy rates at 3, 6, 12 months after laparoscopy among the three groups (LTZ: 30%, 34.3%, 38.6% vs CC: 28.6%, 42.9%, 50.0% vs Control: 18.6%, 24.3%, 31.4%, respectively). No significant difference was observed in live-birth rate among the three groups (p = 1.125). For infertile women with minimal to mild endometriosis, ovulation induction with letrozole or clomiphene citrate after laparoscopy significantly increases ovulation rate, which are comparable between them; but does not demonstrate a significant advantage on improving pregnancy rate and live-birth rate when compared to laparoscopy alone.Impact statementWhat is already known on this subject? Endometriosis significantly decreases fecundity of women. Operative laparoscopy was recommended as an effective option to increase spontaneous pregnancy rate in infertile women with minimal to mild endometriosis. However, there is still no optimum treatment strategy for improving fertility of women with endometriosis.What do the results of this study add? For infertile women with minimal to mild endometriosis, ovulation induction with letrozole or clomiphene citrate after laparoscopy significantly increases ovulation rate, which are comparable between them; but does not demonstrate a significant advantage on improving pregnancy rate and live-birth rate when compared to laparoscopy alone.What are the implications of these findings for clinical practice and/or further research? Our results suggest that operative laparoscopy in conjunction with ovulation induction may improve fertility of women with minimal to mild endometriosis. Further research could focus on prolonging cycles of ovulation induction or choosing alternative ovarian stimulation protocols. More RCTs are still needed to compare the efficacy of letrozole with CC in ovulation induction.

Purification, Characterization, Prebiotic Preparations and Antioxidant Activity of Oligosaccharides from Mulberries.

A water-soluble oligosaccharide termed EMOS-1a was prepared by enzymatic hydrolysis of polysaccharides purified from mulberries by column chromatography. The chemical structure of the purified fraction was investigated by ultraviolet spectroscopy, Fourier-transform infrared spectroscopy, and gas chromatography-mass spectrometry, which indicated that galactose was the main constituent of EMOS-1a. Chemical analyses showed that the uronic acid and sulfate content of EMOS-1a were 5.6% and 8.35%, respectively, while gel permeation chromatography showed that EMOS-1a had an average molecular weight of 987 Da. The antioxidant activities of EMOS-1a were next investigated, and EMOS-1a exhibited concentration-dependent 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity, Trolox equivalent antioxidant capacity, and ferric reducing antioxidant power. The level of proliferation of Lactobacillus rhamnosus reached 1420 ± 16% when 4% (w/v) EMOS-1a was added, where the number of colonies in MRS (de Man, Rogosa, and Sharpe) medium with no added oligosaccharide was defined as 100% proliferation. These results indicate that the oligosaccharide EMOS-1a could be used as a natural antioxidant in prebiotic preparations.

Expression of SOX2, NANOG and OCT4 in a mouse model of lipopolysaccharide-induced acute uterine injury and intrauterine adhesions.

BACKGROUND: Activation of inflammation-mediated endometrial injury is suggested to play a decisive role in pathogenesis of intrauterine adhesion (IUA). The stem cell theory of endometrial diseases has been given a hotspot, in that human endometrial stem cells have been isolated from the endometrium. Three transcription factors that play key roles in maintaining pluripotency and self-renewal in stem cells are sex-determining region Y-box2 (SOX2), Nanog homebox (NANOG), and octamer-binding protein (OCT4), which may be responsible for the damage or repair process of uterine endometrium. We aim to investigate the expression of SOX2, NANOG and OCT4 in a mouse model of acute uterine injury induced by peritoneal injection of lipopolysaccharide (LPS) and also analyze their changes in endometrium of women with IUA. METHODS: The mouse uterine horns were collected at 0 h, 6 h, 12 h, 18 h or 24 h after a single dose of LPS or PBS injection. Meanwhile, we recruited 19 women with IUA diagnosed by hysteroscopy and 16 disease-free women as control group. Endometrial tissue samples were collected. SOX2, NANOG, and OCT4 expression were analyzed with Quantitative Real-time Polymerase Chain Reaction and Western blotting assay. RESULTS: In a mouse model of acute uterine injury, there was significant upregulation of NANOG at 6 h, SOX2 and OCT4 at 12 h compared with the values before injection or PBS injection. NANOG expression reached a peak at 6 h, while SOX2 and OCT4 peaked later at 12 h after LPS treatment. NANOG mRNA and protein expressions were significantly higher in endometrium of IUA patients compared to those of the control group. CONCLUSIONS: Expression of pluripotency factors SOX2, NANOG and OCT4 increased in a mouse model of LPS-induced acute uterine injury. NANOG peaked earlier followed by the other two factors before returning to baseline levels. NANOG but not SOX2 and OCT4 expression was overexpressed in the endometrium of women with IUA. They may be involved in the formation or restoration of IUA, and their roles in pathogenesis of IUA need to be further studied.

Comparison of clomiphene citrate and letrozole for ovulation induction in women with polycystic ovary syndrome: a prospective randomized trial.

To compare the therapeutic efficacy of clomiphene citrate (CC) and letrozole (LE) on ovulation, pregnancy, and live birth in women with polycystic ovary syndrome (PCOS); and to ensure if LE can replace CC as the first-line therapy for ovulation induction in these women. This is a prospectively, randomized, controlled trial in the tertiary hospital. Two-hundred and sixty-eight anovulatory PCOS patients were treated by CC or CC plus metformin and LE or LE plus metformin for three continuous cycles or conception; their ovulation rates, pregnancy rates, and live birth rates were calculated and compared. No significant difference was noted among the four groups regarding to the baseline data of clinical manifestations, serum sex hormone levels, and serum insulin levels. A total of 240 patients completed the therapies. The ovulation rate was significantly higher in the group LE than the group CC; however, no significant difference was noted between the groups LE and CC, CC, and CC + MET, or LE and LE + MET in the pregnancy rate, abortion rate, and live birth rate. No birth defect was found in the total of 63 newborns. CC regimen was still recommended to be the first-line therapy of ovulation induction for PCOS.

[Pregnant Outcomes of Multiparae in Women with Advanced Age (≥35 years)after the 2008 Wenchuan Earthquake].

OBJECTIVE: To evaluate pregnancy outcomes of multiparae in women with advanced age (≥35 yr.) after the 2008 Wenchuan earthquake. METHODS: Clinical data of 542 pregnant women with prenatal care in Wenchuan during 20082013 were reviewed,comparing preconception conditions,pregnant rates,pregnant complications,and perinatal outcomes between those younger ( n=176) and older ( n=366) than 35 years. RESULTS: In the 542 women,622 conceptions were reported,with 517 deliveries and 522 live births. The women with advanced age had lower cumulative pregnancy rate (twoyear),higher incidence of hypertensive disorders of pregnancy,gestational diabetes,multiple pregnancy,fetal distress,low birth weight and birth defects than their younger counterparts. The younger women also had higher term live birth rate and lower miscarriage rate. But the differences showed no statistical significance. CONCLUSION: Prenatal care brings similar pregnant outcomes to multiparae in women with advance aged and younger aged.

miR-196a overexpression activates the MEK/ERK signal and represses the progesterone receptor and decidualization in eutopic endometrium from women with endometriosis.

STUDY QUESTION: Do microRNAs (miRNAs) contribute to aberrant progesterone receptor (PGR) expression in the eutopic endometrium of women with endometriosis? SUMMARY ANSWER: miR-196a upregulates MEK/ERK signalling, mediating a downregulation of PGR expression in the eutopic endometrium of women with minimal or mild endometriosis. WHAT IS KNOWN ALREADY: Implantation failure is strongly suggested as an underlying cause for the observed infertility in minimal or mild endometriosis. Progesterone resistance, which is mainly caused by aberrantly expressed progesterone receptor in the eutopic endometrium, is considered as a key factor of decreased endometrial receptivity; thus far, epigenetics, but not miRNA, has been shown to affect PGR expression in the endometrium. STUDY DESIGN SIZE, DURATION: Microarray analysis was used to analyse the eutopic endometrium. The differential expression of miR-196a was validated. Bioinformatics analysis predicted that miR-196a targets the 3'-untranslated region (UTR) of the PGR. The relationship between the miR-196a level and PGR expression was studied and the role of the MEK/ERK signal pathway was investigated. PARTICIPANTS/MATERIALS, SETTING, METHODS: Total RNA was extracted from eutopic endometrium samples in three infertile women with mild/minimal endometriosis and three disease-free control subjects. The miRNA and mRNA expression levels were analysed by microarray analysis. The miR-196a expression was validated by qRT-PCR [endometriosis (n = 22) and control (n = 20)], while functional analysis utilised in vitro transfection of endometrial stromal cells (ESCs), induction of decidualization of ESCs, and luciferase reporter assays in 293 T cell lines. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 66 dysregulated miRNAs and 357 dysregulated mRNAs were screened by microarray analysis. miR-196a and P-MEK/P-ERK were both found to be significantly upregulated in the eutopic endometrium in patients with mild/minimal endometriosis. PGR and PGR-B mRNA were inhibited by miR-196a overexpression and upregulated by miR-196a inhibition. Luciferase reporter failed to confirm the target regulation of miR-196a on PGR. Transfection of ESCs with a miR-196a mimic led to an increase in the P-MEK/P-ERK protein levels, decrease in the PGR protein levels, and atypical decidualization. Following miR-196a inhibition, the P-MEK/P-ERK protein was downregulated and the PGR protein was upregulated. Inhibition of P-MEK/P-ERK also increased PGR expression. LARGE SCALE DATA: Data are presented in Supplementary Tables SI and SII. LIMITATIONS REASONS FOR CAUTION: This study focused on the role of miR-196a, and therefore does not involve other miRNAs; hence, it is possible that other miRNAs may also be responsible for progestin resistance in endometriosis. WIDER IMPLICATIONS OF THE FINDINGS: Our data revealed altered miRNA expression and activated MEK/ERK signalling in the eutopic endometrium in minimal or mild endometriosis. We showed that the miR-196a level is associated with reduced expression of PGR isoforms through MEK/ERK, suggesting that miR-196a and MEK/ERK are both potential biomarkers of endometriosis. These results provide a novel approach to target the mechanisms behind progesterone resistance in endometriosis. STUDY FUNDING/COMPETING INTERESTS: This research was supported by the National Natural Science Foundation of China (No. 81370693). The authors have no conflicts of interest.

Are serum chemerin levels different between obese and non-obese polycystic ovary syndrome women?

The objective of this study is to measure serum chemerin levels in women with polycystic ovary syndrome (PCOS) and assess their relationship with clinical, metabolic, and hormonal parameters. One hundred eighteen PCOS women and 114 healthy women were recruited in this study. Their blood pressure, body mass index (BMI), waist circumference and waist-to-hip ratio (WHR), fasting insulin (FIN), fasting plasma glucose (FPG), blood serum sex hormone, and blood lipid were measured. Serum chemerin, leptin, and adiponectin were measured by ELISA. Serum chemerin was significantly higher in the obese PCOS group (47.62 ± 11.27 ng/mL) compared with non-obese PCOS (37.10 ± 9.55 ng/mL) and the obese (33.71 ± 6.17 ng/mL) and non-obese (25.78 ± 6.93 ng/mL) control groups (p < 0.05). Serum chemerin was positively related to BMI, waist circumference, WHR, testosterone (T), FPG, FIN, homeostasis model assessment of insulin resistance (HOMA-IR), total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL-C), LDL-C/high-density lipoprotein(HDL-C), TC/HDL-C and serum leptin, while negatively related to glucose-to-insulin ratio (G/I), HDL-C, and adiponectin levels. Multiple linear regression analysis revealed HOMA-IR, leptin, and TC were the significant influencing factors of chemerin levels (p < 0.05). Increased serum chemerin in PCOS woman with or without obesity suggested that chemerin may be involved in the development of the pathogenesis of PCOS.

Outcomes of Bilateral Uterine Artery Chemoembolization in Combination with Surgical Evacuation or Systemic Methotrexate for Cervical Pregnancy.

STUDY OBJECTIVE: To evaluate the use of bilateral uterine artery chemoembolization in combination with surgical evacuation or systemic methotrexate (MTX) in the conservative treatment of cervical pregnancy (CP). DESIGN: Clinical case series (Canadian Task Force classification II-3). SETTING: Tertiary university hospital. PATIENTS: Women with a CP who were treated at West China Second University Hospital of Sichuan University between January 2006 and January 2013. INTERVENTION: Bilateral uterine artery chemoembolization in combination with surgical evacuation or systemic MTX. MEASUREMENTS AND MAIN RESULTS: ß-Human chorionic gonadotropin (ß-hCG), cervical mass, blood transfusion, length of hospital stay, future menstruation, and fertility were assessed. Thirty-nine patients were successfully treated by chemoembolization in combination with surgical evacuation or systemic MTX. All massive bleeding was controlled after chemoembolization, and the 35 subsequent evacuation surgeries were uneventful. Nine patients received blood transfusions. The time for serum ß-hCG normalization was 28.7 ± 9.8 days (range, 7-60). The time for CP mass disappearance by ultrasonography was 27.0 ± 6.9 days (range, 11-48) days. The length of hospital stay was 7.7 ± 4.9 days (range, 3-33). Complications were mainly fever and pain, which were alleviated with symptomatic treatment. Thiry-eight patients had recovered their normal menstruation, and 7 patients had future pregnancies at follow-up. CONCLUSION: Bilateral uterine artery chemoembolization is effective in controlling and preventing massive hemorrhage associated with CP. It is proved to treat CP with optimal recovery time, few outpatient follow-ups, and efficient fertility preservation when combined with surgical evacuation or systemic MTX.

[A pilot study of serum anti-Mullerian hormone in diagnosis of polycystic ovary syndrome based on 2012 Chinese polycystic ovary syndrome diagnosis criteria].

OBJECTIVE: Based on 2012 Chinese polycystic ovary syndrome (PCOS) diagnosis criteria, we detect the serum anti-Müllerian hormone (AMH) levels in PCOS patients, to evaluate the diagnosis value of AMH for PCOS. METHODS: Totally 217 PCOS patients were chosen as study group and 204 non-PCOS women were as controls. Their clinical information (body weight, score for acne and hirsutism), ultrasonography for ovarian volume and the number of small follicle, and blood sample detected for hormonal and metabolic parameters were obtained. Spearman's analysis and the receiver operating characteristic curve (ROC curve) were used to assess relevance and the diagnostic efficiency of AMH in PCOS. RESULTS: Serum AMH level was significantly higher in PCOS group compared with the control group (105.46 versus 26.28 pmol/L, P<0.01). Serum AMH were positively related to Ferriman and Gallwey (F-G) score (r=0.526, P<0.01), global acne grading system (GAGS) score (r=0.359, P<0.01), total testosterone (r=0.514, P<0.01), LH/FSH ratio (r=0.542, P<0.01), fasting plasma glucose (r=0.373, P<0.01), fasting insulin (r=0.168, P=0.008), homeostasis model assessment for insulin resistance (HOMA-IR) index (r=0.182, P=0.004), total cholesterol (r=0.247, P<0.01), triglyceride (r=0.235, P<0.01), total ovarian volume (r=0.204, P=0.008), and mean number of small follicle (r=0.693, P<0.01). The area under the ROC curve for PCOS diagnosed by AMH was 0.954 (P<0.01). the threshold of AMH for PCOS diagnosis was 57.76 pmol/L, diagnostic efficiency was high (sensitivity 95.1%, specificity 89.3%). CONCLUSION: Based on 2012 Chinese PCOS diagnosis criteria, serum AMH level elevated in PCOS, and correlated with women's hormonal imbalance and abnormal follicular development.

Increased expression of the pluripotency markers sex-determining region Y-box 2 and Nanog homeobox in ovarian endometriosis.

BACKGROUND: The precise etiology of endometriosis is not fully understood; the involvement of stem cells theory is a new hypothesis. Related studies mainly focus on stemness-related genes, and pluripotency markers may play a role in the etiology of endometriosis. We aimed to analyze the transcription pluripotency factors sex-determining region Y-box 2 (SOX2), Nanog homeobox (NANOG), and octamer-binding protein 4 (OCT4) in the endometrium of reproductive-age women with and without ovarian endometriosis. METHODS: We recruited 26 women with laparoscopy-diagnosed ovarian endometriosis (endometriosis group) and 16 disease-free women (control group) to the study. Endometrial and endometriotic samples were collected. SOX2, NANOG, and OCT4 expression were analyzed with quantitative real-time polymerase chain reaction, western blotting, and immunohistochemistry. RESULTS: Compared to the control group, SOX2 mRNA and protein expression was significantly higher in the eutopic endometrium of participants in the endometriosis group. In the endometriosis group, SOX2 and NANOG mRNA and protein expression were significantly increased in ectopic endometrium compared with eutopic endometrium; there was a trend towards lower OCT4 mRNA expression and higher OCT4 protein expression in ectopic endometrium. CONCLUSIONS: The transcription pluripotency factors SOX2 and NANOG were overexpression in ovarian endometriosis, their role in pathogenesis of endometriosis should be further studied.

Application of the ankle pump method in a sitting position to evaluate calf perforating veins by color Doppler ultrasound.

OBJECTIVE: We investigated the feasibility and efficacy of assessing calf perforating veins (PVs) using the ankle pump in a sitting position (AP-sit) method by color Doppler ultrasound. METHODS: We performed a multicenter prospective clinical trial between November 2022 and October 2023. Eligible patients with chronic venous disease and healthy controls were enrolled. The calf PVs were assessed using three different methods: manual compression in a standing position, manual compression in a sitting position, and AP-sit method. The reflux durations and detection rate of incompetent PVs (IPVs) were compared among the three methods. The number and diameter of calf PVs and distribution of IPVs were analyzed. RESULTS: A total of 50 patients with chronic venous disease and 50 healthy controls were included. There were 173 calves analyzed, including 97 healthy calves and 76 calves with chronic venous disease. The number of PVs per calf was higher in the diseased calves (median, 7.0; interquartile range [IQR], 6.0-8.0) than in the healthy calves (median, 5.0; IQR, 3.0-6.0; P < .001). The diameter of IPVs (median, 2.3 mm; IQR, 2.0-3.1 mm) was larger than that of competent PVs (median, 1.4 mm; IQR, 1.2-1.7 mm). Most of the IPVs (78.8%) were located in the medial and posterior middle of the calf. The reflux duration induced by the AP-sit method was greater than that induced by the manual compression methods (P < .001). Although the AP-sit method had a higher detection rate (92.0%) of IPVs than the manual compression methods (71.7% and 74.3% for standing and sitting, respectively; P < .001), especially in the distal lower leg, the manual compression methods found IPVs not found using the AP-sit method. CONCLUSIONS: Diseased calves with chronic venous disease have more PVs than do healthy calves. IPVs are commonly larger than competent PVs, with most IPVs located in the medial and posterior middle of the calf. Most importantly, the AP-sit method provides a convenient and effective approach for assessing the calf PVs, especially those located in the distal calf, as an alternative or complementary method to traditional manual compression, which is valuable in the daily practice of sonographers.

Influence of Crosslink Density on Electrical Performance and Rheological Properties of Crosslinked Polyethylene.

To investigate the influence of the crosslinked polyethylene (XLPE) structure on electrical performance, various analytical methods were employed to study polyethylene structures with different degrees of crosslinking. Dynamic rheological analysis was conducted to determine material shear viscosity, dynamic viscosity, storage modulus (G'), loss modulus (G″), and other rheological parameters. Additionally, the electrical performance of the material was analyzed by studying the phenomenon of space charge accumulation under direct current voltage. The results indicate that with an increasing mass fraction of the crosslinking agent, the crosslink density of crosslinked polyethylene initially increases and then decreases. When the dicumyl peroxide (DCP) content exceeds 1.0 wt.%, there is an accumulation of like-polarity space charges. The best rheological processing performance of crosslinked polyethylene is observed when the DCP content is in the range of 1.0-1.5 wt.%.

Quercetin-Loaded Bioglass Injectable Hydrogel Promotes m6A Alteration of Per1 to Alleviate Oxidative Stress for Periodontal Bone Defects.

Periodontal disease ranks third among noncommunicable illnesses, behind cancer and cardiovascular disease, and is closely related to the occurrence and progression of various systemic diseases. However, elucidating the processes of periodontal disease and promoting periodontal bone regeneration remains a challenge. Here, quercetin is demonstrated to reduce the oxidative stress state of orofacial mesenchymal stem cells (OMSCs) in vitro and to affect the osteogenic growth of OMSCs through molecular mechanisms that mediate the m6A change in Per1. Nevertheless, the limited therapeutic efficacy of systemic medication and the limitations of local medication resulting from the small, moist, and highly dynamic periodontal environment make it challenging to treat periodontal tissues with medication. Herein, a biosafe injectable hydrogel drug-controlled delivery system is constructed as a bone-enhancing factory and loaded with quercetin to treat oxidative stress injury in periodontal tissues. This drug-carrying system made up of nanoscale bioglass microspheres and a light-cured injectable hydrogel, allows effective drug particle loading and cementation in the dynamic and moist periodontal environment. Furthermore, the system demonstrates the ability to stimulate OMSCs osteogenic differentiation in a Per1-dependent manner, which ultimately promotes periodontal bone repair, suggesting that this system has potential for clinical periodontal therapy.

Metformin-Mediated Fast Charge-Reversal Nanohybrid for Deep Penetration Piezocatalysis-Augmented Chemodynamic Immunotherapy of Cancer.

Immune checkpoint blockade (ICB) therapy still suffers from insufficient immune response and adverse effect of ICB antibodies. Chemodynamic therapy (CDT) has been demonstrated to be an effective way to synergize with ICB therapy. However, a low generation rate of reactive oxygen species and poor tumor penetration of CDT platforms still decline the immune effects. Herein, a charge-reversal nanohybrid Met@BF containing both Fe3O4 and BaTiO3 nanoparticles in the core and Metformin (Met) on the surface was fabricated for tumor microenvironment (TME)- and ultrasound (US)-activated piezocatalysis-chemodynamic immunotherapy of cancer. Interestingly, Met@BF had a negative charge in blood circulation, which was rapidly changed into positive when exposed to acidic TME attributed to quaternization of tertiary amine in Met, facilitating deep tumor penetration. Subsequently, with US irradiation, Met@BF produced H2O2 based on piezocatalysis of BaTiO3, which greatly enhanced the Fenton reaction of Fe3O4, thus boosting robust antitumor immune response. Furthermore, PD-L1 expression was inhibited by the local released Met to further augment the antitumor immune effect, achieving effective inhibitions for both primary and metastatic tumors. Such a combination of piezocatalysis-enhanced chemodynamic therapy and Met-mediated deep tumor penetration and downregulation of PD-L1 provides a promising strategy to augment cancer immunotherapy.

A multifunctional quercetin/polycaprolactone electrospun fibrous membrane for periodontal bone regeneration.

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A One-Stone-Two-Birds Strategy of Targeting Microbubbles with "Dual" Anti-Inflammatory and Blood-Brain Barrier "Switch" Function for Ischemic Stroke Treatment.

Inflammation is considered to be the main target of the development of new stroke therapies. There are three key issues in the treatment of stroke inflammation: the first one is how to overcome the blood-brain barrier (BBB) to achieve drug delivery, the second one is how to select drugs to treat stroke inflammation, and the third one is how to achieve targeted drug delivery. In this study, we constructed hydrocortisone-phosphatidylserine microbubbles and combined them with ultrasound (US)-targeted microbubble destruction technology to successfully open the BBB to achieve targeted drug delivery. Phosphatidylserine on the microbubbles was used for its "eat me" effect to increase the targeting of the microvesicles. In addition, we found that hydrocortisone can accelerate the closure of the BBB, achieving efficient drug delivery while reducing the entry of peripheral toxins into the brain. In the treatment of stroke inflammation, it was found that hydrocortisone itself has anti-inflammatory effects and can also change the polarization of microglia from the harmful pro-inflammatory M1 phenotype to the beneficial anti-inflammatory M2 phenotype, thus achieving dual anti-inflammatory effects and enhancing the anti-inflammatory effects in ischemic areas after stroke, well reducing the cerebellar infarction volume by inhibiting the inflammatory response after cerebral ischemia. A confocal microendoscope was used to directly observe the polarization of microglial cells in living animal models for dynamic microscopic visualization detection showing the advantage of being closer to clinical work. Taken together, this study constructed a multifunctional targeted US contrast agent with the function of "one-stone-two-birds", which can not only "on-off" the BBB but also have "two" anti-inflammatory functions, providing a new strategy of integrated anti-inflammatory targeted delivery and imaging monitoring for ischemic stroke treatment.